[ERGOGENIC SPORT SUPPLEMENTS FOR ATHLETES].
Arieli, Rakefet; Lahav, Yair
2016-06-01
Use of performance-enhancing supplements occurs at all levels of sports, from recreational athletes to professional athletes. Although some supplements do enhance athletic performance, many have no proven benefits and have adverse effects. Nutritional supplements are categorized into the following categories: I. Apparently Effective. II. Possibly Effective. III. Too Early To Tell. IV. Apparently Ineffective. This article will review 4 ergogenic supplements which are categorized in the first category--"Apparently Effective"--1) Buffer agents 2) Creatine 3) Caffeine and 4 Nitric Oxide. Given the widespread use of performance enhancing supplements, physicians, and dietitians should be prepared to counsel athletes about their effectiveness, safety and legality.
Golder, Su; Loke, Yoon K; Zorzela, Liliane
2014-06-01
Research indicates that the methods used to identify data for systematic reviews of adverse effects may need to differ from other systematic reviews. To compare search methods in systematic reviews of adverse effects with other reviews. The search methodologies in 849 systematic reviews of adverse effects were compared with other reviews. Poor reporting of search strategies is apparent in both systematic reviews of adverse effects and other types of systematic reviews. Systematic reviews of adverse effects are less likely to restrict their searches to MEDLINE or include only randomised controlled trials (RCTs). The use of other databases is largely dependent on the topic area and the year the review was conducted, with more databases searched in more recent reviews. Adverse effects search terms are used by 72% of reviews and despite recommendations only two reviews report using floating subheadings. The poor reporting of search strategies in systematic reviews is universal, as is the dominance of searching MEDLINE. However, reviews of adverse effects are more likely to include a range of study designs (not just RCTs) and search beyond MEDLINE. © 2014 Crown Copyright.
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.
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)
EIA - Its Potential Application to Appropriate Technology in Developing Countries.
ERIC Educational Resources Information Center
Goode, Pamela M.; Johnstone, Alastair I.
1988-01-01
Provided is a definition of "appropriate technology." Describes some of the less apparent adverse effects of such technology on society and the environment. Stresses the need for environmental impact assessment of small-scale projects and the advantages and disadvantages of such practices. (CW)
NASA Technical Reports Server (NTRS)
1971-01-01
The probable environmental impact and adverse effects of the Lewis Research Center are assessed. The Cleveland and Plum Brook facilities are briefly described. It is felt that the absence of harmful environmental impact from the Cleveland site is apparent, and the monitoring at the Plum Brook reactor facility shows the effectiveness of effluent controls. The probable adverse effects are considered for air, water, and noise pollution, and radioactive and hazardous waste storage and disposal; it is concluded that all emissions are maintained below Federal, and local standards. There are no appropriate alternatives to the operation of the Center, and no improvement in environmental quality would result from relocation. The relationship between local short-term productivity is briefly discussed. No adverse comment has been received from public agencies or private organizations or individuals.
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).
Wu, Fuyong; Hu, Junli; Wu, Shengchun; Wong, Ming Hung
2015-06-01
A pot trial was conducted to investigate the effects of three arbuscular mycorrhizal (AM) fungi species, including Glomus geosporum BGC HUN02C, G. versiforme BGC GD01B, and G. mosseae BGC GD01A, on grain yield and arsenic (As) uptake of upland rice (Zhonghan 221) in As-spiked soils. Moderate levels of AM colonization (24.1-63.1 %) were recorded in the roots of upland rice, and up to 70 mg kg(-1) As in soils did not seem to inhibit mycorrhizal colonization. Positive mycorrhizal growth effects in grain, husk, straw, and root of the upland rice, especially under high level (70 mg kg(-1)) of As in soils, were apparent. Although the effects varied among species of AM fungi, inoculation of AM fungi apparently enhanced grain yield of upland rice without increasing grain As concentrations in As-spiked soils, indicating that AM fungi could alleviate adverse effects on the upland rice caused by As in soils. The present results also show that mycorrhizal inoculation significantly (p < 0.05) decreased As concentrations in husk, straw, and root in soils added with 70 mg kg(-1) As. The present results suggest that AM fungi are able to mitigate the adverse effects with enhancing rice production when growing in As-contaminated soils.
Effects of pesticides on Canada Geese
Blus, L.J.; Rusch, Donald H.; Samuel, Michael D.; Humburg, Dale D.; Sullivan, Brian D.
1998-01-01
This paper summarizes published and unpublished sources relating to exposure of Canada geese (Branta canadensis) to pesticides, emphasizing documented episodes of poisoning by organochlorine (OC), organophosphorus (OP), and carbamate compounds. Canada geese accumulate the lipid-soluble OC compounds, although they have a lower potential for biomagnification of these pesticides than animals at higher trophic levels in food webs. Low residues of p,p'-DDT and its metabolite p,p'-DDE were frequently found in tissues and eggs of Canada geese, but they had no apparent adverse effects on reproductive success or eggshell thickness. Likewise, in an orchard system in central Washington state, the OC rodenticide endrin accumulated in tissues and eggs of Canada geese without apparent adverse effect. In contrast, ingestion of seeds treated with the OC heptachlor caused mortality, lowered reproductive success, and caused a local population decline of geese in Oregon and Washington. In recent years, the most persistent OC's have been banned by law and replaced with less persistent carbamate and OP compounds that do not readily accumulate in animal tissues. However, many of these compounds are acutely toxic and have caused numerous die-offs of Canada geese. Among OP compounds, diazinon was responsible for most reported die-offs (41 incidents involving >535 geese), whereas parathion applied alone or jointly with methyl parathion accounted for most reported mortalities (8 incidents involving >3,000 geese). Three other OP's, a carbamate (carbofuran), zinc phosphide, and strychnine also caused goose die-offs. Mortality from anticholinesterase (antiChE) compounds occurs relatively soon after exposure and death can usually be diagnosed by evaluation of brain cholinesterase (thE) activity. Because geese are primarily grazers, the main route of exposure to antiChE's is apparently ingestion of contaminated grasses and forbs; dermal absorption and inhalation are other routes. Despite the widespread die-offs of Canada geese from antiChE insecticides, there is no evidence of adverse effects on population levels. It is not known how sublethal antiChE exposure relates to long-term survival and reproductive success of birds.
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.
Kaidonis, J A
2012-08-01
Non-carious tooth surface loss or tooth wear is becoming an increasingly significant factor affecting the long-term health of the dentition. The adverse effects of tooth wear are becoming increasingly apparent both in young persons and, as more people retain their teeth, into old age. This situation challenges the preventive and restorative skills of dental practitioners.
Military Hospitalizations among Deployed US Service Members Following Anthrax Vaccination, 1998-2001
2006-04-01
be- known severe adverse health effects , excluding mortality and pregnancy-related outcomes , associated with anthrax vaccination. Outcomes were...January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases...talization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax
Effects of low-frequency magnetic fields on embryonic development and pregnancy.
Juutilainen, J
1991-06-01
Experimental and epidemiologic studies on the effects of low-frequency magnetic fields on pregnancy are reviewed. The literature suggests that these fields have adverse effects on chick embryo development. The interaction mechanism is not known. The results of experiments with mammals are inconsistent. There is more evidence of effects on mice than on rats, and the data suggest that fetal loss might be increased rather than malformations. Most of the epidemiologic studies related to pregnancy and low-frequency magnetic fields have concerned operators of a video display terminal (VDT). The results do not provide evidence for an association between adverse pregnancy outcome and use of a VDT. Other (stronger) sources of low-frequency magnetic fields have been addressed in only a few studies. It is not yet possible to conclude whether occupational or residential exposure to low-frequency magnetic fields affects human prenatal development. There is an apparent need for further investigation.
Oily Skin: A review of Treatment Options
Miller, Richard A.
2017-01-01
One of the most common dermatologic concerns is oily skin, and the demand for effective treatment options is ever apparent. This review article addresses numerous topical treatment options such as retinoids, olumacostat glasaretil, and various cosmeceutical agents. several systemic and procedural techniques that incorporate isotretinoin, spironolactone, oral contraceptives, botulinum toxin, photodynamic therapy, and lasers are reviewed as well. Each treatment option is analyzed in terms of the proposed mechanism of action, efficacy reported in the literature, and potential adverse effects. PMID:28979664
Effect of Reiki on symptom management in oncology.
Demir, Melike; Can, Gulbeyaz; Celek, Enis
2013-01-01
Reiki is a form of energy therapy in which the therapist, with or without light touch, is believed to access universal energy sources that can strengthen the body's ability to heal itself, reduce inflammation, and relieve pain and stress. There is currently no licensing for Reiki nor, given its apparent low risk, is there likely to be. Reiki appears to be generally safe, and serious adverse effects have not been reported. So in this article provides coverage of how to use Reiki in oncology services.
[Reversible neurotoxicity secondary to metronidazole: report of one case].
Retamal-Riquelme, Eva; Soto-San Martín, Hernán; Vallejos-Castro, José; Galdames-Poblete, Daniel
2014-03-01
Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.
Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.
Wu, Min; Xiao, Guang-hua; Yao, Min; Zhang, Jian-ming; Zhang, Xin; Zhou, Ya-bing; Zhang, Jing-yan; Wang, Shu-xia; Ma, Bo; Chen, Yan-ping
2009-08-01
To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.
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.
Emerson, E
2013-07-01
People with intellectual disabilities have poorer health than their non-disabled peers. They are also more likely to be exposed to a wide range of environmental adversities in childhood. Research undertaken in the general population has demonstrated that exposure to environmental adversity in childhood can have an adverse impact on health and well-being across the life course. Recently, research in this area has added new breadth and depth to our understanding of: (1) the extent to which cumulative exposure to environmental adversities across the life course, but especially in early childhood, can reduce health and well-being; (2) the social, psychological and biological mediating pathways through which environmental adversities may impair health; (3) the processes associated with resilience and vulnerability in the face of exposure to adversity; and (4) the social significance of these effects in accounting for the magnitude of the inequalities in health that are apparent both between and within populations. This new knowledge is making a significant contribution to the development of social policies that seek to combine health gain with the reduction in health inequalities. This paper attempts to apply this knowledge to research aimed at understanding and improving the health and well-being of people with intellectual disabilities. © 2012 The Author. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.
Ureme, S O; Ibeagha, I D; Maduka, I G; Ibeagbulam, O G
2007-01-01
Methaemoglobin, carboxyhaemoglobin concentrations and some haematological parameters were studied in fifty tobacco snuff addicts (40 males and 10 females) in some villages of Anambra State, Nigeria. The aim was to investigate possible adverse effects of tobacco snuff in addicts in Igbos of Anambra State. Fifty apparently healthy persons (25 males and 25 females) who do not inhale snuff were used as controls. The age range of tests and control subjects was 25-65 years. The results showed no statistically significant difference when the tests group was compared with the control group. A comparison of the results on the basis of sex, age and period of exposure, showed no significant differences. Blood picture in test and control groups was normocytic and normochromic. The results suggest that tobacco snuff may not have any adverse effect on haemoglobin metabolism and erythropoiesis.
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.
McLaren, Lindsay; Patterson, Steven; Thawer, Salima; Faris, Peter; McNeil, Deborah; Potestio, Melissa; Shwart, Luke
2016-06-01
To examine the short-term impact of fluoridation cessation on children's caries experience measured by tooth surfaces. If there is an adverse short-term effect of cessation, it should be apparent when we focus on smooth tooth surfaces, where fluoride is most likely to have an impact for the age group and time frame considered in this study. We examined data from population-based samples of school children (Grade 2) in two similar cities in the province of Alberta, Canada: Calgary, where cessation occurred in May 2011 and Edmonton where fluoridation remains in place. We analysed change over time (2004/2005 to 2013/2014) in summary data for primary (defs) and permanent (DMFS) teeth for Calgary and Edmonton, for all tooth surfaces and smooth surfaces only. We also considered, for 2013/2014 only, the exposed subsample defined as lifelong residents who reported usually drinking tap water. We observed, across the full sample, an increase in primary tooth decay (mean defs - all surfaces and smooth surfaces) in both cities, but the magnitude of the increase was greater in Calgary (F-cessation) than in Edmonton (F-continued). For permanent tooth decay, when focusing on smooth surfaces among those affected (those with DMFS>0), we observed a non-significant trend towards an increase in Calgary (F-cessation) that was not apparent in Edmonton (F-continued). Trends observed for primary teeth were consistent with an adverse effect of fluoridation cessation on children's tooth decay, 2.5-3 years post-cessation. Trends for permanent teeth hinted at early indication of an adverse effect. It is important that future data collection efforts in the two cities be undertaken, to permit continued monitoring of these trends. © 2016 The Authors. Community Dentistry and Oral Epidemiology Published by John Wiley & Sons Ltd.
Assessment of pollution in road runoff using a Bufo viridis biological assay.
Dorchin, A; Shanas, U
2010-12-01
Road runoff is a major source of environmental pollution, significantly threatening nearby aquatic habitats. Chemical analyses indicate high pollutant concentrations in the road's "first flush", but bioassays are more advantageous for addressing the cumulative effects of the numerous pollutants within the runoff. We used Bufo viridis embryos and larvae to assess the toxicity of road runoff from two major highways in Israel. We show, for the first time, that exposure to midseason runoff not only has an adverse effect on growth and development rates of B. viridis larvae but can also lead to increased rates of morphological deformations. Seasonal first flushes, despite having higher metal concentrations, did not adversely affect the toad larvae, apparently due to a counter effect of organic matter that potentially served as a supplementary energy resource. Road runoff can be a major cause for a qualitative decrease in the quality of aquatic habitats threatening amphibians in Israel. Copyright © 2010 Elsevier Ltd. All rights reserved.
Huang, Andrew C; Bishop, Christine A; McKibbin, René; Drake, Anna; Green, David J
2017-08-10
Long-distance migratory birds in North America have undergone precipitous declines over the past half-century. Although the trend is clear, for many migrating species underpinning the exact causes poses a challenge to conservation due to the numerous stressors that they encounter. Climate conditions during all phases of their annual cycle can have important consequences for their survival. Here, using 15 years of capture-recapture dataset, we determined the effects of various climate factors during the breeding, wintering, and migrating stages on the annual survival of a western yellow-breasted chat (Icteria virens auricollis) population breeding in southwestern Canada. El Niño effects over the entire annual cycle had little influence on the annual apparent survival of yellow-breasted chats. However, we found evidence that wind conditions during migration, specifically average westerly wind speed or the frequency of storm events, had significant adverse effects on adult annual apparent survival. In comparison, precipitation levels on wintering ground had little to no influence on adult annual apparent survival, whereas growing degree days on the breeding ground had moderate but positive effects. In the face of climate change and its predicted impacts on climate processes, understanding the influence of weather conditions on the survival of migrating birds can allow appropriate conservation strategies to be adopted for chats and other declining neotropical migrants.
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
Shirom, Arie; Toker, Sharon; Shapira, Itzhak; Berliner, Shlomo; Melamed, Samuel
2008-05-01
The effects of exposure to terror on physical health were investigated by relating objective exposure to terror and fear of terror to self-rated health (SRH), a proxy measure of health status. Our respondents were apparently healthy (N=4,877, 38% women) adults who completed self-report questionnaires. Objective exposure was assessed by the number of terrorist attacks and their casualties in a respondent's urban area prior to her/his completion of the questionnaire. Using several alternative assessments, objective exposure to terror did not predict SRH for both the genders. As hypothesized, fear of terror negatively predicted SRH for both females and males (beta=-0.04, -0.05, respectively). The effects of subjective and objective exposure were not found to be more pronounced among women relative to men, thus disconfirming our hypotheses in this regard. Our findings suggest that living under continuous fear of terror may adversely influence physical health irrespective of objective exposure.
Pharmacology of anabolic steroids.
Kicman, A T
2008-06-01
Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.
Pharmacology of anabolic steroids
Kicman, A T
2008-01-01
Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided. PMID:18500378
Matthiessen, Peter; Wheeler, James R; Weltje, Lennart
2018-03-01
This review critically examines the data on claimed endocrine-mediated adverse effects of chemicals on wildlife populations. It focuses on the effects of current-use chemicals, and compares their apparent scale and severity with those of legacy chemicals which have been withdrawn from sale or use, although they may still be present in the environment. The review concludes that the effects on wildlife of many legacy chemicals with endocrine activity are generally greater than those caused by current-use chemicals, with the exception of ethinylestradiol and other estrogens found in sewage effluents, which are causing widespread effects on fish populations. It is considered that current chemical testing regimes and risk assessment procedures, at least those to which pesticides and biocides are subjected, are in part responsible for this improvement. This is noteworthy as most ecotoxicological testing for regulatory purposes is currently focused on characterizing apical adverse effect endpoints rather than identifying the mechanism(s) responsible for any observed effects. Furthermore, a suite of internationally standardized ecotoxicity tests sensitive for potential endocrine-mediated effects is now in place, or under development, which should ensure further characterization of substances with these properties so that they can be adequately regulated.
Excess iron intake as a factor in growth, infections, and development of infants and young children.
Lönnerdal, Bo
2017-12-01
The provision of iron via supplementation or the fortification of foods has been shown to be effective in preventing and treating iron deficiency and iron deficiency anemia in infants and young children. However, iron is a pro-oxidative element and can have negative effects on biological systems even at moderate amounts. An increasing number of studies have reported adverse effects of iron that was given to infants and young-children populations who initially were iron replete. These effects include decreased growth (both linear growth and weight), increased illness (usually diarrhea), interactions with other trace elements such as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased inflammatory markers, and impaired cognitive and motor development. If these results can be confirmed by larger and well-controlled studies, it may have considerable programmatic implications (e.g., the necessity to screen for iron status before interventions to exclude iron-replete individuals). A lack of understanding of the mechanisms underlying these adverse outcomes limits our ability to modify present supplementation and fortification strategies. This review summarizes studies on the adverse effects of iron on various outcomes; suggests possible mechanisms that may explain these observations, which are usually made in clinical studies and intervention trials; and gives examples from animal models and in vitro studies. With a better understanding of these mechanisms, it may be possible to find novel ways of providing iron in a form that causes fewer or no adverse effects even when subjects are iron replete. However, it is apparent that our understanding is limited, and research in this area is urgently needed. © 2017 American Society for Nutrition.
Fertility and apparent genetic anticipation in Lynch syndrome.
Stupart, Douglas; Win, Aung Ko; Jenkins, Mark; Winship, Ingrid M; Goldberg, Paul; Ramesar, Rajkumar
2014-09-01
Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.
Jahangir Alam, Mohammad; Renter, David G.; Ives, Samuel E.; Thomson, Daniel U.; Sanderson, Michael W.; Hollis, Larry C.; Nagaraja, Tiruvoor G.
2009-01-01
A prospective cohort study was used to assess whether Salmonella fecal shedding in commercial feedlot cattle treated with antimicrobials for respiratory disease was associated with subsequent adverse health outcomes. Feces were collected per rectum from cattle that were examined for apparent respiratory disease, had a rectal temperature ≥40 °C, and subsequently received antimicrobial treatment. Salmonella were recovered from 918 (73.7%) of 1 245 fecal samples and weekly prevalence estimates ranged from 49 to 100% over the 3-month study. Genotypic and phenotypic characteristics of Salmonella strains in the population were determined. Serogroup E Salmonella were most common (73.3%), followed by C1 (11.0%), C3 (8.6%), and B (1.1%). Predominant serotypes were Orion (46.5%), Anatum (19.8%), Kentucky (8.7%), Montevideo (7.5%), and Senftenberg (4.9%). Few isolates (36/918) were positive for antimicrobial resistance-associated integron gene intI1. Phenotypic susceptibility was associated with isolate intI1 status. Crude re-pull, re-treatment and case fatality risks were higher for cattle that were Salmonella-positive versus -negative at initial treatment, but not statistically different on multivariable analysis. However, case fatality risk was higher for cattle shedding Group B Salmonella than for cattle shedding other serogroups. Lots (groups) with a higher Salmonella prevalence at first treatment had a higher proportion of mortalities occur in a hospital pen, higher overall re-treatment risks, and were more likely to be sampled later in the study. Results indicate a high prevalence of Salmonella in this population of cattle treated for apparent respiratory disease, but that effects associated with clinical outcomes may depend on the Salmonella strain. PMID:18817722
Bao, X D
2018-04-09
The strength of endodontically treated teeth were reduced apparently because of structural damage, therefore further reduction of healthy tissue should be avoided as much as possible in restoration. Endocrown made by chair-side CAD/CAM is some kind of minimal invasive restoration, and the retention of restoration is achieved by reliable bonding and macromechanial retention forces. Without post preparation, the root structure could be resevered. Following the indications and use of biomechanical dentin-like CAD/CAM materials could reduce the adverse effect of tensile stress on cervical part.
The Safety of Acupuncture in Patients with Cancer Therapy–Related Thrombocytopenia
Cybularz, Paul A.; Brothers, Karen; Singh, Gurneet M.; Feingold, Jennifer L.; Niesley, Michelle L.
2015-01-01
Abstract Background: Acceptance of acupuncture as an efficacious integrative modality for oncology-related side-effect management is rapidly expanding. It is imperative that guidelines regarding safe treatment supported by clinical experience are established. Oncology patients frequently experience thrombocytopenia as a side-effect of chemotherapy or radiation. However, safety data for acupuncture in adult patients with cancer who are thrombocytopenic is lacking. Materials and Methods: The medical records of 684 patients who received acupuncture treatments in an established acupuncture program at a private cancer treatment hospital were reviewed for adverse events occurring within the context of thrombocytopenia. Results: Of 2135 visits eligible for evaluation, 98 individual acupuncture visits occurred in patients with platelet counts <100,000/μL, including nine visits in which platelet counts were <50,000/μL. No adverse events of increased bruising or bleeding were noted. Medications and nutritional supplements or botanicals that may influence coagulation were also tabulated, with no apparent adverse events in this patient population. Conclusions: Discrepancies in the literature highlight the need to create cohesive safety guidelines backed by clinical research, specifically for groups at higher risk for adverse events. The preliminary evidence put forth in this study lays the foundation that supports the notion that acupuncture can be used safely with a high-need oncology population within an integrated model of care. In this descriptive retrospective case series of adult oncology patients with thrombocytopenia, no adverse events of increased bruising or bleeding were documented. Prospective trials are needed to confirm these initial observations. PMID:26401193
Omisore, Akinlolu G; Adesoji, Richard O; Abioye-Kuteyi, Emmanuel A
2017-10-01
To examine interprofessional rivalry (IPR) between doctors and other health workers and their understanding of its effects. IPR in Nigeria's health system is a burgeoning issue with apparent adverse effects. The most profound rivalry appears to be between doctors and other health workers. A descriptive cross-sectional study involving 120 health workers (24 doctors and 96 other health workers) at the State Specialist Hospital, Okitipupa, Ondo State, Nigeria. Pertinent data were collected via semistructured questionnaire and analyzed using SPSS Version17.0. IPR is perceived to be the leading cause of conflicts among health workers by 70% of respondents. Doctors and other workers had significantly divergent opinions on the leadership of the health team, patient management, establishment positions, and monetary issues as well as on the effects of IPR with more doctors recognizing its hazards. Nearly half of the respondents believe that strikes are justifiable and the most recommended antidote is for the government to attempt to meet group needs. IPR has reached unprecedented levels in Nigeria. However, its adverse effects have not been duly recognized, especially by nondoctors. There is an urgent need for education of health workers on the deleterious effects of IPR.
Gorrell, Lindsay M; Engel, Roger M; Lystad, Reidar P; Brown, Benjamin T
2017-03-14
Reporting of adverse events in randomized clinical trials (RCTs) is encouraged by the authors of The Consolidated Standards of Reporting Trials (CONSORT) statement. With robust methodological design and adequate reporting, RCTs have the potential to provide useful evidence on the incidence of adverse events associated with spinal manipulative therapy (SMT). During a previous investigation, it became apparent that comprehensive search strategies combining text words with indexing terms was not sufficiently sensitive for retrieving records that were known to contain reports on adverse events. The aim of this analysis was to compare the proportion of articles containing data on adverse events associated with SMT that were indexed in MEDLINE and/or EMBASE and the proportion of those that included adverse event-related words in their title or abstract. A sample of 140 RCT articles previously identified as containing data on adverse events associated with SMT was used. Articles were checked to determine if: (1) they had been indexed with relevant terms describing adverse events in the MEDLINE and EMBASE databases; and (2) they mentioned adverse events (or any related terms) in the title or abstract. Of the 140 papers, 91% were MEDLINE records, 85% were EMBASE records, 81% were found in both MEDLINE and EMBASE records, and 4% were not in either database. Only 19% mentioned adverse event-related text words in the title or abstract. There was no significant difference between MEDLINE and EMBASE records in the proportion of available papers (p = 0.078). Of the 113 papers that were found in both MEDLINE and EMBASE records, only 3% had adverse event-related indexing terms assigned to them in both databases, while 81% were not assigned an adverse event-related indexing term in either database. While there was effective indexing of RCTs involving SMT in the MEDLINE and EMBASE databases, there was a failure of allocation of adverse event indexing terms in both databases. We recommend the development of standardized definitions and reporting tools for adverse events associated with SMT. Adequate reporting of adverse events associated with SMT will facilitate accurate indexing of these types of manuscripts in the databases.
Beyond Ether and Chloroform-A Major Breakthrough With Halothane.
Huang, Lisa; Sang, Christine N; Desai, Manisha S
2017-07-01
The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty of anesthesia. We explore whether the manufacturer promptly reported halothane's adverse effects to regulatory agencies and practitioners. We consulted documents submitted by Ayerst Laboratories to federal authorities through the Freedom of Information Act, promotional advertisements, package inserts, published articles, and textbooks. Two major complications associated with the use of halothane, cardiac arrhythmias and the risk of hepatotoxicity, were disclosed by the manufacturer when the drug was first introduced to the US market. Reports appeared timely and complete; there was no apparent attempt to conceal or otherwise downplay these risks. The process of drug discovery and approval for clinical use has always been a lengthy, complex, and extremely expensive undertaking, with only a small minority of compounds receiving approval. The risk of adverse effects or drug interaction directly impacts commercial viability. In the case of halothane, the manufacturer disclosed major adverse effects, and the drug enjoyed decades of popularity until it was replaced by agents with a better drug profile. Copyright © 2017 Elsevier Inc. All rights reserved.
Wood combustion particles induce adverse effects to normal and diseased airway epithelia.
Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne
2017-04-19
Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.
Kung, Shiang-Ju; Choudhary, Cuckoo; McGeady, Stephen J; Cohn, John R
2006-09-01
5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease, but adverse reactions to these medications are relatively common. Because there may be a lack of cross-reactivity among the various 5-ASA formulations, treatment with alternative preparations is sometimes possible even after an apparent allergic reaction to a 5-ASA product. To describe a patient with a possible allergy to 2 different 5-ASA drugs who tolerated a third. A 27-year-old man with Crohn disease developed a rash while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was discontinued, and 6-mercaptopurine and prednisone were prescribed. He then experienced multiorgan failure secondary to herpes simplex infection, which required discontinuation of the immunosuppressive therapy. After recovery from the acute infection, he underwent successful graded challenge with balsalazide. The patient continued treatment with balsalazide for 9 months, with good control of his inflammatory bowel disease and no adverse effects. Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the use of others in the same class. A treatment algorithm for patients with adverse reactions to 5-ASA is outlined based on the case report and review of the literature.
Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects.
Pagano, Giovanni; Guida, Marco; Tommasi, Franca; Oral, Rahime
2015-05-01
In the recent decades, rare earth elements (REE) have undergone a steady spread in several industrial and medical applications, and in agriculture. Relatively scarce information has been acquired to date on REE-associated biological effects, from studies of bioaccumulation and of bioassays on animal, plant and models; a few case reports have focused on human health effects following occupational REE exposures, in the present lack of epidemiological studies of occupationally exposed groups. The literature is mostly confined to reports on few REE, namely cerium and lanthanum, whereas substantial information gaps persist on the health effects of other REE. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, analogous to the recognized redox mechanisms observed for other transition elements. Adverse outcomes of REE exposures include a number of endpoints, such as growth inhibition, cytogenetic effects, and organ-specific toxicity. An apparent controversy regarding REE-associated health effects relates to opposed data pointing to either favorable or adverse effects of REE exposures. Several studies have demonstrated that REE, like a number of other xenobiotics, follow hormetic concentration-related trends, implying stimulatory or protective effects at low levels, then adverse effects at higher concentrations. Another major role for REE-associated effects should be focused on pH-dependent REE speciation and hence toxicity. Few reports have demonstrated that environmental acidification enhances REE toxicity; these data may assume particular relevance in REE-polluted acidic soils and in REE mining areas characterized by concomitant REE and acid pollution. The likely environmental threats arising from REE exposures deserve a new line of research efforts. Copyright © 2015 Elsevier Inc. All rights reserved.
Inspection error and its adverse effects - A model with implications for practitioners
NASA Technical Reports Server (NTRS)
Collins, R. D., Jr.; Case, K. E.; Bennett, G. K.
1978-01-01
Inspection error has clearly been shown to have adverse effects upon the results desired from a quality assurance sampling plan. These effects upon performance measures have been well documented from a statistical point of view. However, little work has been presented to convince the QC manager of the unfavorable cost consequences resulting from inspection error. This paper develops a very general, yet easily used, mathematical cost model. The basic format of the well-known Guthrie-Johns model is used. However, it is modified as required to assess the effects of attributes sampling errors of the first and second kind. The economic results, under different yet realistic conditions, will no doubt be of interest to QC practitioners who face similar problems daily. Sampling inspection plans are optimized to minimize economic losses due to inspection error. Unfortunately, any error at all results in some economic loss which cannot be compensated for by sampling plan design; however, improvements over plans which neglect the presence of inspection error are possible. Implications for human performance betterment programs are apparent, as are trade-offs between sampling plan modification and inspection and training improvements economics.
Carlos, Silvia; de Irala, Jokin; Hanley, Matt; Martínez-González, Miguel Ángel
2014-01-01
A dangerous distortion of priorities seems to be currently apparent in the dominant approaches to major public health problems, including cardiovascular disease, diabetes, obesity, cancer and some infectious diseases. Relevant examples suggest an apparently inappropriate tendency to prioritise technocratic, partial solutions rather than confronting their true behavioural and structural determinants. Technically oriented preventive medicine often takes excessive precedence over simpler, more sensible approaches to modify lifestyles, the environment and the social structure. Structural factors (social, cultural, financial, familiar, educational, political or ideological factors) that act as determinants of individual behaviours should be effectively addressed to confront the essential causes of the most prevalent and important health problems. Some consumer-directed commercial forces seem to be increasingly driving many aspects of the current sociocultural environment, and may eventually compromise the main pursuits of public health. Population-wide strategies are needed to create a healthy sociocultural environment and to empower individuals and make themselves resistant to these adverse environmental and structural pressures. Otherwise most public health interventions will most likely end in failures. PMID:24962820
Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele.
Cui, Yi M; Teng, Choo H; Pan, Alan X; Yuen, Eunice; Yeo, Kwee P; Zhou, Ying; Zhao, Xia; Long, Amanda J; Bangs, Mark E; Wise, Stephen D
2007-10-01
To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects. Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.
Tripp, Daniel W; Rocke, Tonie E; Streich, Sean P; Abbott, Rachel C; Osorio, Jorge E; Miller, Michael W
2015-04-01
Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.
Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.
2015-01-01
Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.
Environmental Assessment for Type III Fuel Hydrant System at Grissom Air Reserve Base
2011-10-01
indicates the Proposed Action would not significantly affect these areas. During the construction phase some of the above areas would see minor ...lowered reproduction rates of indigenous fish downstream. NEGLIGIBLE, MINOR , MODERATE, OR MAJOR. These relative terms are used to characterize the... minor effect is slight, but detectable. A moderate effect is readily apparent. A major effect is one that is severely adverse or exceptionally
Psychosis during pregnancy: treatment considerations.
Pinkofsky, H B
1997-09-01
The onset of psychosis during pregnancy presents several difficult management decisions and a careful risk-benefit analysis is required. Withholding antipsychotic treatment may produce more risks than benefits. Studies on neuroleptic teratogenicity are contradictory. Most of the commonly used neuroleptics exhibit a pregnancy risk of category C. Neuroleptic use during pregnancy may be associated with adverse effects in the pre- and postnatal period. These concerns include compromising uterine blood flow, post-partum neonatal sedation, and extrapyramidal signs expressed in the neonate. Each neuroleptic exhibits a unique pharmacokinetic profile. The antipsychotic properties and side effects considered most significant include sedation, half-life, hypotension, and apparent hydrophilicity. In this case study a decision to select molindone was based on these parameters.
Inadvertent intrathecal injection of labetalol in a patient undergoing post-partum tubal ligation.
Balestrieri, P J; Hamza, M S; Ting, P H; Blank, R S; Grubb, C T
2005-10-01
After receiving a continuous spinal anesthetic for labor following an inadvertent dural puncture with a 17-gauge epidural needle, a morbidly obese parturient underwent post-partum tubal ligation 12 h after vaginal delivery. The patient received a total of 2 mL of 0.75% hyperbaric bupivacaine for the surgery. In response to moderate hypertension the patient received intravenous labetalol hydrochloride 20 mg. She subsequently was inadvertently administered approximately 15 mg of labetalol through the spinal catheter. The spinal catheter was removed immediately after the procedure. She suffered no apparent adverse neurologic effects.
The Return of Two-Class Medicine—III Effects of Medi-Cal Reform
Waitzkin, Howard
1985-01-01
California's drastic Medi-Cal reforms have created great difficulties in health care for the poor. Patients' clinical problems seldom are apparent in descriptions of changes in public insurance programs. Rapidly escalating costs of Medi-Cal led to irresistible pressures for reform, especially from the business community. The new Medi-Cal regulations provide for prospective contracts with hospitals for inpatient services, the transfer of “Medically Indigent Adults” to the responsibility of county governments and various other straightforward funding cutbacks. Confusion, disruption of services and adverse health outcomes have accompanied the Medi-Cal reforms. PMID:3892917
Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.
Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L
2018-06-01
The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.
Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G
2016-04-01
Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Lopez, Carlos E.; Standiford, Harold C.; Tatem, Beverly A.; Calia, Frank M.; Schimpff, Stephen C.; Snyder, Merrill J.; Hornick, Richard B.
1977-01-01
Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone. PMID:404963
Intermittent blood pressure control: potential consequences for outcome.
Leenen, F H
1999-05-01
Although both blood pressure (BP) and left ventricular (LV) mass at initial evaluation predict future cardiovascular risk, the actual BP and LV mass achieved over years of treatment more clearly relate to cardiovascular event rates. Intermittent compliance or noncompliance is the major reason for uncontrolled hypertension and presumably persistent LV hypertrophy. In general, drugs with rapid onset and short duration of action are not desirable because this profile may lead to large variations in BP lowering effect during actual drug intake and rapid disappearance of the antihypertensive effect with missed doses. In addition, intermittent compliance per se introduces the potential for adverse events. For drugs requiring several dose-titrations (e.g., alpha1-blockers), restarting at full doses may lead to excessive drug action and symptomatic hypotension. For other drugs (e.g., short acting beta-blockers or clonidine-like drugs), sudden discontinuation with intermittent compliance may lead to rebound-enhanced sympathetic responsiveness after one to two days, resulting not only in side effects, but also in adverse events, particularly in patients with (silent) coronary artery disease. The rapid onset, short acting dihydropyridines cause intermittent BP control at each dosing, particularly at higher doses. This intermittent control of BP is even more apparent at dosing intervals that are long relative to the duration of action. Thus, sympathetic activation and potential for adverse events can be anticipated at each dosing unless these drugs are being taken frequently at relatively low doses. For diuretics, angiotensin-converting enzyme inhibitors and angiotensin I receptor blockers, no adverse effects have been identified with intermittent compliance. Intermittent BP control is, in general, not an appropriate approach to the management of hypertension and introduces additional risks depending on the type of antihypertensive drug. In contrast, drugs with slow onset and long duration of action provide a more consistent effect during actual drug intake and a more persistent effect during short periods of noncompliance.
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.
Some insects affecting Penstemon seed production
Robert Hammon; Melissa Franklin
2012-01-01
Beardtongue (Penstemon Schmidel [Scrophulariaceae)) seeds are often produced without apparent damage from pests, but several species of native insects can adversely impact seed production fields. Tarnished plant bug (Lygus lineolaris (Palisot)) and western plant bug (Lygus hesperus Knight [Hemiptera: Miridae]), penstemon weevil (Hesperobaris sp. Casey [Coleoptera:...
Questions concerning the potential impact of glyphosate-based herbicides on amphibians.
Wagner, Norman; Reichenbecher, Wolfram; Teichmann, Hanka; Tappeser, Beatrix; Lötters, Stefan
2013-08-01
Use of glyphosate-based herbicides is increasing worldwide. The authors review the available data related to potential impacts of these herbicides on amphibians and conduct a qualitative meta-analysis. Because little is known about environmental concentrations of glyphosate in amphibian habitats and virtually nothing is known about environmental concentrations of the substances added to the herbicide formulations that mainly contribute to adverse effects, glyphosate levels can only be seen as approximations for contamination with glyphosate-based herbicides. The impact on amphibians depends on the herbicide formulation, with different sensitivity of taxa and life stages. Effects on development of larvae apparently are the most sensitive endpoints to study. As with other contaminants, costressors mainly increase adverse effects. If and how glyphosate-based herbicides and other pesticides contribute to amphibian decline is not answerable yet due to missing data on how natural populations are affected. Amphibian risk assessment can only be conducted case-specifically, with consideration of the particular herbicide formulation. The authors recommend better monitoring of both amphibian populations and contamination of habitats with glyphosate-based herbicides, not just glyphosate, and suggest including amphibians in standardized test batteries to study at least dermal administration. Copyright © 2013 SETAC.
Gibson, Sigrid; Gunn, Pippa; Wittekind, Anna; Cottrell, Richard
2013-01-01
We systematically reviewed interventions substituting sucrose for other macronutrients in apparently healthy adults to assess impact on cardiometabolic risk indicators. Multiple databases were searched to January 2012 and abstracts assessed by 2 reviewers. Twenty-five studies (29 papers) met inclusion criteria but varied in quality and duration. Weaknesses included small subject numbers, unclear reporting of allocation, unusual dietary regimes, differences in energy intake, fat composition or fibre between conditions, unhealthy subjects, heterogeneity of results, and selective reporting. Insufficient data were available to draw reliable conclusions except with regard to the substitution of sucrose for starch, where effects on plasma lipids were inconsistent, mostly explicable by other factors, or nonsignificant. Based on fewer studies, there was little evidence for significant effects on plasma glucose or insulin. Sucrose substitution for starch up to 25% energy does not appear to have adverse effects on cardiometabolic risk indicators in apparently healthy adults. Furthermore, there is no consistent evidence that restricting sucrose in an isoenergetic diet would affect risk indicators, except perhaps in people with certain preexisting metabolic abnormalities. Larger, high-quality studies, lasting several months and studying a wider range of outcomes, are needed in order to provide evidence on which to base public health initiatives. PMID:23627502
Cognitive development and low-level lead exposure in poly-drug exposed children.
Min, Meeyoung O; Singer, Lynn T; Kirchner, H Lester; Minnes, Sonia; Short, Elizabeth; Hussain, Zehra; Nelson, Suchitra
2009-01-01
The impact of early postnatal lead exposure measured at age 4 on children's IQ and academic achievement at and 11 years of age was examined. The sample consisted of 278 inner-city, primarily African American children who were polydrug exposed prenatally. Regression analyses indicated a linear effect of lead exposure on outcomes and no moderating effects of polydrug exposure. An IQ loss of about 4.1-5.4 Full Scale IQ points was estimated for each 10 microg/dL increase in blood lead level at ages 4, 9, and 11 years as a function of blood lead level at age 4. Decrements in scores on tests of non-verbal reasoning were consistently associated with higher lead levels at age 4, while verbal decrements became apparent only at age 11. Lower reading summary scores at 9 and 11 years were consistently associated with higher lead exposure, while decrements in mathematics were not apparent until 11 years. Subgroup analyses on children with blood lead levels <10 microg/dL showed detrimental lead effects even at the 5 microg/dL level, providing additional evidence of adverse effects occurring at blood lead levels below the current 10 microg/dL public health blood lead action level.
Jiang, Zhen Hui; Shi, Jiang Lan; Jia, Zhou; Ding, Ting Ting; Tian, Xiao Hong
2016-04-22
A 52-day incubation experiment was conducted to investigate the effects of maize straw decomposition with combined medium element (S) and microelements (Fe and Zn) application on arable soil organic carbon sequestration. During the straw decomposition, the soil microbial biomass carbon (MBC) content and CO 2 -C mineralization rate increased with the addition of S, Fe and Zn, respectively. Also, the cumulative CO 2 -C efflux after 52-day laboratory incubation significantly increased in the treatments with S, or Fe, or Zn addition, while there was no significant reduction of soil organic carbon content in the treatments. In addition, Fe or Zn application increased the inert C pools and their proportion, and apparent balance of soil organic carbon, indicating a promoting effect of Fe or Zn addition on soil organic carbon sequestration. In contrast, S addition decreased the proportion of inert C pools and apparent balance of soil organic carbon, indicating an adverse effect of S addition on soil organic carbon sequestration. The results suggested that when nitrogen and phosphorus fertilizers were applied, inclusion of S, or Fe, or Zn in straw incorporation could promote soil organic carbon mineralization process, while organic carbon sequestration was favored by Fe or Zn addition, but not by S addition.
Cognitive Development and Low-Level Lead Exposure in Poly-Drug Exposed Children
Min, Meeyoung O.; Singer, Lynn T.; Kirchner, H. Lester; Minnes, Sonia; Short, Elizabeth; Hussain, Zehra; Nelson, Suchitra
2009-01-01
The impact of early postnatal lead exposure measured at age 4 on children’s IQ and academic achievement at 4, 9, and 11 years of age was examined. The sample consisted of 278 inner-city, primarily African American children who were polydrug exposed prenatally. Regression analyses indicated a linear effect of lead exposure on outcomes and no moderating effects of polydrug exposure. An IQ loss of about 4.1–5.4 Full Scale IQ points was estimated for each 10 ug/dl increase in blood lead level at ages 4, 9, and 11 years as a function of blood lead level at age 4. Decrements in scores on tests of non-verbal reasoning were consistently associated with higher lead levels at age 4, while verbal decrements became apparent only at age 11. Lower reading summary scores at 9 and 11 years were consistently associated with higher lead exposure, while decrements in mathematics were not apparent until 11 years. Subgroup analyses on children with blood lead levels < 10 μg/dL showed detrimental lead effects even at the 5 μg/dL level, providing additional evidence of adverse effects occurring at blood lead levels below the current 10 μg/dL public health blood lead action level. PMID:19345261
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de
The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 {mu}M and for morin, robinetin and taxifolin between 164 and 268 {mu}M. For myricetin, luteolin, naringenin and quercetin, the apparent Kimore » values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 {mu}M respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients.« less
Verification of surface preparation for adhesive bonding
NASA Technical Reports Server (NTRS)
Myers, Rodney S.
1995-01-01
A survey of solid rocket booster (SRB) production operations identified potential contaminants which might adversely affect bonding operations. Lap shear tests quantified these contaminants' effects on adhesive strength. The most potent contaminants were selected for additional studies on SRB thermal protection system (TPS) bonding processes. Test panels were prepared with predetermined levels of contamination, visually inspected using white and black light, then bonded with three different TPS materials over the unremoved contamination. Bond test data showed that white and black light inspections are adequate inspection methods for TPS bonding operations. Extreme levels of contamination (higher than expected on flight hardware) had an insignificant effect on TPS bond strengths because of the apparent insensitivity of the adhesive system to contamination effects, and the comparatively weak cohesive strength of the TPS materials.
Variations in Hematologic Responses to Increased Lead Absorption in Young Children
Chisolm, J. Julian; Mellits, E. David; Keil, Julian E.; Barrett, Maureen B.
1974-01-01
In the study of human populations, much emphasis is placed on the concentration of lead in whole peripheral blood. There is a considerable body of evidence which indicates that this measurement reflects recent and current assimilation of lead. While broad ranges in blood lead concentration have been associated with differing risks of toxicity for groups, it is not a precise index of adverse effect per se, even at elevated levels. Within the red blood cell itself there is not a close association between the concentration of lead and such adverse metabolic effects as the increased loss of potassium caused by lead. Above the apparent “threshold zone” of approximately 30–50 μg Pb/100 ml whole blood, equivalent metabolic effects on heme synthesis may be seen over an interval of at least 20 μg Pb/100 ml whole blood. This variation will be examined with particular reference to the interrelationship between the concentrations of lead and protoporphyrin in peripheral blood. The data indicate that limitations in both precision and accuracy of measurement account for a relatively small fraction of the observed variations. Together with other experimental and clinical information, they suggest that concurrent dietary deficiency of iron may be one of the important modifying factors in the responses of subjects with increased lead absorption. It is suggested that suspected adverse effects upon the various organ systems associated with increased lead absorption be measured directly and that the CaEDTA mobilization test for lead should be more fully explored as a measure of the “metabolically active” fraction of the total body lead burden. PMID:4831151
Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R
2012-02-01
To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.
Fukuwatari, Tsutomu; Kuzuya, Mako; Satoh, Shiori; Shibata, Katsumi
2009-04-01
To determine the tolerable upper intake levels of vitamin B(1) and vitamin B(2) in humans, we investigated the effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet, corresponding to 900 mg/kg body weight/day.
Thermophilic aerobic digestion process for producing animal nutrients and other digested products
DOE Office of Scientific and Technical Information (OSTI.GOV)
Coulthard, T.L.; Townsley, P.M.; Saben, H.S.
1981-09-29
Waste materials are digested by thermophilic bacteria to produce single-cell protein and vitamin B12. The bacteria are contained in the waste and are not inoculated. Thus, a hog manure slurry containing 10% solids was stirred with aeration in an insulated reactor to allow the temperature to be maintained at greater than 55/sup 0/. The temperature was maintained at 55-65/sup 0/ and the dissolved O/sub 2/ concentration at 1.5-3 ppm for 6 days. After 10 days reaction, the product was fed to hogs as 10% of their nutrient supply with no apparent adverse effects.
Aglepristone: A review on its clinical use in animals.
Gogny, Anne; Fiéni, Francis
2016-03-01
Aglepristone (RU 46534) is a competitive progesterone antagonist that is indicated for the treatment of various progesterone-dependent physiological or pathologic conditions. Aglepristone has proven to be an effective means of terminating pregnancy in most species. When used to induce parturition, aglepristone was effective in all cases in the bitch, cow, and goat, with no apparent adverse effects on neonatal health or milk production. When used to schedule an elective cesarean section, aglepristone treatment was deemed safe for dams and puppies, providing that the ovulation date had been accurately assessed at the time of breeding. Irrespective of the stage of pregnancy at injection, treatment with aglepristone has no apparent negative effects on subsequent fertility. Aglepristone is also a safe and relatively effective means of treating pyometra. However, given the high level of septic risk and the likelihood of rapid deterioration, such therapy is not recommended in emergency situations. Treatment of feline fibroadenomatosis using aglepristone has given promising results, but repeat treatment may be necessary in cats previously treated with long-acting progestagens. The use of aglepristone in other progesterone-dependent diseases has yet to be fully evaluated but may prove valuable, especially in the treatment of insulin-resistant diabetes mellitus, acromegaly, and the treatment of some vaginal tumors in the bitch. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Al-Anazi, Abdullah Foraih; Qureshi, Viquar Fatima; Javaid, Khalida; Qureshi, Shoeb
2011-01-01
Estrogen deficiency is a major risk factor for osteoporosis in postmenopausal women. Although hormone replacement therapy (HRT) has been rampantly used to recompense for the bone loss, but the procedure is coupled with severe adverse effects. Hence, there is a boost in the production of newer synthetic products to ward off the effects of menopause-related osteoporosis. As of today, there are several prescription products available for the treatment of postmenopause osteoporosis; most of these are estrogenic agents and combination products. Nevertheless, in view of the lack of effect and/or toxicity of these products, majority of the postmenopausal women are now fascinated by highly publicized natural products. This is an offshoot of the generalized consensus that these products are more effective and free from any adverse effects. Recently, certain plant-derived natural products, mostly phytoestrogens (isoflavones, lignans, coumestanes, stilbenes, flavonoids) and many more novel estrogen-like compounds in plants have been immensely used to prevent menopause-related depletion in bone mineral density (BMD). Although, a number of papers are published on menopause-related general symptoms, sexual dysfunction, cardiovascular diseases, Alzheimer's disease, diabetes, colon, and breast cancers, there is paucity of literature on the accompanying osteoporosis and its treatment. In view of the controversies on synthetic hormones and drugs and drift of a major population of patients toward natural drugs, it was found worthwhile to investigate if these drugs are suitable to be used in the treatment of postmenopausal osteoporosis. Preparation of this paper is an attempt to review the (a) epidemiology of postmenopausal osteoporosis, (b) treatment modalities of postmenopausal osteoporosis by hormones and synthetic drugs and the associated drawbacks and adverse effects, and (c) prevention and treatment of postmenopausal osteoporosis by phytoestrogens, their drawbacks and toxicity. It is apparent that both the categories of treatment are useful and both have adverse effects, but the plant products are nonscientific and hence are not advised to be used till more studies are undertaken to ensure that the benefits clearly outweigh the risk, in addition to recognition by Food and Drug Administration. PMID:22346228
Witthöft, Michael; Rubin, G James
2013-03-01
Medically unsubstantiated 'intolerances' to foods, chemicals and environmental toxins are common and are frequently discussed in the media. Idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) is one such condition and is characterized by symptoms that are attributed to exposure to electromagnetic fields (EMF). In this experiment, we tested whether media reports promote the development of this condition. Participants (N=147) were randomly assigned to watch a television report about the adverse health effects of WiFi (n=76) or a control film (n=71). After watching their film, participants received a sham exposure to a WiFi signal (15 min). The principal outcome measure was symptom reports following the sham exposure. Secondary outcomes included worries about the health effects of EMF, attributing symptoms to the sham exposure and increases in perceived sensitivity to EMF. 82 (54%) of the 147 participants reported symptoms which they attributed to the sham exposure. The experimental film increased: EMF related worries (β=0.19; P=.019); post sham exposure symptoms among participants with high pre-existing anxiety (β=0.22; P=.008); the likelihood of symptoms being attributed to the sham exposure among people with high anxiety (β=.31; P=.001); and the likelihood of people who attributed their symptoms to the sham exposure believing themselves to be sensitive to EMF (β=0.16; P=.049). Media reports about the adverse effects of supposedly hazardous substances can increase the likelihood of experiencing symptoms following sham exposure and developing an apparent sensitivity to it. Greater engagement between journalists and scientists is required to counter these negative effects. Copyright © 2012 Elsevier Inc. All rights reserved.
Jayanegara, A; Leiber, F; Kreuzer, M
2012-06-01
A meta-analysis was conducted to evaluate the extent to which dietary tannin level is related to methane emissions from ruminants. Data from a total of 30 experiments comprising 171 treatments were entered in a database. In vitro batch culture and in vivo measurements were distinguished as experimental approaches. With any approach, methane declined when dietary tannins increased. The in vitro approach predicted the in vivo response quite accurately. However, in vitro, the response followed a quadratic response pattern (R(2) = 0.66; lower response with increasing tannin level), whereas in vivo, this decline was linear (R(2) = 0.29). This indicates that the in vitro batch culture is of limited accuracy for estimating effects at levels >100 g tannin/kg dry matter. The large variation in methane/digestible organic matter (OM) found at low tannin levels may explain contrasting literature reports. Methane reduction with tannins was associated with a reduced apparent digestion of OM, and especially fibre, but methane/apparently digestible OM declined also. The present findings are helpful as they identified an underlying general antimethanogenic effect of tannins across tannin sources and experimental conditions, thus allowing concentrating the search on sources with satisfactory palatability and low adverse effects on animal performance. © 2011 Blackwell Verlag GmbH.
Pastores, Gregory M; Turkia, Hadhami Ben; Gonzalez, Derlis E; Ida, Hiroyuki; Tantawy, Azza A G; Qin, Yulin; Qiu, Yongchang; Dinh, Quinn; Zimran, Ari
2016-07-01
Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naïve at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses. Copyright © 2016. Published by Elsevier Inc.
21 CFR 7.46 - Firm-initiated recall.
Code of Federal Regulations, 2010 CFR
2010-04-01
... action, e.g., seizure. In such cases, the firm will be asked to provide the Food and Drug Administration... requested a recall. The firm's action also is considered a firm-initiated recall and is subject to... but where it is apparent, e.g., because of complaints or adverse reactions regarding the product, that...
Kortman, Guus A M; Reijnders, Dorien; Swinkels, Dorine W
2017-06-01
Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota. © 2017 International Society for Hemodialysis.
Wildfires, Ecosystem Services, and Biodiversity in Tropical Dry Forest in India.
Schmerbeck, Joachim; Fiener, Peter
2015-08-01
This review is intended to contribute to the understanding of the interlinkage between wildfire in India's tropical dry forest (TDF) and selected ecosystem services (ES), namely forest provisioning and water regulating services, as well as biodiversity. TDF covers approximately 146,000 km(2) (4.4%) of India, whereas according to the MODIS fire product about 2200 km(2) (1.4%) burns per year. As studies on wildfire effects upon ESs and biodiversity in Indian TDFs are rare we partly transferred findings from other (dry) forest areas to the environmental situation in India. In India (intentionally lit) wildfires have a very important connection to local livelihoods and the availability of non-wood forest products. Very important adverse long-term effects are the deterioration of forest ecosystems and soil degradation. The potential for TDF to regulate hydrological cycles is expected to be greater in the absence of fire than with it. A general judgment on the effect of fire on biodiversity is difficult as it depends on the community and species involved but a loss of biodiversity under regular burnings is apparent. Consequently, forest managers need sound knowledge regarding the interplay of wildfires and ecosystem behavior in general and more specific knowledge regarding the effects on taxa being considered for conservation efforts. Generally, much more research is needed to understand the trade-offs between the short-term benefits gained from forest provisioning services and long-term adverse effects.
Wildfires, Ecosystem Services, and Biodiversity in Tropical Dry Forest in India
NASA Astrophysics Data System (ADS)
Schmerbeck, Joachim; Fiener, Peter
2015-08-01
This review is intended to contribute to the understanding of the interlinkage between wildfire in India's tropical dry forest (TDF) and selected ecosystem services (ES), namely forest provisioning and water regulating services, as well as biodiversity. TDF covers approximately 146,000 km2 (4.4 %) of India, whereas according to the MODIS fire product about 2200 km2 (1.4 %) burns per year. As studies on wildfire effects upon ESs and biodiversity in Indian TDFs are rare we partly transferred findings from other (dry) forest areas to the environmental situation in India. In India (intentionally lit) wildfires have a very important connection to local livelihoods and the availability of non-wood forest products. Very important adverse long-term effects are the deterioration of forest ecosystems and soil degradation. The potential for TDF to regulate hydrological cycles is expected to be greater in the absence of fire than with it. A general judgment on the effect of fire on biodiversity is difficult as it depends on the community and species involved but a loss of biodiversity under regular burnings is apparent. Consequently, forest managers need sound knowledge regarding the interplay of wildfires and ecosystem behavior in general and more specific knowledge regarding the effects on taxa being considered for conservation efforts. Generally, much more research is needed to understand the trade-offs between the short-term benefits gained from forest provisioning services and long-term adverse effects.
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.
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.
Value of Low Triiodothyronine and Subclinical Myocardial Injury for Clinical Outcomes in Chest Pain.
Lee, Young-Min; Ki, Young-Jae; Choi, Dong-Hyun; Kim, Bo-Bae; Shin, Byung Chul; Song, Heesang; Kim, Dong-Min
2015-11-01
Low triiodothyronine (T3) levels and subclinical myocardial injury may be associated with adverse cardiac and cerebrovascular (CCV) events in individuals without clinically apparent coronary heart disease (CHD). The aim of this study was to determine the associations of a low T3 level and subclinical myocardial injury with the development of adverse CCV events in individuals without clinically apparent CHD. T3 and high-sensitivity cardiac troponin T (hs-cTnT) levels were analyzed in 250 patients with chest pain free of CHD and heart failure. The primary end point was the composite of sudden cardiac death, ischemic stroke, newly developed atrial fibrillation, pericardial effusion and thrombosis. Throughout a mean follow-up of 15.6 months, the primary end point happened in 17 patients (6.8%). Kaplan-Meier analysis disclosed a notably higher overall occurrence rate in patients with hs-cTnT levels ≥0.014 ng/mL and in patients with T3 <60 ng/dL. An exaggerated hazard was observed in patients with combined high hs-cTnT and low T3 levels. After adjustment, the hazard ratio for overall events in patients with high hs-cTnT/low T3 versus normal hs-cTnT/T3 was 11.72 (95% confidence interval, 2.83-48.57; P = 0.001). In patients with chest pain without clinically obvious CHD, high hs-cTnT combined with low T3 was associated with adverse cardiac/CCV events and was an independent predictor of overall events even after adjustment. These data suggest the importance of systemic factors, such as low T3 syndrome, in the development of adverse cardiac/CCV events beyond advancing clinical atherosclerotic coronary disease in patients with chest pain.
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
Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect.
Andrade, V M; Mateus, M L; Batoréu, M C; Aschner, M; Marreilha dos Santos, A P
2015-07-01
The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As), and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These three metals are commonly detected in different environmental, occupational, and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals may represent an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters, and effects on the hematopoietic system, we address putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture.
Lead, arsenic and manganese metal mixture exposures: focus on biomarkers of effect
Andrade, VL; Mateus, ML; Batoréu, MC; Aschner, M; Marreilha dos Santos, AP
2015-01-01
Summary The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As) and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These 3 metals are commonly detected in different environmental, occupational and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals represents an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters and effects on hematopoietic system, we address putative biomarkers, which may be assist in assessing onset of neurological diseases associated with exposure to this metal mixture. PMID:25693681
The impact of childhood adversities on anxiety and depressive disorders in adulthood.
Marackova, Marketa; Prasko, Jan; Matousek, Stanislav; Latalova, Klara; Hruby, Radovan; Holubova, Michaela; Slepecky, Milos; Vrbova, Kristyna; Grambal, Ales
2016-12-01
The childhood adversities model is generally accepted as a predictor of adult psychopathology vulnerability. It stems from child development theories, but the question remains as of how well solid research supports it. The aim of this article is to give a review of the studies concerning childhood adversities and their impact on the development of anxiety disorders and major depressive disorder in adulthood. A computerized search of the MEDLINE database of publications up to 31 March 2016 was done, using the keywords "childhood adversities, abuse, maltreatment, bullying" and "anxiety disorders, depressive disorder". No backward time constraints were used. Non-original studies, conference abstracts, books and book chapters, commentaries, and dissertations were excluded. The influence of childhood adversities on later age psychopathology is examined in five categories: the negative family atmosphere, abuse, loss of a close person, the social difficulties, and problems at school (including, most importantly bullying). The majority of studies confirmed the connection between childhood adversities and anxiety and depression disorders in adulthood. The character of the adversities is not, apparently, a specific predictor for a concrete psychopathology. Multiple adversities are more frequently connected with depressive and anxiety disorders in adulthood, cumulating together in broader adverse context. Childhood adversities were found to increase vulnerability to the distress, depression, fear and anxiety later in the life. However, specific correlations between a given childhood adversity and a specific form of depression or anxiety disorder were either not found or weak. This is in line with the generally accepted view considering each of these factors a non-specific stressor increasing vulnerability to mood and affect disorders later in life.
Inherent Contrast in Magnetic Resonance Imaging and the Potential for Contrast Enhancement
Brasch, Robert C.
1985-01-01
Magnetic resonance (MR) imaging is emerging as a powerful new diagnostic tool valued for its apparent lack of adverse effects. The excellent inherent contrast between biologic tissues and fluids afforded by MR imaging is one of the foremost characteristics of this technique and depends on physicochemical properties such as hydrogen density and T1 and T2 relaxation rates, on magnetic field strength and on operator-chosen factors for acquiring the MR imaging signal. Pharmaceutical contrast-enhancing agents shorten the MR imaging process and improve sensitivity and diagnostic accuracy. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 8.Figure 9.Figure 10.Figure 11. PMID:2992172
Lockhart, A. Craig; Liu, Yongjian; Dehdashti, Farrokh; Laforest, Richard; Picus, Joel; Frye, Jennifer; Trull, Lauren; Belanger, Stefanie; Desai, Madhuri; Mahmood, Syed; Mendell, Jeanne; Welch, Michael J.; Siegel, Barry A.
2017-01-01
Purpose Evaluate safety, dosimetry and apparent receptor occupancy (RO) of 64Cu-DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors. Procedures Dosimetry subjects (N=5) received 64Cu-DOTA-patritumab and underwent PET/CT at 3, 24, and 48 hours. Evaluable RO subjects (N=3 out of 6) received 64Cu-DOTA-patritumab Day 1 and Day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 hours post injection. Endpoints included safety, tumor uptake and efficacy. Results The tumor SUVmax (±SD) was 5.6±4.5, 3.3±1.7 and 3.0±1.1 at 3, 24 and 48 hours in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044±0.008 mSv/MBq and 0.46±0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00±0.32 at baseline to 0.57±0.17 after stable patritumab, corresponding to a RO of 42.1±3.9%. There were no unexpected adverse events. Conclusion 64Cu-DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor apparent RO. PMID:26567113
7 CFR 1437.10 - Notice of loss, appraisal requirements, and application for payment.
Code of Federal Regulations, 2012 CFR
2012-01-01
... the final planting date, (2) For low yield claims and allowable value loss, the earlier of: (i) 15 calendar days after the damaging weather or adverse natural occurrence, or date loss of the crop or commodity becomes apparent for low yield claims; and (ii) 15 calendar days after the normal harvest date. (b...
7 CFR 1437.10 - Notice of loss, appraisal requirements, and application for payment.
Code of Federal Regulations, 2013 CFR
2013-01-01
... the final planting date, (2) For low yield claims and allowable value loss, the earlier of: (i) 15 calendar days after the damaging weather or adverse natural occurrence, or date loss of the crop or commodity becomes apparent for low yield claims; and (ii) 15 calendar days after the normal harvest date. (b...
7 CFR 1437.10 - Notice of loss, appraisal requirements, and application for payment.
Code of Federal Regulations, 2011 CFR
2011-01-01
... the final planting date, (2) For low yield claims and allowable value loss, the earlier of: (i) 15 calendar days after the damaging weather or adverse natural occurrence, or date loss of the crop or commodity becomes apparent for low yield claims; and (ii) 15 calendar days after the normal harvest date. (b...
7 CFR 1437.10 - Notice of loss, appraisal requirements, and application for payment.
Code of Federal Regulations, 2014 CFR
2014-01-01
... the final planting date, (2) For low yield claims and allowable value loss, the earlier of: (i) 15 calendar days after the damaging weather or adverse natural occurrence, or date loss of the crop or commodity becomes apparent for low yield claims; and (ii) 15 calendar days after the normal harvest date. (b...
Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide
Lheureux, Philippe ER; Zahir, Soheil; Penaloza, Andrea; Gris, Mireille
2005-01-01
The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting. PMID:16356235
2011-01-01
Background When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. Methods Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. Results A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p = 0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p = 0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p = 0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. Conclusions Aromatase inhibitors reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin. PMID:21693037
Ferrero, Simone; Venturini, Pier L; Gillott, David J; Remorgida, Valentino
2011-06-21
When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p=0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p=0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p=0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. Aromatase inhibitors reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin.
Does the Mediterranean diet counteract the adverse effects of abdominal adiposity?
Eguaras, S; Toledo, E; Buil-Cosiales, P; Salas-Salvadó, J; Corella, D; Gutierrez-Bedmar, M; Santos-Lozano, J M; Arós, F; Fiol, M; Fitó, M; Ros, E; Serra-Majem, L; Pintó, X; Martínez, J A; Sorlí, J V; Muñoz, M A; Basora, J; Estruch, R; Martínez-González, M Á
2015-06-01
We tested the hypothesis that an intervention with a Mediterranean diet (MeDiet) could mitigate the well-known harmful effects of abdominal obesity on cardiovascular health. We assessed the relationship between baseline waist-to-height ratio (WHtR) and major cardiovascular events during a median follow-up of 4.8 years in the Prevention with Mediterranean Diet (PREDIMED) randomized primary prevention trial, which tested a MeDiet against a control diet (advice on a low-fat diet). We also examined whether the MeDiet intervention was able to counteract the detrimental cardiovascular effects of an increased WHtR. The trial included 7447 participants (55-80 years old, 57% women) at high cardiovascular risk but free of cardiovascular disease (CVD) at enrollment. An increased risk of CVD events (myocardial infarction, stroke, or cardiovascular death) was apparent for the highest versus the lowest quartile of WHtR (multivariable-adjusted hazard ratio: 1.98) (95% confidence interval: 1.10-3.57; linear trend: p = 0.019) only in the control-diet group, but not in the two groups allocated to intervention with MeDiet (p for interaction = 0.034). This apparent interaction suggesting that the intervention counterbalanced the detrimental cardiovascular effects of adiposity was also significant for body mass index (BMI) (p = 0.01) and waist circumference (p = 0.043). The MeDiet may counteract the harmful effects of increased adiposity on the risk of CVD. Copyright © 2015 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rogan, W.J.; Gladen, B.C.; McKinney, J.D.
1987-10-01
The authors followed 858 children from birth to one year of age to determine whether the presence of polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in breast milk affected their growth or health. Neither chemical showed an adverse effect on weight or frequency of physician visits for various illnesses, although differences were seen between breast-fed and bottle-fed children, with bottle-fed children being heavier and having more frequent gastroenteritis and otitis media. Children of mothers with higher levels of DDE were breast-fed for markedly shorter times, but adjustments for possible confounders and biases did not change the findings. In absence ofmore » any apparent effect on the health of the children, they speculate that DDE may be interfering with the mother's ability to lactate, possibly because of its estrogenic properties.« less
Castellanos, María Ana Martínez; Schwartz, Shulamit; García-Aguirre, Gerardo; Quiroz-Mercado, Hugo
2013-07-01
To evaluate ocular outcome in premature infants treated with intravitreal ranibizumab injections for retinopathy of prematurity (ROP) over a period of 3 years. An interventional case series. Premature infants with high-risk prethreshold or threshold ROP with plus disease received an off label monotherapy with intravitreal injections of ranibizumab. The primary outcome was treatment success defined as regression of neovascularisation (NV) and absence of recurrence. The secondary outcomes were ocular and systemic adverse events and visual acuity. Six eyes were included in the study and treated with intravitreal injections of ranibizumab. All showed complete resolution of NV after a single injection. The anti-angiogenic intravitreal injections allowed for continued normal vessel growth into the peripheral retina, without any signs of disease recurrence or progression during the follow up period. No ocular or systemic adverse effects were observed. Three years of follow up in a small series suggest that intravitreal ranibizumab injections for ROP result in apparently preserved ocular outcome. Further large scale studies are needed to address the long-term safety and efficacy.
Youssef, Jim A.; Orndorff, Douglas G.; Scott, Morgan A.; Ebner, Rachel E.; Knewitz, Allison P.
2014-01-01
Study Design Case report. Objective The objective of this study was to present the unusual case of a 59-year-old woman with a reoccurring sterile postoperative seroma. Methods A patient was observed postoperatively for any complications or adverse side effects resulting from an initial multilevel anterior/posterior lumbar fusion surgery where 2 g (1 g combined with the bone graft used for posterolateral fusion and 1 g placed in the soft tissues) of prophylactic vancomycin powder was placed within the soft tissues posteriorly before wound closure. The patient's progress was monitored through 6 months following the initial procedure. Six weeks postoperatively, the patient sustained a fall and had increased pain. Magnetic resonance imaging, computed tomography, and X-rays demonstrated a displaced sacral fracture, a large epidural fluid collection, and severe compression of the thecal sac at the lumbar operative sites (L3–5). Results On the basis of the aforementioned imaging studies and the patient's progressive neurologic deficit, it was apparent at the 6-week follow-up that emergent surgical intervention was necessary. Drainage and examination of an epidural fluid collection along with treatment of a displaced sacral fracture (S1–S2) were performed. The patient had an uneventful postoperative course with resolution of her back pain and neurologic deficit; however, recurrence of the epidural fluid collection requiring serial aspirations confounded the patients' clinical presentation. Conclusions With the recurrent nature of the seroma being unusual, the cause of the fluid collection and formation is undetermined. With lack of bone morphogenetic protein usage, and few confounding variables accountable, an acute allergic response to topical vancomycin powder is a possible etiology. Analysis with larger patient populations comparing postoperative adverse effects of prophylactic vancomycin powder is recommended. PMID:25364326
Youssef, Jim A; Orndorff, Douglas G; Scott, Morgan A; Ebner, Rachel E; Knewitz, Allison P
2014-10-01
Study Design Case report. Objective The objective of this study was to present the unusual case of a 59-year-old woman with a reoccurring sterile postoperative seroma. Methods A patient was observed postoperatively for any complications or adverse side effects resulting from an initial multilevel anterior/posterior lumbar fusion surgery where 2 g (1 g combined with the bone graft used for posterolateral fusion and 1 g placed in the soft tissues) of prophylactic vancomycin powder was placed within the soft tissues posteriorly before wound closure. The patient's progress was monitored through 6 months following the initial procedure. Six weeks postoperatively, the patient sustained a fall and had increased pain. Magnetic resonance imaging, computed tomography, and X-rays demonstrated a displaced sacral fracture, a large epidural fluid collection, and severe compression of the thecal sac at the lumbar operative sites (L3-5). Results On the basis of the aforementioned imaging studies and the patient's progressive neurologic deficit, it was apparent at the 6-week follow-up that emergent surgical intervention was necessary. Drainage and examination of an epidural fluid collection along with treatment of a displaced sacral fracture (S1-S2) were performed. The patient had an uneventful postoperative course with resolution of her back pain and neurologic deficit; however, recurrence of the epidural fluid collection requiring serial aspirations confounded the patients' clinical presentation. Conclusions With the recurrent nature of the seroma being unusual, the cause of the fluid collection and formation is undetermined. With lack of bone morphogenetic protein usage, and few confounding variables accountable, an acute allergic response to topical vancomycin powder is a possible etiology. Analysis with larger patient populations comparing postoperative adverse effects of prophylactic vancomycin powder is recommended.
Study for Promotion of Health in Recycling Lead - Rationale and design.
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.
Faasse, Kate; Cundy, Tim; Gamble, Greg; Petrie, Keith J
2013-01-01
Generic medications are associated with reduced perceived effectiveness, increased perceived adverse effects, and increased rates of nonadherence compared with brand-name medications. This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects. Sixty-two university students participated in a study purportedly testing the effectiveness of fast-acting β-blocker medications in reducing preexamination anxiety. All tablets were placebos. In session 1, all participants received a yellow tablet ("Betaprol"). In session 2, participants were randomly allocated to receive Betaprol (no change condition) or a white tablet labeled either as "Novaprol" (branded change condition) or "Generic" (generic change condition). Blood pressure and state anxiety were measured before and after tablet ingestion. Side effects attributed to medication were assessed. The no change group showed significantly greater decreases in systolic blood pressure (mean [M] [standard deviation] = -7.72 mm Hg, standard error [SE] = 1.45) than the branded change (M = -2.75 mm Hg, SE = 1.44, p = .02) and generic change (M = -3.26 mm Hg, SE = 1.45, p = .03) groups. The no-change group showed significantly greater decreases in state anxiety (M = -1.53, SE = 0.33) than the branded change (M = -0.50, SE = 0.33, p = .03) and generic change (M = -0.52, SE = 0.33, p = .04) groups. Significantly more side effects were attributed to the medication in the generic change (M = 1.83, SE = 0.23) (but not the branded change) condition when compared with the no change condition (M = 0.87, SE = 0.31, p = .03). Medication formulation change, particularly to generic medication, seems to be associated with reduced subjective and objective measures of medication effectiveness and increased side effects.
2014-01-01
Background This study aimed to determine the effect of the inclusion of corn gluten feed (CGF) on the apparent and standardized ileal digestibility of protein and amino acids and the apparent ileal and total tract digestibility of energy in growing pigs. The study was performed using 16 barrows (weight, 45.3 ± 4.5 kg) that were fitted with a T cannula at the terminal ileum. There were four treatments: a corn-soybean diet without CGF and three corn-soybean diets containing increasing levels of CGF (65, 130, and 195 g/kg). Data were analyzed according to a randomized complete block design, four blocks with four pigs each (one pig per treatment). The trend of the response (linear or quadratic) was determined using orthogonal contrasts, and when a linear effect was determined, a linear equation was obtained. Results The results showed that the inclusion up to 195 g/kg of CGF in the corn-soybean diet did not diminish the ileal digestibility (apparent and standardized) of protein and amino acids (P > 0.05), except that of phenylalanine, cystine, and proline. A linear decrease (P < 0.05) per gram of CGF added to the diet in the apparent and standardized ileal digestibility of phenylalanine (0.011 and 0.015 percentage units, respectively), cystine (0.048 and 0.043 percentage units, respectively), and proline (0.045 and 0.047 percentage units, respectively) was noted. Similarly, ileal digestibility of dry matter and energy were adversely affected (reduced by 0.028 and 0.025 percentage units, respectively, per gram of CGF increment in the diet). A significant (P < 0.05) linear reduction in total tract digestibility with increase in CGF amount in the diet was observed for energy (0.027 percentage units), dry matter (0.027 percentage units), crude protein (0.020 percentage units), and neutral detergent fiber (0.041 percentage units) per gram of CGF added to the diet. Conclusion CGF did not affect the ileal digestibility of protein and most amino acids but reduced the ileal and total tract digestibility of energy. PMID:25279142
Preparation for workplace adversity: Student narratives as a stimulus for learning.
Hanson, Julie; McAllister, Margaret
2017-07-01
Nursing students are not always well prepared for the kind of adverse events they may experience in the workplace and yet it seems apparent that future students could benefit from learning about such experiences so that they can be avoided, or their impact minimised. This research aimed to identify nursing students' experiences of adversity, collaborate with students to discern important lessons for future students in their experiences, and make recommendations for other educators on how to use these adversity stories as lessons. Seven Australian nursing students were interviewed using critical incident technique consisting of 7 questions. This paper focuses on the responses to the questions: "Does this story's message have a place in the curriculum?" and "How would you teach this lesson?" Data were analysed using critical discourse analysis. Four recurring discourses emerged including: power relationships are a two-way street; learn from mistakes to prevent mistakes; begin cultural consciousness-raising in first year, first semester; and become critically self-aware. Narratives derived from original stories of adversity may be a valuable source of learning about the realities of the workplace but to benefit fully, educators need to assist students to notice and analyse embedded messages. Copyright © 2017 Elsevier Ltd. All rights reserved.
Molet, Jenny; Maras, Pamela M; Kinney-Lang, Eli; Harris, Neil G; Rashid, Faisal; Ivy, Autumn S; Solodkin, Ana; Obenaus, Andre; Baram, Tallie Z
2016-12-01
Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Alsaad, Abdulaziz M S; Fox, Colleen; Koren, Gideon
2015-03-05
The rates of muscle aches, sprains, and inflammation are significantly increased during pregnancy. However, women are afraid to use systemic analgesics due to perceptions of fetal risks. Thus, topical products are important alternatives to consider for those women. Of interest, Professional Therapy MuscleCare (PTMC) has shown to be effective in alleviating the myofascial pain as reported in a randomized, placebo-controlled double-blinded comparative clinical study of five topical analgesics. However, to date, there is no complete review or long-term safety studies on the safety of these products during pregnancy and lactation. Thus, the aim of this article was to review toxicological, developmental, and reproductive effects associated with the use of PTMC products. We performed a systematic review on safety of PTMC from all toxicological articles investigating the effects of PTMC's ingredients. This search was conducted through medical and toxicological databases including, Web of Science, EMBASE, Medline, and Micromedix. Both reported and theoretical adverse effects were extensively reviewed. Of the 1500 publications reviewed, 100 papers were retrieved and included in the review. Although some ingredients in PTMC products might cause adverse reproductive effects at high systemic doses, these doses are hundreds to thousands fold greater than those systemically available from topical use at the recommended maximum dose (i.e. 10 g/day). This study provides evidence that, when used as indicated, PTMC is apparently safe for pregnant women and their unborn babies as well as for breastfed infants.
Khoudigian, S; Devji, T; Lytvyn, L; Campbell, K; Hopkins, R; O'Reilly, D
2016-03-01
E-cigarettes are increasingly popular as smoking cessation aids. This review assessed the efficacy of e-cigarettes for smoking cessation as well as desire to smoke, withdrawal symptoms, and adverse events in adult smokers. A systematic review was conducted. Studies comparing e-cigarettes to other nicotine replacement therapies or placebo were included. Data were pooled using meta-analysis. Of 569 articles, 5 were eligible. Study participants were more likely to stop smoking when using nicotine e-cigarettes (43/489, 9 %) versus placebo e-cigarettes (8/173, 5 %); however, this difference was not statistically significant (RR 2.02; 95 % CI 0.97, 4.22). The pooled effect estimates for the desire to smoke (RR -0.22; 95 % CI -0.80, 0.36), irritability (RR -0.03; 95% CI -0.38, 0.31), restlessness (RR -0.03; 95 % CI -0.42, 0.35), poor concentration (RR -0.01; 95 % CI -0.35, 0.32), depression (RR -0.01; 95 % CI -0.22, 0.20), hunger (RR -0.01; 95 % CI -0.32, 0.30), and average number of non-serious adverse events (RR -0.09; 95 % CI -0.28, 0.46) were not statistically significantly different. Only one study reported serious adverse events with no apparent association with e-cigarette use. Limited low-quality evidence of a non-statistically significant trend toward smoking cessation in adults using nicotine e-cigarettes exists compared with other therapies or placebo. Larger, high-quality studies are needed to inform policy decisions.
Acetazolamide in the treatment of metabolic alkalosis in critically ill patients.
Marik, P E; Kussman, B D; Lipman, J; Kraus, P
1991-09-01
Metabolic alkalosis is a common acid-base disturbance in critically ill patients. In many patients correction of fluid and electrolyte status does not fully correct the metabolic derangement. In this study we examined the effect of 500 mg of intravenous acetazolamide, after correcting for fluid and electrolyte abnormalities, on the acid-base status of 30 ventilated patients. In all patients studied there was a fall of total serum bicarbonate; the mean reduction at 24 hours was 6.4 mmol/L, with a normalization of the base excess and pH. The onset of action was rapid (within 2 hours), and the maximal effect occurred at a mean of 15.5 hours, although there was wide variation. The effect of acetazolamide was still apparent at 48 hours. No adverse effects were noted. We conclude that in patients with metabolic alkalosis, once fluid and electrolyte abnormalities have been corrected, acetazolamide is an effective and safe form of therapy with a quick onset and long duration of action.
Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite
Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.
2012-01-01
Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901
Tao, Shi-Qin; Li, Fei; Cao, Lei; Xia, Ru-Shan; Fan, Hua; Fan, Ying; Sun, Hui; Jing, Cheng; Yang, Li-Jia
2015-12-01
The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people.
Gongvatana, Assawin; Morgan, Erin E; Iudicello, Jennifer E; Letendre, Scott L; Grant, Igor; Woods, Steven Paul
2014-10-01
Excessive alcohol use is common among people living with HIV. Given the growing prevalence of older HIV+ adults and observations indicating higher risk for neurocognitive impairment in older adults with either HIV infection or alcoholism, an increased understanding of their combined impact in the context of this increasingly aged population is crucial. We conducted comprehensive neurocognitive assessment in 112 older HIV+ individuals aged 50 to 69 years. Regression analyses were conducted to examine the interaction between age and the presence of lifetime alcohol dependence on neurocognitive measures, controlling for years of education, hepatitis C serostatus, and lifetime non-alcohol substance use disorder. Significant interactions of age and alcohol dependence history were found for global neurocognitive function, which was driven by the domains of executive function, processing speed, and semantic memory. Follow-up analyses indicated adverse effects of alcohol use history on neurocognitive measures that were evident only in HIV+ individuals 60 years and older. While mounting evidence in younger cohorts indicates adverse synergistic HIV/alcohol effects on neurocognitive function, our novel preliminary findings in this elderly HIV+ cohort demonstrated the importance of even a relatively distant alcohol use history on the expression of HIV-associated neurocognitive disorders that may not become apparent until much later in life.
Ranheim, Trine; Halvorsen, Bente
2005-03-01
Coffee is probably the most frequently ingested beverage worldwide. Especially Scandinavia has a high prevalence of coffee-drinkers, and they traditionally make their coffee by boiling ground coffee beans and water. Because of its consumption in most countries in the world, it is interesting, from both a public and a scientific perspective, to discuss its potential benefits or adverse aspects in relation to especially two main health problems, namely cardiovascular disease and type 2 diabetes mellitus. Epidemiological studies suggest that consumption of boiled coffee is associated with elevated risk for cardiovascular disease. This is mainly due to the two diterpenes identified in the lipid fraction of coffee grounds, cafestol and kahweol. These compounds promote increased plasma concentration of cholesterol in humans. Coffee is also a rich source of many other ingredients that may contribute to its biological activity, like heterocyclic compounds that exhibit strong antioxidant activity. Based on the literature reviewed, it is apparent that moderate daily filtered, coffee intake is not associated with any adverse effects on cardiovascular outcome. On the contrary, the data shows that coffee has a significant antioxidant activity, and may have an inverse association with the risk of type 2 diabetes mellitus.
Kim, Miri; Lim, Jihong; Bae, Jung Min; Park, Hyun Jeong
2017-11-01
Various radiofrequency (RF) devices are used to treat skin laxity and face contouring, but few studies have examined ultrahigh-frequency (UHF) electric field (40.68 MHz) RF devices. To evaluate the efficacy and safety of a UHF electric field (40.68 MHz) RF device for skin tightening and face contouring. Ten patients each underwent four sessions of UHF electric field RF device treatment at 2-week intervals. Clinical improvement was evaluated with the patient satisfaction score using a six-point scale, and clinical photographs taken at every visit and 2 months after the RF treatment were assessed. Skin biopsies were obtained from one patient before the first treatment and immediately after the last treatment. Adverse reactions were recorded at every follow-up visit. All patients were women with a mean age of 51.7 ± 7.2 years. The mean satisfaction score was 4.5 ± 0.9 immediately after the last treatment session. Cheek, jawline, and neck enhancement and tightening were apparent in all patients. Side effects were minimal, and there were no burns or major complications. The UHF electric field RF device was effective for skin tightening and facial contouring, without significant adverse reactions.
Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis.
Kitamura, Noboru; Shiraiwa, Hidetaka; Inomata, Hirotake; Nozaki, Takamasa; Ikumi, Natsumi; Sugiyama, Kaita; Nagasawa, Yousuke; Karasawa, Hiromi; Iwata, Mitsuhiro; Matsukawa, Yoshihiro; Takei, Masami
2018-04-01
Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
Hey, Juliane; Thompson-Leduc, Philippe; Kirson, Noam Y; Zimmer, Louise; Wilkins, Dana; Rice, Bernie; Iankova, Irena; Krause, Alexander; Schonfeld, Sophie A; DeBrase, Christopher R; Bozzette, Samuel; Schuetz, Philipp
2018-05-01
Although effective for bacterial lower respiratory tract infections (LRTIs), antibiotic treatment is often incorrectly prescribed for non-bacterial LRTIs. Procalcitonin has emerged as a promising biomarker to diagnose bacterial infections and guide antibiotic treatment decisions. As part of a regulatory submission to the U.S. Food and Drug Administration, this systematic review and meta-analysis summarizes the effects of procalcitonin-guided antibiotic stewardship on antibiotic use and clinical outcomes in adult LRTI patients. PubMed and the Cochrane Database of Systematic Reviews were searched for English-language randomized controlled trials published between January 2004 and May 2016. Random and fixed effects meta-analyses were performed to study efficacy (initiation of antibiotics, antibiotic use) and safety (mortality, length of hospital stay). Eleven trials were retained, comprising 4090 patients. Procalcitonin-guided patients had lower odds of antibiotic initiation (odds ratio: 0.26; 95% confidence interval [CI]: 0.13-0.52) and shorter mean antibiotic use (weighted mean difference: -2.15 days; 95% CI: -3.30 to -0.99) compared to patients treated with standard care. Procalcitonin use had no adverse impact on mortality (relative risk: 0.94; 95% CI: 0.69-1.28) and length of hospital stay (weighted mean difference: -0.15 days; 95% CI: -0.60 to 0.30). Procalcitonin guidance reduces antibiotic initiation and use among adults with LRTIs with no apparent adverse impact on length of hospital stay or mortality.
Instrument comparison for Aerosolized Titanium Dioxide
NASA Astrophysics Data System (ADS)
Ranpara, Anand
Recent toxicological studies have shown that the surface area of ultrafine particles (UFP i.e., particles with diameters less than 0.1 micrometer) has a stronger correlation with adverse health effects than does mass of these particles. Ultrafine titanium dioxide (TiO2) particles are widely used in industry, and their use is associated with adverse health outcomes, such as micro vascular dysfunctions and pulmonary damages. The primary aim of this experimental study was to compare a variety of laboratory and industrial hygiene (IH) field study instruments all measuring the same aerosolized TiO2. The study also observed intra-instrument variability between measurements made by two apparently identical devices of the same type of instrument placed side-by-side. The types of instruments studied were (1) DustTrak(TM) DRX, (2) Personal Data RAMs(TM) (PDR), (3) GRIMM, (4) Diffusion charger (DC) and (5) Scanning Mobility Particle Sizer (SMPS). Two devices of each of the four IH field study instrument types were used to measure six levels of mass concentration of fine and ultrafine TiO2 aerosols in controlled chamber tests. Metrics evaluated included real-time mass, active surface area and number/geometric surface area distributions, and off-line gravimetric mass and morphology on filters. DustTrak(TM) DRXs and PDRs were used for mass concentration measurements. DCs were used for active surface area concentration measurements. GRIMMs were used for number concentration measurements. SMPS was used for inter-instrument comparisons of surface area and number concentrations. The results indicated that two apparently identical devices of each DRX and PDR were statistically not different with each other for all the trials of both the sizes of powder (p < 5%). Mean difference between mass concentrations measured by two DustTrak DRX devices was smaller than that measured by two PDR devices. DustTrak DRX measurements were closer to the reference method, gravimetric mass concentration, than the PDRs. Two apparently identical DC devices were statistically different with each other for fine particles but not for UFP. DC devices and SMPS were statistically different with each other for both sizes of particles. Two apparently identical GRIMM devices were statistically different with each other for fine particles. For UFP, results of GRIMM device were statistically different than SMPS but not for fine particles. These observations suggest that inter-device within instrument and inter-instrument agreements depend on particle size and instrument characteristics to measure nanoparticles at different concentration levels.
Acute hepatitis after amiodarone infusion.
Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco
2015-10-16
Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.
The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy.
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.
Xie, Wei; Ludewig, Gabriele; Wang, Kai; Lehmler, Hans-Joachim
2009-01-01
Perfluorooctanesulfonic acid (PFOS) is a persistent environmental pollutant that may cause adverse health effects in humans and animals by interacting with and disturbing of the normal properties of biological lipid assemblies. To gain further insights into these interactions, we investigated the effect of PFOS potassium salt on dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) model membranes using fluorescence anisotropy measurements and differential scanning calorimetry (DSC) and on the cell membrane of HL-60 human leukemia cells and freshly isolated rat alveolar macrophages using fluorescence anisotropy measurements. PFOS caused a concentration-dependent decrease of the main phase transition temperature (Tm) and an increased peak width (ΔTw) in both the fluorescence anisotropy and the DSC experiments, with a rank order DMPC > DPPC > DSPC. PFOS caused a fluidization of the gel phase of all phosphatidylcholines investigated, but had the opposite effect on the liquid crystalline phase. The apparent partition coefficients of PFOS between the phosphatidylcholine bilayer and the bulk aqueous phase were largely independent of the phosphatidylcholine chain length and ranged from 4.4 × 104 to 8.8 × 104. PFOS also significantly increased the fluidity of membranes of cells. These findings suggest that PFOS readily partitions into lipid assemblies, independent of their composition, and may cause adverse biological effects by altering their fluidity in a manner that depends on the membrane cooperativity and state (e.g., gel versus liquid crystalline phase) of the lipid assembly. PMID:19932010
Schumm, Walter R
2008-08-01
Academic and policy effects of eight early dissertations on gay and lesbian parenting are discussed with a focus on their having been cited at least 234 times in over 50 literature reviews, beginning with Gottman in 1989 and 1990. Most literature reviews, referencing these eight early dissertations and agreeing with Gottman's early conclusions, have reiterated the theme that parenting by gay men or lesbians has outcomes no different than parenting by heterosexual parents. Here it is proposed that certain potential adverse findings may have been obscured by suppressor effects which could have been evaluated had multivariate analyses been implemented. Further, several adverse findings were detected by reanalyzing data where sufficient information was yet available. Some of the dissertations' results (absent controls for social desirability and other differences between homosexual and heterosexual parents) supported the 2001 "no differences" hypothesis discussed by Stacey and Biblarz. Yet, differences were also observed, including some evidence in more recent dissertations, suggesting that parental sexual orientation might be associated with children's later sexual orientation and adult attachment style, among other outcomes. Odds ratios associated with some of the apparent effects were substantial in magnitude as well as statistically significant. Also, more recent research on gay and lesbian parenting continues to be flawed by many of the same limitations as previous research in this area of study, including overlooked suppressor effects.
Rodopoulou, Sophia; Samoli, Evangelia; Analitis, Antonis; Atkinson, Richard W; de'Donato, Francesca K; Katsouyanni, Klea
2015-11-01
Epidemiological time series studies suggest daily temperature and humidity are associated with adverse health effects including increased mortality and hospital admissions. However, there is no consensus over which metric or lag best describes the relationships. We investigated which temperature and humidity model specification most adequately predicted mortality in three large European cities. Daily counts of all-cause mortality, minimum, maximum and mean temperature and relative humidity and apparent temperature (a composite measure of ambient and dew point temperature) were assembled for Athens, London, and Rome for 6 years between 1999 and 2005. City-specific Poisson regression models were fitted separately for warm (April-September) and cold (October-March) periods adjusting for seasonality, air pollution, and public holidays. We investigated goodness of model fit for each metric for delayed effects up to 13 days using three model fit criteria: sum of the partial autocorrelation function, AIC, and GCV. No uniformly best index for all cities and seasonal periods was observed. The effects of temperature were uniformly shown to be more prolonged during cold periods and the majority of models suggested separate temperature and humidity variables performed better than apparent temperature in predicting mortality. Our study suggests that the nature of the effects of temperature and humidity on mortality vary between cities for unknown reasons which require further investigation but may relate to city-specific population, socioeconomic, and environmental characteristics. This may have consequences on epidemiological studies and local temperature-related warning systems.
Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.
McGowan, K T; Elfenbein, J R; Robertson, S A; Sanchez, L C
2013-07-01
Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals. To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose-dependent manner in both neonatal and older pony foals. Seven healthy neonatal pony foals (age 1-2 weeks), and 11 healthy older pony foals (age 4-8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2-way repeated measures ANOVA, followed by a Holm-Sidak multiple comparison procedure if warranted. There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups. Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects. Butorphanol shows analgesic potential in foals for management of somatic painful conditions. © 2012 EVJ Ltd.
NASA Astrophysics Data System (ADS)
Rodopoulou, Sophia; Samoli, Evangelia; Analitis, Antonis; Atkinson, Richard W.; de'Donato, Francesca K.; Katsouyanni, Klea
2015-11-01
Epidemiological time series studies suggest daily temperature and humidity are associated with adverse health effects including increased mortality and hospital admissions. However, there is no consensus over which metric or lag best describes the relationships. We investigated which temperature and humidity model specification most adequately predicted mortality in three large European cities. Daily counts of all-cause mortality, minimum, maximum and mean temperature and relative humidity and apparent temperature (a composite measure of ambient and dew point temperature) were assembled for Athens, London, and Rome for 6 years between 1999 and 2005. City-specific Poisson regression models were fitted separately for warm (April-September) and cold (October-March) periods adjusting for seasonality, air pollution, and public holidays. We investigated goodness of model fit for each metric for delayed effects up to 13 days using three model fit criteria: sum of the partial autocorrelation function, AIC, and GCV. No uniformly best index for all cities and seasonal periods was observed. The effects of temperature were uniformly shown to be more prolonged during cold periods and the majority of models suggested separate temperature and humidity variables performed better than apparent temperature in predicting mortality. Our study suggests that the nature of the effects of temperature and humidity on mortality vary between cities for unknown reasons which require further investigation but may relate to city-specific population, socioeconomic, and environmental characteristics. This may have consequences on epidemiological studies and local temperature-related warning systems.
Céspedes, Miguel Angel; Galindo, Maximo Ibo; Couso, Juan Pablo
2010-01-01
The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function. PMID:21079739
Bianchi, Maria Luisa; Colombo, Carla; Assael, Baroukh M; Dubini, Antonella; Lombardo, Mariangela; Quattrucci, Serena; Bella, Sergio; Collura, Mirella; Messore, Barbara; Raia, Valeria; Poli, Furio; Bini, Rita; Albanese, Carlina V; De Rose, Virginia; Costantini, Diana; Romano, Giovanna; Pustorino, Elena; Magazzù, Giuseppe; Bertasi, Serenella; Lucidi, Vincenzina; Traverso, Gabriella; Coruzzo, Anna; Grzejdziak, Amelia D
2013-07-01
Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. Telethon Foundation (Italy). Copyright © 2013 Elsevier Ltd. All rights reserved.
[Extracorporeal ventriculoatrial shunt with the use of one-way ball valve].
Kubo, Shigeki; Takimoto, Hiroshi; Hosoi, Kazuki; Toyota, Shingo; Takakura, Shuji; Hayashi, Yasuhiro; Ueno, Masato; Morisako, Toshitaka; Karasawa, Jun; Ninaga, Hideo; Yoshimine, Toshiki
2002-04-01
We developed a simple system of an "extracorporeal" ventriculoatrial (VA) shunt using a one-way ball valve (Acty valve II, Kaneka Medix) to release the patient from postoperative constraint during the ventricular drainage. The system is constructed in such a way that the ventricular drainage tube is connected to the central venous catheter via a one-way valve. The CSF is regulated by using the valve and is diverted into the systemic circulation as in the conventional ventriculoatrial shunt. After 2 or 3 weeks of CSF diversion through the extracorporeal VA shunt, a ventriculoperitoneal shunt is placed if hydrocephalus is apparent by temporary occlusion of the system. We applied this system to 4 patients with hydrocephalus, and we found it useful and free from adverse effects. The patient was freed from physical constraint involved in conventional ventricular drainage and an effective program of early rehabilitation was able to be started.
[Beta-blockers in septic shock: a review].
Vela-Vásquez, R S; Grigorov-Tzenkov, I; Aguilar, J L
2015-02-01
In septic shock, high adrenergic stress is associated with cardiovascular and systemic adverse effects, which can negatively affect the results. Beta-adrenergic receptor block has been shown to be effective in controlling the disproportionate increase in heart rate, maintaining a favorable hemodynamic profile and apparently improving the efficiency of the cardiovascular system in order to maintain tissue perfusion. They have also been shown to modulate favorably catecholamine-induced immunosuppression and to decrease insulin resistance, protein catabolism, and proinflammatory cytokine expression associated with cardiovascular dysfunction. Selective beta-1 blockers appear to provide better results than non-selective blockers, even suggesting a positive impact on mortality. Future clinical trials are still needed to confirm these findings and define the scope of their benefits. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Safety of topical minoxidil solution: a one-year, prospective, observational study.
Shapiro, Jerry
2003-01-01
Topical minoxidil solution (TMS) is widely used for androgenetic alopecia (AGA), and this is the first report of a large safety trial. The aim of the study was to evaluate the safety profile of TMS by comparing hospitalization and death rates among subjects using TMS with controls. Cardiovascular safety and pregnancy outcomes were evaluated, and usage patterns were described. All subjects were followed at baseline, 3, 6, 9, and 12 months. Usage patterns, pregnancy status, overnight hospital stays, and cardiovascular risk factors were evaluated. Subjects rated effectiveness of TMS in the treatment of AGA. Statistical analyses were conducted to determine if TMS was associated with an increased risk of death or hospitalization. TMS is a safe and effective treatment for AGA. There were no increases in cardiovascular events and no apparent increased risk for adverse pregnancy outcomes. This large, prospective study demonstrated the overall safety of TMS in the treatment of AGA.
Developing an in vitro technology to study the inflammation potential of ambient particle types
NASA Astrophysics Data System (ADS)
Haddrell, Allen E.
Elevated levels of suspended particles in the troposphere, termed particulate matter, elicit a myriad of adverse health effects in humans, ranging from shortness of breath and wheezing to myocardial infarction and death. It is currently believed that the adverse health effects associated with particulate matter are mediated by the inflammatory response initiated by the lung following particulate matter inhalation. What remains an area of much interest is elucidating the specific properties of particulate matter, physical or chemical, that cause the upregulation of proinflammatory mediators. The basic premise of this thesis was to identify the specific chemical components of particulate matter responsible for its adverse health effects. To address this issue, instrumentation and methodology were developed wherein one could design, create, levitate and deposit particles of both known chemical composition and size onto lung cells, in vitro, followed by the monitoring of the downstream biological response. An initial study focused on the role of the endotoxin component in particulate matter toxicity. Through a series of blocking studies we found that endotoxin acted synergistically with the particle core to elicit upregulation of proinflammatory mediators, including IL-1beta, TNF-alpha and ICAM-1; all of which are associated with the NF-kappaB pathway. Through characterizing this relatively simple system, one observation became apparent: the presence of the insoluble particle core had a profound effect on the cellular response; that is to say, the particle core was not simply a delivery vector, but a determinant factor in the final intracellular location of the toxic chemical. The latter observation held true as other particle types were studied and in addition, it was found that the nature of the actual chemical species itself plays a dual role in particle toxicity; first by retaining its toxic properties and second by altering the physical properties of the particle. It stems from these findings that the toxicity of the chemical components must be studied in concert and not as individual entities.
Toward fisheries sustainability in North America: Issues, challenges, and strategies for action
MacDonald, D.D.; Knudsen, E.E.
2004-01-01
Many fisheries in North America are severely depleted and trending downwards. In an effort to find ways of reversing this disturbing situation, the American Fisheries Society and the Sustainable Fisheries Foundation invited leading experts in fisheries science and aquatic resource management to share their thoughts and insights in this book. These experts were asked to identify the factors that are currently impairing our ability to effectively manage fisheries resources and propose creative solutions for addressing the most challenging issues affecting fisheries sustainability. Based on the information that was provided by the experts (i.e., as presented in the earlier chapters of this book), it is apparent that a wide range of human activities are adversely affecting our shared fisheries resources and the aquatic habitats upon which they depend. The most challenging problems stem from causes that are largely beyond the scope of traditional fisheries management (e.g., human population growth, resource consumption patterns, global climate change, broad land-use patterns). It is also apparent that resolution of these challenges will require a new approach to fisheries management - one that effectively integrates economic, social, and environmental interests into a decision-making framework that supports fisheries sustainability. The key strategies for supporting such a transition toward a more holistic and comprehensive approach to managing the human activities that influence fisheries and aquatic resources are summarized in this chapter. ?? 2004 by the American Fisheries Society.
Guida, Edoardo; Rosati, Ubaldo; Pini Prato, Alessio; Avanzini, Stefano; Pio, Luca; Ghezzi, Michele; Jasonni, Vincenzo; Mattioli, Girolamo
2015-06-01
To measure the feasibility of using FMECA applied to the surgery and then compare the vulnerabilities of laparoscopic versus open appendectomy by using FMECA. The FMECA study was performed on each single selected phase of appendectomy and on complication-related data during the period January 1, 2009, to December 31, 2010. The risk analysis phase was completed by evaluation of the criticality index (CI) of each appendectomy-related failure mode (FM). The CI is calculated by multiplying the estimated frequency of occurrence (O) of the FM, by the expected severity of the injury to the patient (S), and the detectability (D) of the FM. In the first year of analysis (2009), 177 appendectomies were performed, 110 open and 67 laparoscopic. Eleven adverse events were related to the open appendectomy: 1 bleeding (CI: 8) and 10 postoperative infections (CI: 32). Three adverse events related to the laparoscopic approach were recorded: 1 postoperative infection (CI: 8) and 2 incorrect extractions of the appendix through the umbilical port (CI: 6). In the second year of analysis (2010), 158 appendectomies were performed, 69 open and 89 laparoscopic. Four adverse events were related to the open appendectomy: 1 incorrect management of the histological specimen (CI: 2), 1 dehiscence of the surgical wound (CI: 6), and 2 infections (CI: 6). No adverse events were recorded in laparoscopic approach. FMECA helped the staff compare the 2 approaches through an accurate step-by-step analysis, highlighting that laparoscopic appendectomy is feasible and safe, associated with a lower incidence of infection and other complications, reduced length of hospital stay, and an apparent lower procedure-related risk.
Immune responses in dogs with cutaneous adverse food reactions.
Veenhof, E Z; Knol, E F; Willemse, T; Rutten, V P M G
2012-06-01
Adverse food reactions (AFR) in dogs are reactions due to apparently harmless food antigens, with an unknown aetiology, i.e. immunopathogenesis. Despite the entry of food allergens via the intestinal tract, in the majority of dogs with AFR, clinical symptoms are only associated with the skin (CAFR). In the present review, factors are presented of relevance in triggering the differentiation of naive T cells into effector T cell types and the role of these T cell types in allergy. More specifically, the allergic immune responses in intestine and skin are discussed in this article as well as the potential pathways, e.g. homing of antigen presenting cells or allergen-induced T cells to the skin, of induction of cutaneous symptoms.
Heursen, Eva-Marie; Zuazo Ojeda, Amaya; Benavente Fernández, Isabel; Jimenez Gómez, Gema; Campuzano Fernández-Colima, Rosalía; Paz-Expósito, José; Lubián López, Simón Pedro
2017-01-01
Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome. © 2017 S. Karger AG, Basel.
Chavez-Tapia, Norberto C; Mendiola-Pastrana, Indira; Ornelas-Arroyo, Victoria J; Noreña-Herrera, Camilo; Vidaña-Perez, Desiree; Delgado-Sanchez, Guadalupe; Uribe, Misael; Barrientos-Gutierrez, Tonatiuh
2015-01-01
Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.
Waldron, I
1977-01-01
Drug prescriptions per capita in the United States have more than doubled since 1950 without a commensurate improvement in health. Drugs are often prescribed for clinical conditions in which therapeutic benefits do not outweigh the risk of adverse drug reactions. Deaths due to adverse drug reactions are roughly as frequent as deaths due to automobile accidents. Valium and Librium are the first and fourth most commonly prescribed drugs in the U.S., used by one ten adults each year. The rapid rise in use of these drugs has occurred during a period of rising social stress, as indicated by increases in alcohol consumption, suicide, and homicide, Valium and Librium are frequently prescribe for patients who go to doctors with social or other nonmedical problems, often in lieu of attempts to resolve these underlying problems. Overprescribing occurs because the decision to prescribe is influenced not only by consideration of therapeutic benefit, but also by nonmedical factors, for example the widespread expectation by both patient and doctor that the doctor will provide a drug or some other technological treatment. Prescribing decisions are also influenced by the profit-motivated activities of drug companies, including the expenditure of almost one-quarter of every sales dollar on drug promotion. The most widely used source of drug information for doctors is the industry-sponsored Physicians' Desk Reference, which overrates the therapeutic value of Valium and Librium as compared to disinterested medical sources. Drug companies also contribute to overprescribing by introducing numerous minor variants of existing drugs. The therapeutic benefits of such new drugs are often overestimated in the early years of use when adverse side effects are not well known and apparent efficacy is enhanced by placebo effects in uncontrolled observations.
Natural disasters and dialysis care in the Asia-Pacific.
Gray, Nicholas A; Wolley, Martin; Liew, Adrian; Nakayama, Masaaki
2015-12-01
The impact of natural disasters on the provision of dialysis services has received increased attention in the last decade following Hurricane Katrina devastating New Orleans in 2005. The Asia-Pacific is particularly vulnerable to earthquakes, tsunami, typhoons (also known as cyclones and hurricanes) or storms and flooding. These events can seriously interrupt provision of haemodialysis with adverse effects for patients including missed dialysis, increased hospitalization and post-traumatic stress disorder. Furthermore, haemodialysis patients may need to relocate and experience prolonged periods of displacement from family and social supports. In contrast to haemodialysis, most literature suggests peritoneal dialysis in a disaster situation is more easily managed and supported. It has become apparent that dialysis units and patients should be prepared for a disaster event and that appropriate planning will result in reduced confusion and adverse outcomes should a disaster occur. Numerous resources are now available to guide dialysis units, patients and staff in preparation for a possible disaster. This article will examine the disaster experiences of dialysis units in the Asia-Pacific, the impact on patients and staff, methods employed to manage during the disaster and suggested plans for reducing the impact of future disasters. © 2015 Asian Pacific Society of Nephrology.
Finasteride use during pregnancy and early neonatal outcome: a case report.
AlSaad, Doua; Lee, Ben H; Al-Obaidly, Sawsan
2018-06-01
The use of antiandrogen drugs such as finasteride during pregnancy may carry the risk of birth defects, especially hypospadias. We report a 39-year-old woman, with 5 weeks unplanned pregnancy, the patient conceived while receiving daily dose of finasteride 2.5 mg for treatment of alopecia. The patient's partner was concurrently using finasteride for the same purpose. Ultrasound scans including detailed anatomy were normal throughout pregnancy and the fetal gender was detected to be male. The patient had her delivery at 38 +5 weeks' gestation, by elective cesarean section, a male infant with a weight of 3.58 kg and Apgar score of 9 and 10 at 1 and 5-min, respectively. The infant was healthy with no obvious dysmorphic features. In this case report, maternal use of finasteride in early pregnancy was not associated with external genitalia abnormalities of a male baby. Moreover, maternal exposure to the semen of partner who received finasteride did not adversely affect the short term neonatal outcomes. However, absence of apparent neonatal adverse effects in a single case report does not indicate safety of use. Population-based long term neonatal outcomes are yet to be established.
Diffuse Parenchymal Diseases Associated With Aluminum Use and Primary Aluminum Production
2014-01-01
Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers—despite the extensive industrial use of aluminum—the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed. PMID:24806728
Biology Division. Progress report, August 1, 1982-September 30, 1983
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1984-01-01
The Biology Division is the component of the Oak Ridge National Laboratory that investigates the potential adverse health effects of energy-related substances. The body of this report provides summaries of the aims, scope and progress of the research of groups of investigators in the Division during the period of August 1, 1982, through September 30, 1983. At the end of each summary is a list of publications covering the same period (published or accepted for publication). For convenience, the summaries are assembled under Sections in accordance with the current organizational structure of the Biology Division; each Section begins with anmore » overview. It will be apparent, however, that currents run throughout the Division and that the various programs support and interact with each other.« less
Safety profile of bilastine: 2nd generation H1-antihistamines.
Scaglione, F
2012-12-01
Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.
Medicaid program choice, inertia and adverse selection.
Marton, James; Yelowitz, Aaron; Talbert, Jeffery C
2017-12-01
In 2012, Kentucky implemented Medicaid managed care statewide, auto-assigned enrollees to three plans, and allowed switching. Using administrative data, we find that the state's auto-assignment algorithm most heavily weighted cost-minimization and plan balancing, and placed little weight on the quality of the enrollee-plan match. Immobility - apparently driven by health plan inertia - contributed to the success of the cost-minimization strategy, as more than half of enrollees auto-assigned to even the lowest quality plans did not opt-out. High-cost enrollees were more likely to opt-out of their auto-assigned plan, creating adverse selection. The plan with arguably the highest quality incurred the largest initial profit margin reduction due to adverse selection prior to risk adjustment, as it attracted a disproportionate share of high-cost enrollees. The presence of such selection, caused by differential degrees of mobility, raises concerns about the long run viability of the Medicaid managed care market without such risk adjustment. Copyright © 2017 Elsevier B.V. All rights reserved.
Milder, Tamara Y; Williams, Kenneth M; Ritchie, Jan E; Lipworth, Wendy L; Day, Richard O
2011-03-01
non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly to treat osteoarthritis in older patients. to explore the understandings of risk that older-aged primary care patients have in the context of the use of oral NSAIDs to treat osteoarthritis. semi-structured interviews were conducted with 15 patients who were recruited from four general practices located in Sydney, Australia. Patients were aged at least 65 years and were currently taking, or in the past 2 years had taken, an NSAID for osteoarthritis. Emergent themes were identified from the transcripts and were compared within and across transcripts to develop more abstract concepts. patients demonstrated three key 'modes of disengagement' from medication-specific risk information, each of which could also be a mode of modulating a sense of danger and each of which would demand a unique clinical response. These were: 'transference of responsibility'-transferring the responsibility to their GP, 'general versus specific risk'-considering the risk of taking medicine in general as opposed to the specific risk of taking an NSAID, and 'personal immunity'-some patients with a long history of NSAID use without apparent toxicity believed they were, therefore, not at risk of future adverse effects, while a few patients believed they were immune to adverse effects of drugs in general. there is a need for greater recognition of these 'modes of disengagement'/'hazard modulation' in order to attain a clinical response leading to safer, more effective and more ethical use of medicines.
Champagne, Frances A
2010-09-01
Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies. © The Author(s) 2010.
The Complement System and Adverse Pregnancy Outcomes
Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.
2015-01-01
Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092
Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management.
Eisenhofer, Graeme; Rivers, Graham; Rosas, Alejandro L; Quezado, Zena; Manger, William M; Pacak, Karel
2007-01-01
The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D(2) receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications.
Garland, Rebecca M.; Matooane, Mamopeli; Engelbrecht, Francois A.; Bopape, Mary-Jane M.; Landman, Willem A.; Naidoo, Mogesh; van der Merwe, Jacobus; Wright, Caradee Y.
2015-01-01
Regional climate modelling was used to produce high resolution climate projections for Africa, under a “business as usual scenario”, that were translated into potential health impacts utilizing a heat index that relates apparent temperature to health impacts. The continent is projected to see increases in the number of days when health may be adversely affected by increasing maximum apparent temperatures (AT) due to climate change. Additionally, climate projections indicate that the increases in AT results in a moving of days from the less severe to the more severe Symptom Bands. The analysis of the rate of increasing temperatures assisted in identifying areas, such as the East African highlands, where health may be at increasing risk due to both large increases in the absolute number of hot days, and due to the high rate of increase. The projections described here can be used by health stakeholders in Africa to assist in the development of appropriate public health interventions to mitigate the potential health impacts from climate change. PMID:26473895
NASA Technical Reports Server (NTRS)
Higuchi, Yoshinori; Nelson, Gregory A.; Vazquez, Marcelo; Laskowitz, Daniel T.; Slater, James M.; Pearlstein, Robert D.
2002-01-01
Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. CONCLUSIONS: These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the CNS. ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process.
Press-Sandler, Olga; Freud, Tamar; Volkov, Ilya; Peleg, Roni; Press, Yan
2016-06-01
Behavioral and psychological symptoms of dementia (BPSD) are a common problem among patients with dementia. This problem is usually treated by drugs, but they have limited efficacy and often cause adverse effects. Aromatherapy is a nonpharmacologic treatment that is simple to use and devoid of significant adverse effects. To review the literature on the effectiveness of aromatherapy treatment in patients with BPSD. A descriptive analysis of randomized clinical trials (RCTs) published in the English-language literature and cited in PubMed. Eleven articles on RCTs were found, of which 1 had fewer than 10 participants, 2 were mistakenly presented as RCTs, and another did not report treatment for BPSD. In all, 7 articles with 417 participants total (range, 15-114) were reviewed. The mean age in all studies was greater than 69 years (range, 69-85 years), and the percentage of women was 55% (range, 50%-57%). The intervention period ranged from 10 days to 12 weeks. Two studies used Melissa oil and 5 others used lavender oil. The studies described different methods of administration for the oils, including spraying and rubbing over various body organs. The duration of treatment differed among the studies. In 3 studies the investigators concluded that the treatment was not effective and in 3 that it was effective; in 1 study no clear conclusion could be drawn. The difference between positive and negative studies was not explained by differences in the study population, the type of oil, or the duration of treatment. The significant difference apparently stems from the method of administration. When the oil was applied close to the olfactory system the outcome was positive. A study should be designed to assess the effect of the site of application of aromatherapy.
Self‐reported side‐effects associated with use of dietary supplements in an armed forces population
Austin, Krista G.; Farina, Emily K.
2015-01-01
Approximately 60–70% of Armed Forces personnel consume a dietary supplement (DS) at least once a week and there have been numerous reports of severe adverse events among DS users. This study assessed patterns of DS use and self‐reported side‐effects among 4400 Armed Forces personnel using a paper‐and‐pencil survey. Multivariable logistic regression was used to examine associations between patterns of DS use and self‐reported side‐effects. Sixty‐nine percent of personnel surveyed reported using a DS. Seven percent of DS users reported experiencing abnormal heart beats, 6% tremors, 5% stomach pain, 3% dizziness, and 3% numbness/tingling and they believed these symptoms were associated with the use of DS. After adjustment for use of other DS classes, total supplement use, and demographic characteristics, protein supplement users were more likely than non‐users to report numbness/tingling; combination product users were more likely to report experiencing abnormal heart beats, stomach pain, dizziness, tremors, and numbness/tingling; and users of purported steroid analogues were more likely to report dizziness. Use of more than one DS per week was associated with an increased likelihood of reporting side‐effects. Respondents with a higher body mass index were more likely to report side‐effects. Further research is necessary to determine whether self‐reported side‐effects associated with multiple DS use and some DS classes impact the long‐term health or performance of service members. Surveillance of military populations using surveys like this one may provide a method for detecting adverse health events of DS before they are apparent in the civilian population. © 2015 The Authors. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:26526399
Ma, Liang; Salas, Omar; Bowler, Kyle; Oren-Young, Liat; Bar-Peled, Maor; Sharon, Amir
2017-02-01
Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. Treatments with wall stressors suggest the alteration of cell wall integrity. Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. © 2016 BSPP AND JOHN WILEY & SONS LTD.
Liu, Y L; Meng, G Q; Wang, H R; Zhu, H L; Hou, Y Q; Wang, W J; Ding, B Y
2011-04-01
1. A study was conducted to investigate the effects of an esterified glucomannan (EGM), a hydrated sodium calcium aluminosilicate (HSCAS) and a compound mycotoxin adsorbent (CMA) on performance, nutrient retention and meat quality in broilers fed on mould-contaminated feed. Mould-contaminated diets were prepared by replacing half of the non-contaminated maize in the basal diets with mould-contaminated maize, which contained 450·6 µg/kg of aflatoxin B1, 68·4 µg/kg of ochratoxin A and 320·5 µg/kg of T-2 toxin. 2. The mould-contaminated diet significantly decreased body weight gain (BWG) between 10 and 21 d, feed intake (FI) between 35 and 42 d, the apparent retention of crude lipid and phosphorus, and the lightness (L*) value of breast and thigh muscle. It also significantly increased the redness (a*) and yellowness (b*) value in breast muscle and the b* value in thigh muscle. 3. The addition of 0·2% HSCAS significantly increased FI between 35 and 42 d and the apparent retention of phosphorus. Supplementation with 0·1% CMA in the contaminated diet significantly improved BWG from 10 to 21 d, and increased FI from 35 to 42 d and from 10 to 42 d. CMA also significantly increased the apparent retention of crude lipid, crude protein, ash and phosphorus. All three mycotoxin-adsorbent treatments significantly improved the L* values of breast and thigh muscle when compared with the mould-contaminated group. Supplementation with 0·1% CMA in the contaminated diet significantly decreased b* value and improved tenderness in thigh muscle. 0·05% EGM significantly decreased b* value of thigh muscle compared to mould-contaminated group. 4. The results indicated that mycotoxins in contaminated feed retard growth, nutrient retention and meat quality, whereas the addition of 0·05% EGM, 0·2% HSCAS or 0·1% CMA prevents the adverse effects of mycotoxins to varying extents, with 0·1% CMA being the most effective adsorbent treatment.
Nature and Nurturing: Parenting in the Context of Child Temperament
Kiff, Cara J.; Lengua, Liliana J.; Zalewski, Maureen
2011-01-01
Accounting for both bidirectional and interactive effects between parenting and child temperament can fine-tune theoretical models of the role of parenting and temperament in children's development of adjustment problems. Evidence for bidirectional and interactive effects between parenting and children's characteristics of frustration, fear, self-regulation, and impulsivity was reviewed, and an overall model of children's individual differences in response to parenting is proposed. In general, children high in frustration, impulsivity and low in effortful control are more vulnerable to the adverse effects of negative parenting, while in turn, many negative parenting behaviors predict increases in these characteristics. Frustration, fearfulness, and effortful control also appear to elicit parenting behaviors that can predict increases in these characteristics. Irritability renders children more susceptible to negative parenting behaviors. Fearfulness operates in a very complex manner, sometimes increasing children's responses to parenting behaviors and sometimes mitigating them and apparently operating differently across gender. Important directions for future research include the use of study designs and analytic approaches that account for the direction of effects and for developmental changes in parenting and temperament over time. PMID:21461681
Krum, Henry; Roecker, Ellen B; Mohacsi, Paul; Rouleau, Jean L; Tendera, Michal; Coats, Andrew J S; Katus, Hugo A; Fowler, Michael B; Packer, Milton
2003-02-12
Beta-blockers remain underused despite their established utility for improving outcome in heart failure. Concerns that initiation of treatment produces few immediate benefits and may have important risks may be deterring widespread use. To evaluate the early effects of the beta-blocker carvedilol in patients with severe heart failure. Randomized, double-blind, placebo-controlled trial conducted from October 28, 1997, to March 20, 2000, at 334 hospital centers in 21 countries among 2289 patients with symptoms of heart failure at rest or with minimal exertion who were clinically euvolemic and had a left ventricular ejection fraction of less than 25%. Patients were randomly assigned to receive carvedilol, with start dosage of at 3.125 mg twice daily with uptitration to a target dosage of 25 mg twice daily (n = 1156), or placebo (n = 1133), in addition to their usual medications for heart failure. Death, hospitalization, or permanent withdrawal from study drug, as well as adverse events during the first 8 weeks of treatment. The carvedilol group experienced no increase in cardiovascular risk but instead had fewer patients who died (19 vs 25; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.41-1.35); who died or were hospitalized (134 vs 153; HR, 0.85; 95% CI, 0.67-1.07); or who died, were hospitalized, or were permanently withdrawn from treatment (162 vs 188; HR, 0.83; 95% CI, 0.68-1.03). These effects were similar in direction and magnitude to those observed during the entire study, and were apparent particularly in the 624 patients with recent or recurrent decompensation or a very depressed left ventricular ejection fraction. Differences in favor of carvedilol became apparent as early as 14 to 21 days following initiation of treatment. Worsening heart failure was the only serious adverse event with a frequency greater than 2% and was reported with similar frequency in the placebo and carvedilol groups (6.4% vs 5.1%). These data suggest that, in clinically euvolemic patients, the relation of benefit to risk during initiation of treatment with carvedilol is similar to that seen during long-term therapy with the drug. Our findings should provide the reassurance needed to encourage the high levels of use that are warranted by the results of long-term clinical trials.
Immunization update and hot topics in clinical immunology: how does this relate to my practice?
Bellanti, Joseph A
2006-01-01
The prevention of infectious diseases by the use of vaccines represents one of medicine's greatest triumphs during the 20th century. This era has witnessed the global eradication of smallpox as a result of Jennerian cowpox vaccination, the elimination of paralytic poliomyelitis from the western hemisphere, and within 5-10 years the anticipated eradication of poliomyelitis worldwide as a result of the poliovirus vaccines. Next slated for worldwide eradication is measles, the great killer of infants and children, which each year extracts a global mortality of one million victims. Throughout the 20th century the percutaneous (i.e., subcutaneous or intramuscular) route has almost exclusively been the preferred way to administer vaccines. However, as a result of several important scientific discoveries made during the 20th century, including new tissue-culturing techniques, the development of recombinant DNA technology, and genetic sequencing, a whole new generation of tailor-made modern vaccines has become available, including DNA vaccines and transgenic plant vaccines. Moreover, it became apparent that alternative routes of administration of vaccines, such as by aerosol immunization might be more appropriate and more effective than immunization via the parenteral route. The overall success in vaccine development, however, has not been without cost. For every new vaccine that has been developed, an adverse effect has been seen. Thus, although modern vaccines are extremely safe and effective, they are neither completely safe nor completely effective. The goal of vaccine development, therefore, is to achieve the highest degree of protection and the lowest rate of adverse effects. This paper describes some of the recent advances in vaccine development and will focus on some hot topics relating to the recent development and use of respiratory aerosolized vaccines.
Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy.
Ross, D S
1988-12-01
Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.
Messinger, Terrence
2004-01-01
Polycyclic aromatic hydrocarbons (PAHs), including some on the U.S. Environmental Protection Agency's priority pollutant list, were found in bottom sediment in streams in the coal-producing region of the Kanawha River Basin in 1996-1998, and in and near the New River Gorge National River in 2002, in concentrations exceeding those thought likely to cause adverse effects to wildlife. Very low concentrations of bioavailable PAHs were measured in streams in and near the New River Gorge National River by the use of semipermeable membrane devices. The apparent contradiction between the high concentrations of total PAHs and the low concentrations of bioavailable PAHs may result from the presence of a substantial amount of particulate coal in bottom sediment.
Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi
2016-01-01
Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.
Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi
2016-01-01
Background Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. Methods and Findings We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Conclusions Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase. PMID:27119382
Roberts, Jessica K.; Birg, Anna V.; Lin, Tong; Daryani, Vinay M.; Panetta, John C.; Broniscer, Alberto; Robinson, Giles W.; Gajjar, Amar J.
2016-01-01
For infants and very young children with brain tumors, chemotherapy after surgical resection is the main treatment due to neurologic and neuroendocrine adverse effects from whole brain irradiation. Topotecan, an anticancer drug with antitumor activity against pediatric brain tumors, can be given intravenous or orally. However, high interpatient variability in oral drug bioavailability is common in children less than 3 years old. Therefore, this study aimed to determine the population pharmacokinetics of oral topotecan in infants and very young children, specifically evaluating the effects of age and ABCG2 and ABCB1 on the absorption rate constant (Ka), as well as other covariate effects on all pharmacokinetic parameters. A nonlinear mixed effects model was implemented in Monolix 4.3.2 (Lixoft, Orsay, France). A one-compartment model with first-order input and first-order elimination was found to adequately characterize topotecan lactone concentrations with population estimates as [mean (S.E.)]; Ka = 0.61 (0.11) h−1, apparent volume of distribution (V/F) = 40.2 (7.0) l, and apparent clearance (CL/F) = 40.0 (2.9) l/h. After including the body surface area in the V/F and CL/F as a power model centered on the population median, the ABCG2 rs4148157 allele was found to play a significant role in the value of Ka. Patients homozygous or heterozygous for G>A demonstrated a Ka value 2-fold higher than their GG counterparts, complemented with a 2-fold higher maximal concentration as well. These results demonstrate a possible role for the ABCG2 rs4148157 allele in the pharmacokinetics of oral topotecan in infants and very young children, and warrants further investigation. PMID:27052877
Consensus sediment quality guidelines for polycyclic aromatic hydrocarbon mixtures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Swartz, R.C.
1999-04-01
Sediment quality guidelines (SQGs) for polycyclic aromatic hydrocarbons (PAHs) have been derived from a variety of laboratory, field, and theoretical foundations. They include the screening level concentration, effects ranges-low and -median, equilibrium partitioning concentrations, apparent effects threshold, {Sigma}PAH model, and threshold and probable effects levels. The resolution of controversial differences among the PAH SQGs lies in an understanding of the effects of mixtures. Polycyclic aromatic hydrocarbons virtually always occur in field-collected sediment as a complex mixture of covarying compounds. When expressed as a mixture concentration, that is, total PAH (TPAH), the guidelines form three clusters that were intended in theirmore » original derivations to represent threshold (TEC = 290 {micro}g/g organic carbon [OC]), median (MEC = 1,800 {micro}g/g OC), and extreme (EEC = 10,000 {micro}g/g OC) effects concentrations. The TEC/MEC/EEC consensus guidelines provide a unifying synthesis of other SQGs, reflect causal rather than correlative effects, account for mixtures, and predict sediment toxicity and benthic community perturbations at sites of PAH contamination. The TEC offers the most useful SQG because PAH mixtures are unlikely to cause adverse effects on benthic ecosystems below the TEC.« less
Muething, S E; Conway, P H; Kloppenborg, E; Lesko, A; Schoettker, P J; Seid, M; Kotagal, U
2010-10-01
To describe how in-depth analysis of adverse events can reveal underlying causes. Triggers for adverse events were developed using the hospital's computerised medical record (naloxone for opiate-related oversedation and administration of a glucose bolus while on insulin for insulin-related hypoglycaemia). Triggers were identified daily. Based on information from the medical record and interviews, a subject expert determined if an adverse drug event had occurred and then conducted a real-time analysis to identify event characteristics. Expert groups, consisting of frontline staff and specialist physicians, examined event characteristics and determined the apparent cause. 30 insulin-related hypoglycaemia events and 34 opiate-related oversedation events were identified by the triggers over 16 and 21 months, respectively. In the opinion of the experts, patients receiving continuous-infusion insulin and those receiving dextrose only via parenteral nutrition were at increased risk for insulin-related hypoglycaemia. Lack of standardisation in insulin-dosing decisions and variation regarding when and how much to adjust insulin doses in response to changing glucose levels were identified as common causes of the adverse events. Opiate-related oversedation events often occurred within 48 h of surgery. Variation in pain management in the operating room and post-anaesthesia care unit was identified by the experts as potential causes. Variations in practice, multiple services writing orders, multidrug regimens and variations in interpretation of patient assessments were also noted as potential contributing causes. Identification of adverse drug events through an automated trigger system, supplemented by in-depth analysis, can help identify targets for intervention and improvement.
Development of an expert system for power quality advisement using CLIPS 6.0
NASA Technical Reports Server (NTRS)
Chandrasekaran, A.; Sarma, P. R. R.; Sundaram, Ashok
1994-01-01
Proliferation of power electronic devices has brought in its wake both deterioration in and demand for quality power supply from the utilities. The power quality problems become apparent when the user's equipment or systems maloperate or fail. Since power quality concerns arise from a wide variety of sources and the problem fixes are better achieved from the expertise of field engineers, development of an expert system for power quality advisement seems to be a very attractive and cost-effective solution for utility applications. An expert system thus developed gives an understanding of the adverse effects of power quality related problems on the system and could help in finding remedial solutions. The paper reports the design of a power quality advisement expert system being developed using CLIPS 6.0. A brief outline of the power quality concerns is first presented. A description of the knowledge base is next given and details of actual implementation include screen output from the program.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rankin, J.; Bates, J.; Claremont, A.
1986-10-01
A total of 310 grain handlers was studied, with attention to prevalence and characteristics of clinical, psychological, immunological, radiological, serological blood and urine parameters to determine any apparent effects from grain-dust exposure. Grain handlers had a higher prevalence of respiratory symptoms and signs than did the city workers who comprised the comparison group. Evidence of accumulative respiratory effect due to recurring exposures to grain dust was found. Acute and chronic airway reactions were induced by exposure to grain dust. Wheezing and dyspnea on exposure were related to length of employment. Grain fever syndrome was prevalent. Cases of acute recurrent conjunctivitismore » and rhinitis were found along with skin pruritus, mainly on exposure to barley dust. Pesticide exposure caused temporary disabling symptoms. Lung function was adversely affected by grain-dust exposure. Exposure to grain mites and insects in contaminated cereal grain caused a reaction among grain workers.« less
Placental transport and in vitro effects of Bisphenol A.
Mørck, Thit J; Sorda, Giuseppina; Bechi, Nicoletta; Rasmussen, Brian S; Nielsen, Jesper B; Ietta, Francesca; Rytting, Erik; Mathiesen, Line; Paulesu, Luana; Knudsen, Lisbeth E
2010-08-01
Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion models, all of human origin. Results showed BPA cytotoxicity in BeWo cells with an apparent EC50 at 100-125 microM. BPA exposure significantly increased beta-hCG secretion and caspase-3 expression in placental explants at an environmentally relevant concentration of 1 nM. In the transport studies, a rapid transfer of BPA was observed across the term placentae and the BeWo cell monolayer. Further, transdermal transport of BPA was observed. These results indicate that fetal BPA exposure through placental exchange occurs with potential adverse implications for placental and fetal development. This battery of test systems within the realm of human implantation and fetal development represents important elements in risk assessment of reproductive toxicity. Copyright 2010 Elsevier Inc. All rights reserved.
Nitrous oxide in pediatric anesthesia: friend or foe?
Schmitt, Erica L; Baum, Victor C
2008-06-01
Nitrous oxide has been used in clinical practice for over 150 years, often for pediatric procedures. Not only are there problems when used in patients with a variety of inborn errors of metabolism, but effects of nitrous oxide on the developing human brain are unknown. A recent adult human trial found that the use of nitrous oxide was associated with increased adverse outcome. Animal studies in several species have shown that nitrous oxide can be associated with apoptosis in the developing brain. Nitrous oxide can also inhibit major enzymatic pathways and repeated exposure may lead to neurologic damage. Single nucleotide polymorphisms in at least one of these enzymes are common in the population. There is a growing body of evidence that supports avoidance of nitrous oxide in both pediatric and adult patients, but the thousands of patients who have been exposed to nitrous oxide without apparent complications would suggest that further studies on long-term side effects and possible neurologic consequences need to be done.
Use of Ketorolac Is Associated with Decreased Pneumonia Following Rib Fractures
Yang, Yifan; Young, Jason B.; Schermer, Carol R.; Utter, Garth H.
2015-01-01
Background The effectiveness of the non-steroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity following rib fractures remains largely unknown. Methods We conducted a retrospective cohort study spanning January, 2003 to June, 2011, comparing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac within four days post-injury to a random sample of those who did not. Results Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia [odds ratio 0.14 (95% confidence interval 0.04–0.46)] and increased ventilator- and intensive care unit-free days [1.8 (95% confidence interval 1.1–2.5) and 2.1 (95% confidence interval 1.3–3.0) days, respectively] within 30 days. The rates of acute kidney injury, gastrointestinal hemorrhage, and fracture non-union were not different. Conclusions Early administration of ketorolac to patients with rib fractures is associated with a decreased likelihood of pneumonia, without apparent risks. PMID:24112670
Use of ketorolac is associated with decreased pneumonia following rib fractures.
Yang, Yifan; Young, Jason B; Schermer, Carol R; Utter, Garth H
2014-04-01
The effectiveness of the nonsteroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity after rib fractures remains largely unknown. A retrospective cohort study was conducted spanning January 2003 to June 2011 assessing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac <4 days after injury compared with a random sample of those who did not. Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia (odds ratio, .14; 95% confidence interval, .04 to .46) and increased ventilator-free days (difference, 1.8 days; 95% confidence interval, 1.1 to 2.5) and intensive care unit-free days (difference, 2.1 days; 95% confidence interval, 1.3 to 3.0) within 30 days. The rates of acute kidney injury, gastrointestinal hemorrhage, and fracture nonunion were not different. Early administration of ketorolac to patients with rib fractures is associated with a decreased likelihood of pneumonia, without apparent risks. Copyright © 2014 Elsevier Inc. All rights reserved.
Wong, Irene O L; Lindner, Michael J; Cowling, Benjamin J; Lau, Eric H Y; Lo, Su-Vui; Leung, Gabriel M
2010-04-01
To evaluate the presence of moral hazard, adjusted for the propensity to have self-purchased insurance policies, employer-based medical benefits, and welfare-associated medical benefits in Hong Kong. Based on 2005 population survey, we used logistic regression and zero-truncated negative binomial/Poisson regressions to assess the presence of moral hazard by comparing inpatient and outpatient utilization between insured and uninsured individuals. We fitted each enabling factor specific to the type of service covered, and adjusted for predisposing socioeconomic and demographic factors. We used a propensity score approach to account for potential adverse selection. Employment-based benefits coverage was associated with increased access and intensity of use for both inpatient and outpatient care, except for public hospital use. Similarly, welfare-based coverage had comparable effect sizes as employment-based schemes, except for the total number of public ambulatory episodes. Self-purchased insurance facilitated access but did not apparently induce greater demand of services among ever users. Nevertheless, there was no evidence of moral hazard in public hospital use. Our findings suggest that employment-based benefits coverage lead to the greatest degree of moral hazard in Hong Kong. Future studies should focus on confirming these observational findings using a randomized design. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Evaluation of jojoba oil as a low-energy fat. 1. A 4-week feeding study in rats.
Verschuren, P M
1989-01-01
The nutritional properties of jojoba oil (JO) were examined in a 4-wk feeding study of rats fed a diet with JO at dose levels of 2.2, 4.5 and 9%, supplemented with a conventional fat up to 18%. General health, survival and food intake were not adversely affected. Body-weight gains showed a dose-related decline, which amounted to 20% of the body weight in the high-dose group of both sexes. Clinical chemistry revealed significantly increased levels of various enzymes that were indicative of cell damage. Haematology showed a dose-related increase in white blood cells. On necropsy an apparent distension of the small intestine was found. Histopathological evaluation revealed marked intestinal changes characterized by massive vacuolization and lipid deposition in the enterocytes, accompanied by distension of the villi and an increased cell turnover of small intestinal cells. Faeces production and faeces lipid content were increased with increasing JO levels. The recovery of JO in the faeces also increased in a dose-related manner and was found to be correlated with the intestinal histopathological changes. The significant adverse clinical and histopathological effects observed in this study imply that JO cannot be considered as a promising alternative dietary fat with a low digestibility.
Tang, Qiaohong; Mo, Zhongjun; Yao, Jie; Li, Qi; Du, Chenfei; Wang, Lizhen; Fan, Yubo
2014-12-01
This study was aimed to estimate the effect of different ProDisc-C arthroplasty designs after it was implanted to C5-C6 cervicalspine. Finite element (FE) model of intact C5-C6 segments including the vertebrae and disc was developed and validated. Ball-and-socket artificial disc prosthesis model (ProDisc-C, Synthes) was implanted into the validated FE model and the curvature of the ProDisc-C prosthesis was varied. All models were loaded with compressed force 74 N and the pure moment of 1.8 Nm along flexion-extension and bilateral bending and axial torsion separately. The results indicated that the variation in the curvature of ball and socket configuration would influence the range of motion in flexion/extension, while there were not apparently differences under other conditions of loads. The method increasing the curvature will solve the stress concentration of the polyethylene, but it will also bring adverse outcomes, such as facet joint force increasing and ligament tension increasing. Therefore, the design of artificial discs should be considered comprehensively to reserve the range of motion as well as to avoid the adverse problems, so as not to affect the long-term clinical results.
Sunitinib-related fulminant hepatic failure: case report and review of the literature.
Mueller, Eric W; Rockey, Michelle L; Rashkin, Mitchell C
2008-08-01
Drug-induced hepatotoxicity is an infrequent but life-threatening complication. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma and gastrointestinal stromal tumor. However, results from preapproval clinical trials suggest an equivocal hepatic risk profile for sunitinib. We describe a 75-year-old woman with renal cell carcinoma who was admitted to the intensive care unit after experiencing fulminant hepatic failure during sunitinib therapy. The patient's hepatic and renal chemistries had been within normal limits throughout four previous cycles of sunitinib therapy spanning 9 months. After the fifth cycle, she complained of a 3-day history of severe diarrhea and dehydration. Her abnormal laboratory test results included the following: total bilirubin level 5.9 mg/dl, aspartate aminotransferase level 3872 U/L, alanine aminotransferase level 3332 U/L, ammonia level 897 microg/dl, and an international normalized ratio of 4.8. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between sunitinib and hepatotoxicity. Supportive care including aggressive intravenous hydration and reversal of coagulopathy was successful. The patient was discharged home on hospital day 7 without apparent longstanding sequelae. Clinicians should be aware of this possible adverse effect of sunitinib, and continued pharmacovigilance is imperative to accurately quantify the possible risk of sunitinib-related hepatotoxicity.
Combating adverse selection in secondary PC markets.
Hickey, Stewart W; Fitzpatrick, Colin
2008-04-15
Adverse selection is a significant contributor to market failure in secondary personal computer (PC) markets. Signaling can act as a potential solution to adverse selection and facilitate superior remarketing of second-hand PCs. Signaling is a means whereby usage information can be utilized to enhance consumer perception of both value and utility of used PCs and, therefore, promote lifetime extension for these systems. This can help mitigate a large portion of the environmental impact associated with PC system manufacture. In this paper, the computer buying and selling behavior of consumers is characterized via a survey of 270 Irish residential users. Results confirm the existence of adverse selection in the Irish market with 76% of potential buyers being unwilling to purchase and 45% of potential vendors being unwilling to sell a used PC. The so-called "closet affect" is also apparent with 78% of users storing their PC after use has ceased. Results also indicate that consumers place a higher emphasis on specifications when considering a second-hand purchase. This contradicts their application needs which are predominantly Internet and word-processing/spreadsheet/presentation applications, 88% and 60% respectively. Finally, a market solution utilizing self monitoring and reporting technology (SMART) sensors for the purpose of real time usage monitoring is proposed, that can change consumer attitudes with regard to second-hand computer equipment.
Probiotics in Helicobacter pylori-induced peptic ulcer disease.
Boltin, Doron
2016-02-01
The ideal treatment regimen for the eradication Helicobacter pylori infection has yet to be identified. Probiotics, particularly Lactobacillus, Bifidobacterium and Saccharomyces, have been suggested as adjuncts to antibiotics for the treatment of H. pylori. There is in vitro evidence that probiotics dampen the Th1 response triggered by H. pylori, attenuate H. pylori associated hypochlorhydria and secrete bacteriocidal metabolites. Probiotics interact with the innate host immune system through adherence to the gastric epithelium and secretion of bacterial adhesins. In prospective human studies, probiotic monotherapy effectively decrease H. pylori density (expired (13)CO2) by 2.0%-64.0%. Probiotic monotherapy has also been shown to eradicate H. pylori in up to 32.5%, although subsequent recrudescence is likely. Eleven meta-analyses have evaluated the efficacy of probiotics as adjuvants to antibiotics for the eradication of H. pylori. The addition of a probiotic increased treatment efficacy, OR 1.12-2.07. This benefit is probably strain-specific and may only be significant with relatively ineffective antibiotic regimens. The pooled prevalence of adverse effects was 12.9%-31.5% among subjects receiving adjuvant probiotics, compared with 24.3%-45.9% among controls. Diarrhea in particular was significantly reduced in subjects receiving adjuvant probiotics, compared with controls (OR 0.16-0.47). A reduction in adverse events other than diarrhea is variable. Despite the apparent benefit on efficacy and side effects conferred by probiotics, the optimal probiotic species, dose and treatment duration has yet to be determined. Further studies are needed to identify the probiotic, antibiotic and patient factors which might predict benefit from probiotic supplementation. Copyright © 2015 Elsevier Ltd. All rights reserved.
[New technologies for evaluation of health status of apparently healthy people].
Ushakov, I B; Orlov, O I; Baevskiĭ, R M; Bersenev, E Iu; Chernikova, A G
2013-03-01
The article considers the questions of development of new technologies for evaluation of health of apparently healthy people based on experience of long-term researches of cosmonauts' performed at Russian Academy of Sciences Institute of Biomedical Problems under the direction of academician A. I. Grigoriev. In 2007 in monograph "Concept of Health and Space Medicine" the principle of health estimation in apparently healthy people working in conditions of chronic stress was described. These approaches were realized the same year to produce a new hard and software "Ecosan-2007". In the following 2008 the device has been tested for inspection of bus drivers and pilots of civil aircraft and since 2009 it has been used in the international project "Mars-500". All these developments and researches were supported by the Fundamental Sciences-to-Medicine Program maintained by the Presidium of the Russian Academy of Sciences under guidance of academician A. I. Grigoriev. In the project 'Mars-500" in the "artificial confinement", simulating the interplanetary ship, 6 members of the international "Martian crew" were medically and psycho physiologically surveyed. Among set of various devices the "Ecosan-2007" was also used. With application of the same device, not less that 125 volunteers were examined, who lived usual life in natural and socially-industrial conditions. The investigation was simultaneously conducted in 12 various regions of the world. These long-term medico-ecological researches allowed to receive important experimental substantiations for preclinical approach to state of health estimation. In the frame of these researches the methodology of remote monitoring of adverse ecological factor effects on health initiated telemedical ecology, a new applied discipline. The article concludes with discussion of the issues of health conception and new preclinical diagnostic technologies adapting by the public health services.
NASA Astrophysics Data System (ADS)
Shieh, J.; Wu, K. C.; Chen, C. S.
2007-04-01
The polarization switching characteristics of lead-free a(Bi 1/2Na 1/2)TiO 3-bBaTiO 3-c(Bi 1/2K 1/2)TiO 3 (abbreviated as BNBK 100a/100b/100c) ferroelectric ceramics are investigated. This is achieved through examining their polarization and strain hystereses inside and outside the morphotropic phase boundary (MPB). The total induced electrostrain (ɛ 33,total) and apparent piezoelectric charge coefficient (d 33) first increase dramatically and then decrease gradually as the BNBK composition moves from the tetragonal phase to the MPB and then to the rhombohedral phase. The measured polarization hystereses indicate that the BNBK compositions situated near the rhombohedral side of the MPB typically possess higher coercive field (E c) and remanent polarization (P r), while the compositions situated near the tetragonal side of the MPB possess higher apparent permittivity. Adverse effects on the ferroelectric properties are observed when BNBK is doped with donor dopants such as La and Nb. On the contrary, intricate hysteresis behaviors are observed when acceptor dopant Mn is introduced into BNBK. Under an alternating electric field of +/-5.0 MVm -1, BNBK 85.4/2.6/12, a composition well within the MPB, exhibits an ɛ 33,total of ~0.14%, an apparent d 33 of 295 pCN -1, an E c of 2.5 MVm -1 and a Pr of 22.5 μCcm -2. These notable ferroelectric property values suggest a candidate material for lead-free actuator applications. The present study provides a systematic set of hysteresis measurements which can be used to characterize the switching behaviors of BNBK-based lead-free ferroelectrics.
Enders, M; Biber, M; Exler, S
2007-11-01
Measles, mumps and rubella are common childhood diseases. Therefore, frequent and intense contact with children of preschool age may be associated with a higher infection risk for childcare providers. This overview summarizes current knowledge on possible adverse effects of these infections on pregnant women, pregnancy outcome and the fetus. Acute rubella or mumps virus infections are apparently not more severe in pregnant than non-pregnant women. In contrast, measles virus infection in pregnancy is linked to a higher incidence of pneumonitis and hospitalization. Evidence of congenital defects due to fetal infection is only provided in case of rubella virus infection in early pregnancy. Following rubella virus infection in the first trimester an increased fetal loss rate was reported. In 1966, a prospective study showed also a significant association between maternal mumps in the first trimester and an increased risk of abortion. But other investigators could not confirm this association. Measles and rubella but not mumps virus infections are linked to an increased premature birth rate. Occurring in late pregnancy, all three infections can result in birth of an infected infant. But severe disease occurs rarely and is mostly reported for premature infants with early neonatal measles. Preventive measures, aimed to reduce the risk of infection or severe complications for pregnant childcare providers, should consider the individual history of the employee (e.g. previous immunizations or antibody test results), the current epidemiological situation and possible interventions like passive immunization in case of exposure to measles.
Suwantarat, Nuntra; Tice, Alan D.; Khawcharoenporn, Thana; Chow, Dominic C.
2010-01-01
OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 103 cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit. PMID:20107528
Eguaras, Sonia; Toledo, Estefanía; Hernández-Hernández, Aitor; Cervantes, Sebastián; Martínez-González, Miguel A
2015-11-05
Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou's Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93-2.25) for ≥25 - <30 kg/m² of BMI and 2.00 (1.04-3.83) for ≥30 kg/m² of BMI, compared to a BMI < 25 kg/m². In contrast, these estimates were 0.77 (0.35-1.67) and 1.15 (0.39-3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity.
Licorice abuse: time to send a warning message
Komarova, Irina; El-Ghonemi, Mohamed; Fathy, Ahmed; Rashad, Rania; Abdelmalak, Hany D.; Yerramadha, Muralidhar Reddy; Ali, Yaseen; Helal, Engy; Camporesi, Enrico M.
2012-01-01
Licorice extract has always been recognized as a sweetener and a thirst quencher. Its nutritive value is overrated by many who consume significant amounts and are prone to complications. Glycyrrhetic acid, the active metabolite in licorice, inhibits the enzyme 11-ß-hydroxysteroid dehydrogenase enzyme type 2 with a resultant cortisol-induced mineralocorticoid effect and the tendency towards the elevation of sodium and reduction of potassium levels. This aldosterone-like action is the fundamental basis for understanding its health benefits and the wide spectrum of adverse effects. Herein, we present a comprehensive review of licorice along with the reported complications related to excess intake. Despite its apparent use in a few clinical scenarios, the daily consumption of licorice is never justified because its benefits are minor compared to the adverse outcomes of chronic consumption. The review highlights the importance of investigating the dietary habits and herbal remedies which are being used worldwide on cultural and habitual bases rather than reliable scientific evidence. Licorice is a US Food and Drug Administration (FDA) approved food supplement used in many products without precise regulations to prevent toxicity. Increased awareness among the public is required through TV commercials, newspapers, internet sites, magazines and product labels regarding the upper limit of ingestion and health hazards associated with excess intake. We hope that this review will serve as a warning message that should be transmitted from physicians to patients to avoid excessive licorice intake as well as a message to the FDA to start regulating the use of this substance. PMID:23185686
Martino, Tommaso; Melchionda, Donato; Tonti, Paolo; De Francesco, Vincenzo; Lalla, Alessandra; Specchio, Luigi Maria; Avolio, Carlo
2016-12-01
Apparently, unexplained weight loss is a common symptom experienced by patients affected by Parkinson's disease, especially in those treated by levodopa-carbidopa infusion gel (LCIG) with a poor control of dyskinesias. Weight loss is considered part of gastrointestinal dysfunction seen in patients affected by Parkinson's disease, along with gastroparesis and reduced bowel peristalsis. In patients treated with LCIG, weight loss needs to be accurately evaluated, because of possible underlying life-threatening adverse events, like duodenum decubitus ulcer.
Reuse water: Exposure duration, seasonality and treatment affect tissue responses in a model fish.
Blunt, B J; Singh, A; Wu, L; Gamal El-Din, M; Belosevic, M; Tierney, K B
2017-12-31
Partially remediated gray (reuse) water will likely find increasing use in a variety of applications owing to the increasing scarcity of freshwater. We aimed to determine if a model fish, the goldfish, could sense reuse water using olfaction (smell), and if 30min or 7d (acute) and 60d (sub-chronic) exposures would affect their olfactory responses to natural odorants. We examined olfaction as previous studies have found that numerous chemicals can impair the olfactory sense, which is critical to carrying out numerous life-sustaining behaviors from feeding to mating. We also examined if fish olfactory and liver tissues would mount a response in terms of biotransformation enzyme gene expression, and whether treatment of reuse water with UV/H 2 O 2 ameliorated adverse effects following reuse water exposure. We found that fish olfactory tissue responded to reuse water as it would to a natural odorant and that UV/H 2 O 2 treatment had no influence on this. With acute exposures, olfactory impairment was apparent regardless of water type (e.g. responses of 23-55% of control), but in sub-chronic exposures, only the untreated reuse water caused olfactory impairment. The exposure of fish to reuse water increased the expression of one enzyme (CYP1A; >2.5-6.5 fold change) and reuse water treatment with UV/H 2 O 2 reversed the effect. There was a seasonal effect that was likely due to changes in water quality (60d summer exposure impaired olfaction whereas spring and fall exposures did not). Overall, the data suggest that reuse water may be detected by olfaction, impair olfactory responses in fish receiving unavoidable exposures, and that exposure duration and season are important factors to consider regarding adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.
Rohatagi, Shashank; Luo, Yongyi; Shen, Liduo; Guo, Zuyu; Schemm, Christina; Huang, Yongqing; Chen, Kelly; David, Michael; Nave, Ruediger; King, S Peter
2005-01-01
Freely circulating, protein unbound, active inhaled corticosteroid (ICS) can cause systemic adverse effects. Desisobutyryl-ciclesonide (des-CIC) is the active metabolite of ciclesonide, an effective, novel ICS for persistent asthma. This study examines the free fraction of ciclesonide and des-CIC and determines whether the presence of other agents or disease states affects protein binding. Protein binding of des-CIC (0.5, 5.0, 25, 100, and 500 ng/mL) was determined, using both equilibrium dialysis and ultrafiltration, in plasma from humans (healthy and either renally or hepatically impaired) and several animal species and in the presence of either salicylates or warfarin. Dialyzed samples were analyzed by liquid chromatography with tandem mass spectroscopy to determine both free and bound concentrations of des-CIC. After ultrafiltration, spiked plasma plus H-des-CIC was separated into free and bound fractions by centrifugation and quantified by scintillation counting. Additionally, in another study, protein binding of ciclesonide was determined by equilibrium dialysis. For equilibrium dialysis, the mean percentages of des-CIC (0.5-500 ng/mL) plasma protein binding across species were high, approximately 99%, and no apparent saturation of protein binding was observed. Results were similar for ultrafiltration analysis. Protein binding of des-CIC did not change in the presence of warfarin or salicylates or in the plasma of renally or hepatically impaired patients. The protein binding of ciclesonide was 99.4% in human serum. The very low fraction of unbound des-CIC in the systemic circulation suggests minimal systemic exposure of unbound des-CIC, thus suggesting a low potential for systemic adverse effects after administration of inhaled ciclesonide.
The pharmacokinetics of colistin in patients with cystic fibrosis.
Reed, M D; Stern, R C; O'Riordan, M A; Blumer, J L
2001-06-01
The safety and pharmacokinetics of colistin were determined after first dose (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t1/2), mean residence time (MRT), steady-state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first-dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first-dose and steady-state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty-one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin-induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin-induced nephrotoxicity. No relationship between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.
Radiation to the head, neck, and upper thorax of the young and thyroid neoplasia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schreiner, R.L.
1976-03-01
It is now generally accepted that an association exists between external radiation administered to the head, neck and upper thorax of infants, children and adolescents and the subsequent development of neoplastic changes in the thyroid gland. Until recent years external radiation was frequently administered to shrink an enlarged thymus, or for the treatment of tonsillitis, adenoiditis, hearing loss, hemangioma, acne, tinea capitis and other conditions. During the course of these treatments, the thyroid gland was exposed to scattered radiation. It is stressed that the use of external radiation therapy was then accepted practice and its value was attested by many.more » The likelihood of adverse effects was not initially apparent, primarily because of the long periods of time between the administration of the therapy and the recognition of changes in the thyroid. The availability and effectiveness of other therapeutic measures and the growing concern about the delayed effects of radiation therapy when administered to the young for relatively benign conditions has, in recent years, largely eliminated use of this form of therapy, except in a few unusual conditions.« less
Commentary: selenium study on endangered razorback sucker is flawed
Hamilton, Steven J.
2005-01-01
The razorback sucker (Xyrauchen texanus) is listed as federally endangered throughout its range. A massive recovery effort by the Recovery Implementation Program for Endangered Fish Species in the Upper Colorado River Basin has focused its efforts in the upper Colorado River. The upper Colorado River basin also has two locations that have been identified by the National Irrigation Water Quality Program as having substantial selenium contamination. Selenium is toxic to fishes, affecting reproductive success. Thus, there is concern about potential effects of selenium on the endangered razorback sucker. Two sets of studies have investigated the effects of selenium on razorback suckers, but study results are conflicting. This commentary evaluates studies that claim selenium is not a problem for razorback sucker. We find that study bias was so pervasive that purported conclusions were unwarranted. Contaminated control water, older life stages of fish tested, lack of methodology for analysis of selenium in water, diet, or fish, use of rotifer food, low feeding rates, low growth rates of fish, and improper storage of site waters resulted in an apparent erroneous linkage of high selenium in whole-body residues with no adverse effects.
Nagai, Aiko; Shibamoto, Yuta; Ogawa, Keiko
2013-01-01
Despite the development of radiotherapy machines and technologies, a proportion of patients suffer from radiation-induced lymphedema. Saireito (SRT) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in conditions such as nephritic disease. This study investigated the effect of SRT on lymphedema caused by radiotherapy. Four patients were treated with SRT at a dose of 9 g/day. The severity of lymphedema was evaluated using the Common Terminology Criteria for Adverse Events version 4 and Numerical Rating Scale before and after SRT treatment. After the treatment with SRT, 2 of 4 patients (50%) showed apparent improvement in lymphedema. One of the cases had difficulty in wearing the custom-made thermoplastic cast, but after SRT administration, he could wear the mask easily. One case decided to stop taking SRT 3 days after initiation because cough and fever appeared. In conclusion, it is important to control the side effects of radiotherapy, which leads to improved tumor control rates. Prospective randomized studies are necessary to confirm the findings of this case series study.
Some factors influencing the nonexpert's perception and evaluation of environmental risks
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vaughan, E.
Policy makers and decision analysts have been limited somewhat in their ability to predict public reactions to regulatory decisions about hazardous substances or technologies. Most studies of the nonexpert's evaluation of environmental risks have relied on survey data and correlational analyses which preclude the determination of interactive effects, effects that could explain apparent inconsistencies. Three experimental studies were designed to test empirically the effect of six dimensions of environmental risk on judgments of (1) perceived risk, (2) acceptability of risk, (3) subjective probability of negative outcomes due to exposure, and (4) perceived severity of consequences. Factors examined included: (a) familiaritymore » with the terms used to describe a hazard, (b) environmental persistence of a chemical, (c) personal relevance of data used to evaluate cancer-causing potential, (d) personal relevance of possible adverse consequences, (e) perceived control over exposure, and (f) vividness of the exposure pathway. The findings were discussed in terms of their implications for the nonexpert's formulation of risk perceptions, and public policy in the domain of environmental risks.« less
Role of preoperative carbohydrate loading: a systematic review.
Bilku, D K; Dennison, A R; Hall, T C; Metcalfe, M S; Garcea, G
2014-01-01
Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery. All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles. Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported. Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.
Toxicity and Fate Comparison between Several Brass and Titanium Dioxide Powders
1993-07-01
the entire gut without showing any apparent effects . 14. UBJET TEMS1I. NUMBER OF PAGES 27 Daphnia Algae EC50 Aquatic toxicity 11T.PRICE CODE 9...levels of soluble copper and zinc in solution. 3. RESULTS The titanium dioxide ( TiO2 ) materials did not show any apparent toxic effects to daphnia up to...The extended exposure did not show any apparent toxic effects . Long term effects on aquatic org.rnisms exposed to TiO2 are not known. It is apparent
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.
Are adverse effects incorporated in economic models? An initial review of current practice.
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.
Adverse effects of aromatherapy: a systematic review of case reports and case series.
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.
Role of selenium toxicity and oxidative stress in aquatic birds
Hoffman, D.J.
2002-01-01
Adverse effects of selenium (Se) in wild aquatic birds have been documented as a consequence of pollution of the aquatic environment by subsurface agricultural drainwater and other sources. These effects include mortality, impaired reproduction with teratogenesis, reduced growth, histopathological lesions and alterations in hepatic glutathione metabolism. A review is provided, relating adverse biological effects of Se in aquatic birds to altered glutathione metabolism and oxidative stress. Laboratory studies, mainly with an organic form of Se, selenomethionine, have revealed oxidative stress in different stages of the mallard (Anas platyrhynchos) life cycle. As dietary and tissue concentrations of Se increase, increases in plasma and hepatic GSH peroxidase activities occur, followed by dose-dependent increases in the ratio of hepatic oxidized to reduced glutathione (GSSG:GSH) and ultimately hepatic lipid peroxidation measured as an increase in thiobarbituric acid reactive substances (TBARS). One or more of these oxidative effects were associated with teratogenesis (4.6 ppm wet weight Se in eggs), reduced growth in ducklings (15 ppm Se in liver), diminished immune function (5 ppm Se in liver) and histopathological lesions (29 ppm Se in liver) in adults. Manifestations of Serelated effects on glutathione metabolism were also apparent in field studies in seven species of aquatic birds. Reduced growth and possibly immune function but increased liver:body weight and hepatic GSSG:GSH ratios were apparent in American avocet (Recurvirostra americana) hatchlings from eggs containing 9 ppm Se. In blacknecked stilts (Himantopus mexicanus), which contained somewhat lower Se concentrations, a decrease in hepatic GSH was apparent with few other effects. In adult American coots (Fulica americana), signs of Se toxicosis included emaciation, abnormal feather loss and histopathological lesions. Mean liver concentrations of 28 ppm Se (ww) in the coots were associated with elevated hepatic GSH peroxidase, depletion of hepatic protein bound thiols and total thiols, but a small increase in GSH. Diving ducks in the San Francisco Bay area exhibited a positive correlation between hepatic Se concentration and GSH peroxidase activity (r=0.63, P<0.05), but a negative correlation between hepatic Se and GSH concentration (r=0.740, P<0.05). In willets (Catoptrophorus semipalmatus) from the San Diego area, positive correlations occurred between hepatic Se concentration and GSSG (r=0.70, P<0.001), GSSG:GSH ratio, and TBARS. In emperor geese (Chen canagica) from western Alaska, blood levels of up to 9.4 ppm occurred and were associated with increased plasma GSH peroxidase activity (r=0.62, P<0.001), but with decreased plasma GSSG reductase activity. When evaluating Se toxicity, interactive nutritional factors, including other elements and dietary protein, should also be taken into consideration. Further studies are needed to examine the relationship between different forms of environmentally occurring selenium, arsenic and mercury on reproduction, hepatotoxicity and immune function of aquatic birds. Further selenium nutritional interaction studies may also help to illucidate the mechanism of selenium induced teratogenesis, by optimizing GSH and other antioxidant defense mechanisms in a manner that would stabilize or raise the cell's threshold for susceptibility to toxic attack from excess selenium. It is concluded that Se-related manifestations of oxidative stress may serve as useful bioindicators of Se exposure and toxicity in wild aquatic birds.
Effect of air gap on apparent temperature of body wearing various sizes of T-shirt
NASA Astrophysics Data System (ADS)
Takatera, M.; Uchiyama, E.; Zhu, C.; Kim, KO; Ishizawa, H.
2017-10-01
We investigated the effect of air gap on the apparent temperature. Using the developed thermocouple fabric and a thermal manikin, we measured temperature distribution of the measuring garments due to the change of T-shirt sizes. We were able to measure the apparent temperature distribution at points near a body while wearing different sizes of T-shirts. It was observed that the temperature distribution depending on different air gap between clothing and body. The apparent temperature depends on garment size and place. The effect of air gap on apparent temperature of body was experimentally confirmed.
Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists
Di Stasi, Stephanie L.; MacLeod, Toran D.; Winters, Joshua D.
2010-01-01
Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy. PMID:20688875
Vibrations transmitted from human hands to upper arm, shoulder, back, neck, and head.
Xu, Xueyan S; Dong, Ren G; Welcome, Daniel E; Warren, Christopher; McDowell, Thomas W; Wu, John Z
2017-12-01
Some powered hand tools can generate significant vibration at frequencies below 25 Hz. It is not clear whether such vibration can be effectively transmitted to the upper arm, shoulder, neck, and head and cause adverse effects in these substructures. The objective of this study is to investigate the vibration transmission from the human hands to these substructures. Eight human subjects participated in the experiment, which was conducted on a 1-D vibration test system. Unlike many vibration transmission studies, both the right and left hand-arm systems were simultaneously exposed to the vibration to simulate a working posture in the experiment. A laser vibrometer and three accelerometers were used to measure the vibration transmitted to the substructures. The apparent mass at the palm of each hand was also measured to help in understanding the transmitted vibration and biodynamic response. This study found that the upper arm resonance frequency was 7-12 Hz, the shoulder resonance was 7-9 Hz, and the back and neck resonances were 6-7 Hz. The responses were affected by the hand-arm posture, applied hand force, and vibration magnitude. The transmissibility measured on the upper arm had a trend similar to that of the apparent mass measured at the palm in their major resonant frequency ranges. The implications of the results are discussed. Musculoskeletal disorders (MSDs) of the shoulder and neck are important issues among many workers. Many of these workers use heavy-duty powered hand tools. The combined mechanical loads and vibration exposures are among the major factors contributing to the development of MSDs. The vibration characteristics of the body segments examined in this study can be used to help understand MSDs and to help develop more effective intervention methods.
Vibrations transmitted from human hands to upper arm, shoulder, back, neck, and head
Xu, Xueyan S.; Dong, Ren G.; Welcome, Daniel E.; Warren, Christopher; McDowell, Thomas W.; Wu, John Z.
2016-01-01
Some powered hand tools can generate significant vibration at frequencies below 25 Hz. It is not clear whether such vibration can be effectively transmitted to the upper arm, shoulder, neck, and head and cause adverse effects in these substructures. The objective of this study is to investigate the vibration transmission from the human hands to these substructures. Eight human subjects participated in the experiment, which was conducted on a 1-D vibration test system. Unlike many vibration transmission studies, both the right and left hand-arm systems were simultaneously exposed to the vibration to simulate a working posture in the experiment. A laser vibrometer and three accelerometers were used to measure the vibration transmitted to the substructures. The apparent mass at the palm of each hand was also measured to help in understanding the transmitted vibration and biodynamic response. This study found that the upper arm resonance frequency was 7–12 Hz, the shoulder resonance was 7–9 Hz, and the back and neck resonances were 6–7 Hz. The responses were affected by the hand-arm posture, applied hand force, and vibration magnitude. The transmissibility measured on the upper arm had a trend similar to that of the apparent mass measured at the palm in their major resonant frequency ranges. The implications of the results are discussed. Relevance to industry Musculoskeletal disorders (MSDs) of the shoulder and neck are important issues among many workers. Many of these workers use heavy-duty powered hand tools. The combined mechanical loads and vibration exposures are among the major factors contributing to the development of MSDs. The vibration characteristics of the body segments examined in this study can be used to help understand MSDs and to help develop more effective intervention methods. PMID:29123326
Nagaya, Teruo; Hibino, Minoru; Kondo, Yasuaki
2018-01-01
Headache in employees may be linked with both overwork and sleep restriction induced by long working hours. Inter-relationships among working hours, sleep duration and headache were investigated. Cross-sectional analyses for prevalent headache (n = 35,908) and 1-year follow-up analyses for incident headache (n = 19,788) were conducted in apparently healthy white-collar men aged 25-59 years. Headache (yes/no), working hours and sleep duration were based on self-administered questionnaire. After determination of relationships between working hours and sleep duration, logistic regression analysis estimated odds ratio (OR) and 95% confidence interval for prevalent and incident headache according to working hours (35-44, 45-49, 50-59 and ≥60 h/week) and sleep duration (≥7, 6-6.9, 5-5.9 and <5 h/day), and tested linear trends in OR. Additionally, interactive effects of working hours and sleep duration on OR were checked. Covariates in the analyses were age, body mass index, drinking, smoking and exercise. Prevalent and incident headache was found in 1979 (5.5%) men and 707 (3.6%) men, respectively. Working hours were inversely associated with sleep duration. OR for prevalent and incident headache rose with increasing working hours and with reducing sleep duration, regardless of influences of the covariates. Working hours and sleep duration had no interactive effects on OR for prevalent or incident headache. The results indicate that long working hours directly and indirectly (via short sleep duration) induce headache even in apparently healthy white-collar men. Headache in employees may be useful for early detection of adverse health effects by long working hours.
Biometrological assessment of the preventive effect of a miconazole spray powder on athlete's foot.
Piérard, G E; Wallace, R; De Doncker, P
1996-09-01
Prevention of athlete's foot is a difficult problem. Using non-invasive biometrological methods, we evaluated the changes induced in the stratum corneum by a 3-week treatment with miconazole spray powder. A total of 16 athletes apparently at risk of developing tinea pedis, but without any evidence for the disease at the time of inclusion, participated in the study. They applied the medicated powder to one foot daily, while the other foot remained untreated to serve as a control. No adverse events occurred. In comparison with the control site, the capacitance of the toeweb skin was significantly reduced by the treatment. The ex vivo bioassay of dermatophyte culture on stratum corneum demonstrated a significant inhibition of growth of Trichophyton mentagrophytes var. interdigital at the treated site. The results of this study provide indirect evidence that the regular use of miconazole spray powder decreases the risk of developing athlete's foot.
The risks of risk aversion in drug regulation.
Eichler, Hans-Georg; Bloechl-Daum, Brigitte; Brasseur, Daniel; Breckenridge, Alasdair; Leufkens, Hubert; Raine, June; Salmonson, Tomas; Schneider, Christian K; Rasi, Guido
2013-12-01
Drugs are approved by regulatory agencies on the basis of their assessment of whether the available evidence indicates that the benefits of the drug outweigh its risks. In recent years, regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, which reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before drug approval. The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent. Here, we discuss the consequences of regulatory risk-aversion for public health and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health.
Sample stream distortion modeled in continuous-flow electrophoresis
NASA Technical Reports Server (NTRS)
Rhodes, P. H.
1979-01-01
Buoyancy-induced disturbances in an electrophoresis-type chamber were investigated. Five tracer streams (latex) were used to visualize the flows while a nine-thermistor array sensed the temperature field. The internal heating to the chamber was provided by a 400 Hz electrical field. Cooling to the chamber was provided on the front and back faces and, in addition, on both chamber side walls. Disturbances to the symmetric base flow in the chamber occurred in the broad plane of the chamber and resulted from the formation of lateral and axial temperature gradients. The effect of these gradients was to retard or increase local flow velocities at different positions in the chamber cross section, which resulted in lateral secondary flows being induced in the broad plane of the chamber. As the adverse temperature gradients increased in magnitude, the critical Rayleigh number was approached and reverse (separated) flow became apparent, which, subsequently, led to the onset of time variant secondary flows.
Multiple Weather Factors Affect Apparent Survival of European Passerine Birds
Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang
2013-01-01
Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for phenotypic and microevolutionary adaptations. PMID:23593131
Purification and Thermal Dependence of Glutathione Reductase from Two Forage Legume Species 1
Kidambi, Saranga P.; Mahan, James R.; Matches, Arthur G.
1990-01-01
Alfalfa (Medicago sativa L.) and sainfoin (Onobrychis viciifolia Scop.) are forage legumes that differ in their responses to high and low temperature stresses. Thermal limitations on the function of glutathione reductase (EC 1.6.4.2) could adversely affect the ability of the plant to cope with adverse temperatures. Our objectives were to (a) purify glutathione reductase from `Cimarron' alfalfa and `PI 212241' sainfoin and (b) investigate the intraspecies variation in the thermal dependency of glutathione reductase from each of three cultivars of alfalfa and two cultivars and an introduction of sainfoin. Glutathione reductase was purified 1222-and 1948-fold to a specific activity of 281 and 273 units per milligram of protein, from one species each of alfalfa and sainfoin, respectively. The relative molecular mass of the protein was approximately 140 kilodaltons with subunits of 57 and 37 kilodaltons under denaturing conditions. The activation energies were approximately 50 kilojoules per mole for both species. Over a 5 to 45°C temperature gradient, large variation among species and genotypes within species was found for: (a) the minimum apparent Michaelis constant (0.6-2.1 micromoles of NADPH), (b) the temperature at which the minimum apparent Michaelis constant was observed (10-25°C), and (c) the thermal kinetic windows (6-19°C width). Future studies will focus on relating the thermal dependence of the Michaelis constant of the glutathione reductases and plant growth rates and forage quality of these species throughout the growing season. PMID:16667283
Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.
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.
Stults-Kolehmainen, Matthew A.; Tuit, Keri; Sinha, Rajita
2015-01-01
Both cumulative adversity, an individual's lifetime exposure to stressors, and insufficient exercise are associated with poor health outcomes. The purpose of this study was to ascertain whether exercise buffers the association of cumulative adverse life events (CALE) with health in a community-wide sample of healthy adults (ages 18–50 years; women: n 219, 29.5 ± 9.2 years; men: n = 176, 29.4 ± 8.7 years, mean ± standard deviation). Participants underwent the Cumulative Adversity Interview, which divides life events into three subsets: major life events (MLE), recent life events (RLE) and traumatic experiences (TLE). These individuals also completed the Cornell Medical Index and a short assessment for moderate or greater intensity exercise behavior, modified from the Nurses’ Health Study. Results indicated that higher CALE was associated with greater total health problems (r = 0.431, p<0.001). Interactions between stress and exercise were not apparent for RLE and TLE. However, at low levels of MLE, greater exercise was related to fewer total, physical, cardiovascular and psychological health problems (p value<0.05). Conversely, at high levels of MLE, the benefits of exercise appear to be absent. Three-way interactions were observed between sex, exercise and stress. Increased levels of exercise were related to better physical health in men, at all levels of CALE. Only women who reported both low levels of CALE and high levels of exercise had more favorable physical health outcomes. A similar pattern of results emerged for RLE. Together, these data suggest that increased exercise is related to better health, but these effects may vary by cumulative stress exposure and sex. PMID:24392966
Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.
2013-01-01
Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881
Stults-Kolehmainen, Matthew A; Tuit, Keri; Sinha, Rajita
2014-03-01
Both cumulative adversity, an individual's lifetime exposure to stressors, and insufficient exercise are associated with poor health outcomes. The purpose of this study was to ascertain whether exercise buffers the association of cumulative adverse life events (CALE) with health in a community-wide sample of healthy adults (ages 18-50 years; women: n = 219, 29.5 ± 9.2 years; men: n = 176, 29.4 ± 8.7 years, mean ± standard deviation). Participants underwent the Cumulative Adversity Interview, which divides life events into three subsets: major life events (MLE), recent life events (RLE) and traumatic experiences (TLE). These individuals also completed the Cornell Medical Index and a short assessment for moderate or greater intensity exercise behavior, modified from the Nurses' Health Study. Results indicated that higher CALE was associated with greater total health problems (r = 0.431, p < 0.001). Interactions between stress and exercise were not apparent for RLE and TLE. However, at low levels of MLE, greater exercise was related to fewer total, physical, cardiovascular and psychological health problems (p value <0.05). Conversely, at high levels of MLE, the benefits of exercise appear to be absent. Three-way interactions were observed between sex, exercise and stress. Increased levels of exercise were related to better physical health in men, at all levels of CALE. Only women who reported both low levels of CALE and high levels of exercise had more favorable physical health outcomes. A similar pattern of results emerged for RLE. Together, these data suggest that increased exercise is related to better health, but these effects may vary by cumulative stress exposure and sex.
Chi, Chia-Yu; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih-Min; Thinh, Le Quoc; Lin, Chia-Chun; Wu, Han-Chieh; Wang, Jen-Ren; Hung, Nguyen Thanh; Thuong, Tang Chi; Chang, Chung-Ming; Su, Ih-Jen; Liu, Ching-Chuan
2013-07-01
Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. Prospective, unicenter, open-label, randomized, controlled study. Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.
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.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-23
... Request Regarding Guatemala's Apparent Failure to Effectively Enforce its Labor Laws AGENCY: Office of the... (CAFTA-DR), the United States requested consultations with the Government of Guatemala to discuss Guatemala's apparent failure to meet its obligation under Article 16.2.1(a) to effectively enforce its labor...
Stattmiller, S; Lavecchia, M; Czuzoj-Shulman, N; Spence, A R; Abenhaim, H A
2016-10-01
The purpose of this study was to evaluate the risk of adverse maternal outcomes associated with trial of labor (TOL) after cesarean during subsequent pregnancies in the low-risk population. We conducted a retrospective cohort study using the Nationwide Inpatient Sample and ICD-9 diagnostic and procedure codes from the years 2003 to 2011. A cohort of low-risk pregnant women with a history of previous cesarean delivery were identified and separated into two groups: TOL and no TOL. Logistic regression analysis was used to calculate odds ratios (ORs) comparing adverse maternal outcomes between these two groups. Out of 7 290 474 registered deliveries, there were 685 137 low-risk women who met inclusion criteria. Of these women, 144 066 (21.0%) underwent a TOL, with rates remaining steady over the course of our study. The TOL group was at increased risk of overall morbidity (OR 1.74, 95% confidence interval (CI), 1.66-1.79), most notably uterine rupture (OR 22.52, 95% CI, 19.35-26.20, P<0.01). A secondary analysis showed no apparent correlation between TOL and concomitant adverse maternal outcomes in cases of uterine rupture. Although these outcomes remain rare, low-risk women undergoing a TOL remain at increased risk of adverse maternal events as compared with those who chose elective repeat cesarean delivery.
The mental health gender-gap in urban India: patterns and narratives.
Das, Jishnu; Das, Ranendra Kumar; Das, Veena
2012-11-01
Women report significantly higher levels of mental distress than men in community studies around the world. We provide further evidence on the origins of this mental health gender-gap using data from 789 adults, primarily spousal pairs, from 300 families in Delhi, India. These data were collected between 2001 and 2003. We first confirm that, like in other studies, women report higher levels of mental distress and that gender differences in education, household expenditures and age do not explain the mental health gender-gap. In contrast, women report significantly higher levels of distress than men in families with adverse reproductive outcomes, particularly the death of a child. Controlling for adverse reproductive outcomes sharply reduces the mental health gender-gap. Finally, mental health is strongly correlated with physical health for both men and women, but there is little evidence of a differential response by sex. We complement this empirical description with anthropological analysis based on ethnographic interviews with 100 men and 100 women. With the help of these ethnographic interviews we show how adverse life events for women are experienced as the inability to maintain the domestic, which seems to be at stake within their life worlds. We raise issues for further research on the apparent finding that the mental health of women and men are differentially affected by adverse reproductive events in the family in this sample. Copyright © 2012 Elsevier Ltd. All rights reserved.
Mesbah, H A; El-Sayed, N A; El-Kady, M B; Mourad, A K; Kordy, A M; Henaidy, Z M
2014-01-01
The present study is carried out to evaluate the toxic efficiency and delayed effects of five botanical oils on the greasy cut worm Agrotis ipsilon (Lepidoptera: Noctuidae), as a trial for the attainment of a possible use of an alternative safe and effective phytochemicals against the insect-pest. So as to minimize or prevent the repeated usage of conventional insecticides, then reduce the environmental pollution as well as the occurring hazards to man and domestic animal due to the use of the pesticides alone. Four tested concentrations (0.5, 1.0, 1.5 and 2.5% v/v) from each of camphor, red basil, menthol, rose and anise oils, were bioassayed by treating the offered castor oil bean leaves, to the 4th instar larvae along 48h, under the laboratory higrothermic conditions of 25±2 °C and 65±5% R.H. The obtained results showed that the five tested oils were found to have more or less toxic activity and drastic effects on the inspected parameters of fitness components of the treated parent generation of the insect, in particular, pupae, emerged adult moths and laid eggs/female. In this respect camphor and red basil oils were highly effective, followed by menthol oil, anise oil and the least effective one was rose oil. Moreover, the assessed unprofitable delayed effects on the going on of the biological performance within the treated insects showed the adverse effects on the fitness components of the consequent generations (fs) post (p) one treatment with each of the bioassyed oils. The prevalence of adverse effects and disturbance in the going on biological performance through the period of (p) generation; which is followed by the distinct failure of insect development in (f1) generation were recorded for each of the tested menthol oil at 0.5 and 1.5% (v/v); camphor oil at 1.5 and 2.5% and red basil oil at 2.5% (v/v). While anise and rose oils were somewhat less efficient causing the distinct failure of the following generations up to the 3rd and/or the 6th ones. That observed distinct failure of the insect development could be attributed to the rapid or/and slow cumulative effect of the induced recessive lethal genes in both influenced sexes along the interval of the following developed generations (fs) after (p) one treatment, causing apparent adverse disturbance of the normal biological performance, which finally appears at the beginning of the failed generation.
Mechanisms of morphine enhancement of spontaneous seizure activity.
Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam
2007-12-01
High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.
Maternal effects of drought stress and inbreeding in Impatiens capensis (Balsaminaceae).
Riginos, Corinna; Heschel, M Shane; Schmitt, Johanna
2007-12-01
Maternal effects can have substantial impacts on plant fitness and plant populations. Stressful environmental conditions can cause a maternal plant to inadequately provision its progeny, resulting in poor seedling growth, low reproductive success, and decreased competitive ability. Maternal effects consist of environmental and genetic load components, but the interactions between these two components have rarely been considered. To determine the effects of maternal drought stress and maternal inbreeding on progeny biomass (a fitness correlate) and physiological responses to drought stress, we conducted a greenhouse experiment with genetic lines from two populations (mesic site vs. dry site) of the herbaceous annual Impatiens capensis (Balsaminaceae). Seeds were collected from cleistogamous flowers of inbred or outcrossed maternal plants that were subject to either a drought or control treatment. These seeds were grown into juvenile plants that were also subject to either a drought stress or a control treatment. Plants from the mesic site had significantly reduced biomass from maternal drought stress, while plants from the dry site maintained biomass despite adverse maternal environmental conditions. Juvenile plants of both populations had reduced biomass only as a result of maternal inbreeding. Interestingly, inbreeding depression was more apparent when maternal environmental conditions were benign.
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.
Franson, J. Christian; Hoffman, David; Wells-Berlin, Alicia M.; Perry, Matthew C.; Shearn-Bochsler, Valerie I.; Finley, Daniel L.; Flint, Paul L.; Hollmén, Tuula E.
2007-01-01
Common eiders (Somateria mollissima) were fed added Se (as L-selenomethionine) in concentrations increasing from 10 to 80 ppm in a pilot study (Study 1) or 20 (low exposure) and up to 60 (high exposure) ppm Se in Study 2. Body weights of Study 1 ducks and high-exposure ducks in Study 2 declined rapidly. Mean concentrations of Se in blood reached 32.4 ppm wet weight in Study 1 and 17.5 ppm wet weight in high-exposure birds in Study 2. Mean Se concentrations in liver ranged from 351 (low exposure, Study 2) to 1252 ppm dry weight (Study 1). Oxidative stress was evidenced by Se-associated effects on glutathione metabolism. As Se concentrations in liver increased, Se-dependent glutathione peroxidase activity, glutathione reductase activity, oxidized glutathione levels, and the ratio of hepatic oxidized to reduced glutathione increased. In Study 2, the T-cell-mediated immune response was adversely affected in high-exposure eiders, but ducks in the low-exposure group exhibited evidence of an enhanced antibody-mediated immune response. Gross lesions in high-exposure ducks included emaciation, absence of thymus, and loss of nails from digits. Histologic lesions included severe depletion of lymphoid organs, hepatopathy, and necrosis of feather pulp and feather epithelium. Field studies showed that apparently healthy sea ducks generally have higher levels of Se in liver than healthy fresh-water birds, but lower than concentrations found in our study. Data indicate that common eiders and probably other sea ducks possess a higher threshold, or adverse effect level, for Se in tissues than fresh-water species. However, common eiders developed signs of Se toxicity similar to those seen in fresh-water birds.
Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R
1996-09-01
Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.
Johnston, Carol S; Tjonn, Sherrie L; Swan, Pamela D
2004-03-01
Although popular and effective for weight loss, low-carbohydrate, high-protein, high-fat (Atkins) diets have been associated with adverse changes in blood and renal biomarkers. High-protein diets low in fat may represent an equally appealing diet plan but promote a more healthful weight loss. Healthy adults (n = 20) were randomly assigned to 1 of 2 low-fat (<30% energy), energy-restricted groups: high-protein (30% energy) or high-carbohydrate (60% energy); 24-h intakes were strictly controlled during the 6-wk trial. One subject from each group did not complete the trial due to out-of-state travel; two subjects in the high-carbohydrate group withdrew from the trial due to extreme hunger. Body composition and metabolic indices were assessed pre- and post-trial. Both diets were equally effective at reducing body weight (-6%, P < 0.05) and fat mass (-9 to -11%, P < 0.05); however, subjects consuming the high-protein diet reported more satisfaction and less hunger in mo 1 of the trial. Both diets significantly lowered total cholesterol (-10 to -12%), insulin (-25%), and uric acid (-22 to -30%) concentrations in blood from fasting subjects. Urinary calcium excretion increased 42% in subjects consuming the high-protein diet, mirroring the 50% increase in dietary calcium with consumption of this diet; thus, apparent calcium balance was not adversely affected. Creatinine clearance was not altered by diet treatments, and nitrogen balance was more positive in subjects consuming the high-protein diet vs. the high-carbohydrate diet (3.9 +/- 1.4 and 0.7 +/- 1.7 g N/d, respectively, P < 0.05). Thus, low-fat, energy-restricted diets of varying protein content (15 or 30% energy) promoted healthful weight loss, but diet satisfaction was greater in those consuming the high-protein diet.
Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E
2017-05-12
Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.
Weiner, Jonathan M.; Lovley, Derek R.
1998-01-01
Sediments from the sulfate-reduction zone of a petroleum-contaminated aquifer, in which benzene persisted, were inoculated with a benzene-oxidizing, sulfate-reducing enrichment from aquatic sediments. Benzene was degraded, with apparent growth of the benzene-degrading population over time. These results suggest that the lack of benzene degradation in the sulfate-reduction zones of some aquifers may result from the failure of the appropriate benzene-degrading sulfate reducers to colonize the aquifers rather than from environmental conditions that are adverse for anaerobic benzene degradation. PMID:9464422
Bhandari, Ramji K.; vom Saal, Frederick S.; Tillitt, Donald E.
2015-01-01
The transgenerational consequences of environmental contaminant exposures of aquatic vertebrates have the potential for broad ecological impacts, yet are largely uninvestigated. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are two ubiquitous estrogenic chemicals present in aquatic environments throughout the United States and many other countries. Aquatic organisms, including fish, are exposed to varying concentrations of these chemicals at various stages of their life history. Here, we tested the ability of embryonic exposure to BPA or EE2 to cause adverse health outcomes at later life stages and transgenerational abnormalities in medaka fish. Exposures of F0 medaka to either BPA (100 μg/L) or EE2 (0.05 μg/L) during the first 7 days of embryonic development, when germ cells are differentiating, did not cause any apparent phenotypic abnormalities in F0 or F1 generations, but led to a significant reduction in the fertilization rate in offspring two generations later (F2) as well as a reduction of embryo survival in offspring three generations later (F3). Our present observations suggest that BPA or EE2 exposure during development induces transgenerational phenotypes of reproductive impairment and compromised embryonic survival in fish of subsequent generations. These adverse outcomes may have negative impacts on populations of fish inhabiting contaminated aquatic environments.
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.
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
Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.
Pergola, Pablo E; Krauth, Melissa; Huff, J Warren; Ferguson, Deborah A; Ruiz, Stacey; Meyer, Colin J; Warnock, David G
2011-01-01
Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Copyright © 2011 S. Karger AG, Basel.
Mustafa, A F; Baurhoo, B
2017-03-01
A study was conducted to investigate the effects of partial replacing corn and soybean meal with dried cabbage leaf residues (DCR) on broiler growth performance, apparent ileal nutrient digestibility, and apparent total tract nutrient utilization. Dietary treatments include 4 levels of DCR (0, 3, 6, and 9%). Two hundred and twenty-four day-old male broilers were randomly assigned to one of 4 groups (8 cage replicates; 7 birds/cage) and grown over a 35-d experimental period. Results showed that feeding DCR had no effects on daily body weigh gain (average 53.4 g/d), daily feed intake (average 94.9 g/d), and feed conversion ratio (average 1.78 g of feed/g of gain). Inclusion of DCR reduced apparent ileal DM (quadratic effect, P < 0.001), OM (linear effect, P = 0.012), and CP (quadratic effect, P = 0.001) digestibility of younger birds (d 21) while incremental levels of DCR had no effect on apparent ileal nutrient digestibilities of older birds (d 35). Apparent total tract digestibility of DM, OM, and CP increased (linear effect, P < 0.001) as the level of DCR increased. It was concluded that the inclusion of DCR in broiler diets up to 9% had no negative impact on bird performance and apparent ileal digestibility of older birds and improved apparent total tract nutrient digestibility. © 2016 Poultry Science Association Inc.
Temperature and Term Low Birth Weight in California.
Basu, Rupa; Rau, Reina; Pearson, Dharshani; Malig, Brian
2018-06-12
Few investigations have explored temperature and birth outcomes. In a retrospective cohort study, we examined apparent temperature, a combination of temperature and relative humidity, and term low birth weight (LBW) among 43,629 full-term LBW infants and 2,032,601 normal weight infants in California from 1999 to 2013. The California Department of Public Health provided birth certificate data, while meteorologic data came from the California Irrigation Management Information System, US Environmental Protection Agency, and National Centers for Environmental Information. After considering several temperature metrics, we observed the best model fit for term LBW over the full gestation (13.0% change, 95% confidence interval: 4.1, 22.7 per 10 degrees Fahrenheit (°F) increase in apparent temperature) above 55°F and the greatest association for third trimester exposure above 60°F (15.8%, 95% confidence interval: 5.0, 27.6). Apparent temperature during the first month of pregnancy exhibited no significant risk, while the first trimester had a significantly negative association, and second trimester, last month and last two weeks had slightly increased risks. Mothers who were Black, older, delivered male infants, or gave birth during the warm season conferred the highest risks. This study provides further evidence for adverse birth outcomes from heat exposure for vulnerable subgroups of pregnant women.
Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature
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
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...
The influence of the environment on dairy cow behavior, claw health and herd lameness dynamics.
Cook, Nigel B; Nordlund, Kenneth V
2009-03-01
Free stall housing increases the exposure of dairy cows' claws to concrete walk-ways and to manure between periods of rest, and generally shows the highest rate of lameness compared with other dairy management systems. However, there is great variation within a system, and the rate of new cases of lameness can be reduced to very low levels provided time spent resting per day is maximized through good stall design, access to stalls through stocking density control and comfortable transition cow facilities, limiting the time spent milking, provision of adequate heat abatement, and good leg hygiene. Sand bedded stalls are useful as they also permit lame cows to maintain adequate daily rest. Rubberized alley flooring surfaces benefit the cow by reducing claw wear and trauma compared to concrete, making them ideal for parlor holding areas and long transfer lanes and walk ways. However, caution is required when using rubber floors in pens with uncomfortable stalls due to apparent adverse effects on cow time budgets, which may in turn have a detrimental effect on lameness.
Takahashi, Masaya; Wehrli, Felix W.; Hilaire, Luna; Zemel, Babette S.; Hwang, Scott N.
2002-01-01
Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment. PMID:11904367
Myocardial protection using diadenosine tetraphosphate with pharmacological preconditioning.
Ahmet, I; Sawa, Y; Nishimura, M; Yamaguchi, T; Kitakaze, M; Matsuda, H
2000-09-01
We have reported a similar cardioprotective effect and mechanism of diadenosine tetraphosphate (AP4A) and ischemic preconditioning in rat hearts. In this study, the applicability of AP4A administration to cardiac surgery was tested by using a canine cardiopulmonary bypass model. Hearts underwent 60 minutes of cardioplegic arrest (34 degrees C) by a single dose of cardioplegia. Cardioplegia contained either AP4A (40 micromol/L; n = 6) or saline (n = 6). Beagles were weaned from cardiopulmonary bypass 30 minutes after reperfusion, and left ventricular function was evaluated after another 30 minutes by using the cardiac loop analysis system. Administration of AP4A significantly improved the postischemic recovery of cardiac function and reduced the leakage of serum creatine kinase compared with saline. Systemic vascular resistance, mean aortic blood pressure, and the electrocardiographic indices were not significantly altered by AP4A administration. Administration of AP4A was cardioprotective without apparent adverse effects. Because the cardioprotective mechanism may be similar to that of ischemic preconditioning, the addition of AP4A into cardioplegia may be a novel safe method for clinical application of preconditioning cardioprotection.
Zhang, Zhanquan; Chen, Jian; Li, Boqiang; He, Chang; Chen, Yong; Tian, Shiping
2017-01-01
The limitations of chemical fungicides for the control of postharvest diseases have recently become more apparent. The utilization of antagonistic microorganisms is a promising alternative to that of fungicides to control postharvest decay. In previous studies, the antagonistic yeast Cryptococcus laurentii has shown excellent effects of biocontrol and great potential for practical application. Adverse conditions, such as oxidative stress, limit the practical application of antagonistic yeast. In this study, we investigated the oxidative stress tolerance of C. laurentii and the associated mechanisms. The results indicated that exogenous oxidative stress has a significant effect on the viability and biocontrol efficiency of C. laurentii . H 2 O 2 -induced oxidative stress led to the accumulation of reactive oxygen species. The results of flow cytometric analysis suggested that apoptosis is responsible for the reduced survival rate of C. laurentii under oxidative stress. Using tests of antioxidant activity, we found that C. laurentii could employ enzymatic systems to resist exogenous oxidative stress. The addition of exogenous glutathione, a non-enzymatic antioxidant, to the media can significantly enhance oxidative tolerance and biocontrol efficiency of C. laurentii .
Zhang, Zhanquan; Chen, Jian; Li, Boqiang; He, Chang; Chen, Yong; Tian, Shiping
2017-01-01
The limitations of chemical fungicides for the control of postharvest diseases have recently become more apparent. The utilization of antagonistic microorganisms is a promising alternative to that of fungicides to control postharvest decay. In previous studies, the antagonistic yeast Cryptococcus laurentii has shown excellent effects of biocontrol and great potential for practical application. Adverse conditions, such as oxidative stress, limit the practical application of antagonistic yeast. In this study, we investigated the oxidative stress tolerance of C. laurentii and the associated mechanisms. The results indicated that exogenous oxidative stress has a significant effect on the viability and biocontrol efficiency of C. laurentii. H2O2-induced oxidative stress led to the accumulation of reactive oxygen species. The results of flow cytometric analysis suggested that apoptosis is responsible for the reduced survival rate of C. laurentii under oxidative stress. Using tests of antioxidant activity, we found that C. laurentii could employ enzymatic systems to resist exogenous oxidative stress. The addition of exogenous glutathione, a non-enzymatic antioxidant, to the media can significantly enhance oxidative tolerance and biocontrol efficiency of C. laurentii. PMID:28210254
Aging and visual 3-D shape recognition from motion.
Norman, J Farley; Adkins, Olivia C; Dowell, Catherine J; Hoyng, Stevie C; Shain, Lindsey M; Pedersen, Lauren E; Kinnard, Jonathan D; Higginbotham, Alexia J; Gilliam, Ashley N
2017-11-01
Two experiments were conducted to evaluate the ability of younger and older adults to recognize 3-D object shape from patterns of optical motion. In Experiment 1, participants were required to identify dotted surfaces that rotated in depth (i.e., surface structure portrayed using the kinetic depth effect). The task difficulty was manipulated by limiting the surface point lifetimes within the stimulus apparent motion sequences. In Experiment 2, the participants identified solid, naturally shaped objects (replicas of bell peppers, Capsicum annuum) that were defined by occlusion boundary contours, patterns of specular highlights, or combined optical patterns containing both boundary contours and specular highlights. Significant and adverse effects of increased age were found in both experiments. Despite the fact that previous research has found that increases in age do not reduce solid shape discrimination, our current results indicated that the same conclusion does not hold for shape identification. We demonstrated that aging results in a reduction in the ability to visually recognize 3-D shape independent of how the 3-D structure is defined (motions of isolated points, deformations of smooth optical fields containing specular highlights, etc.).
Bennell, K L; Brukner, P D; Malcolm, S A
1996-09-01
It is apparent that bone density in male athletes can be reduced without a concomitant decrease in testosterone, suggesting that bone density and testosterone concentrations in the normal range are not closely related in male athletes. Further research is necessary to monitor concurrent changes in bone density and testosterone over a period of time in exercising males. In any case, the effect of exercise on the male reproductive system does not appear as extreme as that which can occur in female athletes, and any impact on bone density is not nearly as evident. These results imply that factors apart from testosterone concentrations must be responsible for the observed osteopenia in some male athletes. Many factors have the potential to adversely affect bone density, independently of alterations in reproductive function. These include low calcium intake, energy deficit, weight loss, psychological stress, and low body fat, all of which may be associated with intense endurance training. Future research investigating skeletal health in male athletes should include a thorough assessment of reproductive function in addition to these other factors.
A rare adverse effect of metronidazole: nervous system symptoms.
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.
36 CFR 800.5 - Assessment of adverse effects.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native Hawaiian...
Food-chain contamination evaluations in ecological risk assessments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Linder, G.
Food-chain models have become increasingly important within the ecological risk assessment process. This is the case particularly when acute effects are not readily apparent, or the contaminants of concern are not readily detoxified, have a high likelihood for partitioning into lipids, or have specific target organs or tissues that may increase their significance in evaluating their potential adverse effects. An overview of food-chain models -- conceptual, theoretical, and empirical -- will be considered through a series of papers that will focus on their application within the ecological risk assessment process. Whether a food-chain evaluation is being developed to address relativelymore » simple questions related to chronic effects of toxicants on target populations, or whether a more complex food-web model is being developed to address questions related to multiple-trophic level transfers of toxicants, the elements within the food chain contamination evaluation can be generalized to address the mechanisms of toxicant accumulation in individual organisms. This can then be incorporated into more elaborate models that consider these organismal-level processes within the context of a species life-history or community-level responses that may be associated with long-term exposures.« less
The adverse health effects of chronic cannabis use.
Hall, Wayne; Degenhardt, Louisa
2014-01-01
This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. Copyright © 2013 John Wiley & Sons, Ltd.
Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc
2016-01-01
Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.
Evaluation of skin permeation of β-blockers for topical drug delivery.
Chantasart, Doungdaw; Hao, Jinsong; Li, S Kevin
2013-03-01
β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. The present results suggest the possibility of topical treatment of hemangioma using β-blockers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Hao
Recently, we reported that Ilexgenin A exhibits anti-cancer activities and induces cell arrest. Here, we investigated the effect of Ilexgenin A on the inflammation, angiogenesis and tumor growth of hepatocellular carcinoma (HCC). Our current study revealed that Ilexgenin A significantly inhibited the inflammatory cytokines TNF-α and IL-6 levels and downregulated pro-angiogenic factor VEGF production and transcription in HepG2 cells. The underlying mechanism for Ilexgenin A effects appears to be through inhibiting STAT3 and PI3K pathways. Furthermore, we found that not only Ilexgenin A inhibited STAT3 and PI3K pathways in HepG2 cells but also blocked these signaling pathways in HUVECs. Mostmore » importantly, by employing two HCC xenografts models - HepG2 and H22, we showed that Ilexgenin A reduced tumor growth and exhibited synergy effect with Sorafenib. ELISA assay, histological analysis and immunohistochemistry examination revealed that the expression of VEGF and MVD was significantly decreased after the treatment with Ilexgenin A and the combination. Moreover, Ilexgenin A could enhance caspase-3/7 activity in vitro and transmission electron microscope indicated that the combination induced evident apoptosis of tumor cells and caused the structural changes of mitochondria in vivo. Although no apparent adverse effects occurred during the treatment period, Sorafenib monotherapy elicited hepatotoxicity for specific expression in the increased level of AST and the ratio of AST/ALT. However, the combination could remedy this adverse effect. In conclusion, the results described in the present study identifies Ilexgenin A as a promising therapeutic candidate that modulates inflammation, angiogenesis, and HCC growth. - Highlights: • Ilexgenin A exerts anti-inflammatory and anti-angiogenesis effects in hepatoma. • Ilexgenin A may exert these effects through inhibition of STAT3 and PI3K pathways. • Ilexgenin A exhibits synergistic effects with Sorafenib on hepatoma growth. • Ilexgenin A can remedy the potential liver toxicity of Sorafenib.« less
The current deconstruction of paradoxes: one sign of the ongoing methodological "revolution".
Porta, Miquel; Vineis, Paolo; Bolúmar, Francisco
2015-10-01
The current deconstruction of paradoxes is one among several signs that a profound renewal of methods for clinical and epidemiological research is taking place; perhaps for some basic life sciences as well. The new methodological approaches have already deconstructed and explained long puzzling apparent paradoxes, including the (non-existent) benefits of obesity in diabetics, or of smoking in low birth weight. Achievements of the new methods also comprise the elucidation of the causal structure of long-disputed and highly complex questions, as Berkson's bias and Simpson's paradox, and clarifying reasons for deep controversies, as those on estrogens and endometrial cancer, or on adverse effects of hormone replacement therapy. These are signs that the new methods can go deeper and beyond the methods in current use. A major example of a highly relevant idea is: when we condition on a common effect of a pair of variables, then a spurious association between such pair is likely. The implications of these ideas are potentially vast. A substantial number of apparent paradoxes may simply be the result of collider biases, a source of selection bias that is common not just in epidemiologic research, but in many types of research in the health, life, and social sciences. The new approaches develop a new framework of concepts and methods, as collider, instrumental variables, d-separation, backdoor path and, notably, Directed Acyclic Graphs (DAGs). The current theoretical and methodological renewal-or, perhaps, "revolution"-may be changing deeply how clinical and epidemiological research is conceived and performed, how we assess the validity and relevance of findings, and how causal inferences are made. Clinical and basic researchers, among others, should get acquainted with DAGs and related concepts.
Identification and Characterization of Adverse Effects in 21st Century Toxicology
The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...
First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.
Stevens, Misty W; Henry, Ralph L; Owens, S Michael; Schutz, Ralph; Gentry, W Brooks
2014-01-01
This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17-19 d in the 3 highest dose groups and volume of distribution of 5-6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration.
Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro
2015-01-01
The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.
Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach
Nasim, Aashir; Rosas, Scott
2016-01-01
Abstract Introduction: Electronic cigarette (ECIG) use has grown rapidly in popularity within a short period of time. As ECIG products continue to evolve and more individuals begin using ECIGs, it is important to understand the potential adverse effects that are associated with ECIG use. The purpose of this study was to examine and describe the acute adverse effects associated with ECIG use. Methods: This study used an integrated, mixed-method participatory approach called concept mapping (CM). Experienced ECIG users ( n = 85) provided statements that answered the focus prompt “A specific negative or unpleasant effect (ie, physical or psychological) that I have experienced either during or immediately after using an electronic cigarette device is…” in an online program. Participants sorted these statements into piles of common themes and rated each statement. Using multidimensional scaling and hierarchical cluster analysis, a concept map of the adverse effects statements was created. Results: Participants generated 79 statements that completed the focus prompt and were retained by researchers. Analysis generated a map containing five clusters that characterized perceived adverse effects of ECIG use: Stigma, Worry/Guilt, Addiction Signs, Physical Effects, and Device/Vapor Problems. Conclusions: ECIG use is associated with adverse effects that should be monitored as ECIGs continue to grow in popularity. If ECIGs are to be regulated, policies should be created that minimize the likelihood of user identified adverse effects. Implications: This article provides a list of adverse effects reported by experienced ECIG users. This article organizes these effects into a conceptual model that may be useful for better understanding the adverse outcomes associated with ECIG use. These identified adverse effects may be useful for health professionals and policy makers. Health professionals should be aware of potential negative health effects that may be associated with ECIG use and policy makers could design ECIG regulations that minimize the risk of the adverse effects reported by ECIG users in this study. PMID:26563262
Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia
2017-08-01
Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.
Orca Behavior and Subsequent Aggression Associated with Oceanarium Confinement
Anderson, Robert; Waayers, Robyn; Knight, Andrew
2016-01-01
Simple Summary Orca behaviors interacting with humans within apparent friendship bonds are reviewed, and some impediments to the human evaluation of delphinid intelligence are discussed. The subsequent involvement of these orcas and their offspring in aggressive incidents with humans is also documented and examined. This is particularly relevant given that the highest recorded rates of aggressive incidents have occurred among orcas who had previously established unstructured human friendship bonds prior to their inclusion within oceanaria performances. It is concluded that the confinement of orcas within aquaria, and their use in entertainment programs, is morally indefensible, given their high intelligence, complex behaviors, and the apparent adverse effects on orcas of such confinement and use. Abstract Based on neuroanatomical indices such as brain size and encephalization quotient, orcas are among the most intelligent animals on Earth. They display a range of complex behaviors indicative of social intelligence, but these are difficult to study in the open ocean where protective laws may apply, or in captivity, where access is constrained for commercial and safety reasons. From 1979 to 1980, however, we were able to interact with juvenile orcas in an unstructured way at San Diego’s SeaWorld facility. We observed in the animals what appeared to be pranks, tests of trust, limited use of tactical deception, emotional self-control, and empathetic behaviors. Our observations were consistent with those of a former Seaworld trainer, and provide important insights into orca cognition, communication, and social intelligence. However, after being trained as performers within Seaworld’s commercial entertainment program, a number of orcas began to exhibit aggressive behaviors. The orcas who previously established apparent friendships with humans were most affected, although significant aggression also occurred in some of their descendants, and among the orcas they lived with. Such oceanaria confinement and commercial use can no longer be considered ethically defensible, given the current understanding of orcas’ advanced cognitive, social, and communicative capacities, and of their behavioral needs. PMID:27548232
Yun, Oliver; Lima, M. Angeles; Ellman, Tom; Chambi, Wilma; Castillo, Sandra; Flevaud, Laurence; Roddy, Paul; Parreño, Fernando; Albajar Viñas, Pedro; Palma, Pedro Pablo
2009-01-01
Background Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. Methodology From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999–2002); Olopa, Guatemala (2003–2006); Entre Ríos, Bolivia (2002–2006); and Sucre, Bolivia (2005–2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. Results Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. Conclusions These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed. PMID:19582142
Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.
2013-01-01
SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828
Code of Federal Regulations, 2013 CFR
2013-04-01
... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...
Code of Federal Regulations, 2012 CFR
2012-04-01
... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...
Code of Federal Regulations, 2011 CFR
2011-04-01
... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...
Code of Federal Regulations, 2014 CFR
2014-04-01
... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...
Code of Federal Regulations, 2010 CFR
2010-04-01
... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...
Hays, Stephen Robert; Deshpande, Jayant K
2013-04-01
General anesthetics can induce apoptotic neurodegeneration and subsequent maladaptive behaviors in animals. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes. The relevance of animal data to clinical practice is unclear and to our knowledge the causality underlying observed associations in humans is unknown. We reviewed newly postulated neurodevelopmental risks of pediatric anesthesia and discuss implications for the surgical care of children. We queried the MEDLINE®/PubMed® and EMBASE® databases for citations in English on pediatric anesthetic neurotoxicity with the focus on references from the last decade. Animal studies in rodents and primates demonstrate apoptotic neuropathology and subsequent maladaptive behaviors after exposure to all currently available general anesthetics with the possible exception of α2-adrenergic agonists. Similar adverse pathological and clinical effects occur after untreated pain. Anesthetic neurotoxicity in animals develops only after exposure above threshold doses and durations during a critical neurodevelopmental window of maximal synaptogenesis in the absence of concomitant painful stimuli. Anesthetic exposure outside this window or below threshold doses and durations shows no apparent neurotoxicity, while exposure in the context of concomitant painful stimuli is neuroprotective. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes, particularly after multiple exposures. The causality underlying the associations is unknown. Ongoing investigations may clarify the risks associated with current practice. Surgical care of all patients mandates appropriate anesthesia. Neurotoxic doses and the duration of anesthetic exposure in animals may have little relevance to clinical practice, particularly surgical anesthesia for perioperative pain. The causality underlying the observed associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes is unknown. Anesthetic exposure may be a marker of increased risk. Especially in young children, procedures requiring general anesthesia should be performed only as necessary and general anesthesia duration should be minimized. Alternatives to general anesthesia and the deferral of elective procedures beyond the first few years of life should be considered, as appropriate. Participation in ongoing efforts should be encouraged to generate further data. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
The journey from infertility to parenting multiples: a dream come true?
Baor, Liora; Blickstein, Isaac
2005-01-01
Infertility deeply affects psychosocial aspects of young couples, who often erroneously take fertility for granted. The inevitable transformation from apparently healthy adults into patients can lead to loss of self-esteem, confidence, health, close relationships, security, and hope. Frequently, when emotional and psychological resources are diminished after prolonged infertility, the couple may express their desperate wish for a family in the form of accepting without reservation the risks of a multiple pregnancy, ignoring the undeniable increased morbidity and mortality associated with these gestations. It is unclear why a couple embarking on the journey of infertility treatment may prefer a pregnancy that is tenfold as likely to have a serious adverse outcome. Of the three potential explanations for such an attitude--desperation, denial, and ignorance--only the last one can be solved with patient education and adequate counseling. At the same time, it is unjustified to avoid assisted reproductive technologies because of potential adverse outcome, however necessary it is to acknowledge the risk of multiple births.
Cui, Yuechong; Zhu, Bin; Zheng, Fei
2018-01-01
The aim of the present meta-analysis study was to evaluate the efficacy of low-dose aspirin, commenced at ≤16 weeks of gestation, in preventing preterm and term preeclampsia, as well as associated maternal and neonatal adverse events in women at risk of preeclampsia. The Embase, PubMed, Cochrane Central Register of Controlled Trials and the Web of Science databases were searched for relevant random controlled trials (RCTs) published between January 1979 and October 2017. After quality assessment and data extraction, a meta-analysis was performed using RevMan 5.3 software. Outcomes of interest were preeclampsia with subgroups of preterm preeclampsia (delivery at <37 weeks) and term preeclampsia, as well as maternal adverse outcomes, including gestational hypertension, postpartum hemorrhage and preterm birth, and neonatal adverse outcomes, including intrauterine growth retardation (IUGR) or small for gestation age infant (SGA), stillbirth or death, and newborn weight. A total of 10 RCTs involving 3,168 participants were included. The meta-analysis demonstrated that, compared with placebo or no treatment, low-dose aspirin was associated with a significant reduction in the overall risk ratio (RR) of preeclampsia regardless of the time to delivery [RR=0.67; 95% confidence interval (CI)=0.57–0.80]. This was apparent for preterm preeclampsia (RR=0.35; 95% CI=0.13–0.94) but not for term preeclampsia (RR=1.01; 95% CI=0.60–1.70). Except for postpartum hemorrhage, low-dose aspirin also significantly reduced the risk of maternal and neonatal adverse outcomes. In conclusion, low-dose aspirin in women at risk of preeclampsia, commenced at ≤16 weeks of gestation, was associated with a reduced risk of preterm preeclampsia, and of adverse maternal and neonatal outcomes. PMID:29725376
Inadvertent transarterial insertion of atrial and ventricular defibrillator leads.
Issa, Ziad F; Rumman, Syeda S; Mullin, James C
2009-01-01
Inadvertent placement of pacemaker and implantable cardioverter-defibrillator (ICD) leads in the left ventricle (LV) is a rare but well-recognized complication of device implantation [1]. We report a case of inadvertent transarterial implantation of dual-chamber ICD leads; the ventricular lead positioned in the LV and the atrial lead positioned in the aortic root. The tip of the atrial lead migrated across the aortic wall and captured the epicardial surface of the left atrium. The diagnosis was made 5 years after the implantation procedure with no apparent adverse events directly related to left heart lead placement.
Giordano, Simona
2011-09-01
Gender Identity Disorder (GID) is classified as a mental illness and included in the DSM-IV and ICD-1O. It will also be included in the DSM-V. The psychiatric diagnosis, in spite of some apparent advantages, has significant psychological and social adverse implications. This paper discusses some of the main epistemological reasons to consider gender variance as a mental disorder. It will also evaluate whether reasons of other kinds (pragmatic, rather than epistemological) may justify the inclusion of gender variance amongst mental illnesses.
Apparent size contrasts of retinal images and size constancy as determinants of the moon illusion.
Smith, O W; Smith, P C; Geist, C C; Zimmermann, R R
1978-06-01
Kaufman and Rock (1962) and Rock and Kaufman (1962) concluded that the moon illusion is a function of and attributable to apparent distance. They also reported a large framing effect as an exception. Analysis of the effect suggests two components which can account for the illusion independently of apparent distance. These are apparent size contrasts of visual images of discriminable features or objects of the earth with the moon's image and size constancy of the features or objects plus the interactions of the two. Apparent distances to horizons are always a consequence of the necessary conditions for the illusion. They are related to the illusion but are not a determinant of it.
[Clinical research of analgesic for labor with acupoint injection and electroacupuncture].
Liu, Xiaohui; Wu, Lingling; Yi, Wei
2015-11-01
To explore a safe and effective scheme of analgesic for labor. Eighty-four primiparas without contraindication of vaginal delivery were divided into an observation group and a control group, 42 cases in each one. In the observation group, the acupoint injection was given at Zusanli (ST 36) combined with electroacupuncture (EA) at Hegu (LI 4) and Sanyinjiao (SP 6) till the cervical opening at the end of first stage labor. In the control group, the routine respiratory instruction was applied. In 5 min, 10 min and 60 min of acupuncture (the same time points in the control group) as well as at the end of the first and second stage labor, the analgesic effect was assessed for the primiparas of the two groups. The labor stages, adverse reactions, postpartum hemorrhage, postpartum urine retention, newborn asphyxia rate and usage rate of oxytocin were compared between the two groups. In the observation group, in 5 min, 10 min and 60 min of acupuncture as well as at the end of the first and second stages, the visual analogue scale (VAS) was lower apparently as compared with the control group at the corresponding time points (all P < 0.05). The differences in the time limit in the active period, the second and third stages were not significant between the two groups (all P > 0.05). The incidence of adverse reactions and the usage rate of oxytocin were lower than those in the control group [2.4% (1/42) vs 31.0% (13/42); 2.4% (1/42) vs 23.8% (10/42), both P < 0.05]. The differences in postpartum hemorrhage, postpartum urine retention and newborn asphyxia rate were not significant between the two groups (all P > 0.05). The combination of acupoint injection and EA is the effective analgesic scheme for labor. This scheme effectively alleviates labor pain and has no maternal and child complications.
Alvarez-Alfageme, Fernando; Bigler, Franz; Romeis, Jörg
2011-06-01
Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant.
Prenatal alcohol exposure and childhood balance ability: findings from a UK birth cohort study
Humphriss, Rachel; Hall, Amanda; May, Margaret; Zuccolo, Luisa; Macleod, John
2013-01-01
Objective To investigate the association of prenatal alcohol exposure with balance in10-year-old children. Design Population-based prospective longitudinal study. Setting Former Avon region of UK (Southwest England). Participants 6915 children from the Avon Longitudinal Study of Parents and Children who had a balance assessment at age 10 and had data on maternal alcohol consumption. Outcome measures 3 composite balance scores: dynamic balance (beam-walking), static balance eyes open, static balance eyes closed (heel-to-toe balance on a beam and standing on one leg, eyes open or closed). Results Most mothers (95.5%) consumed no-to-moderate amounts (3–7 glasses/week) of alcohol during pregnancy. Higher total-alcohol consumption was associated with maternal-social advantage, whereas binge drinking (≥4 units/day) and abstinence were associated with maternal social disadvantage. No evidence was found of an adverse effect of maternal-alcohol consumption on childhood balance. Higher maternal-alcohol use during pregnancy was generally associated with better offspring outcomes, with some specific effects appearing strong (static balance eyes open and moderate total alcohol exposure at 18 weeks, adjusted OR 1.23 (95% CI 1.01 to 1.49); static balance eyes closed and moderate total alcohol exposure at 18 weeks, adjusted OR 1.25 (95% CI 1.06 to 1.48). Similar results were found for both paternal and postnatal maternal alcohol exposure. A Mendelian-randomization approach was used to estimate the association between maternal genotype and offspring balance using the non-synonymous variant rs1229984*A (ADH1B) to proxy for lower maternal alcohol consumption; no strong associations were found between this genotype/proxy and offspring balance. Conclusions No evidence was found to indicate that moderate maternal alcohol consumption in this population sample had an adverse effect on offspring balance at age 10. An apparent beneficial effect of higher total maternal alcohol consumption on offspring balance appeared likely to reflect residual confounding. PMID:23794556
Clinical cosmobiology: The Lithuanian study 1990 1992
NASA Astrophysics Data System (ADS)
Stoupel, Eliyahu; Petrauskiene, Jadviga; Kalediene, Ramune; Abramson, Evgeny; Sulkes, Jacqueline
1995-12-01
The numbers of deaths from ischaemic heart disease (IHD), stroke (CVA), all accidents except vehicular, vehicular accidents and suicide (overall total, totals for men and women) per month for 36 months (1990 1992) in Lithuania were analysed in relation to: (1) month of the year (1 12); (2) geomagnetic activity; and (3) solar activity. A total of 122227 deaths (64490 men and 57737 women) was studied, and the results compared with those obtained in an earlier study in Israel, differing geographically and climatically from Lithuania. It was shown that the time of year, solar activity, and geomagnetic activity were related to the monthly death distribution, especially regarding death from IHD and suicide. Age and gender differences were apparent in the relationship between death distribution and physical environmental factors. At age >70 years, many of these relationships change. The monthly distribution of deaths from IHD and suicide are adversely correlated with solar activity and with each other. Differences are presumed in serotoninergic effects as caused by environmental influences.
Mahmoud, Soheil S; Williams, Matthew; Croteau, Rodney
2004-03-01
cDNA clones encoding limonene synthase and limonene-3-hydroxylase, both driven by the CaMV 35S promoter, were independently transformed into peppermint (Menthaxpiperita) to alter the production and disposition of (-)-limonene, the first committed intermediate of essential oil biosynthesis in this species. Although both genes were constitutively expressed in leaves of transformed plants, the corresponding enzyme activities were not significantly increased in the glandular trichome sites of essential oil biosynthesis; thus, there was no effect on oil yield or composition in the regenerated plants. Cosuppression of the hydroxylase gene, however, resulted in the accumulation of limonene (up to 80% of the essential oil compared to about 2% of the oil in wild type plants), without influence on oil yield. These results indicate that limonene does not impose negative feedback on the synthase, or apparently influence other enzymes of monoterpene biosynthesis in peppermint, and suggests that pathway engineering can be employed to significantly alter essential oil composition without adverse metabolic consequences.
Antibody response of sandhill and whooping cranes to an eastern equine encephalitis virus vaccine
Clark, G.G.; Dein, F.J.; Crabbs, C.L.; Carpenter, J.W.; Watts, D.M.
1987-01-01
As a possible strategy to protect whooping cranes (Grus americana) from fatal eastern equine encephalitis (EEE) viral infection, studies were conducted to determine the immune response of this species and sandhill cranes (Grus canadensis) to a formalin-inactivated EEE viral vaccine. Viral-specific neutralizing antibody was elicited in both species after intramuscular (IM) vaccination. Subcutaneous and intravenous routes of vaccination failed to elicit detectable antibody in sandhill cranes. Among the IM vaccinated cranes, the immune response was characterized by nondetectable or low antibody titers that waned rapidly following primary exposure to the vaccine. However, one or more booster doses consistently elicited detectable antibody and/or increased antibody titers in the whooping cranes. In contrast, cranes with pre-existing EEE viral antibody, apparently induced by natural infection, exhibited a rapid increase and sustained high-antibody titers. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to determine the protective efficacy of the antibody.
Fülöp, Ibolya; Gyéresi, Árpád; Kiss, Lóránd; Deli, Mária A; Croitoru, Mircea Dumitru; Szabó-Révész, Piroska; Aigner, Zoltán
2015-12-01
Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.
The fetal safety of Levetiracetam: a systematic review.
Chaudhry, Shahnaz Akhtar; Jong, Geert't; Koren, Gideon
2014-07-01
To systematically review the available published evidence on the fetal safety of Levetiracetam with focus on birth defects. Eight studies met the inclusion criteria; five pregnancy registries and one population based cohort study. A total of 27 major congenital malformations were reported among 1213 Levetiracetam monotherapy - exposed pregnant women, yielding an overall major malformation rate of 2.2% (27/1213) [95% confidence interval of 1.53-3.22]. In contrast, Levetiracetam polytherapy was associated with significantly higher malformation rate of 6.3% (34/541) [95% CI of 4.53-8.65] (P<0.001). Additionally 2 studies investigating child neurodevelopment in Levetiracetam - exposed children revealed that the measured achievements were well above those children exposed to valproic acid, and similar to unexposed controls. The current evidence suggests that the overall risk of major malformation after first trimester exposure to Levetiracetam is within the population baseline risk of 1-3%, with no apparent adverse effects on long term child development. Copyright © 2014 Elsevier Inc. All rights reserved.
2010-01-01
Background The strongest causal evidence that customary spanking increases antisocial behavior is based on prospective studies that control statistically for initial antisocial differences. None of those studies have investigated alternative disciplinary tactics that parents could use instead of spanking, however. Further, the small effects in those studies could be artifactual due to residual confounding, reflecting child effects on the frequency of all disciplinary tactics. This study re-analyzes the strongest causal evidence against customary spanking and uses these same methods to determine whether alternative disciplinary tactics are more effective in reducing antisocial behavior. Methods This study re-analyzed a study by Straus et al.[1] on spanking and antisocial behavior using a sample of 785 children who were 6 to 9 years old in the 1988 cohort of the American National Longitudinal Survey of Youth. The comprehensiveness and reliability of the covariate measure of initial antisocial behavior were varied to test for residual confounding. All analyses were repeated for grounding, privilege removal, and sending children to their room, and for psychotherapy. To account for covarying use of disciplinary tactics, the analyses were redone first for the 73% who had reported using at least one discipline tactic and second by controlling for usage of other disciplinary tactics and psychotherapy. Results The apparently adverse effect of spanking on antisocial behavior was replicated using the original trichotomous covariate for initial antisocial behavior. A similar pattern of adverse effects was shown for grounding and psychotherapy and partially for the other two disciplinary tactics. All of these effects became non-significant after controlling for latent comprehensive measures of externalizing behavior problems. Conclusions These results are consistent with residual confounding, a statistical artifact that makes all corrective actions by parents and psychologists appear to increase children's antisocial behavior due to child effects on parents. Improved research methods are needed to discriminate between effective vs. counterproductive implementations of disciplinary tactics. How and when disciplinary tactics are used may be more important than which type of tactic is used. PMID:20175902
Larzelere, Robert E; Cox, Ronald B; Smith, Gail L
2010-02-22
The strongest causal evidence that customary spanking increases antisocial behavior is based on prospective studies that control statistically for initial antisocial differences. None of those studies have investigated alternative disciplinary tactics that parents could use instead of spanking, however. Further, the small effects in those studies could be artifactual due to residual confounding, reflecting child effects on the frequency of all disciplinary tactics. This study re-analyzes the strongest causal evidence against customary spanking and uses these same methods to determine whether alternative disciplinary tactics are more effective in reducing antisocial behavior. This study re-analyzed a study by Straus et al.1 on spanking and antisocial behavior using a sample of 785 children who were 6 to 9 years old in the 1988 cohort of the American National Longitudinal Survey of Youth. The comprehensiveness and reliability of the covariate measure of initial antisocial behavior were varied to test for residual confounding. All analyses were repeated for grounding, privilege removal, and sending children to their room, and for psychotherapy. To account for covarying use of disciplinary tactics, the analyses were redone first for the 73% who had reported using at least one discipline tactic and second by controlling for usage of other disciplinary tactics and psychotherapy. The apparently adverse effect of spanking on antisocial behavior was replicated using the original trichotomous covariate for initial antisocial behavior. A similar pattern of adverse effects was shown for grounding and psychotherapy and partially for the other two disciplinary tactics. All of these effects became non-significant after controlling for latent comprehensive measures of externalizing behavior problems. These results are consistent with residual confounding, a statistical artifact that makes all corrective actions by parents and psychologists appear to increase children's antisocial behavior due to child effects on parents. Improved research methods are needed to discriminate between effective vs. counterproductive implementations of disciplinary tactics. How and when disciplinary tactics are used may be more important than which type of tactic is used.
Rare and very rare adverse effects of clozapine
De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina
2015-01-01
Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202
Circadian System, Sleep and Endocrinology
Morris, Christopher J.; Aeschbach, Daniel; Scheer, Frank A.J.L.
2011-01-01
Levels of numerous hormones vary across the day and night. Such fluctuations are not only attributable to changes in sleep/wakefulness and other behaviors but also to a biological timing system governed by the suprachiasmatic nucleus of the hypothalamus. Sleep has a strong effect on levels of some hormones such as growth hormone but little effect on others which are more strongly regulated by the biological timing system (e.g., melatonin). Whereas the exact mechanisms through which sleep affects circulating hormonal levels are poorly understood, more is known about how the biological timing system influences the secretion of hormones. The suprachiasmatic nucleus exerts its influence on hormones via neuronal and humoral signals but it is also now apparent that peripheral cells can rhythmically secrete hormones independent of signals from the suprachiasmatic nucleus. Under normal circumstances, behaviors and the biological timing system are synchronized and consequently hormonal systems are exquisitely regulated. However, many individuals (e.g., shift-workers) frequently undergo circadian misalignment by desynchronizing their sleep/wake cycle from the biological timing system. Recent experiments indicate that circadian misalignment has an adverse effect on metabolic and hormonal factors such as glucose and insulin. Further research is needed to determine the underlying mechanisms that cause the negative effects induced by circadian misalignment. Such research could aid the development of countermeasures for circadian misalignment. PMID:21939733
DIAZINON AND PARATHION DIVERGE IN THEIR EFFECTS ON DEVELOPMENT OF NORADRENERGIC SYSTEMS
Slotkin, Theodore A.; Skavicus, Samantha; Seidler, Frederic J.
2017-01-01
Organophosphate pesticides elicit developmental neurotoxicity through mechanisms over and above their shared property as cholinesterase inhibitors. We compared the consequences of neonatal exposure (postnatal days PN1-4) to diazinon or parathion on development of norepinephrine systems in rat brain, using treatments designed to produce equivalent effects on cholinesterase, straddling the threshold for barely-detectable inhibition. Norepinephrine levels were measured throughout development from the immediate posttreatment period (PN5), to early adolescence (PN30), young adulthood (PN60) and full adulthood (PN100); we assessed multiple brain regions containing all the major noradrenergic synaptic projections. Diazinon elicited a significant overall deficit of norepinephrine, whereas parathion produced a net increase. The effects were not immediately apparent (PN5) but rather emerged over the course of development, indicating that the organophosphate effects represent alteration of the trajectory of development, not just continuance of an initial injury. There were no comparable effects on β-adrenergic receptors, indicating that the presynaptic changes were not an adaptation to an underlying, primary effect on postsynaptic receptor signaling. Because we used the cholinesterase inhibition benchmark, the absolute dose of diazinon was much higher than that of parathion, since the latter is a more potent cholinesterase inhibitor. Our results are consistent with the growing evidence that the various organophosphates can differ in their impact on brain development and that consequently, the cholinesterase benchmark is an inadequate predictor of adverse neurodevelopmental effects. PMID:28235599
Low plasma vitamin D levels and muscle-related adverse effects in statin users.
Eisen, Alon; Lev, Eli; Iakobishvilli, Zaza; Porter, Avital; Brosh, David; Hasdai, David; Mager, Aviv
2014-01-01
Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.
Cavalieri, John
2017-06-01
Chemical sterilisation can be used as an alternative to surgical castration in some circumstances. This review focuses on responses to treatment with zinc- or CaCl 2 -based chemosterilants, factors that have affected treatments and their potential use to sterilise female cattle. Successful treatment with a low incidence of adverse side effects in male animals has occurred with the use of zinc gluconate (ZG), neutralised in arginine and a 20% solution of CaCl 2 in ethanol. Injection technique plays an important role in success. Less satisfactory results appear to occur following use in animals with relatively larger testes. In animals with relatively small testes adjustment of the dose according to testicular size appears to optimise results. The techniques appear to be most suited to population control strategies in companion animals where low cost treatment of animals in environments where surgical facilities and specialised aftercare are lacking. The need for careful administration and likely slower speed of administration compared to surgical castration are likely to hamper application within the cattle industries. Recently transvaginal, intraovarian administration of CaCl 2 in ethanol has been shown to cause complete ovarian atrophy without apparent pain in some heifers, although variable responses were found. Chemical sterilisation can play a role in the sterilisation of animals but careful attention to dose, volume, chemical composition, administration technique are needed to avoid adverse side effects and variability in responses associated with some treatments. Application in female animals requires further study but CaCl 2 in ethanol can potentially cause complete ovarian atrophy when administered to heifers. Copyright © 2017 Elsevier B.V. All rights reserved.
Adverse Effects Associated With Newer Diabetes Therapies.
Akiyode, Oluwaranti F; Adesoye, Adebola A
2017-04-01
The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.
Naumann, M; Lowe, N J
2001-01-01
Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks PMID:11557704
Adverse effects of ketoconazole in dogs--a retrospective study.
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.
Adverse health effects of non-medical cannabis use.
Hall, Wayne; Degenhardt, Louisa
2009-10-17
For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.
Li, Yan; Zhang, Fan; Xu, Yanmei; Hu, Joice; Li, Huafang
2018-03-26
In this open-label, single-center study, the pharmacokinetics, safety, and tolerability of lamotrigine chewable/dispersible tablets were assessed in healthy Chinese volunteers. Each volunteer (N = 16) received repeat doses of oral lamotrigine titrated from 25 mg to 50 mg to 100 mg over 42 days and was followed up for 10-17 days. Safety and tolerability were assessed throughout the study. Lamotrigine pharmacokinetic parameters were estimated using noncompartmental analysis. Overall, 15 (94%) volunteers completed the study. Lamotrigine serum concentrations peaked 2.5 hours postdose, with a mean terminal half-life of 36.8 hours. The apparent lamotrigine oral clearance was 1577.88 mL/h. The accumulation ratios (day 14 vs day 1) were 2.53 and 2.58 for area under the curve and peak concentration, respectively. Lamotrigine 25 to 100 mg once daily exhibited dose-proportional pharmacokinetics (based on area under the curve and peak concentration), following repeat dosing. Nine volunteers reported adverse events, 2 experienced oropharyngeal pain, each receiving 25 mg and 50 mg. One volunteer withdrew due to an increase in liver enzymes. No deaths, serious adverse effects, or skin rashes were reported during the study. No new safety concerns were observed. Overall, the pharmacokinetic profiles after repeat doses of lamotrigine chewable/dispersible tablets once daily in a Chinese population were similar to those observed in Western populations. © 2018, The American College of Clinical Pharmacology.
The relation of depression and anxiety to life-stress and achievement in students.
Andrews, Bernice; Wilding, John M
2004-11-01
An apparent increase in seriously disturbed students consulting student health services in the UK has led to concern that increasing financial difficulties and other outside pressures may affect student mental health and academic performance. The current research investigated whether student anxiety and depression increases after college entry, the extent to which adverse life experiences contribute to any increases, and the impact of adversity, anxiety and depression on exam performance. 351 UK-domiciled undergraduates completed questionnaires one month before university entry and mid-course. The Hospital Anxiety and Depression Scale (HADS: Zigmond & Snaith, 1983) was administered at both time points and a modified List of Threatening Experiences (Brugha, Bebbington, Tennant, & Hurry, 1985) was administered mid-course. By mid-course 9% of previously symptom-free students became depressed and 20% became anxious at a clinically significant level. Of those previously anxious or depressed 36% had recovered. After adjusting for pre-entry symptoms, financial difficulties made a significant independent contribution to depression and relationship difficulties independently predicted anxiety. Depression and financial difficulties mid-course predicted a decrease in exam performance from first to second year. This is the first study to confirm empirically that financial and other difficulties can increase British students' levels of anxiety and depression and that financial difficulties and depression can affect academic performance. However, university life may also have a beneficial effect for some students with pre-existing conditions. With widening participation in higher education, the results have important implications for educational and health policies.
Impact of antibiotic restrictions: the ethical perspective.
Garau, J
2006-08-01
Antibiotic restrictions present difficult choices for physicians, patients and payors. Physicians must choose between the welfare of the patient and the directive of healthcare systems to restrict antibiotics. These may be supported with incentives or penalties, causing a conflict of interest. The patient has an expectation of best care, but will often be unaware of antibiotic restriction policies and is therefore not fully informed about his/her treatment. For payors, reducing the volume of antibiotic prescribing and/or prescribing less expensive antibiotics are apparently attractive targets for cost savings. However, we are only now beginning to understand the downstream consequences of restricting antibiotics on outcomes and costs. We are hampered by the lack of a universal ethical framework and information on outcomes. In addition, the concept of 'effective' or 'best' therapy will vary among different groups. Balancing the risks of treating or not treating with antibiotics is complex. Suboptimal therapy, that fails to eradicate the bacterial infection, exposes the patient to the risk of poor outcome, adverse events and the wider risk of antimicrobial resistance. Failure to treat where the risk of a poor outcome exceeds the risk of an adverse event is also ethically unacceptable. The key to rational antibiotic prescribing is to identify those patients who need antibiotic therapy and optimise therapy to achieve the fastest bacterial and clinical cure. We are only now beginning to assemble the information and tools to be able to make such decisions. Above all, we should treat on the basis of knowledge.
2013-01-01
Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised trials. Case reports supported an association between iatrogenic overdose of magnesium sulphate and life-threatening consequences. Conclusions Appropriate administration of antenatal magnesium sulphate was not shown to be associated with serious maternal adverse effects, though an increase in 'minor’ adverse effects and treatment cessation was shown. Larger trials are needed to determine optimal regimens, achieving maximal effectiveness with minimal adverse effects, for each antenatal indication for use. Vigilance in the use of magnesium sulphate is essential for women’s safety. PMID:24139447
Erickson, J Alan; Grenache, David G
2016-01-15
Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.
DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T
2017-03-22
Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.
Herrick, Amy; Stall, Ron; Egan, James; Schrager, Sheree; Kipke, Michele
2014-10-01
Research shows that young men who have sex with men (YMSM) engage in higher rates of health risk behaviors and experience higher rates of negative health outcomes than their peers. The purpose of this study is to determine if the effects of adversity on HIV risk are mediated by syndemics (co-occurring health problems). Participants were 470 ethnically diverse YMSM ages 18 to 24 recruited between 2005 and 2006 and surveyed every 6 months for 24 months. Regression analyses examined the impact of adversity on syndemics (emotional distress, substance use, and problematic alcohol use) and the effects of both adversity and syndemics on HIV risk behaviors over time. Gay-related discrimination and victimization-among other adversity variables-were significantly associated with syndemics and condomless sex (CS). Syndemics mediated the effects of adversity on CS in all models. Adverse events impact HIV risk taking among YMSM through syndemics. These findings suggest that prevention programs aimed at reducing adversity may reduce both the synergistic effect of multiple psychosocial health problems and HIV risk taking.
Factor, Stewart A; Remington, Gary; Comella, Cynthia L; Correll, Christoph U; Burke, Joshua; Jimenez, Roland; Liang, Grace S; O'Brien, Christopher F
Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period. The extension phase was conducted from December 16, 2014, to August 3, 2016. Participants who received placebo and entered the VE period were re-randomized 1:1 to valbenazine 80 or 40 mg while others continued valbenazine at the KINECT 3 dose. Safety assessments included treatment-emergent adverse events (TEAEs) and scales for suicidal ideation/behavior, treatment-emergent akathisia or parkinsonism, and psychiatric symptoms. Efficacy assessments included the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD). 198 participants entered the VE period, 124 (62.6%) completed treatment (week 48), and 121 (61.1%) completed the follow-up visit after washout (week 52). During the VE period, 69.2% of participants had ≥ 1 TEAE, 14.6% had a serious TEAE, and 15.7% discontinued due to a TEAE. During washout, 13.1% of participants experienced a TEAE. No apparent risk for suicidal ideation or behavior was found. Long-term valbenazine treatment did not appear to induce or worsen akathisia or parkinsonism. Participants generally remained psychiatrically stable during the study. AIMS and CGI-TD measures indicated sustained tardive dyskinesia improvement, with scores returning toward baseline after 4 weeks of valbenazine washout. The long-term safety and tolerability of valbenazine were generally favorable, and maintenance of treatment effect was apparent with both doses during this long-term study. ClinicalTrials.gov identifier: NCT02274558. © Copyright 2017 Physicians Postgraduate Press, Inc.
Toward, Martin G R; Griffin, Michael J
2010-01-01
Models of the vertical apparent mass of the human body are mostly restricted to a sitting posture unsupported by a backrest and ignore the variations in apparent mass associated with changes in posture and changes in the magnitude of vibration. Using findings from experimental research, this study fitted a single degree-of-freedom lumped parameter model to the measured vertical apparent mass of the body measured with a range of sitting postures and vibration magnitudes. The resulting model reflects the effects of reclining a rigid backrest or reclining a foam backrest (from 0 to 30 degrees), the effects of moving the hands from the lap to a steering wheel, the effects of moving the horizontal position of the feet, and the effects of vibration magnitude (from 0.125 to 1.6 ms(-2) r.m.s.). The error between the modelled and the measured apparent mass was minimised, for both the apparent masses of individual subjects and the median apparent masses of groups of 12 subjects, for each sitting posture and each vibration magnitude. Trends in model parameters, the damping ratios, and the damped natural frequencies were identified as a function of the model variables and show the effects of posture and vibration magnitude on body dynamics. For example, contact with a rigid backrest increased the derived damped natural frequency of the principal resonance as a result of reduced moving mass and increased stiffness. When the rigid backrest was reclined from 0 to 30º, the damping decreased and the resonance frequency increased as a result of reduced moving mass. It is concluded that, by appropriate variations in model parameters, a single degree-of-freedom model can provide a useful fit to the vertical apparent mass of the human body over a wide range of postures and vibration magnitudes. When measuring or modelling seat transmissibility, it may be difficult to justify an apparent mass model with more than a single degree-of-freedom if it does not reflect the large influences of vibration magnitude, body posture, and individual variability.
Palgi, Yuval; Shrira, Amit
2015-01-01
Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the lifespan, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs’ mental and physical health than on Jews’ health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. PMID:25961862
Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults.
Derry, Sheena; Wiffen, Philip J; Häuser, Winfried; Mücke, Martin; Tölle, Thomas Rudolf; Bell, Rae F; Moore, R Andrew
2017-03-27
Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain in fibromyalgia, despite being considered not to be effective. To assess the analgesic efficacy, tolerability (drop-out due to adverse events), and safety (serious adverse events) of oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing any oral NSAID with placebo or another active treatment for relief of pain in fibromyalgia, with subjective pain assessment by the participant. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)) or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC), serious adverse events, and withdrawals due to adverse events; secondary outcomes were adverse events, withdrawals due to lack of efficacy, and outcomes relating to sleep, fatigue, and quality of life. Where pooled analysis was possible, we used dichotomous data to calculate risk difference (RD) and number needed to treat for an additional beneficial outcome (NNT), using standard methods. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Our searches identified six randomised, double-blind studies involving 292 participants in suitably characterised fibromyalgia. The mean age of participants was between 39 and 50 years, and 89% to 100% were women. The initial pain intensity was around 7/10 on a 0 to 10 pain scale, indicating severe pain. NSAIDs tested were etoricoxib 90 mg daily, ibuprofen 2400 mg daily, naproxen 1000 mg daily, and tenoxicam 20 mg daily; 146 participants received NSAID and 146 placebo. The duration of treatment in the double-blind phase varied between three and eight weeks.Not all studies reported all the outcomes of interest. Analyses consistently showed no significant difference between NSAID and placebo: substantial benefit (at least 50% pain intensity reduction) (risk difference (RD) -0.07 (95% confidence interval (CI) -0.18 to 0.04) 2 studies, 146 participants; moderate benefit (at least 30% pain intensity reduction) (RD -0.04 (95% CI -0.16 to 0.08) 3 studies, 192 participants; withdrawals due to adverse events (RD 0.04 (95% CI -0.02 to 0.09) 4 studies, 230 participants; participants experiencing any adverse event (RD 0.08 (95% CI -0.03 to 0.19) 4 studies, 230 participants; all-cause withdrawals (RD 0.03 (95% CI -0.07 to 0.14) 3 studies, 192 participants. There were no serious adverse events or deaths. Although most studies had some measures of health-related quality of life, fibromyalgia impact, or other outcomes, none reported the outcomes beyond saying that there was no or little difference between the treatment groups.We downgraded evidence on all outcomes to very low quality, meaning that this research does not provide a reliable indication of the likely effect. The likelihood that the effect could be substantially different is very high. This is based on the small numbers of studies, participants, and events, as well as other deficiencies of reporting study quality allowing possible risks of bias. There is only a modest amount of very low-quality evidence about the use of NSAIDs in fibromyalgia, and that comes from small, largely inadequate studies with potential risk of bias. That bias would normally be to increase the apparent benefits of NSAIDs, but no such benefits were seen. Consequently, NSAIDs cannot be regarded as useful for treating fibromyalgia.
[Sleep disorder of schizophrenia treated with shallow needling: a randomized controlled trial].
Huang, Yanxi; Zheng, Ying
2015-09-01
To compare the clinical effective differences between shallow needling and medication for the sleep disorder of schizophrenia. Ninety-six patients with the sleep disorder of schizophrenia were randomly divided into a shallow needling group and a medication group, 48 cases in each one (one case dropping in the shallow needling group and two cases dropping in the medication group). The same dose paliperidone tablets were adopted in the two groups. In the shallow needling group, the main acupoints were Baihui (GV 20), Shangenxue (Extra) and Ezhongxian (MS 1), and the acupoints based on syndrome differentiation were selected. The shallow needling manipulation was used once a day, 5 times a week. In the medication group, 3 mg eszopiclone tablets were prescribed orally before sleep once every night. The patients were treated for 6 weeks in the two groups. Sleep condition was evaluated by Pittsburgh sleep quality index (PSQI) before and after treatment, and the clinical efficacy and the adverse reaction were assessed by positive and negative symptoms scale (PANSS) and treatment emergent symptom scale (TESS) before and after 2-week, 4-week and 6-week treatment. The clinical effects between the two groups were compared. After treatment in the two groups, both the total scores and the each factor score of the PSQI and the PANSS were apparently decreased (P<0. 05, P<0. 01). As for the PSQI scale, after treatment the daytime dysfunctional score of the shallow needling group was reduced more obviously than that of the medication group (P<0. 05), and the falling asleep time in the medication group was declined more markedly compared with that in the shallow needling group (P<0. 05). Regarding the PANSS, the improvement of the pathological factor in the shallow needling group was better than that in the medication group after treatment (P<0. 05), and the improvement of the positive factor in the medication group was superior to that in the shallow needling group after treatment (P<0. 05). The total scores and each factor score of the PSQI and the PANSS were not statistically different between the two groups after treatment (P>0. 05). At the end of the 6th week, the curative and effective rate was 63. 9% (30/47) and the total effective rate was 95. 8% (45/47) in the shallow needling group;the curative and effective rate was 58. 7% (27/46) and the total effective rate was 91. 3% (42/46) in the medication group. The difference of the effect was not statistically significant between the two groups (P>0. 05). The scores of TESS in the shallow needling group were lower than those in the medication group (P<0. 01, P<0. 05). The effect of shallow needling for assisting the sleeping disorder of schizophrenia is reliable and it is similar with the efficacy of eszopiclone. Also, the shallow needling can improve the daytime dysfunction and the pathological factor apparently without adverse reaction and pain. Its safety is obviously better than that of eszopiclone.
Adverse effects of methotrexate in three psoriatic arthritis patients.
Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei
2014-04-01
Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.
Post-term surveillance and birth outcomes in South Asian-born compared with Australian-born women.
Yim, C; Wong, L; Cabalag, C; Wallace, E M; Davies-Tuck, M
2017-02-01
To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75; 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.
Pomerantz, H; Weinstock, M A
2014-09-01
Topical tretinoin is commonly prescribed, but its frequent adverse effects are barriers to use. Predictors of resistance or susceptibility to retinoid irritation are not known. To identify baseline patient characteristics associated with adverse effects of topical tretinoin. This cohort study used data collected from 324 participants in the Veterans Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply tretinoin cream on the face and ears. Univariate and multivariate logistic regression models were used to examine the associations between baseline characteristics and local adverse effects. One hundred and ninety-seven patients (61% of those randomized to tretinoin) reported local adverse effects within 6 months. Clinical signs of severe photodamage at baseline [odds ratio (OR) 0·15, 95% confidence interval (CI) 0·04-0·54] and history of acne (OR 0·46, 95% CI 0·27-0·77) were associated with a decreased risk of adverse effects to tretinoin. The use of other topical medications at enrolment (OR 1·88, 95% CI 1·15-3·08) predicted an increase in adverse effects. In this study population, the common indications of topical tretinoin treatment were associated with lower risks of adverse effects. The concurrent use of other topical medications may worsen irritation caused by tretinoin. © 2014 British Association of Dermatologists.
Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.
Vinay, Keshavamurthy; Yanamandra, Uday; Dogra, Sunil; Handa, Sanjeev; Suri, Vikas; Kumari, Savita; Khadwal, Alka; Prakash, Gaurav; Lad, Deepesh; Varma, Subhash; Malhotra, Pankaj
2018-03-01
Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. © 2017 The International Society of Dermatology.
Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.
Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia
2015-12-01
Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.
Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents
ERIC Educational Resources Information Center
Correll, Christoph U.; Carlson, Harold E.
2006-01-01
Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…
[Severe apparent life-threatening event during "skin-to-skin": treatment with hypothermia].
Marin, N; Valverde, E; Cabañas, F
2013-10-01
'Skin-to-skin' in healthy newborn infants is currently routine practice in Spanish maternity wards. This practice has shown benefits in increasing the duration of breast-feeding and maternal bonding behaviour with no significant adverse events. Early sudden deaths and severe apparent life-threatening events (ALTE) during the first 24 hours of life are infrequent, but well recognised. Risk factors during 'skin to skin' have been established. These events can lead to high neonatal morbidity and mortality. Hypothermia is now the standard of care for moderate to severe hypoxic-ischaemic encephalopathy and has shown to reduce mortality and neurological morbidity in children with hypoxic-ischaemic brain injury. Although there are no clinical trials that evaluate hypothermia after a severe ALTE, neonates who suffer it should be considered for this treatment. We present a case of a healthy newborn who had an ALTE during skin-to-skin with his mother and was treated with hypothermia. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Risk assessment of the amnesic shellfish poison, domoic acid, on animals and humans.
Kumar, K Prem; Kumar, Sreeletha Prem; Nair, G Achuthan
2009-05-01
Risk assessment of the amnesic shellfish poison, domoic acid, a potent neurotoxin, is evaluated based on its current knowledge and its harmful effects, and is presented under four headings, viz., (1) hazard identification, (2) dose response assessment, (3) exposure assessment and (4) risk characterization. Domoic acid binds the glutamate receptor site of the central nervous system (CNS) of humans and causes depolarization of neurons and an increase in cellularcalcium. In nature, domoic acid is produced by the algae, Pseudonitzschia spp. and they enter into the body of shellfish through their consumption. This toxin is reported to cause gastroenteritis, renal insufficiency confusion and memory loss in humans, since it affects the hippocampus of the brain. In rats, intraperitonial and oral administration of domoic acid result in scratching, tremor and convulsions, and in monkeys, the toxic symptoms like mastication, salivation, projectile vomiting, weakness, teeth grinding and lethargy are apparent. The no-observed-adverse-effect-level (NOAEL) in animals reveals that pure toxin is more effective than those isolated from shellfish. Based on LD50 values, it is found that intraperitonial administration of this toxin in animals is 31 fold more effective than oral administration. Low levels of domoic acid (0.20-0.75 ppm) show no toxic symptoms in non-human primates, but clinical effects are apparent in them and in humans, at a concentration of 1.0 ppm. The tolerable daily intake (TDI) of domoic acid for humans is calculated as 0.075 ppm, whereas for razor clams and crabs, the TDI are 19.4 and 31.5 ppm respectively. The hazard quotient (HQ) is found to be 2. Being an irreversible neurotoxin, domoic acid has severe public health implications. Death occurs in those above 68 years old. In order to ensure adequate protection to public health, the concentration of domoic acid in shellfish and shellfish parts at point of sale shall not exceed the current permissible limit of 20 microg g(-1) tissue. While processing shellfish, it maybe advisable to pay attention to factors such as environmental conditions, inter-organ variability in concentrations of domoic acid and cross contaminations.
Jin, Chun-Lan; Wei, Li-Xin; Zhao, Ji-Ping; Wu, Zhong-Chao
2014-12-01
To compare the difference in clinical efficacy on polycystic ovary syndrome (PCOS) between electroacupuncture (EA) and dyne-35 and to explore the effect mechanism. Sixty-five patients were randomized into an EA group (33 cases) and a western medication group (32 cases). In the EA group, the selected acupoints were Danzhong (CV 17), Qimen (LR 14), Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Zigong (EX-CA 1), Sanyinjiao (SP 6), Zusanli (ST 36) and Taichong (LR 3), etc. After the arrival of qi, electric stimulation was attached to the acupoints for 30 min. The treatment was given 3 times a week. In the western medication group, dyne-35 was prescribed on the 5th day of natural menstruation or withdrawal bleeding, one tablet a day, continuously for 21 days. The treatment cycle was 3 months in the two groups. The menstrual condition, body mass, body mass index (BMI), serum testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH were compared before and after treatment in the two groups. The clinical efficacy was assessed in the two groups. The total effective rate was 90.6% (29/32) in the EA group and was 93.3% (28/30) in the western medication group. The efficacy was similar in the two groups (P > 0.05). After treatment, the levels of LH and LH/FSH were all reduced significantly in the two groups (all P < 0.01). After treatment, T level in serum was reduced apparently in the western medication group (P < 0.05). Before and after treatment, the differences in body mass and BMI in the EA group were more significant than those in the western medication group (P < 0.01, P < 0.05). EA is the effective method for PCOS, similar to that of dyne-35. The effect of it for weight loss is superior to dyne-35 and no apparent adverse reactions happen. The effect mechanism of EA is related to the regulation of serum sexual hormone levels and their ratio, as well as to the regulation of body lipid metabolism.
DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.
2017-01-01
Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508
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.
Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping
2016-06-01
Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Meng, Qingxin; Hu, Xiangyun; Pan, Heping; Xi, Yufei
2018-04-01
We propose an algorithm for calculating all-time apparent resistivity from transient electromagnetic induction logging. The algorithm is based on the whole-space transient electric field expression of the uniform model and Halley's optimisation. In trial calculations for uniform models, the all-time algorithm is shown to have high accuracy. We use the finite-difference time-domain method to simulate the transient electromagnetic field in radial two-layer models without wall rock and convert the simulation results to apparent resistivity using the all-time algorithm. The time-varying apparent resistivity reflects the radially layered geoelectrical structure of the models and the apparent resistivity of the earliest time channel follows the true resistivity of the inner layer; however, the apparent resistivity at larger times reflects the comprehensive electrical characteristics of the inner and outer layers. To accurately identify the outer layer resistivity based on the series relationship model of the layered resistance, the apparent resistivity and diffusion depth of the different time channels are approximately replaced by related model parameters; that is, we propose an apparent resistivity correction algorithm. By correcting the time-varying apparent resistivity of radial two-layer models, we show that the correction results reflect the radially layered electrical structure and the corrected resistivities of the larger time channels follow the outer layer resistivity. The transient electromagnetic fields of radially layered models with wall rock are simulated to obtain the 2D time-varying profiles of the apparent resistivity and corrections. The results suggest that the time-varying apparent resistivity and correction results reflect the vertical and radial geoelectrical structures. For models with small wall-rock effect, the correction removes the effect of the low-resistance inner layer on the apparent resistivity of the larger time channels.
Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics.
Gaunt, Hannah J; Vasudev, Naveen S; Beech, David J
2016-10-01
Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca 2+ entry because of the critical roles played by Ca 2+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (-)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling.
Stress urinary incontinence in women: Current and emerging therapeutic options
Shamout, Samer; Campeau, Lysanne
2017-01-01
Surgical management of stress urinary incontinence (SUI) is most commonly achieved by midurethral synthetic sling (MUS) insertion as a first-line surgical option. A great deal of research continues to evolve new management strategies to reach an optimal balance of high efficacy and minimal adverse events. This expert opinion review provides a brief and comprehensive discussion of recent advances and ongoing research in the management of SUI, with an emphasis on single-incision mini-slings, vaginal laser treatment, and cell-based therapy. It is based on data obtained from numerous published meta-analyses and original studies identified through literature search. Single-incision mini-slings appear equally effective initially compared with standard MUS (retropubic or transobturator) for the treatment of female SUI; however, this efficacy lacks durability evidence beyond one-year followup. There is a lack of sufficient clinical evidence to currently confirm long-term safety and effectiveness of cell-therapy and non-ablative vaginal laser therapy, besides suggestion of apparent initial safety. There are still significant challenges to overcome before widespread clinical practice of the latter two modalities. Future research should be aimed at identifying groups of patients who might benefit from these minimally invasive therapeutic options. PMID:28616118
Sustainable liquid biofuels from biomass: the writing's on the walls.
Gomez, Leonardo D; Steele-King, Clare G; McQueen-Mason, Simon J
2008-01-01
Domination of the global biosphere by human beings is unprecedented in the history of the planet, and our impact is such that substantive changes in ecosystems, and the global environment as a whole, are now becoming apparent. Our activity drives the steady increase in global temperature observed in recent decades. The realization of the adverse effects of greenhouse gas emissions on the environment, together with declining petroleum reserves, has ensured that the quest for sustainable and environmentally benign sources of energy for our industrial economies and consumer societies has become urgent in recent years. Consequently, there is renewed interest in the production and use of fuels from plants. The 'first-generation' biofuels made from starch and sugar appear unsustainable because of the potential stress that their production places on food commodities. Second-generation biofuels, produced from cheap and abundant plant biomass, are seen as the most attractive solution to this problem, but a number of technical hurdles must be overcome before their potential is realized. This review will focus on the underpinning research necessary to enable the cost-effective production of liquid fuels from plant biomass, with a particular focus on aspects related to plant cell walls and their bioconversion.
Changes in cell proliferation kinetics in the mouse cerebellum after total asphyxia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yoshioka, H.; Mino, M.; Morikawa, Y.
1985-12-01
This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO/sub 2/ gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO/sub 2/-exposed and control mice by /sup 3/H-thymidine autoradiography.more » At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This prolongation was apparent for about five days and thereafter growth caught up. These results suggest that neonatal asphyxia has an adverse effect on cerebellar neuronal proliferation that may revert to normal spontaneously in older animals.« less
NASA Astrophysics Data System (ADS)
Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang
2015-01-01
Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.
Wang, Tao; Jiang, Xue-Jun; Lin, Tao; Ren, Shan; Li, Xiao-Yan; Zhang, Xian-Zheng; Tang, Qi-zhu
2009-09-01
Erythropoietin (EPO) can protect myocardium from ischemic injury, but it also plays an important role in promoting polycythaemia, the potential for thrombo-embolic complications. Local sustained delivery of bioactive agents directly to impaired tissues using biomaterials is an approach to limit systemic toxicity and improve the efficacy of therapies. The present study was performed to investigate whether local intramyocardial injection of EPO with hydrogel could enhance cardioprotective effect without causing polycythaemia after myocardial infarction (MI). To test the hypothesis, phosphate buffered solution (PBS), alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel, recombined human erythropoietin (rhEPO) in PBS, or rhEPO in hydrogel were injected into the infarcted area immediately after MI in rats. The hydrogel allowed a sustained release of EPO, which inhibited cell apoptosis and increased neovasculature formation, and subsequently reduced infarct size and improved cardiac function compared with other groups. Notably, there was no evidence of polycythaemia from this therapy, with no differences in erythrocyte count and hematocrit compared with the animals received PBS or hydrogel blank injection. In conclusion, intramyocardial delivery of rhEPO with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel may lead to cardiac performance improvement after MI without apparent adverse effect.
21 CFR 812.46 - Monitoring investigations.
Code of Federal Regulations, 2010 CFR
2010-04-01
... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Unanticipated adverse device effects. (1) A sponsor shall immediately conduct an evaluation of any unanticipated adverse device effect. (2) A sponsor who determines that an unanticipated adverse device effect presents...
Evidence for a neural dual-process account for adverse effects of cognitive control.
Zink, Nicolas; Stock, Ann-Kathrin; Colzato, Lorenza; Beste, Christian
2018-06-09
Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.
Evaluation of Skin Permeation of β-blockers for Topical Drug Delivery
Chantasart, Doungdaw; Hao, Jinsong; Li, S. Kevin
2013-01-01
Purpose β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Methods Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. Results The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. Conclusions The present results suggest the possibility of topical treatment of hemangioma using β-blockers. PMID:23208385
Palgi, Yuval; Shrira, Amit
2016-03-01
Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the life span, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs' mental and physical health than on Jews' health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. (c) 2016 APA, all rights reserved).
Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H
2016-09-25
Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively( P <0.01). Total and subclassification of adverse effects decreased significantly( P <0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P > 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.
Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, José M; Fichera, Epifanio; Reed, Steven G; Coler, Rhea N; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav; Cordeiro-da-Silva, Anabela
2017-11-01
The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".
Airline Safety Improvement Through Experience with Near-Misses: A Cautionary Tale.
Madsen, Peter; Dillon, Robin L; Tinsley, Catherine H
2016-05-01
In recent years, the U.S. commercial airline industry has achieved unprecedented levels of safety, with the statistical risk associated with U.S. commercial aviation falling to 0.003 fatalities per 100 million passengers. But decades of research on organizational learning show that success often breeds complacency and failure inspires improvement. With accidents as rare events, can the airline industry continue safety advancements? This question is complicated by the complex system in which the industry operates where chance combinations of multiple factors contribute to what are largely probabilistic (rather than deterministic) outcomes. Thus, some apparent successes are realized because of good fortune rather than good processes, and this research intends to bring attention to these events, the near-misses. The processes that create these near-misses could pose a threat if multiple contributing factors combine in adverse ways without the intervention of good fortune. Yet, near-misses (if recognized as such) can, theoretically, offer a mechanism for continuing safety improvements, above and beyond learning gleaned from observable failure. We test whether or not this learning is apparent in the airline industry. Using data from 1990 to 2007, fixed effects Poisson regressions show that airlines learn from accidents (their own and others), and from one category of near-misses-those where the possible dangers are salient. Unfortunately, airlines do not improve following near-miss incidents when the focal event has no clear warnings of significant danger. Therefore, while airlines need to and can learn from certain near-misses, we conclude with recommendations for improving airline learning from all near-misses. © 2015 Society for Risk Analysis.
The Frontal View of the Nose: Lighting Effects and Photographic Bias.
Strub, Benedikt; Mende, Konrad; Meuli-Simmen, Claudia; Bessler, Stephan
2015-07-01
Most aesthetic rhinosurgeons rely on proper photographic documentation of the nose using several different views. The frontal view is probably the most important, but it is also the most demanding. In the frontal view, delicate, 3-dimensional (3D) anatomic structures require special photographic skills. Lighting is crucial for detail rendition and 3D reproduction of the nose, and for apparent photographic bias. We compared the quality of reproduction and photographic bias with different symmetric and asymmetric lighting in common clinical practice described in the literature. The photographs were compared for anatomic reproduction, shadowing, 3-dimensionality, and apparent changes of nasal shape (bias). Symmetric lighting did not satisfy the demands of the rhinosurgeons because of marginal 3-dimensionality, reduced detail rendition, or photographic bias. Strongly asymmetric lighting altered the nasal shape adversely for bias depending on the side of illumination, but led to very good 3-dimensionality. Slightly asymmetric lighting demonstrated the best results for detail rendition and 3-dimensionality. Classic symmetric quarter light is a practicable lighting technique with limitations in the rendition of detail and 3-dimensionality. Slightly asymmetric lighting offered a perfect compromise, with substantially improved detail rendition and 3-dimensionality. Strongly asymmetric lighting may lead to photographic bias depending on the side of illumination. Frontal documentation of the nose with asymmetric lighting should, therefore, always be performed in duplicate, with asymmetric lighting from the right side and from the left side, to prevent misleading interpretations. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.
Effect of temperature and heating rate on apparent lethal concentrations of pyrolysis products
NASA Technical Reports Server (NTRS)
Hilado, C. J.; Solis, A. N.; Marcussen, W. H.; Furst, A.
1976-01-01
The apparent lethal concentrations for 50 percent of the test animals of the pyrolysis products from twelve polymeric materials were studied as a function of temperature and heating rate. The materials were polyethylene, nylon 6, ABS, polycarbonate, polyether sulfone, polyaryl sulfone, wool fabric, aromatic polyamide fabric, polychloroprene foam, polyvinyl fluoride film, Douglas fir, and red oak. The apparent lethal concentration values of most materials vary significantly with temperature and heating rate. The apparent lethal concentration values, based on weight of sample charged, appears to effectively integrate the thermophysical, thermochemical, and physiological responses from a known quantity of material under specified imposed conditions.
Smilanich, Angela M; Fincher, R Malia; Dyer, Lee A
2016-05-01
According to the plant-apparency hypothesis, apparent plants allocate resources to quantitative defenses that negatively affect generalist and specialist herbivores, while unapparent plants invest more in qualitative defenses that negatively affect nonadapted generalists. Although this hypothesis has provided a useful framework for understanding the evolution of plant chemical defense, there are many inconsistencies surrounding associated predictions, and it has been heavily criticized and deemed obsolete. We used a hierarchical Bayesian meta-analysis model to test whether defenses from apparent and unapparent plants differ in their effects on herbivores. We collected a total of 225 effect sizes from 158 published papers in which the effects of plant chemistry on herbivore performance were reported. As predicted by the plant-apparency hypothesis, we found a prevalence of quantitative defenses in woody plants and qualitative defenses in herbaceous plants. However, the detrimental impacts of qualitative defenses were more effective against specialists than generalists, and the effects of chemical defenses did not significantly differ between specialists and generalists for woody or herbaceous plants. A striking pattern that emerged from our data was a pervasiveness of beneficial effects of secondary metabolites on herbivore performance, especially generalists. This pattern provides evidence that herbivores are evolving effective counteradaptations to putative plant defenses. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
Toxicity of selenium and other elements in food organisms to razorback sucker larvae
Hamilton, Steven J.; Holley, Kathy M.; Buhl, Kevin J.; Bullard, Fern A.; Weston, L. Ken; McDonald, Susan F.
2002-01-01
Elevated selenium concentrations documented in water, sediment, and biota in irrigation drain water studies by U.S. Department of the Interior agencies and academia have raised concerns that selenium may be adversely affecting endangered fish in the upper Colorado River basin. The objective of the study was to determine the effects on endangered razorback sucker (Xyrauchen texanus) larvae from exposure to selenium and other trace elements in water and zooplankton collected from sites adjacent to the Colorado River near Grand Junction, CO. A 30-day study was initiated with 5-day-old larvae exposed in a 4×4 factor experiment with four food and four water treatments, and the biological endpoints measured were survival, growth, development, and whole-body residues of selenium. Mean selenium concentration in reference water (24-Road) was <0.7 μg/l, in reference food (brine shrimp) was 3.2 μg/g, at Horsethief was 1.6 μg/l in water and 6.0 μg/g in zooplankton, at Adobe Creek was 3.4 μg/l in water and 32 μg/g in zooplankton, and at Walter Walker was 13 μg/l in water and 52 μg/g in zooplankton. Although there were differences in concentrations of inorganic elements in water and biota among the three sites, selenium was apparently the only element elevated to concentrations of concern. Effects on survival were more prominent from dietary exposure compared to waterborne exposure. Selenium concentrations of ≥4.6 μg/g in food organisms adversely affected the survival of razorback sucker larvae. The onset of mortality in larvae exposed to food and water from Walter Walker seemed delayed compared to mortality in larvae exposed to food and water from Horsethief, which has been observed in two other studies. Elevated arsenic in one food source seemed to interact with selenium to reduce the toxic effects of selenium.
Effect of aircraft-cabin altitude on passenger discomfort.
Muhm, J Michael; Rock, Paul B; McMullin, Dianne L; Jones, Stephen P; Lu, I L; Eilers, Kyle D; Space, David R; McMullen, Aleksandra
2007-07-05
Acute mountain sickness occurs in some unacclimatized persons who travel to terrestrial altitudes at which barometric pressures are the same as those in commercial aircraft during flight. Whether the effects are similar in air travelers is unknown. We conducted a prospective, single-blind, controlled hypobaric-chamber study of adult volunteers to determine the effect of barometric pressures equivalent to terrestrial altitudes of 650, 4000, 6000, 7000, and 8000 ft (198, 1219, 1829, 2134, and 2438 m, respectively) above sea level on arterial oxygen saturation and the occurrence of acute mountain sickness and discomfort as measured by responses to the Environmental Symptoms Questionnaire IV during a 20-hour simulated flight. Among the 502 study participants, the mean oxygen saturation decreased with increasing altitude, with a maximum decrease of 4.4 percentage points (95% confidence interval, 3.9 to 4.9) at 8000 ft. Overall, acute mountain sickness occurred in 7.4% of the participants, but its frequency did not vary significantly among the altitudes studied. The frequency of reported discomfort increased with increasing altitude and decreasing oxygen saturation and was greater at 7000 to 8000 ft than at all the lower altitudes combined. Differences became apparent after 3 to 9 hours of exposure. Persons older than 60 years of age were less likely than younger persons and men were less likely than women to report discomfort. Four serious adverse events, 1 of which may have been related to the study exposures, and 15 adverse events, 9 of which were related to study exposures, were reported. Ascent from ground level to the conditions of 7000 to 8000 ft lowered oxygen saturation by approximately 4 percentage points. This level of hypoxemia was insufficient to affect the occurrence of acute mountain sickness but did contribute to the increased frequency of reports of discomfort in unacclimatized participants after 3 to 9 hours. (ClinicalTrials.gov number, NCT00326703 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
Adverse effects of cannabis on health: an update of the literature since 1996.
Kalant, Harold
2004-08-01
Recent research has clarified a number of important questions concerning adverse effects of cannabis on health. A causal role of acute cannabis intoxication in motor vehicle and other accidents has now been shown by the presence of measurable levels of Delta(9)-tetrahydrocannabinol (THC) in the blood of injured drivers in the absence of alcohol or other drugs, by surveys of driving under the influence of cannabis, and by significantly higher accident culpability risk of drivers using cannabis. Chronic inflammatory and precancerous changes in the airways have been demonstrated in cannabis smokers, and the most recent case-control study shows an increased risk of airways cancer that is proportional to the amount of cannabis use. Several different studies indicate that the epidemiological link between cannabis use and schizophrenia probably represents a causal role of cannabis in precipitating the onset or relapse of schizophrenia. A weaker but significant link between cannabis and depression has been found in various cohort studies, but the nature of the link is not yet clear. A large body of evidence now demonstrates that cannabis dependence, both behavioral and physical, does occur in about 7-10% of regular users, and that early onset of use, and especially of weekly or daily use, is a strong predictor of future dependence. Cognitive impairments of various types are readily demonstrable during acute cannabis intoxication, but there is no suitable evidence yet available to permit a decision as to whether long-lasting or permanent functional losses can result from chronic heavy use in adults. However, a small but growing body of evidence indicates subtle but apparently permanent effects on memory, information processing, and executive functions, in the offspring of women who used cannabis during pregnancy. In total, the evidence indicates that regular heavy use of cannabis carries significant risks for the individual user and for the health care system.
Toxicity of selenium and other elements in food organisms to razorback sucker larvae.
Hamilton, Steven J; Holley, Kathy M; Buhl, Kevin J; Bullard, Fern A; Weston, L Ken; McDonald, Susan F
2002-09-24
Elevated selenium concentrations documented in water, sediment, and biota in irrigation drain water studies by U.S. Department of the Interior agencies and academia have raised concerns that selenium may be adversely affecting endangered fish in the upper Colorado River basin. The objective of the study was to determine the effects on endangered razorback sucker (Xyrauchen texanus) larvae from exposure to selenium and other trace elements in water and zooplankton collected from sites adjacent to the Colorado River near Grand Junction, CO. A 30-day study was initiated with 5-day-old larvae exposed in a 4 x 4 factor experiment with four food and four water treatments, and the biological endpoints measured were survival, growth, development, and whole-body residues of selenium. Mean selenium concentration in reference water (24-Road) was <0.7 microg/l, in reference food (brine shrimp) was 3.2 microg/g, at Horsethief was 1.6 microg/l in water and 6.0 microg/g in zooplankton, at Adobe Creek was 3.4 microg/l in water and 32 microg/g in zooplankton, and at Walter Walker was 13 microg/l in water and 52 microg/g in zooplankton. Although there were differences in concentrations of inorganic elements in water and biota among the three sites, selenium was apparently the only element elevated to concentrations of concern. Effects on survival were more prominent from dietary exposure compared to waterborne exposure. Selenium concentrations of >or=4.6 microg/g in food organisms adversely affected the survival of razorback sucker larvae. The onset of mortality in larvae exposed to food and water from Walter Walker seemed delayed compared to mortality in larvae exposed to food and water from Horsethief, which has been observed in two other studies. Elevated arsenic in one food source seemed to interact with selenium to reduce the toxic effects of selenium.
40 CFR 174.71 - Submission of information regarding adverse effects.
Code of Federal Regulations, 2011 CFR
2011-07-01
... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...
40 CFR 174.71 - Submission of information regarding adverse effects.
Code of Federal Regulations, 2014 CFR
2014-07-01
... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...
40 CFR 174.71 - Submission of information regarding adverse effects.
Code of Federal Regulations, 2012 CFR
2012-07-01
... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...
40 CFR 174.71 - Submission of information regarding adverse effects.
Code of Federal Regulations, 2010 CFR
2010-07-01
... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...
40 CFR 174.71 - Submission of information regarding adverse effects.
Code of Federal Regulations, 2013 CFR
2013-07-01
... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...
Comparison of moxalactam and cefazolin as prophylactic antibiotics during cesarean section.
Rayburn, W; Varner, M; Galask, R; Petzold, C R; Piehl, E
1985-01-01
Prophylactic antibiotics have been shown to be effective in decreasing the incidence of febrile morbidity associated with cesarean section after labor. However, the relative effectiveness of different single antibiotics has been studied infrequently, and these investigations have been limited by small patient samples. Several new, broad-spectrum antibiotics are now available, and any further benefit from more traditional antibiotics for surgical prophylaxis remains untested. A randomized prospective double-blind therapeutic trial was therefore undertaken to compare the value of a first-generation cephalosporin (cefazolin) with a new third-generation cephalosporin (moxalactam). Between July 1981 and June 1983, 254 qualifying women who underwent primary cesarean section after labor were randomly chosen for either of the two treatment groups. Although not statistically significant, the rates of febrile morbidity, wound infection, and endometritis were less for those treated with cefazolin (4.0, 3.2, and 0.8%, respectively) than for those treated with moxalactam (9.2, 7.7, and 1.6%, respectively). No serious adverse effects were apparent in the mother and newborn infant from short-term exposure to either drug. Although the newer, more expensive, and broader-spectrum cephalosporin, moxalactam, was associated with a low postoperative febrile morbidity rate and short postpartum hospitalization, it was no more beneficial than cefazolin. PMID:3994348
Novel AgoshRNA molecules for silencing of the CCR5 co-receptor for HIV-1 infection
Herrera-Carrillo, Elena
2017-01-01
Allogeneic transplantation of blood stem cells from a CCR5-Δ32 homozygous donor to an HIV-infected individual, the “Berlin patient”, led to a cure. Since then there has been a search for approaches that mimic this intervention in a gene therapy setting. RNA interference (RNAi) has evolved as a powerful tool to regulate gene expression in a sequence-specific manner and can be used to inactivate the CCR5 mRNA. Short hairpin RNA (shRNA) molecules can impair CCR5 expression, but these molecules may cause unintended side effects and they will not be processed in cells that lack Dicer, such as monocytes. Dicer-independent RNAi pathways have opened opportunities for new AgoshRNA designs that rely exclusively on Ago2 for maturation. Furthermore, AgoshRNA processing yields a single active guide RNA, thus reducing off-target effects. In this study, we tested different AgoshRNA designs against CCR5. We selected AgoshRNAs that potently downregulated CCR5 expression on human T cells and peripheral blood mononuclear cells (PBMC) and that had no apparent adverse effect on T cell development as assessed in a competitive cell growth assay. CCR5 knockdown significantly protected T cells from CCR5 tropic HIV-1 infection. PMID:28542329
Serio-Silva, Juan Carlos; Olguín, Eugenia J; Garcia-Feria, Luis; Tapia-Fierro, Karla; Chapman, Colin A
2015-01-01
To construct informed conservation plans, researchers must go beyond understanding readily apparent threats such as habitat loss and bush-meat hunting. They must predict subtle and cascading effects of anthropogenic environmental modifications. This study considered a potential cascading effect of deforestation on the howler monkeys (Alouatta pigra) of Balancán, Mexico. Deforestation intensifies flooding. Thus, we predicted that increased flooding of the Usumacinta River, which creates large bodies of water that slowly evaporate, would produce increased lead content in the soils and plants, resulting in lead exposure in the howler monkeys. The average lead levels were 18.18 ± 6.76 ppm in the soils and 5.85 ± 4.37 ppm in the plants. However, the average lead content of the hair of 13 captured howler monkeys was 24.12 ± 5.84 ppm. The lead levels in the animals were correlated with 2 of 15 blood traits (lactate dehydrogenase and total bilirubin) previously documented to be associated with exposure to lead. Our research illustrates the urgent need to set reference values indicating when adverse impacts of high environmental lead levels occur, whether anthropogenic or natural, and the need to evaluate possible cascading effects of deforestation on primates.
Islam, Md Soriful; Akhtar, Most Mauluda; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina
2017-11-22
Uterine fibroids (myomas or leiomyomas) are common benign tumors of reproductive aged women. Fibroids are clinically apparent in 20-50% of women, and cause abnormal uterine bleeding, abdominal pain and discomfort, pregnancy complications and infertility. Unfortunately, limited numbers of medical treatment are available but no effective preventive strategies exist. Moreover, the benefits of medical treatments are tempered by lack of efficacy or serious adverse side effects. Fibrosis has recently been recognized as a key pathological event in leiomyoma development and growth. It is defined by the excessive deposition of extracellular matrix (ECM). ECM plays important role in making bulk structure of leiomyoma, and ECM-rich rigid structure is believed to be a cause of abnormal bleeding and pelvic pain/pressure. Dietary phytochemicals are known to regulate fibrotic process in different biological systems, and being considered as potential tool to manage human health. At present, very few dietary phytochemicals have been studied in uterine leiomyoma, and they are mostly known for their antiproliferative effects. Therefore, in this review, our aim was to introduce some dietary phytochemicals that could target fibrotic processes in leiomyoma. Thus, this review could serve as useful resource to develop antifibrotic drugs for possible prevention and treatment of uterine fibroids.
The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).
Dorato, Michael A; Engelhardt, Jeffery A
2005-08-01
The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.
Adverse mood effects of combined oral contraceptives in relation to personality traits.
Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger
2008-12-01
Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.
Dietary sodium restriction: a neglected therapeutic opportunity in chronic kidney disease
Humalda, Jelmer K.; Navis, Gerjan
2014-01-01
Purpose of review Restriction of dietary sodium is recommended at a population level as well as for groups at high cardiovascular risk, and chronic kidney disease (CKD). This review addresses recent evidence for the protective effect of dietary sodium restriction in CKD patients specifically. Recent findings Sodium intake in CKD populations is generally high, and often above population average. Recent data demonstrated that moderately lower sodium intake in CKD patients is associated with substantially better long-term outcome of renin–angiotensin–aldosterone system (RAAS)-blockade, in diabetic and nondiabetic CKD, related to better effects of RAAS-blockade on proteinuria, independent of blood pressure. This is in line with better short-term efficacy of RAAS-blockade during moderate sodium restriction in diabetic and nondiabetic CKD. This effect of sodium restriction is likely mediated by its effects on volume status. Sustainable sodium restriction can be achieved by approaches on the basis of behavioral sciences. Summary Moderate restriction of dietary sodium can substantially improve the protective effects of RAAS-blockade in CKD, by specific renal effects apparent from proteinuria reduction. The latter precludes straightforward extrapolation of data from nonrenal populations to CKD. Concerns regarding the adverse effects of a very low sodium intake should not distract from the protective effects of moderate sodium restriction. Prospective studies should assess the efficacy and sustainability of different strategies to target high sodium intake in CKD, along with measures at population level. Video abstract http://links.lww.com/CONH/A14 PMID:25222815
40 CFR 350.21 - Adverse health effects.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...
40 CFR 350.21 - Adverse health effects.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...
40 CFR 350.21 - Adverse health effects.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...
40 CFR 350.21 - Adverse health effects.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...
40 CFR 350.21 - Adverse health effects.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...
30 CFR 875.15 - Reclamation priorities for noncoal program.
Code of Federal Regulations, 2011 CFR
2011-07-01
... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...
30 CFR 875.15 - Reclamation priorities for noncoal program.
Code of Federal Regulations, 2010 CFR
2010-07-01
... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...
30 CFR 875.15 - Reclamation priorities for noncoal program.
Code of Federal Regulations, 2012 CFR
2012-07-01
... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...
30 CFR 875.15 - Reclamation priorities for noncoal program.
Code of Federal Regulations, 2014 CFR
2014-07-01
... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...
75 FR 38521 - Registration Review; Biopesticide Dockets Opened for Review and Comment
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-02
... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...
75 FR 60117 - Registration Review; Biopesticides Dockets Opened for Review and Comment
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-29
... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...
77 FR 74479 - Registration Review; Pesticide Dockets Opened for Review and Comment
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-14
... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... function without unreasonable adverse effects on human health or the environment. Registration review...
77 FR 59188 - Registration Review; Pesticide Dockets Opened for Review and Comment
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-26
... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... without unreasonable adverse effects on human health or the environment. Registration review dockets...
White, Isabelle; Smith, Lee; Aggio, Daniel; Shankar, Sahana; Begum, Saima; Matei, Raluca; Fox, Kenneth R; Hamer, Mark; Iliffe, Steve; Jefferis, Barbara J; Tyler, Nick; Gardner, Benjamin
2017-01-01
Of all age groups, older adults spend most of the time sitting and are least physically active. This sequential, mixed-methods feasibility study used a randomised controlled trial design to assess methods for trialling a habit-based intervention to displace older adults' sedentary behaviour with light activity and explore impact on behavioural outcomes. Eligibility criteria were age 60-74 years, retired, and ≥6 h/day leisure sitting. Data were collected across four sites in England. The intervention comprised a booklet outlining 15 'tips' for disrupting sedentary habits and integrating activity habits into normally inactive settings, and eight weekly self-monitoring sheets. The control was a non-habit-based factsheet promoting activity and sedentary reduction. A computer-generated 1:1 block-randomisation schedule was used, with participants blinded to allocation. Participants self-reported sedentary behaviour (two indices), sedentary habit, physical activity (walking, moderate, vigorous activity) and activity habit, at pre-treatment baseline, 8- and 12-week follow-ups and were interviewed at 12 weeks. Primary feasibility outcomes were attrition, adverse events and intervention adherence. The secondary outcome was behavioural change. Of 104 participants consented, 103 were randomised (intervention N = 52, control N = 51). Of 98 receiving allocated treatment, 91 (93%; intervention N = 45; control N = 46) completed the trial. One related adverse event was reported in the intervention group. Mean per-tip adherence across 7 weeks was ≥50% for 9/15 tips. Qualitative data suggested acceptability of procedures, and, particularly among intervention recipients, the allocated treatment. Both groups appeared to reduce sedentary behaviour and increase their physical activity, but there were no apparent differences between groups in the extent of change. Trial methods were acceptable and feasible, but the intervention conferred no apparent advantage over control, though it was not trialled among the most sedentary and inactive population for whom it was developed. Further development of the intervention may be necessary prior to a large-scale definitive trial. One possible refinement would combine elements of the intervention with an informational approach to enhance effectiveness. ISRCTN47901994 (registration date: 16th January 2014; trial end date 30th April 2015).
Viral Infections in Pregnancy: A Focus on Ebola Virus.
Olgun, Nicole S
2018-01-30
During gestation, the immune response of the placenta to viruses and other pathogens plays an important role in determining a pregnant woman's vulnerability toward infectious diseases. Located at the maternal- fetal interface, trophoblast cells serve to minimize the spread of viruses between the host and developing fetus through an intricate system of innate antiviral immune signaling. Adverse pregnancy outcomes, ranging from learning disabilities to preterm birth and fetal death, are all documented results of a viral breach in the placental barrier. Viral infections during pregnancy can also be spread through blood and vaginal secretions, and during the post-natal period, via breast milk. Thus, even in the absence of vertical transmission of viral infection to the fetus, maternal health can still be compromised and threaten the pregnancy. The most common viral DNA isolates found in gestation are adenovirus, cytomegalovirus, and enterovirus. However, with the recent pandemic of Ebola virus, and the first documented case of a neonate to survive due to experimental therapies in 2017, it is becoming increasingly apparent that the changing roles and impacts of viral infection during pregnancy needs to be better understood, while strategies to minimize adverse pregnancy outcomes need to be identified. This review focuses on the adverse impacts of viral infection during gestation, with an emphasis on Ebola virus. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P
2017-01-01
Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.
Vilar, Santiago; Hripcsak, George
2016-01-01
Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.
Spielmans, Glen I.; Berman, Margit I.; Linardatos, Eftihia; Rosenlicht, Nicholas Z.; Perry, Angela; Tsai, Alexander C.
2013-01-01
Background Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk–benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. Methods and Findings We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48–2.73), OFC (OR, 1.42; 95% CI, 1.01–2.0), quetiapine (OR, 1.79; 95% CI, 1.33–2.42), and risperidone (OR, 2.37; 95% CI, 1.31–4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58–2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87–1.93), quetiapine (OR, 1.53, 95% CI, 1.17–2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16–2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery–Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49). Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events. Conclusions Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm. Please see later in the article for the Editors' Summary PMID:23554581
77 FR 40048 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Actions
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2012-07-06
... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...
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2012-03-28
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2010-09-29
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2011-06-29
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Adverse effects of public health interventions: a conceptual framework.
Lorenc, Theo; Oliver, Kathryn
2014-03-01
Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.
The Neurobiology of Intervention and Prevention in Early Adversity.
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.
Kim, Paul J; Hicks, Rodney J; Wirth, Andrew; Ryan, Gail; Seymour, John F; Prince, H Miles; Mac Manus, Michael P
2009-07-01
To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.
Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni
2016-12-01
Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Howell, Kathryn H; Miller-Graff, Laura E; Schaefer, Lauren M; Scrafford, Kathryn E
2017-08-01
This study examined the indirect effects of individual, relational, and contextual resilience in the relationship between adverse childhood experiences and prenatal depression. Participants included 101 pregnant women. Adverse childhood experiences had a direct effect on depression, B = 1.11, standard error = .44, p = .01, and relational resilience, B = -1.15, standard error = .19, p < .001, but not individual or contextual resilience. With resilience as a mediator, the effect of adverse childhood experiences on depression was no longer significant. Specifically, relational resilience had a significant indirect effect (IE) on the association between adverse childhood experiences and depression, IE = 1.04, boot standard error = .28 (95% confidence interval = .58, 1.68). Results emphasize the associated role of relational qualities, such as sense of security and belongingness, with childhood adversity and mental health.
Influence of food on the pharmacokinetic profile of fesoterodine.
Malhotra, B; Sachse, R; Wood, N
2009-06-01
Fesoterodine is a new, once-daily, oral, antimuscarinic agent indicated for the treatment of overactive bladder. It undergoes rapid and extensive metabolism by plasma esterases to form its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). The sustained-release formulation of fesoterodine delivers 5-HMT with linear, dose-proportional pharmacokinetics (PK) suitable for once-daily dosing. This study was designed for the definitive assessment of the effect of food on 5-HMT PK using the commercial formulation of fesoterodine. In this randomized, open-label, single-dose, 2-way, crossover study, fesoterodine 8 mg was administered orally to healthy subjects in either a fed (after a high-fat, high-calorie breakfast) or fasted state. Blood samples for PK were drawn up to 36 hours after dosing. Primary endpoints for food effect assessment were area under the concentration-versus-time curve up to the last sample (AUC(0-tz)), and maximum plasma concentration (C(max)) for 5-HMT. Adverse events, vital signs, hematology, clinical chemistry, and electrocardiograms were monitored for safety assessment. A total of 16 healthy male subjects enrolled and completed the study. Mean values of both primary PK parameters of 5-HMT (AUC(0-tz) and C(max)) were approximately 19% higher after fesoterodine administration in the fed versus the fasted state. The upper limits of the corresponding 90% confidence intervals for the "fed/fasted" ratios of AUC(0-tz) (104%, 137%) and C(max) (94%, 149%) were not included in the prespecified acceptance range (80%, 125%) for concluding "no food effect." Secondary PK variables, (i.e. time to maximum plasma concentration terminal elimination half-life and mean residence time), did not differ markedly between the fed and fasted states. Fesoterodine was well tolerated, and adverse events were mild, with no apparent difference in frequency between fed and fasted states. The hypothesis of "no food effect" could not be statistically confirmed; however, only modest increases of approximately 19% were observed for C(max) and AUC(0-tz) of 5-HMT. This magnitude of PK effects is unlikely to be of clinical relevance based on Phase 2 and 3 clinical experience with fesoterodine, supporting its administration without regard to meals.
Azolla filiculoides Nitrogenase Activity Decrease Induced by Inoculation with Chlamydomonas sp. †
Habte, Mitiku
1986-01-01
Experiments were conducted to determine the influence of Chlamydomonas sp. on nitrogen fixation (C2H2 → C2H4) in Azolla filiculoides and on the nitrogen fixation and growth of free-living Anabaena azollae 2B organisms. Inoculation of azolla medium with Chlamydomonas sp. was associated with decreased nitrogenase activity in A. filiculoides and with increases in the density of a fungal population identified as Acremonium sp. Subsequent inoculation of azolla medium with this fungus was also accompanied by a significant decrease in nitrogenase activity of A. filiculoides. However, the extent of depression of nitrogenase activity was significantly higher when azolla medium was inoculated with Chlamydomonas sp. than when it was inoculated with Acremonium sp. Inoculation of nitrogen-free Stanier medium with either Acremonium sp. or Chlamydomonas sp. did not adversely affect the growth or nitrogenase activity of free-living A. azollae. Decreased nitrogenase activity in A. filiculoides is apparently related to the adverse influence of the green alga and the fungus on the macrosymbiont. The mechanisms that might be involved are discussed. PMID:16347211
Testing an integral conceptual model of frailty.
Gobbens, Robbert J; van Assen, Marcel A; Luijkx, Katrien G; Schols, Jos M
2012-09-01
This paper is a report of a study conducted to test three hypotheses derived from an integral conceptual model of frailty. The integral model of frailty describes the pathway from life-course determinants to frailty to adverse outcomes. The model assumes that life-course determinants and the three domains of frailty (physical, psychological, social) affect adverse outcomes, the effect of disease(s) on adverse outcomes is mediated by frailty, and the effect of frailty on adverse outcomes depends on the life-course determinants. In June 2008 a questionnaire was sent to a sample of community-dwelling people, aged 75 years and older (n = 213). Life-course determinants and frailty were assessed using the Tilburg frailty indicator. Adverse outcomes were measured using the Groningen activity restriction scale, the WHOQOL-BREF and questions regarding healthcare utilization. The effect of seven self-reported chronic diseases was examined. Life-course determinants, chronic disease(s), and frailty together explain a moderate to large part of the variance of the seven continuous adverse outcomes (26-57%). All these predictors together explained a significant part of each of the five dichotomous adverse outcomes. The effect of chronic disease(s) on all 12 adverse outcomes was mediated at least partly by frailty. The effect of frailty domains on adverse outcomes did not depend on life-course determinants. Our finding that the adverse outcomes are differently and uniquely affected by the three domains of frailty (physical, psychological, social), and life-course determinants and disease(s), emphasizes the importance of an integral conceptual model of frailty. © 2011 Blackwell Publishing Ltd.
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.
Synthesis and therapeutic effect of styrene–maleic acid copolymer-conjugated pirarubicin
Tsukigawa, Kenji; Liao, Long; Nakamura, Hideaki; Fang, Jun; Greish, Khaled; Otagiri, Masaki; Maeda, Hiroshi
2015-01-01
Previously, we prepared a pirarubicin (THP)-encapsulated micellar drug using styrene–maleic acid copolymer (SMA) as the drug carrier, in which active THP was non-covalently encapsulated. We have now developed covalently conjugated SMA-THP (SMA-THP conjugate) for further investigation toward clinical development, because covalently linked polymer–drug conjugates are known to be more stable in circulation than drug-encapsulated micelles. The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation. Consequently, SMA-THP conjugate showed significantly prolonged circulation time compared to free THP and high tumor-targeting efficiency by the enhanced permeability and retention (EPR) effect. As a result, remarkable antitumor effect was achieved against two types of tumors in mice without apparent adverse effects. Significantly, metastatic lung tumor also showed the EPR effect, and this conjugate reduced metastatic tumor in the lung almost completely at 30 mg/kg once i.v. (less than one-fifth of the maximum tolerable dose). Although SMA-THP conjugate per se has little cytotoxicity in vitro (1/100 of free drug THP), tumor-targeted accumulation by the EPR effect ensures sufficient drug concentrations in tumor to produce an antitumor effect, whereas toxicity to normal tissues is much less. These findings suggest the potential of SMA-THP conjugate as a highly favorable candidate for anticancer nanomedicine with good stability and tumor-targeting properties in vivo. PMID:25529761
Zar-Kessler, Claire A M; Belkind-Gerson, Jaime; Bender, Suzanne; Kuo, Braden M
2017-07-01
Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.
Norris, T; Johnson, W; Farrar, D; Tuffnell, D; Wright, J; Cameron, N
2015-01-01
Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinically recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age (SGA: birth weight <10th centile) and large-for-gestational age (LGA: birth weight >90th centile). Design Prospective cohort study. Setting Born in Bradford (BiB) study, UK. Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age, birth weight, ethnicity, maternal height, weight and parity. Main outcome measures Prevalence of SGA and LGA, using the three charts and indicators of diagnostic utility (sensitivity, specificity and area under the receiver operating characteristic (AUROC)) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome. Results In White British and Pakistani infants, the prevalence of SGA and LGA differed depending on the chart used. Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart, while the opposite was apparent when classifying LGA infants. However, the predictive utility of all three charts to identify adverse clinical outcomes was poor, with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts. Conclusions Despite being recommended in national clinical guidelines, the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes. Being small or large may increase the risk of an adverse outcome; however, size alone is not sensitive or specific enough with current detection to be useful. However, a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations. PMID:25783424
Effects of cold and hot temperature on dehydration: a mechanism of cardiovascular burden.
Lim, Youn-Hee; Park, Min-Seon; Kim, Yoonhee; Kim, Ho; Hong, Yun-Chul
2015-08-01
The association between temperature (cold or heat) and cardiovascular mortality has been well documented. However, few studies have investigated the underlying mechanism of the cold or heat effect. The main goal of this study was to examine the effect of temperature on dehydration markers and to explain the pathophysiological disturbances caused by changes of temperature. We investigated the relationship between outdoor temperature and dehydration markers (blood urea nitrogen (BUN)/creatinine ratio, urine specific gravity, plasma tonicity and haematocrit) in 43,549 adults from Seoul, South Korea, during 1995-2008. We used piece-wise linear regression to find the flexion point of apparent temperature and estimate the effects below or above the apparent temperature. Levels of dehydration markers decreased linearly with an increase in the apparent temperature until a point between 22 and 27 °C, which was regarded as the flexion point of apparent temperature, and then increased with apparent temperature. Because the associations between temperature and cardiovascular mortality are known to be U-shaped, our findings suggest that temperature-related changes in hydration status underlie the increased cardiovascular mortality and morbidity during high- or low-temperature conditions.
[Adverse effects of oxcarbazepine].
Fang, Shu; Gong, Zhi-Cheng
2015-04-01
Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.
Golder, Su; Wright, Kath; Loke, Yoon Kong
2018-06-01
Search filter development for adverse effects has tended to focus on retrieving studies of drug interventions. However, a different approach is required for surgical interventions. To develop and validate search filters for medline and Embase for the adverse effects of surgical interventions. Systematic reviews of surgical interventions where the primary focus was to evaluate adverse effect(s) were sought. The included studies within these reviews were divided randomly into a development set, evaluation set and validation set. Using word frequency analysis we constructed a sensitivity maximising search strategy and this was tested in the evaluation and validation set. Three hundred and fifty eight papers were included from 19 surgical intervention reviews. Three hundred and fifty two papers were available on medline and 348 were available on Embase. Generic adverse effects search strategies in medline and Embase could achieve approximately 90% relative recall. Recall could be further improved with the addition of specific adverse effects terms to the search strategies. We have derived and validated a novel search filter that has reasonable performance for identifying adverse effects of surgical interventions in medline and Embase. However, we appreciate the limitations of our methods, and recommend further research on larger sample sizes and prospective systematic reviews. © 2018 The Authors Health Information and Libraries Journal published by John Wiley & Sons Ltd on behalf of Health Libraries Group.
Adverse Effects of Collagenase in the Treatment of Dupuytren Disease: A Systematic Review.
Sanjuan-Cerveró, Rafael; Carrera-Hueso, Francisco J; Vazquez-Ferreiro, Pedro; Gomez-Herrero, Diego
2017-04-01
Collagenase clostridium histolyticum (CCH) has proven to be both safe and effective in the treatment of Dupuytren disease (DD). The medium-term outcomes are similar to those achieved with surgery, and most adverse effects are self-limiting and considered to be mild or moderate. Our objective was to conduct a systematic review of the adverse effects of CCH in DD since the release of the drug to evaluate the incidence, severity, classification, and definitions of these effects. We analyzed the literature in terms of modifications to the original treatment protocol and grouped adverse effects according to their pathophysiological origin. We included 28 clinical studies and five case reports or case series analyzing 4456 patients with a mean age of 63.6 years. Mean follow-up was 7.07 months (range 3-24); the mean number of patients per study was 148 (range 5-1082). The studies did not classify the adverse effects they reported into groups. The most common effects were peripheral edema (54.4%), bruising (42.9%), and upper limb pain (28.3%). Significant biases were observed for use of terminology, demarcation of sites of involvement, severity criteria, and assessment methods. A simpler and clearer consensus-based classification system would enable better evaluation and comparison of the adverse effects of CCH in the treatment of DD. Consideration of inflammatory phenomena as part of the drug's mechanism of action would significantly reduce overall rates of adverse effects.
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.
Rasmussen, Keith G; Ritter, Matthew J
2014-12-01
Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.
Lewis, Tyler; Esler, Daniel N.; Uher-Koch, Brian D.; Dickson, Rian D.; Anderson, Eric M.; Evenson, Joseph R.; Hupp, Jerry W.; Flint, Paul L.
2017-01-01
A major challenge of wildlife telemetry is choosing an attachment technique that maximizes transmitter retention while minimizing negative side effects. For waterbirds, attachment of transmitters with subcutaneous anchors has been an effective and well-established technique, having been used on >40 species. This method was recently modified to include a second subcutaneous anchor, presumably increasing transmitter retention beyond that of single-anchor attachments. This putative benefit may be offset, however, by increased health risks related to additional incisions and subcutaneous protrusions. To test this potential trade-off, we attached radiotransmitters to molting and wintering surf (Melanitta perspicillata) and white-winged scoters (M. fusca) during 2008 and 2009 in Washington State and southeast Alaska, USA, using single- (121 scoters) and double-anchor (128 scoters) attachment techniques. We estimated daily probabilities of survival and radio retention for each group, this being apparent retention for wintering scoters because we could not differentiate shed transmitters from flighted emigration. For scoters during the flightless remigial molt, we found that addition of a second anchor increased cumulative retention probability (±SE) over a 49-day period from 0.69 ± 0.11 for single-anchor to 0.88 ± 0.07 for double-anchor attachments, while having no effect on survival. However, during winter, scoters with double-anchor attachments experienced no improvement in apparent retention, while having significantly lower survival during their first 14 days following transmitter attachment; of 15 mortalities during this period, 11 had 2 subcutaneous anchors. From day 15 onward, winter survival rates were nearly identical for single- versus double-anchor attachments, indicating that adverse effects of subcutaneous anchors were mainly limited to the 14-day postattachment period. Overall, given that the survival cost of adding a second subcutaneous anchor was substantial for wintering scoters—decreasing 14-day survival by 12% for adults and 23% for juveniles—we recommend that researchers opt for single-anchor attachments under most circumstances, especially during winter when birds may be energetically challenged.
The Nature and Timing of Tele-Pseudoscopic Experiences
Hill, Harold; Allison, Robert S
2016-01-01
Interchanging the left and right eye views of a scene (pseudoscopic viewing) has been reported to produce vivid stereoscopic effects under certain conditions. In two separate field studies, we examined the experiences of 124 observers (76 in Study 1 and 48 in Study 2) while pseudoscopically viewing a distant natural outdoor scene. We found large individual differences in both the nature and the timing of their pseudoscopic experiences. While some observers failed to notice anything unusual about the pseudoscopic scene, most experienced multiple pseudoscopic phenomena, including apparent scene depth reversals, apparent object shape reversals, apparent size and flatness changes, apparent reversals of border ownership, and even complex illusory foreground surfaces. When multiple effects were experienced, patterns of co-occurrence suggested possible causal relationships between apparent scene depth reversals and several other pseudoscopic phenomena. The latency for experiencing pseudoscopic phenomena was found to correlate significantly with observer visual acuity, but not stereoacuity, in both studies. PMID:27482368
Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.
Hall, Wayne
2017-04-01
The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.
Abandoned Mine Lands Program - Division of Mining, Land, and Water
, safety, general welfare and property from extreme danger resulting from the adverse effects of past coal mining practices. 2. Protection of public health, safety and general welfare from adverse effects of past lands and waters and the environment previously degraded by adverse effects of past coal mining
Where to Start with Pesticide Incidents
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2010-12-22
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2013-03-27
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Effects of occupational lead exposure.
Wang, Y L; Lu, P K; Chen, Z Q; Liang, Y X; Lu, Q M; Pan, Z Q; Shao, M
1985-01-01
Fifty-three workers in a battery factory, 52 solderers in a television factory, and 50 embroidery workers (a reference group) were studied. The average air lead levels of the three workplaces were 0.578 mg/m3, 0.002 mg/m3, and 0.001 mg/m3, respectively. Adverse effects in terms of clinical manifestations and biochemical criteria were evident among the battery factory workers. A significant dose-response relationship existed between the toxic effects and the air lead levels. The solderers showed no apparent abnormalities in comparison with the embroidery workers. The early clinical manifestations were dysfunction of the central nervous system, indigestion, arthralgia, and myalgia in the extremities. A positive association was observed between the prevalence of fatigue, mild abdominal pain, and arthralgia and the blood lead (PbB), urinary lead (PbU), and zinc protoporphyrin (ZPP) levels. The symptomatic threshold values of PbB, PbU, and ZPP were 30 micrograms/dl (1.5 mumol/l), 0.045 mg/l (0.2 mumol/l), and 40 micrograms/dl (0.7 mumol/l), respectively. The PbB, PbU, free erythrocyte protoporphyrin, and ZPP levels and the blood aminolevulinic dehydratase ratio could be used as indicators of lead exposure, although ZPP is preferred for a preventive monitoring program. The motor and sensory conduction velocities of the median nerve were slower in the exposed groups than in the reference group. No effects on behavioral function were observed among the solderers.
Vakkalagadda, Blisse; Lubin, Susan; Reynolds, Laurie; Liang, Dan; Marion, Alan S; LaCreta, Frank; Boulton, David W
2016-08-01
This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered. Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25. The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported. These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
Biosafety of parenteral Brucella abortus RB51 vaccine in bison calves
Roffe, T.J.; Olsen, S.C.; Gidlewski, T.; Jensen, A.E.; Palmer, M.V.; Huber, R.
1999-01-01
Vaccination is considered among the primary management tools for reducing brucellosis prevalence in Greater Yellowstone Area (GYA) ungulates. Before their use, however, vaccine safety and efficacy must be demonstrated. Twenty-seven female bison (Bison bison) calves (approx 5 months old) were vaccinated with Brucella abortus Strain RB51 (1.5 x 1010 colony forming units [CFU], subcutaneously) as part of routine management. We assessed the persistence, pathology, shedding, and transmission associated with RB51 by serial necropsy, bacteriology, histopathology, and serology of 20 of these 27 vaccinated calves, and RB51 serology of 10 nonvaccinated, commingling adult females. With the exception of 1 calf, RB51 dot-blot titers at necropsy were <1:80. Strain RB51 was cultured from lymph nodes in 4 of 4 calves at 14 weeks postvaccination (PV), 4 of 4 calves at 18 weeks PV, 1 of 4 calves at 22 weeks PV, 3 of 4 at 26 weeks PV, and 0 of 4 calves at 30 weeks PV. No gross lesions were observed. Mild histologic changes occurred only in a few draining lymph nodes early in sampling. Adverse clinical effects were not observed in vaccinates. Swabs from nasopharynx, conjunctiva, rectum, and vagina were uniformly culture negative for RB51. Strain RB51 dot-blot assays of bison cows were negative at a 1:20 dilution at 26 weeks PV. Our results suggest that RB51 persists longer in bison calves than in domestic cattle and is systemically distributed within lymphatic tissues. However, bison apparently clear the RB51 vaccine strain without shedding, transmission, or significant adverse reactions.
Gestational diabetes mellitus screening and outcomes.
Aktün, Hale Lebriz; Uyan, Derya; Yorgunlar, Betül; Acet, Mustafa
2015-01-01
To verify the usefulness of the World Health Organization criteria for the diagnosis of gestational diabetes mellitus in pregnant women and its effectiveness in the prevention of maternal and neonatal adverse results in women younger than 35 years without apparent risk factors for gestational diabetes mellitus. This is a retrospective study based on population involving 1360 pregnant women who delivered and who were followed-up in a university hospital in Istanbul. All women underwent the 75-g oral glucose tolerance test screening, usually in between the 24(th)-28(th) weeks of pregnancy. In all cases, the identification of gestational diabetes mellitus was determined in accordance with the World Health Organization criteria. Approximately 28% of the pregnant women aged younger than 35 years with no risk factors for gestational diabetes mellitus were diagnosed with the oral glucose tolerance test in this study. In the gestational diabetes mellitus group, the primary cesarean section rate was importantly higher than that in the non-gestational diabetes mellitus group. Preterm delivery was also associated with gestational diabetes mellitus. The diagnosis of gestational diabetes mellitus was strongly associated with admittance to the neonatal intensive care unit. Neonatal respiratory problems didn't showed any significant deviation between the groups. There was a moderate association between gestational diabetes mellitus and metabolic complications. Pregnant women with no obvious risk factors were diagnosed with gestational diabetes mellitus using the World Health Organization criteria. The treatment of these women potentially reduced their risk of adverse maternal and neonatal hyperglycemia-related events, such as cesarean section, polyhydramnios, preterm delivery, admission to neonatal intensive care unit, large for gestational age, and higher neonatal weight.
[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].
Uesawa, Yoshihiro
2018-01-01
Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.
Llabre, Maria M; Schneiderman, Neil; Gallo, Linda C; Arguelles, William; Daviglus, Martha L; Gonzalez, Franklyn; Isasi, Carmen R; Perreira, Krista M; Penedo, Frank J
Adverse childhood experiences (ACEs) are implicated in diseases of adulthood. We report the prevalence of ACEs in Hispanics/Latinos in the US and their association with major risk factors and diseases in adulthood. Data from the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were used. The Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos is an epidemiological study conducted in four urban communities in the US: Bronx, Chicago, Miami, and San Diego. The analytic sample comprised 5117 participants, ages 18 to 74 at baseline. Linear and logistic models, adjusted for sociodemographic factors, were used to examine associations of ACEs and risk factors (depressive symptoms, obesity, smoking, and alcohol use) and chronic disease (coronary heart disease, stroke, diabetes, asthma, chronic obstructive pulmonary disease, and cancer); the latter were also adjusted for risk factors. Most participants (77.2%) experienced at least one ACE, and 28.7% experienced four or more. Adverse childhood experiences were common among all ancestry groups, with variability among them. Prevalence of four or more ACEs was higher among women than men (31.2% and 25.8%, respectively). Adverse childhood experiences were associated with depressive symptoms, body mass index, smoking, alcohol use, cancer, coronary heart disease, and chronic obstructive pulmonary disease, but not asthma, diabetes, or stroke. Associations were not moderated by social support. Adverse childhood experiences are prevalent among US Hispanics/Latinos and are involved in disease in adulthood. The apparent higher prevalence of ACEs in US Hispanics/Latinos did not correspond with stronger associations with disease. Further studies are needed to identify factors that may moderate the associations of ACE with adult disease.
Ono, Hideki; Okamura, Maya; Fukushima, Akihiro
2018-06-20
Vince, L; Kleter, G A; Kostov, K; Pfeiffer, D U; Guitian, J
2018-04-20
A facultative post market monitoring of potential health impacts of genetically modified (GM) feedstuffs on livestock consuming these feeds after pre-market risk assessment is under ongoing consideration. Within the IPAFEED database, scientific studies on health effects beyond performance in livestock and the results of a systematic search for evidence of outcome effects due to GM feed are consolidated. These outcomes were reviewed and checked for consistency in order to identify plausible syndromes suitable for conducting surveillance. The 24 selected studies showed no consistent changes in any health parameter. There were no repeated studies in any species by GM crop type and animal species. As such, there is insufficient evidence to inform the design of surveillance systems for detecting known adverse effects. Animal health surveillance systems have been proposed for the post market monitoring of potential adverse effects in animals. Such systems were evaluated for their applicability to the detection of hypothetical adverse effects and their strengths and weaknesses to detect syndromes of concern are presented. For known adverse effects, applied controlled post-market studies may yield conclusive and high-quality evidence. For detecting unknown adverse effects, the use of existing surveillance systems may still be of interest. A simulation tool developed within the project can be adapted and applied to existing surveillance systems to explore their applicability to the detection of potential adverse effects of GM feed. Copyright © 2018. Published by Elsevier Ltd.
Discrimination of excess toxicity from baseline level for ionizable compounds: Effect of pH.
Li, Jin J; Zhang, Xu J; Wang, Xiao H; Wang, Shuo; Yu, Yang; Qin, Wei C; Su, Li M; Zhao, Yuan H
2016-03-01
The toxic effect can be affected by pH in water through affecting the degree of ionization of ionizable compounds. Wrong classification of mode of action can be made from the apparent toxicities. In this paper, the toxicity data of 61 compounds to Daphnia magna determined at three pH values were used to investigate the effect of pH on the discrimination of excess toxicity. The results show that the apparent toxicities are significantly less than the baseline level. Analysis on the effect of pH on bioconcentration factor (BCF) shows that the log BCF values are significantly over-estimated for the strongly ionizable compounds, leading to the apparent toxicities greatly less than the baseline toxicities and the toxic ratios greatly less than zero. A theoretical equation between the apparent toxicities and pH has been developed basing on the critical body residue (CBR). The apparent toxicities are non-linearly related to pH, but linearly to fraction of unionized form. The determined apparent toxicities are well fitted with the toxicities predicted by the equation. The toxicities in the unionized form calculated from the equation are close to, or greater than the baseline level for almost all the strongly ionizable compounds, which are very different from the apparent toxicities. The studied ionizable compounds can be either classified as baseline, less inert or reactive compounds in D. magna toxicity. Some ionizable compounds do not exhibit excess toxicity at a certain pH, due not to their poor reactivity with target molecules, but because of the ionization in water. Copyright © 2015 Elsevier Ltd. All rights reserved.
Yu, Daoyong; Huang, Guihong; Xu, Fengxi; Ge, Baosheng; Liu, Shuang; Xu, Hai; Huang, Fang
2014-11-01
Surfactants play a significant role in solubilization of photosystem I (PSI) in vitro. Triton X-100 (TX), n-Dodecyl-β-D-maltoside (DDM), and sodium dodecyl sulfate (SDS) were employed to solubilize PSI particles in MES buffer to compare the effect of surfactant and its dosage on the apparent oxygen consumption rate of PSI. Through a combined assessment of sucrose density gradient centrifugation, Native PAGE and 77 K fluorescence with the apparent oxygen consumption, the nature of the enhancement of the apparent oxygen consumption activity of PSI by surfactants has been analyzed. Aggregated PSI particles can be dispersed by surfactant molecules into micelles, and the apparent oxygen consumption rate is higher for surfactant-solubilized PSI than for integral PSI particles. For DDM, PSI particles are solubilized mostly as the integral trimeric form. For TX, PSI particles are solubilized as incomplete trimeric and some monomeric forms. For the much harsher surfactant, SDS, PSI particles are completely solubilized as monomeric and its subunit forms. The enhancement of the oxygen consumption rate cannot be explained only by the effects of surfactant on the equilibrium between monomeric and trimeric forms of solubililized PSI. Care must be taken when the electron transfer activity of PSI is evaluated by methods based on oxygen consumption because the apparent oxygen consumption rate is influenced by uncoupled chlorophyll (Chl) from PSI, i.e., the larger the amount of uncoupled Chl, the higher the rate of apparent oxygen consumption. 77 K fluorescence spectra can be used to ensure that there is no uncoupled Chl present in the system. In order to eliminate the effect of trace uncoupled Chl, an efficient physical quencher of (1)O2, such as 1 mM NaN3, may be added into the mixture.
Green, Christopher T.; Böhlke, John Karl; Bekins, Barbara A.; Phillips, Steven P.
2010-01-01
Gradients in contaminant concentrations and isotopic compositions commonly are used to derive reaction parameters for natural attenuation in aquifers. Differences between field‐scale (apparent) estimated reaction rates and isotopic fractionations and local‐scale (intrinsic) effects are poorly understood for complex natural systems. For a heterogeneous alluvial fan aquifer, numerical models and field observations were used to study the effects of physical heterogeneity on reaction parameter estimates. Field measurements included major ions, age tracers, stable isotopes, and dissolved gases. Parameters were estimated for the O2 reduction rate, denitrification rate, O2 threshold for denitrification, and stable N isotope fractionation during denitrification. For multiple geostatistical realizations of the aquifer, inverse modeling was used to establish reactive transport simulations that were consistent with field observations and served as a basis for numerical experiments to compare sample‐based estimates of “apparent” parameters with “true“ (intrinsic) values. For this aquifer, non‐Gaussian dispersion reduced the magnitudes of apparent reaction rates and isotope fractionations to a greater extent than Gaussian mixing alone. Apparent and true rate constants and fractionation parameters can differ by an order of magnitude or more, especially for samples subject to slow transport, long travel times, or rapid reactions. The effect of mixing on apparent N isotope fractionation potentially explains differences between previous laboratory and field estimates. Similarly, predicted effects on apparent O2threshold values for denitrification are consistent with previous reports of higher values in aquifers than in the laboratory. These results show that hydrogeological complexity substantially influences the interpretation and prediction of reactive transport.
Chau, Sek Hung; Sluiter, Reinier L; Kievit, Wietske; Wensing, Michel; Teichert, Martina; Hugtenburg, Jacqueline G
2017-05-01
The present study aimed to assess the cost effectiveness of concomitant proton pump inhibitor (PPI) treatment in low-dose acetylsalicylic acid (LDASA) users at risk of upper gastrointestinal (UGI) adverse effects as compared with no PPI co-medication with attention to the age-dependent influence of PPI-induced adverse effects. We used a Markov model to compare the strategy of PPI co-medication with no PPI co-medication in older LDASA users at risk of UGI adverse effects. As PPIs reduce the risk of UGI bleeding and dyspepsia, these risk factors were modelled together with PPI adverse effects for LDASA users 60-69, 70-79 (base case) and 80 years and older. Incremental cost-utility ratios (ICURs) were calculated as cost per quality-adjusted life-year (QALY) gained per age category. Furthermore, a budget impact analysis assessed the expected changes in expenditure of the Dutch healthcare system following the adoption of PPI co-treatment in all LDASA users potentially at risk of UGI adverse effects. PPI co-treatment of 70- to 79-year-old LDASA users, as compared with no PPI, resulted in incremental costs of €100.51 at incremental effects of 0.007 QALYs with an ICUR of €14,671/QALY. ICURs for 60- to 69-year-old LDASA users were €13,264/QALY and €64,121/QALY for patients 80 years and older. Initiation of PPI co-treatment for all Dutch LDASA users of 60 years and older at risk of UGI adverse effects but not prescribed a PPI (19%) would have cost €1,280,478 in the first year (year 2013 values). PPI co-medication in LDASA users at risk of UGI adverse effects is generally cost effective. However, this strategy becomes less cost effective with higher age, particularly in patients aged 80 years and older, mainly due to the increased risks of PPI-induced adverse effects.
Caregivers' willingness-to-pay for Alzheimer's disease medications in Canada.
Oremus, Mark; Tarride, Jean-Eric; Pullenayegum, Eleanor; Clayton, Natasha; Mugford, Gerry; Godwin, Marshall; Huan, Allen; Bacher, Yves; Villalpando, Juan-Manual; Gill, Sudeep S; Lanctôt, Krista L; Herrmann, Nathan; Raina, Parminder
2015-01-01
We studied caregivers' willingness-to-pay for Alzheimer's disease drug therapy. We recruited 216 caregivers of persons with mild or moderate Alzheimer's disease and presented them with four scenarios describing a hypothetical Alzheimer's disease medication. The scenarios described the medication as capable of either treating the symptoms of disease or modifying the course of disease. The scenarios also presented two different probabilities of adverse effects occurrence, i.e., 0% or 30%. Most caregivers said they would pay out-of-pocket for the medication, with support for such payment ranging from 68% to 93%, depending on the specific scenario. The highest level of support was for the 'disease modifying and no adverse effects' scenario, while the lowest level was for the 'symptom treatment and 30% chance of adverse effects' scenario. On average, caregivers' monthly willingness-to-pay out-of-pocket for the medication ranged from $214 to $277 (Canadian dollars). Dollar amounts were highest for the 'disease modifying and no adverse effects' scenario and lowest for the 'symptom treatment and 30% chance of adverse effects' scenario. Support for out-of-pocket payment and specific dollar amounts were highest when the medication did not involve adverse effects. Caregivers placed more value on the absence of adverse effects than on drug efficacy. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela
2017-09-02
BACKGROUND This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. MATERIAL AND METHODS The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. RESULTS Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. CONCLUSIONS We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy.
Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela
2017-01-01
Background This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. Material/Methods The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. Results Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. Conclusions We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy. PMID:28864818
Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes.
Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C
2014-01-01
Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications.
Meglumine Exerts Protective Effects against Features of Metabolic Syndrome and Type II Diabetes
Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C.
2014-01-01
Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications. PMID:24587200
Structural and ultrastructural study of rat testes influenced by electromagnetic radiation.
Almášiová, Viera; Holovská, Katarína; Cigánková, Viera; Račeková, Enikö; Fabianová, Kamila; Martončíková, Marcela
2014-01-01
This study was conducted to investigate the influence of whole-body electromagnetic radiation (EMR) on testicular parenchyma of Wistar rats. Sexually mature rats were subjected to pulsed electromagnetic field at frequency of 2.45 GHz and mean power density 2.8 mW/cm(2) by 3-h daily applications for 3 wk. Tissue samples were obtained 3 h after the last irradiation and processed by histological techniques for light and transmission electron microscopy. Testes showed apparent degenerative changes of seminiferous epithelium. The seminiferous tubules were mostly irregular in shape, and seminiferous epithelium contained a number of empty spaces of different size. Subsequently, groups of sloughed epithelial cells were often found inside the lumina of tubules. Except for relatively unchanged Sertoli cells, some locations of basal compartment of seminiferous epithelium contained shriveled Sertoli cells with dark cytoplasm. These areas showed degenerative features including necrotizing and shriveled spermatogonia surrounded by empty irregular spaces, and undulating basement membrane. The intertubular spaces were enlarged but interstitial Leydig cells did not show any marked morphological changes. Evidence demonstrates the adverse effects of EMR on testicular parenchyma in rats.
Magin, Parker J; Adams, Jon; Heading, Gaynor S; Pond, Dimity C; Smith, Wayne
2006-06-01
The aim of this study was to explore the use of complementary and alternative medicine (CAM) therapies in patients with acne, psoriasis, or atopic eczema and the attitudes about CAM of these patients. This was a qualitative study, utilizing semistructured interviews and thematic analysis. Patients were recruited from the practices of dermatologists and general practitioners in a noncapital Australian city. Twenty-six (26) interviews were conducted with patients with acne, 29 with psoriasis, and 7 with atopic eczema. Use of CAM therapies was common. Participants tended to value CAM over orthodox therapies because of their preference for natural approaches to their skin diseases and the perceived lesser potential for adverse effects of CAM therapies. Respondents with acne were more confident about the efficacy of CAM than were those with psoriasis or eczema. The resulting sense of control attenuated psychologic sequelae of acne. This was not apparent in psoriasis or eczema. Practitioners should be cognizant of the likely use of CAM and its implications (including the potential for attenuation of psychologic morbidity) in their patients who have skin diseases.
Lewis, D F; Brody, K; Edwards, M S; Brouillette, R M; Burlison, S; London, S N
1996-11-01
To assess the effectiveness of corticosteroids in patients with preterm premature rupture of membranes (PROM) after treatment with a broad-spectrum antibiotic, ampicillin-sulbactam. A randomized clinical trial of corticosteroids in patients with preterm PROM was undertaken after treating these patients for a minimum of 12 hours with ampicillin-sulbactam. No digital vaginal examinations were performed on these patients. Antibiotics were continued for 7 days and the steroids were repeated weekly. No tocolytics were used. The primary outcome measure was the incidence of respiratory distress syndrome (RDS). Secondary outcome measures included latency period and neonatal and maternal infectious morbidity. Seventy-seven patients were enrolled and data about their pregnancies were analyzed. No statistically significant difference in latency period was noted (14.7 days in the steroid group, 15.8 days in the no-steroid group). Both neonatal and maternal infectious morbidity were similar. A significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were observed in the steroid group. These data suggest that treating preterm PROM patients with a broad-spectrum antibiotic before corticosteroids decreases RDS without apparent adverse sequelae.
Standardizing the care of detox patients to achieve quality outcomes.
Becker, Kathy; Semrow, Sue
2006-03-01
Providing appropriate treatment for detoxification patients is both challenging and difficult because alcohol abuse and dependence are largely underestimated in the acute hospital setting. Alcohol withdrawal syndrome is treated not only by addictionologists on chemical dependency units, but also by primary care physicians in acute inpatient settings. The need for consistent inpatient treatment through the use of identified protocols can help provide safe and effective care. The need for consistent, inpatient medical-surgical detoxification treatment in our organization became apparent with the staff's identification of patient care concerns. Using an organizational approach, a multidisciplinary team was created to standardize the care of detoxification patients, beginning with patient admission and ending with discharge and referral for outpatient management. Standardization would ensure consistent assessment and intervention, and improve communication among the clinical team members. A protocol was developed for both the emergency department and the inpatient units. The goals of the team were to decrease the adverse events related to detoxification, such as seizures and aggression, and provide a consistent method of treatment for staff to follow.
How the initial level of visibility and limited resource affect the evolution of cooperation
NASA Astrophysics Data System (ADS)
Han, Dun; Li, Dandan; Sun, Mei
2016-06-01
This work sheds important light on how the initial level of visibility and limited resource might affect the evolution of the players’ strategies under different network structure. We perform the prisoner’s dilemma game in the lattice network and the scale-free network, the simulation results indicate that the average density of death in lattice network decreases with the increases of the initial proportion of visibility. However, the contrary phenomenon is observed in the scale-free network. Further results reflect that the individuals’ payoff in lattice network is significantly larger than the one in the scale-free network. In the lattice network, the visibility individuals could earn much more than the invisibility one. However, the difference is not apparent in the scale-free network. We also find that a high Successful-Defection-Payoff (SDB) and a rich natural environment have relatively larger deleterious cooperation effects. A high SDB is beneficial to raising the level of visibility in the heterogeneous network, however, that has adverse visibility consequences in homogeneous network. Our result reveals that players are more likely to cooperate voluntarily under homogeneous network structure.
NASA Technical Reports Server (NTRS)
Hardman, P.; Klement, B. J.; Spooner, B. S.
1993-01-01
Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.
Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem.
Pelin, Marco; Brovedani, Valentina; Sosa, Silvio; Tubaro, Aurelia
2016-02-04
Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential.
FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology
Knudsen, Thomas B.; Keller, Douglas A.; Sander, Miriam; Carney, Edward W.; Doerrer, Nancy G.; Eaton, David L.; Fitzpatrick, Suzanne Compton; Hastings, Kenneth L.; Mendrick, Donna L.; Tice, Raymond R.; Watkins, Paul B.; Whelan, Maurice
2015-01-01
FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology. PMID:25628403
Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem
Pelin, Marco; Brovedani, Valentina; Sosa, Silvio; Tubaro, Aurelia
2016-01-01
Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential. PMID:26861356
Orrock, John L; Dutra, Humberto P; Marquis, Robert J; Barber, Nicholas
2015-04-01
Direct and indirect effects can play a key role in invasions, but experiments evaluating both are rare. We examined the roles of direct competition and apparent competition by exotic Amur honeysuckle (Lonicera maackii) by manipulating (1) L. maackii vegetation, (2) presence of L. maackii fruits, and (3) access to plants by small mammals and deer. Direct competition with L. maackii reduced the abundance and richness of native and exotic species, and native consumers significantly reduced the abundance and richness of native species. Although effects of direct competition and consumption were more pervasive, richness of native plants was also reduced through apparent competition, as small-mammal consumers reduced richness only when L. maackii fruits were present. Our experiment reveals the multiple, interactive pathways that affect the success and impact of an invasive exotic plant: exotic plants may directly benefit from reduced attack by native consumers, may directly exert strong competitive effects on native plants, and may also benefit from apparent competition.
de Almeida, Tailah Bernardo; de Azevedo, Marcelo Costa Velho Mendes; Pinto, Jorge Francisco da Cunha; Ferry, Fernando Rafael de Almeida; da Silva, Guilherme Almeida Rosa; de Castro, Izana Junqueira; Baker, Paxton; Tanuri, Amilcar; Haas, David W; Cardoso, Cynthia C
2018-06-03
There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.
Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara
2017-01-01
ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. PMID:28538774
Integrative Approaches to Evaluating Neurotoxicity Data for Risk Assessment.
Risk assessment classically has been based on single adverse outcomes identified as the Lowest Observable Adverse Effect Level (LOAEL) or the highest dose level in a credible study producing a No Observable Adverse Effect Level (NOAEL). While this approach has been useful overal...
Thurston, George D; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T; Rich, David; Ritz, Beate; Samet, Jonathan M; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert
2017-01-01
The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. Copyright ©ERS 2017.
Thurston, George D.; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D.; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W.; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J.; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T.; Rich, David; Ritz, Beate; Samet, Jonathan M.; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert
2017-01-01
The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies. This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. PMID:28077473
De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo
2018-05-01
Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.
Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov
2010-06-01
Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.
Surveillance of adverse effects during a vaccination campaign against meningitis C.
Laribière, Anne; Miremont-Salamé, Ghada; Reyre, Hadrien; Abouelfath, Abdelilah; Liège, Ludovic; Moore, Nicholas; Haramburu, Françoise
2005-12-01
To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.
Iwamoto, Naoki; Kawakami, Atsushi
2016-06-01
Abatacept (ABT) is a recombinant fusion protein comprising the extracellular domain of human CTLA4, which inhibits the activation of T cells. Several clinical trials have provided evidence of efficacy and safety of ABT in the patients with rheumatoid athritis (RA) with various clinical characteristics such as MTX inadequate responders (IR), TNF inhibitor-IR. Moreover, indirect comparison of ABT to other biologics reported in Cochrane review revealed that ABT has better safety profile in serious adverse events and serious infection Thus the features of ABT in the treatment of RA have gradually become apparent and knowledge of these features is helpful for better use of biologics. In this review we will discuss the efficacy and safety of ABT in the management of RA.
Visibility graph analysis of very short-term heart rate variability during sleep
NASA Astrophysics Data System (ADS)
Hou, F. Z.; Li, F. W.; Wang, J.; Yan, F. R.
2016-09-01
Based on a visibility-graph algorithm, complex networks were constructed from very short-term heart rate variability (HRV) during different sleep stages. Network measurements progressively changed from rapid eye movement (REM) sleep to light sleep and then deep sleep, exhibiting promising ability for sleep assessment. Abnormal activation of the cardiovascular controls with enhanced 'small-world' couplings and altered fractal organization during REM sleep indicates that REM could be a potential risk factor for adverse cardiovascular event, especially in males, older individuals, and people who are overweight. Additionally, an apparent influence of gender, aging, and obesity on sleep was demonstrated in healthy adults, which may be helpful for establishing expected sleep-HRV patterns in different populations.
ERIC Educational Resources Information Center
Krogh, Carmen M. E.; Gillis, Lorrie; Kouwen, Nicholas; Aramini, Jeff
2011-01-01
Industrial wind turbines have been operating in many parts of the globe. Anecdotal reports of perceived adverse health effects relating to industrial wind turbines have been published in the media and on the Internet. Based on these reports, indications were that some residents perceived they were experiencing adverse health effects. The purpose…
20 CFR 655.200 - General description of this subpart and definition of terms.
Code of Federal Regulations, 2011 CFR
2011-04-01
... designee. Adverse effect rate means the wage rate which the OFLC Administrator has determined must be... the prevailing wage rate in the area and/or occupation is the adverse effect rate, if the use (or non... may determine that a wage rate higher than the prevailing wage rate is the adverse effect rate if the...
20 CFR 655.200 - General description of this subpart and definition of terms.
Code of Federal Regulations, 2012 CFR
2012-04-01
... designee. Adverse effect rate means the wage rate which the OFLC Administrator has determined must be... the prevailing wage rate in the area and/or occupation is the adverse effect rate, if the use (or non... may determine that a wage rate higher than the prevailing wage rate is the adverse effect rate if the...
20 CFR 655.200 - General description of this subpart and definition of terms.
Code of Federal Regulations, 2013 CFR
2013-04-01
... designee. Adverse effect rate means the wage rate which the OFLC Administrator has determined must be... the prevailing wage rate in the area and/or occupation is the adverse effect rate, if the use (or non... may determine that a wage rate higher than the prevailing wage rate is the adverse effect rate if the...
20 CFR 655.200 - General description of this subpart and definition of terms.
Code of Federal Regulations, 2010 CFR
2010-04-01
... designee. Adverse effect rate means the wage rate which the OFLC Administrator has determined must be... the prevailing wage rate in the area and/or occupation is the adverse effect rate, if the use (or non... may determine that a wage rate higher than the prevailing wage rate is the adverse effect rate if the...
32 CFR 223.6 - Procedures-identifying and controlling DoD UCNI.
Code of Federal Regulations, 2013 CFR
2013-07-01
... information could reasonably be expected to have an adverse effect on the health and safety of the public or... nuclear weapons in DoD custody. This is called the “adverse effects test.” (2) DoD UCNI shall be... adverse effects test. (2) Information shall be protected as DoD UCNI if it qualifies for one or more of...
32 CFR 223.6 - Procedures-identifying and controlling DoD UCNI.
Code of Federal Regulations, 2014 CFR
2014-07-01
... information could reasonably be expected to have an adverse effect on the health and safety of the public or... nuclear weapons in DoD custody. This is called the “adverse effects test.” (2) DoD UCNI shall be... adverse effects test. (2) Information shall be protected as DoD UCNI if it qualifies for one or more of...
Transmission of vibration through glove materials: effects of contact force.
Md Rezali, Khairil Anas; Griffin, Michael J
2018-04-26
This study investigated effects of applied force on the apparent mass of the hand, the dynamic stiffness of glove materials and the transmission of vibration through gloves to the hand. For 10 subjects, 3 glove materials and 3 contact forces, apparent masses and glove transmissibilities were measured at the palm and at a finger at frequencies in the range 5-300 Hz. The dynamic stiffnesses of the materials were also measured. With increasing force, the dynamic stiffnesses of the materials increased, the apparent mass at the palm increased at frequencies greater than the resonance and the apparent mass at the finger increased at low frequencies. The effects of force on transmissibilities therefore differed between materials and depended on vibration frequency, but changes in apparent mass and dynamic stiffness had predictable effects on material transmissibility. Depending on the glove material, the transmission of vibration through a glove can be increased or decreased when increasing the applied force. Practitioner summary: Increasing the contact force (i.e. push force or grip force) can increase or decrease the transmission of vibration through a glove. The vibration transmissibilities of gloves should be assessed with a range of contact forces to understand their likely influence on the exposure of the hand and fingers to vibration.
Search strategies to identify information on adverse effects: a systematic review
Golder, Su; Loke, Yoon
2009-01-01
Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498
Childhood abuse affects emotional closeness with family in mid- and later life.
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.
Lin, Abigail; Turner, Zahava; Doerrer, Sarah C; Stanfield, Anthony; Kossoff, Eric H
2017-03-01
Many centers still admit children for several days to start the ketogenic diet. The exact incidence of adverse effects during the admission and their potential later impact on seizure reduction has not been widely studied. We performed a retrospective study of children with intractable epilepsy electively admitted for ketogenic diet initiation at our institution from 2011 to 2016. Charts were reviewed for adverse effects during the admission period and then examined for seizure reduction and compliance at three months. A rating scale (1 to 4) was created for severity of any adverse events. A total of 158 children were included, with the mean age 4.6 years. Potentially attributable adverse effects occurred in 126 (80%) children, most commonly emesis, food refusal, and hypoglycemia. Seventy-three (46%) children received some form of intervention by the medical team, most commonly the administration of juice (24%). Younger age was correlated with an increased likelihood of moderate to severe adverse effects during admission, often repeated hypoglycemia (3.6 versus 4.9 years, P = 0.04). Fasting was more likely to result in lethargy and a single blood glucose in the 30 to 40 mg/dL range, but it was not correlated with emesis, repeated hypoglycemia, or higher adverse effect scores. There was no statistically significant correlation between the severity of adverse effects and the three-month seizure reduction. Mild easily treated adverse effects occurred in most children admitted for the ketogenic diet. Younger children were at greater risk for significant difficulties and should be monitored closely. Because fasting led to more lethargy and hypoglycemia, it may be prudent to avoid this in younger children. Copyright © 2017 Elsevier Inc. All rights reserved.
Dai, Li; Huang, Ying; Wang, Ying; Han, Huan-Li; Li, Qu-Bei; Jiang, Yong-Hui
2014-01-01
To retrospectively assess serious systemic adverse effects of standardized dust-mite vaccine in children with asthma. Medical records of 704 children (5-17 years in age) with asthma between January, 2005 and December, 2011 were reviewed. Serious systemic adverse events following treatment with a standardized dust-mite vaccine in these children were analyzed. A total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3), 318 (94.6%) were not serious (below level 3), and no single case of anaphylactic shock (level 4) was recorded. Systemic adverse events occurred most frequently in the 5 to 11-year age group and in the summer season (from June to August). In the 18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after the vaccine injection, and other major clinical symptoms included cough, wheezing and urticaria. All children with serious systemic adverse effects were given inhaled hormone and atomized short-acting beta agonists, oral antihistamines, intravenous dexamethasone and/or intramuscular adrenaline. After these treatments, the clinical symptoms were significantly relieved. The rate of serious systemic adverse events following allergen-specific immunotherapy is relatively low in children with allergic asthma. Conventional medications are effective in managing these immunotherapy-associated adverse events.
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.
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
Effect of reactivity loss on apparent reaction order of burning char particles
DOE Office of Scientific and Technical Information (OSTI.GOV)
Murphy, Jeffrey J.; Shaddix, Christopher R.
Considerable debate still exists in the char combustion community over the expected and observed reaction orders of carbon reacting with oxygen. In particular, very low values of the reaction order (approaching zero) are commonly observed in char combustion experiments. These observations appear to conflict with porous catalyst theory as first expressed by Thiele, which suggests that the apparent reaction order must be greater than 0.5. In this work, we propose that this conflict may be resolved by considering the decrease in char reactivity with burnout due to ash effects, thermal annealing, or other phenomena. Specifically, the influence of ash dilutionmore » of the available surface area on the apparent reaction order is explored. Equations describing the ash dilution effect are combined with a model for particle burnout based on single-film nth-order Arrhenius char combustion and yield an analytical expression for the effective reaction order. When this expression is applied for experimental conditions reflecting combustion of individual pulverized coal particles in an entrained flow reactor, the apparent reaction order is shown to be lower than the inherent char matrix reaction order, even for negligible extents of char conversion. As char conversion proceeds and approaches completion, the apparent reaction order drops precipitously past zero to negative values. Conversely, the inclusion of the ash dilution model has little effect on the char conversion profile or char particle temperature until significant burnout has occurred. Taken together, these results suggest that the common experimental observation of low apparent reaction orders during char combustion is a consequence of the lack of explicit modeling of the decrease in char reactivity with burnout. (author)« less
Verdenelli, Maria Cristina; Cecchini, Cinzia; Coman, Maria Magdalena; Silvi, Stefania; Orpianesi, Carla; Coata, Giuliana; Cresci, Alberto; Di Renzo, Gian Carlo
2016-10-01
The purpose of this study was to investigate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether it promotes normalization and maintenance of pH and Nugent score. A single-arm, open-label controlled towards the baseline (pre-post) study including 35 apparently healthy women was conducted. Each woman was examined three times during the study. Women were instructed to receive daily for 7 days, the probiotic suppositories SYNBIO(®) gin (Lactobacillus rhamnosus IMC 501(®) and Lactobacillus paracasei IMC 502(®)). Vaginal swabs were collected during visit 1, 2, and 3 to determine the total lactobacilli count, the presence of the two administered bacteria, the measure of the pH, and the estimation of Nugent score. Evaluation of treatment tolerability was based on analysis of the type and occurrence of adverse events. The probiotic vaginal suppository was well tolerated and no side effects were reported. Intermediate Nugent score was registered in 40 % of women at visit 1 and these intermediate scores reverted to normal at day 7 (end of treatment) in 20 % of subjects. Administration of SYNBIO(®) gin contributed to a significant increase in the lactobacilli level at visit 2. Molecular typing revealed the presence of the two strains originating from SYNBIO(®) gin in 100 % of women at visit 2 and 34 % at visit 3. No significant changes were registered for pH between visits. The SYNBIO(®) gin product is safe for daily use in healthy women and it could be useful to restore and maintain a normal vaginal microbiota.
Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, José M.; Fichera, Epifanio; Reed, Steven G.; Coler, Rhea N.; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G.; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav
2017-01-01
The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the “natural infection”. PMID:29176865
Wong, Dana E; Talbert, Joey N; Goddard, Julie M
2013-06-01
Active packaging is utilized to overcome limitations of traditional processing to enhance the health, safety, economics, and shelf life of foods. Active packaging employs active components to interact with food constituents to give a desired effect. Herein we describe the development of an active package in which lactase is covalently attached to low-density polyethylene (LDPE) for in-package production of lactose-free dairy products. The specific goal of this work is to increase the total protein content loading onto LDPE using layer by layer (LbL) deposition, alternating polyethylenimine, glutaraldehyde (GL), and lactase, to enhance the overall activity of covalently attached lactase. The films were successfully oxidized via ultraviolet light, functionalized with polyethylenimine and glutaraldehyde, and layered with immobilized purified lactase. The total protein content increased with each additional layer of conjugated lactase, the 5-layer sample reaching up to 1.3 μg/cm2 . However, the increase in total protein did not lend to an increase in overall lactase activity. Calculated apparent Km indicated the affinity of immobilized lactase to substrate remains unchanged when compared to free lactase. Calculated apparent turnover numbers (kcat ) showed with each layer of attached lactase, a decrease in substrate turnover was experienced when compared to free lactase; with a decrease from 128.43 to 4.76 s(-1) for a 5-layer conjugation. Our results indicate that while LbL attachment of lactase to LDPE successfully increases total protein mass of the bulk material, the adverse impact in enzyme efficiency may limit the application of LbL immobilization chemistry for bioactive packaging use. © 2013 Institute of Food Technologists®
Taenia solium taeniosis/cysticercosis and the co-distribution with schistosomiasis in Africa.
Braae, Uffe Christian; Saarnak, Christopher F L; Mukaratirwa, Samson; Devleesschauwer, Brecht; Magnussen, Pascal; Johansen, Maria Vang
2015-06-12
This study aimed to map the distribution of Taenia solium taeniosis/cysticercosis and the co-distribution with schistosomiasis in Africa. These two major neglected tropical diseases are presumed to be widely distributed in Africa, but currently the level of co-distribution is unclear. A literature search on T. solium taeniosis/cysticercosis was performed to compile all known studies on the presence of T. solium and apparent prevalence of taeniosis and porcine cysticercosis in Africa. Studies were geo-referenced using an online gazetteer. A Bayesian framework was used to combine the epidemiological data on the apparent prevalence with external information on test characteristics to estimate informed district-level prevalence of taeniosis and porcine cysticercosis. Districts with T. solium taeniosis/cysticercosis presence were cross-referenced with the Global Neglected Tropical Diseases Database for schistosomiasis presence. The search strategies identified 141 reports of T. solium in Africa from 1985 to 2014 from a total of 476 districts in 29 countries, 20 with porcine cysticercosis, 22 with human cysticercosis, and 16 with taeniosis, in addition to 2 countries identified from OIE reports. All 31 countries were considered, on national scale, to have co-distribution with schistosomiasis. Presence of both parasites was confirmed in 124 districts in 17 countries. The informed prevalence of taeniosis and porcine cysticercosis were estimated for 14 and 41 districts in 10 and 13 countries, respectively. With the paucity of data, T. solium infection is grossly under-reported and expected to be more widespread than this study suggests. In areas where co-distribution occurs there is a need for increased emphasis on evaluation of integrated intervention approaches for these two helminth infections and allocation of resources for evaluating the extent of adverse effects caused by mass drug administration.
Robin, Elisabeth M; Pey, Pascaline B; de Fornel-Thibaud, Pauline; Moissonnier, Pierre H M; Freiche, Valérie
2018-02-01
CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for evaluation because of a 2-month history of regurgitation and weight loss, despite no apparent change in appetite. The dog had received antiemetic and antacid treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a low body condition score (2/5), but other findings were unremarkable. Diffuse, global esophageal dilatation was noted on plain thoracic radiographs, and normal motility was confirmed through videofluoroscopic evaluation of swallowing. Transhepatic ultrasonographic and CT examination revealed a circumferential, intraparietal lesion in the distal portion of the esophagus causing distal esophageal or cardial subobstruction and no metastases. Incisional biopsy of the lesion was performed, and findings of histologic examination supported a diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous possible complications associated with esophageal surgery, the decision was made to palliatively treat the dog by transcardial placement of a self-expanding, covered, nitinol esophageal stent under endoscopic guidance. Two weeks after stent placement, radiography revealed complete migration of the stent into the gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in place. Twenty-four months after initial stent placement, the dog had a healthy body condition and remained free of previous clinical signs. CLINICAL RELEVANCE Diffuse benign muscular neoplasia should be considered as a differential diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the dog of this report, transcardial stent placement resulted in resolution of the clinical signs, with no apparent adverse effect on digestive function. The described procedure could be beneficial for nonsurgical treatment of benign esophageal tumors in dogs.
Nakaoka, Masahiro
2018-01-01
Coastal fisheries are in decline worldwide, and aquaculture has become an increasingly popular way to meet seafood demand. While finfish aquaculture can have substantial adverse effects on coastal ecosystems due mostly to necessary feed inputs, bivalves graze on natural phytoplankton and are often considered for their positive ecosystem services. We conducted two independent studies to investigate the effects of long-line Crassostrea gigas oyster aquaculture on Zostera marina seagrass beds and associated epibiont communities in Akkeshi-ko estuary, Japan. Results from both studies yielded no evidence of an effect of oyster aquaculture on the morphology, density, or biomass of Z. marina, but significant differences were apparent in the epibiont community. Reference seagrass beds located away from aquaculture had higher seagrass epiphyte loads and higher abundances of amphipods. Conversely, seagrass beds below aquaculture lines had higher sessile polychaete biomass and higher isopod abundances. Our results suggest that the presence of oyster aquaculture may have indirect effects on seagrass by changing epibiont community composition and relative abundances of species. One proposed mechanism is that cultured oysters feed on epiphytic diatoms and epiphyte propagules before they can settle on the seagrass, which reduces epiphyte loads and influences subsequent faunal settlement. If carefully implemented and monitored, long-line oyster aquaculture may be a sustainable option to consider as bivalve aquaculture expands to meet global seafood demand, but further work is needed to fully assess and generalize the community-level effects on seagrass epibionts. PMID:29795609
Smith, Carter S; Ito, Minako; Namba, Mizuho; Nakaoka, Masahiro
2018-01-01
Coastal fisheries are in decline worldwide, and aquaculture has become an increasingly popular way to meet seafood demand. While finfish aquaculture can have substantial adverse effects on coastal ecosystems due mostly to necessary feed inputs, bivalves graze on natural phytoplankton and are often considered for their positive ecosystem services. We conducted two independent studies to investigate the effects of long-line Crassostrea gigas oyster aquaculture on Zostera marina seagrass beds and associated epibiont communities in Akkeshi-ko estuary, Japan. Results from both studies yielded no evidence of an effect of oyster aquaculture on the morphology, density, or biomass of Z. marina, but significant differences were apparent in the epibiont community. Reference seagrass beds located away from aquaculture had higher seagrass epiphyte loads and higher abundances of amphipods. Conversely, seagrass beds below aquaculture lines had higher sessile polychaete biomass and higher isopod abundances. Our results suggest that the presence of oyster aquaculture may have indirect effects on seagrass by changing epibiont community composition and relative abundances of species. One proposed mechanism is that cultured oysters feed on epiphytic diatoms and epiphyte propagules before they can settle on the seagrass, which reduces epiphyte loads and influences subsequent faunal settlement. If carefully implemented and monitored, long-line oyster aquaculture may be a sustainable option to consider as bivalve aquaculture expands to meet global seafood demand, but further work is needed to fully assess and generalize the community-level effects on seagrass epibionts.
Interface-Dependent Effective Mobility in Graphene Field-Effect Transistors
NASA Astrophysics Data System (ADS)
Ahlberg, Patrik; Hinnemo, Malkolm; Zhang, Shi-Li; Olsson, Jörgen
2018-03-01
By pretreating the substrate of a graphene field-effect transistor (G-FET), a stable unipolar transfer characteristic, instead of the typical V-shape ambipolar behavior, has been demonstrated. This behavior is achieved through functionalization of the SiO2/Si substrate that changes the SiO2 surface from hydrophilic to hydrophobic, in combination with postdeposition of an Al2O3 film by atomic layer deposition (ALD). Consequently, the back-gated G-FET is found to have increased apparent hole mobility and suppressed apparent electron mobility. Furthermore, with addition of a top-gate electrode, the G-FET is in a double-gate configuration with independent top- or back-gate control. The observed difference in mobility is shown to also be dependent on the top-gate bias, with more pronounced effect at higher electric field. Thus, the combination of top and bottom gates allows control of the G-FET's electron and hole mobilities, i.e., of the transfer behavior. Based on these observations, it is proposed that polar ligands are introduced during the ALD step and, depending on their polarization, result in an apparent increase of the effective hole mobility and an apparent suppressed effective electron mobility.
Gas Phase Pressure Effects on the Apparent Thermal Conductivity of JSC-1A Lunar Regolith Simulant
NASA Technical Reports Server (NTRS)
Yuan, Zeng-Guang; Kleinhenz, Julie E.
2011-01-01
Gas phase pressure effects on the apparent thermal conductivity of a JSC-1A/air mixture have been experimentally investigated under steady state thermal conditions from 10 kPa to 100 kPa. The result showed that apparent thermal conductivity of the JSC-1A/air mixture decreased when pressure was lowered to 80 kPa. At 10 kPa, the conductivity decreased to 0.145 W/m/degree C, which is significantly lower than 0.196 W/m/degree C at 100 kPa. This finding is consistent with the results of previous researchers. The reduction of the apparent thermal conductivity at low pressures is ascribed to the Knudsen effect. Since the characteristic length of the void space in bulk JSC-1A varies over a wide range, both the Knudsen regime and continuum regime can coexist in the pore space. The volume ratio of the two regimes varies with pressure. Thus, as gas pressure decreases, the gas volume controlled by Knudsen regime increases. Under Knudsen regime the resistance to the heat flow is higher than that in the continuum regime, resulting in the observed pressure dependency of the apparent thermal conductivity.
Role of Viscous Dissipative Processes on the Wetting of Textured Surfaces
Grewal, H. S.; Nam Kim, Hong; Cho, Il-Joo; Yoon, Eui-Sung
2015-01-01
We investigate the role of viscous forces on the wetting of hydrophobic, semi-hydrophobic, and hydrophilic textured surfaces as second-order effects. We show that during the initial contact, the transition from inertia- to viscous-dominant regime occurs regardless of their surface topography and chemistry. Furthermore, we demonstrate the effect of viscosity on the apparent contact angle under quasi-static conditions by modulating the ratio of a water/glycerol mixture and show the effect of viscosity, especially on the semi-hydrophobic and hydrophobic textured substrates. The reason why the viscous force does not affect the apparent contact angle of the hydrophilic surface is explained based on the relationship between the disjoining pressure and surface chemistry. We further propose a wetting model that can predict the apparent contact angle of a liquid drop on a textured substrate by incorporating a viscous force component in the force balance equation. This model can predict apparent contact angles on semi-hydrophobic and hydrophobic textured surfaces exhibiting Wenzel state more accurately than the Wenzel model, indicating the importance of viscous forces in determining the apparent contact angle. The modified model can be applied for estimating the wetting properties of arbitrary engineered surfaces. PMID:26390958
Environmental Assessment of the General Plan and Maintenance of Patrick Air Force Base, Florida
2012-07-17
water consumption . Per the National Energy Conservation Policy Act, sustainable design principles and life-cycle cost- effective technologies will...attached EA concluded that no significant adverse effects will result. No significant adverse cumulative impacts will result from activities associated...resources will be considered an adverse effect , however, sufficient documentation had been received for Facilities 1322, 1327, 1330, 1425, 1432, 1437 and
referred a disputed no adverse effect finding to the ACHP pursuant to 36 CFR § 800.5(c)(3) or provided the ACHP a notice of an adverse effect pursuant to 36 CFR § 800.6(a)(1), the deadline for a response from , if the ACHP received a referral of a disputed no adverse effect finding five days before the shutdown
Dahl, Signe Kirk; Larsen, Janne Tidselbak; Petersen, Liselotte; Ubbesen, Mads Bonde; Mortensen, Preben Bo; Munk-Olsen, Trine; Musliner, Katherine Louise
2017-05-01
Early adversity is a known risk factor for unipolar depression. We examined the impact of 9 types of early adversity on risk for moderate to severe unipolar depression in adolescence or adulthood, and evaluated whether these effects were moderated by gender and adversity timing. We conducted a prospective, population-based cohort study using Danish national registers. The sample included all individuals born in Denmark between 1980 and 1998 (N=978,647). Exposure to early adversity was assessed from ages 0-15. Types of adversity included parental illness, incarceration, death, disability, and psychiatric diagnosis; family disruption; out-of-home care; and childhood abuse. Individuals were followed from age 15 until first in- or outpatient depression diagnosis (ICD-10 codes F32, F33) in a psychiatric hospital, death, emigration, or December 31st, 2013, whichever came first. Hazard ratios (HRs) were calculated using Cox regressions. All adversities were significantly associated with increased risk for moderate to severe adolescent/adult depression (HR range: 1.30-2.72), although the effects were attenuated after mutual adjustment (adjusted HR range: 1.06-1.70). None of the effects were moderated by gender. The effect of family disruption was strongest between ages 0-4 (HR=1.66, 95% CI=1.61-1.71), while the effect of out-of-home care was strongest between ages 10-14 (HR=2.45, 95% CI=2.28-2.64). Untreated and primary-care treated depression were not measured. Our results support past findings that multiple types of early adversity increase risk for moderate to severe unipolar depression in adolescence and adulthood. Certain adversities may be more harmful if they occur during specific developmental time periods. Copyright © 2017 Elsevier B.V. All rights reserved.
Potential adverse effects of omega-3 Fatty acids in dogs and cats.
Lenox, C E; Bauer, J E
2013-01-01
Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions. Copyright © 2013 by the American College of Veterinary Internal Medicine.
Cinnamon: A systematic review of adverse events.
Hajimonfarednejad, Mahdie; Ostovar, Mohadeseh; Raee, Mohammad Javad; Hashempur, Mohammad Hashem; Mayer, Johannes Gottfried; Heydari, Mojtaba
2018-04-05
Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Schreiber, R; Häussinger, D
1995-01-01
Short-term cultivated rat hepatocytes were allowed to endocytose fluorescein isothiocyanate (FITC)-coupled dextran and the apparent vesicular pH (pHves) was measured by single-cell fluorescence. After 2 h of exposure to FITC-dextran, the apparent pH in the vesicular compartments accessible to endocytosed FITC-dextran was 6.01 +/- 0.05 (n = 39) in normo-osmotic media. Hypo-osmotic exposure increased, whereas hyper-osmotic exposure decreased apparent pHves. by 0.18 +/- 0.02 (n = 26) and 0.12 +/- 0.01 (n = 23) respectively. Incubation of the cells with unlabelled dextran for 2h before a 2-h FITC-dextran exposure had no effect on apparent pHves and its osmosensitivity. When, however, hepatocytes were exposed to unlabelled dextran for 5 h after a 2 h exposure to FITC-dextran, in order to allow transport of endocytosed FITC-dextran to late endocytotic/lysosomal compartments, apparent pHves. decreased to 5.38 +/- 0.04 (n = 12) and the apparent pH in the vesicular compartment containing the dye was no longer sensitive to aniso-osmotic exposure. These findings indicate that the osomosensitivity of pHves. is apparently restricted to early endocytotic compartments. Aniso-osmotic regulation of apparent pHves. in freshly FITC-loaded hepatocytes was not accompanied by aniso-osmolarity-induced changes of the cytosolic free calcium concentration, and neither vasopressin nor extracellular ATP, which provoked a marked Ca2+ signal, affected apparent pHves. Dibutyryl-cyclic AMP (cAMP) or vanadate (0.5 mmol/l) were without effect on apparent pHves. and its osmosensitivity. However, pertussis toxin-treatment or genistein (but not daidzein) or the erbstatin analogue methyl 2,5-dihydroxycinnamate fully abolished the osmo-sensitivity of apparent pHves., but did not affect apparent pHves. It is concluded that regulation of pHves. by cell volume occurs in early endocytotic compartments, but probably not in lysosomes, and is mediated by a G-protein and tyrosine kinase-dependent, but Ca2+- and cAMP-independent mechanism. PMID:7542446
Pacurari, M; Qian, Y; Fu, W; Schwegler-Berry, D; Ding, M; Castranova, V; Guo, NL
2011-01-01
Multi-walled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level. PMID:22129238
Nie, Yaguang; Liu, Xiaodong; Sun, Liguang; Emslie, Steven D
2012-09-01
Total mercury (Hg) concentration and several other geochemical parameters were determined for five sediment profiles from the Antarctic Ross Sea region. Our data exhibit significant positive correlations between Hg concentration and total organic carbon (TOC) content in all profiles, suggesting the predominant role of organic matter (OM) as a Hg carrier. The OM in the sediments originates primarily from penguin guano and algae. High Hg content in guano and a positive correlation between Hg and a guano bio-element (phosphorus, P) in the ornithogenic sediment profiles (MB6, BI and CC) indicate that Hg was strongly influenced by guano input. The bottom sediments of MB6 with seal hairs contain relatively high Hg. This increase is attributed to the input of seal excrement, suggesting that sedimentary Hg may be an effective trophic-level indicator from seals to penguins. The enrichment factor (EF) for Hg was calculated and the results indicated apparent Hg enrichment in the sediment profiles from the Ross Sea region caused by bio-vectors such as penguins and seals. Compared with typical sediments from other sites in Antarctica and the SQGs (sediment quality guidelines), the total amount of Hg in our study area is still not considered to be adversely high. Copyright © 2012 Elsevier B.V. All rights reserved.
Association Between High Ambient Temperature and Risk of Stillbirth in California.
Basu, Rupa; Sarovar, Varada; Malig, Brian J
2016-05-15
Recent studies have linked elevated apparent temperatures with adverse birth outcomes, such as preterm delivery, but other birth outcomes have not been well studied. We examined 8,510 fetal deaths (≥20 weeks' gestation) to estimate their association with mean apparent temperature, a combination of temperature and humidity, during the warm season in California (May-October) from 1999 to 2009. Mothers whose residential zip codes were within 10 km of a meteorological monitor were included. Meteorological data were provided by the California Irrigation Management Information System, the US Environmental Protection Agency, and the National Climatic Data Center, while the California Department of Public Health provided stillbirth data. Using a time-stratified case-crossover study design, we found a 10.4% change (95% confidence interval: 4.4, 16.8) in risk of stillbirth for every 10°F (5.6°C) increase in apparent temperature (cumulative average of lags 2-6 days). Risk varied by maternal race/ethnicity and was greater for younger mothers, less educated mothers, and male fetuses. The highest risks were observed during gestational weeks 20-25 and 31-33. No associations were found during the cold season (November-April), and the observed associations were independent of air pollutants. This study adds to the growing body of literature identifying pregnant women and their fetuses as subgroups vulnerable to heat exposure. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Paul J.; Hicks, Rodney J.; Wirth, Andrew
2009-07-01
Purpose: To evaluate the impact of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Methods and Materials: Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Results: Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%).more » Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). Conclusions: FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.« less
Are we pharmacovigilant enough in ophthalmic practice?
Dubey, Ashok; Handu, Shailendra S
2013-01-01
No drug is absolutely safe. Pharmacovigilance is the science related to detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems. The ocular medications and devices can cause localized and systemic adverse effects. Not all adverse effects are known when a drug or device is launched in market because of limitations of clinical trials. Many adverse effects are recognized due to the spontaneous reporting of the vigilant doctors who observe and report such events encountered in their practice. Despite a large ophthalmic patient population base, India does not have robust adverse drug reaction (ADR) database because of lack of reporting culture. Government of India recently launched the Pharmacovigilance Programme of India (PvPI) to monitor ADRs and create awareness among the healthcare professionals about the importance of ADRs. Suspecting and reporting a possible drug reaction is very important in developing a safe and rational ophthalmic practice. PMID:23571233
[Occupational epidemiology: from analysis of the apparent to investigation of the unknown].
Zocchetti, C; Pesatori, Angela; Consonni, D
2003-01-01
This paper, as a contribution for the centenary celebration of the establishment of the "Clinica del Lavoro Luigi Devoto" in Milan (Italy), presents a brief 30 year history of the activities of its Department of Occupational Epidemiology. Studies and methodological contributions that characterized the first decade of activity are presented and grouped under the heading of analysis of known health effects. The second decade was dominated by the studies and activities that originated from the Seveso accident (dioxin), with an initial interest towards molecular epidemiology, which became increasingly relevant during the third decade when we addressed topics like melanoma, lung cancer, and benzene, in addition to dioxin. More traditional occupational approaches were not dismissed and cohort mortality studies are currently under way (textile dyeing and finishing industry, sulfuric acid, tetrafluoroethylene). Pros and cons of the epidemiologic approach are discussed in the context of occupational health and the strength of its methodological apparatus is suggested as a fundamental tool for studying adverse occupational health effects. In contrast, it is stressed how occupational epidemiology has been poorly used in the application of law 626/94. Considering that contemporary epidemiology is much more inclined towards the discovery of new work-related risks (electromagnetic fields, air pollution) than the description of known health effects, the paper suggests that occupational epidemiology enlarge its interests: people and environment outside the factories might be good candidates for study.
Apata, David Friday
2011-01-01
A feeding experiment was conducted to investigate the effect of fermented Terminalia catappa fruit meal (FTCM) with Aspergillus niger as replacement for maize on broiler growth performance, nutrient digestibility, and serum biochemical constituents. Dietary maize was replaced by FTCM at 0, 20, 40, 60, or 80%. One hundred and eighty one-day-old Shaver broiler chicks were randomly allocated to the five dietary treatments, three replicate groups of twelve chicks each for a 42-day period. There was no significant difference (P > .05) in the feed intake, weight gain, and feed; gain ratio between the broilers fed on 40% FTCM diet and the control group. The apparent digestibilities of nitrogen, crude fibre, and fat decreased significantly in broilers fed higher levels (>40%) of FTCM replacement diets compared with the control or lower FTCM diets. Serum concentrations of total protein, albumin, and globulin were decreased (P < .05) on 80% FTCM fed broilers. Serum cholesterol, creatinine, and glucose were not significantly (P > .05) altered among treatments. The activities of aspartate and alanine aminotransferases and alkaline phosphatase were significantly (P < .05) increased with higher FTCM replacement. The results indicate that FTCM could replace up to 40% of dietary maize in the diets of broiler chickens without adverse effect on growth performance or serum constituents. PMID:21350670
NASA Astrophysics Data System (ADS)
Mai, Kangsen; Zhang, Yanjiao; Chen, Wei; Xu, Wei; Ai, Qinghui; Zhang, Wenbing
2012-12-01
An 8-week feeding trial was conducted to investigate the effects of dietary soy isoflavones on feeding intake, growth performance, and digestion of juvenile Japanese flounder ( Paralichthys olivaceus). Four isonitrogenous (49% crude protein) and isoenergetic (20.1 MJ kg-1) diets were formulated to contain four graded levels of soy isoflavones, namely, 0, 1, 4 and 8 g soy isoflavones in 1 kg of diet. Each diet was randomly fed to triplicate tanks of fish (Initial average weight: 2.58 g ± 0.01 g), and each tank was stocked with 35 fish. No significant difference was observed among diets with levels of 0, 1 and 4 g kg-1 soy isoflavones in feed intake, weight gain, feed efficiency ratio (FER), proximate composition of fish whole body and apparent digestibility coefficients (ADC) of nutrients and energy ( P>0.05). However, high dietary soy isoflavones level (8 g kg-1) significantly depressed weight gain, FER, whole-body crude lipid content of fish and ADC of nutrients ( P<0.05). These results indicate that high level of dietary soy isoflavones (above 4 g kg-1) significantly depresses growth responses and FER of Japanese flounder. However, as the content of soy isoflavones in soybean meal is around 1 to 3 g kg-1, the adverse effects might be neglected when soybean products are used as a fish feed ingredient.
Jarratt, Michael
2004-11-01
A new topical solution containing 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% (Solagé) was compared with its active components, its vehicle, and hydroquinone (HQ) 3% in the treatment of solar lentigines. In a randomized, parallel-group, double-masked study, 216 subjects applied the treatments twice daily for 16 weeks and were followed up for a further 24 weeks. A significantly higher proportion (P < or = .05) of subjects achieved clinical success with mequinol 2%/tretinoin 0.01% compared with HQ 3% as measured by both the lesional pigmentation on the forearm and the physician global assessment at the end of treatment. The proportion of subjects achieving clinical success on the face in the mequinol 2%/tretinoin 0.01% group was consistently higher than that in the HQ 3% group. Some treatment effects remained at the end of the treatment-free follow-up, with trends apparent on the face in favor of mequinol 2%/tretinoin 0.01% over HQ 3%. In all treatment groups, skin-related adverse events were mild or moderate and transient. In conclusion, the mequinol 2%/tretinoin 0.01% solution is a highly effective and well-tolerated treatment for solar lentigines and related hyperpigmented lesions, being superior to HQ 3% for lesions on the forearm and of similar efficacy for lesions on the face.
West, K P; Khatry, S K; LeClerq, S C; Adhikari, R; See, L; Katz, J; Shrestha, S R; Pradhan, E K; Pokhrel, R P; Sommer, A
1992-01-01
A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects.
Apata, David Friday
2011-01-01
A feeding experiment was conducted to investigate the effect of fermented Terminalia catappa fruit meal (FTCM) with Aspergillus niger as replacement for maize on broiler growth performance, nutrient digestibility, and serum biochemical constituents. Dietary maize was replaced by FTCM at 0, 20, 40, 60, or 80%. One hundred and eighty one-day-old Shaver broiler chicks were randomly allocated to the five dietary treatments, three replicate groups of twelve chicks each for a 42-day period. There was no significant difference (P > .05) in the feed intake, weight gain, and feed; gain ratio between the broilers fed on 40% FTCM diet and the control group. The apparent digestibilities of nitrogen, crude fibre, and fat decreased significantly in broilers fed higher levels (>40%) of FTCM replacement diets compared with the control or lower FTCM diets. Serum concentrations of total protein, albumin, and globulin were decreased (P < .05) on 80% FTCM fed broilers. Serum cholesterol, creatinine, and glucose were not significantly (P > .05) altered among treatments. The activities of aspartate and alanine aminotransferases and alkaline phosphatase were significantly (P < .05) increased with higher FTCM replacement. The results indicate that FTCM could replace up to 40% of dietary maize in the diets of broiler chickens without adverse effect on growth performance or serum constituents.
Collision effects of wind-power generators and other obstacles on birds.
Drewitt, Allan L; Langston, Rowena H W
2008-01-01
There is extensive literature on avian mortality due to collision with man-made structures, including wind turbines, communication masts, tall buildings and windows, power lines, and fences. Many studies describe the consequences of bird-strike rather than address the causes, and there is little data based on long-term, standardized, and systematic assessments. Despite these limitations, it is apparent that bird-strike is a significant cause of mortality. It is therefore important to understand the effects of this mortality on bird populations. The factors which determine avian collision risk are described, including location, structural attributes, such as height and the use of lighting, weather conditions, and bird morphology and behavior. The results of incidental and more systematic observations of bird-strike due to a range of structures are presented and the implications of collision mortality for bird populations, particularly those of scarce and threatened species susceptible to collisions, are discussed. Existing measures for reducing collision mortality are described, both generally and specifically for each type of structure. It is concluded that, in some circumstances, collision mortality can adversely affect bird populations, and that greater effort is needed to derive accurate estimates of mortality levels locally, regionally, and nationally to better assess impacts on avian populations. Priority areas for future work are suggested, including further development of remote technology to monitor collisions, research into the causes of bird-strike, and the design of new, effective mitigation measures.
Konze, Anne-Kathrin; Rivkin, Wladislaw; Schmidt, Klaus-Helmut
2017-12-20
Previous meta-analytic findings have provided ambiguous evidence on job control as a buffering moderator of the adverse impact of job demands on psychological well-being. To disentangle these mixed findings, we examine the moderating effect of job control on the adverse effects of quantitative workload and emotional dissonance as distinct work-related demands on emotional exhaustion over time. Drawing on the job demands-control model, the limited strength model of self-control, and the matching principle we propose that job control can facilitate coping with work-related demands but at the same time may also require employees' self-control. Consequently, we argue that job control buffers the adverse effects of quantitative workload while it reinforces the adverse effects of emotional dissonance, which also necessitates self-control. We examine the proposed relations among employees from an energy supplying company ( N = 139) in a cross-lagged panel study with a six-month time lag. Our results demonstrate a mix of causal and reciprocal effects of job characteristics on emotional exhaustion over time. Furthermore, as suggested, our data provides evidence for contrasting moderating effects of job control. That is, job control buffers the adverse effects of quantitative workload while it reinforces the adverse effects of emotional dissonance on emotional exhaustion.
Rivkin, Wladislaw; Schmidt, Klaus-Helmut
2017-01-01
Previous meta-analytic findings have provided ambiguous evidence on job control as a buffering moderator of the adverse impact of job demands on psychological well-being. To disentangle these mixed findings, we examine the moderating effect of job control on the adverse effects of quantitative workload and emotional dissonance as distinct work-related demands on emotional exhaustion over time. Drawing on the job demands-control model, the limited strength model of self-control, and the matching principle we propose that job control can facilitate coping with work-related demands but at the same time may also require employees’ self-control. Consequently, we argue that job control buffers the adverse effects of quantitative workload while it reinforces the adverse effects of emotional dissonance, which also necessitates self-control. We examine the proposed relations among employees from an energy supplying company (N = 139) in a cross-lagged panel study with a six-month time lag. Our results demonstrate a mix of causal and reciprocal effects of job characteristics on emotional exhaustion over time. Furthermore, as suggested, our data provides evidence for contrasting moderating effects of job control. That is, job control buffers the adverse effects of quantitative workload while it reinforces the adverse effects of emotional dissonance on emotional exhaustion. PMID:29261116
De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo
2018-01-01
Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248
Raposo, Sarah M; Mackenzie, Corey S; Henriksen, Christine A; Afifi, Tracie O
2014-11-01
We aimed to examine the prevalence of several types of childhood adversity across adult cohorts, whether age moderates the effect of childhood adversity on mental health, the relationship between childhood adversity and psychopathology among older adults, the dose-response relationship between number of types of childhood adversities and mental disorders in later life, and whether lifetime mental health treatment reduces the odds of psychopathology among older survivors of childhood adversity. In a population-based, cross-sectional study on a nationally representative U.S. sample, we studied 34,653 community-dwelling Americans 20 years and older, including 7,080 adults 65 years and older from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Trained lay interviewers assessed past-year mood and anxiety disorders and lifetime personality disorders. Participants self-reported childhood adversity based on questions from the Adverse Childhood Experiences Study. Childhood adversity was prevalent across five age cohorts. In our adjusted models, age did not moderate the effect of childhood adversity on mental disorders. Older adults who experienced childhood adversity had higher odds of having mood (odds ratio: 1.73; 95% confidence interval: 1.32-2.28), anxiety (odds ratio: 1.48; 95% confidence interval: 1.20-1.83), and personality disorders (odds ratio: 2.11; 95% confidence interval: 1.75-2.54) after adjusting for covariates. An increasing number of types of childhood adversities was associated with higher odds of personality disorders and somewhat higher odds of anxiety disorders. Treatment-seeking was associated with a reduced likelihood of anxiety and, especially, mood disorders in older adult childhood adversity survivors. These results emphasize the importance of preventing childhood adversity and intervening once it occurs to avoid the negative mental health effects that can last into old age. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Abravanel, Benjamin T; Sinha, Rajita
2015-02-01
Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and "at-risk" remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. Copyright © 2014 Elsevier Ltd. All rights reserved.
Abravanel, Benjamin T.; Sinha, Rajita
2014-01-01
Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and “at-risk” remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. PMID:25528603
Ballard, C; Sauter, M; Scheltens, P; He, Y; Barkhof, F; van Straaten, E C W; van der Flier, W M; Hsu, C; Wu, S; Lane, R
2008-09-01
The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD). VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects. NCT00099216. 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance. Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.
Effects of contaminants on naiad mollusks (Unionidae): a review
Havlik, M.E.; Marking, L.L.
1987-01-01
Although the uptake, storage, and elimination of contaminants by naiad mollusks has been studied, relatively little information is available on toxicity. Contaminants appear to have destroyed some populations directly by exerting toxic effects, or indirectly by causing or contributing to the elimination of essential food organisms or host fish. The most frequently studied contaminants are Cd, Cu, Mn-Mn64, Pb-Pb210. and Zn-Zn65. Manganese seems to be most readily taken up and stored in tissues; no apparent damage has been reported from tissue concentrations of thousands of parts per million (ppm) and the element appears to be essential to metabolism. Zinc and cadmium also accumulate at high levels in tissues. Lead was never found to be lethal in the studies reviewed. Various common contaminants have been reported to be toxic at the following concentrations (ppm): cadmium. 2; copper sulfate, 2 to 18.7; ammonia, 5; potassium. 11; chromium, 12.4; arsenic trioxide, 16; copper, 19; and zinc, 66. In long-term exposures, concentrations of copper as low as 25 parts per billion (ppb) were lethal. Fry of fish infected with 20-35 glochidia were more sensitive than uninfected fish to toluene, naphthalene, and crude oil. Although few specific adverse impacts of contaminants have become clearly evident, circumstantial evidence leaves little doubt that contaminants have been responsible for decreases in population density, range, and diversity. Stresses that have been responsible for the disappearance of naiad mollusks in contaminated areas have not generally been identified, and the components of the stresses have seldom been quantitatively and qualitatively correlated with the composition and size of the naiad fauna. Often two or more factors appear to work in combination to produce the total stress that adversely affects populations. Naiad mollusks are important indio caters of contaminants in the environment; residues in soft tissue indicate recent or current exposure, and residues in shells indicate past exposure.
Thai-Cuarto, Dao; O'Brien, Christopher F; Jimenez, Roland; Liang, Grace S; Burke, Joshua
2018-04-01
Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults. Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication. Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters. The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment. Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.
Energy drinks and their adverse health effects: A systematic review of the current evidence.
Ali, Fahad; Rehman, Hiba; Babayan, Zaruhi; Stapleton, Dwight; Joshi, Divya-Devi
2015-04-01
With the rising consumption of so-called energy drinks over the last few years, there has been a growing body of literature describing significant adverse health events after the ingestion of these beverages. To gain further insight about the clinical spectrum of these adverse events, we conducted a literature review. Using PubMed and Google-Scholar, we searched the literature from January 1980 through May 2014 for articles on the adverse health effects of energy drinks. A total of 2097 publications were found. We then excluded molecular and industry-related studies, popular media reports, and case reports of isolated caffeine toxicity, yielding 43 reports. Energy drink consumption is a health issue primarily of the adolescent and young adult male population. It is linked to increased substance abuse and risk-taking behaviors. The most common adverse events affect the cardiovascular and neurological systems. The most common ingredient in energy drinks is caffeine, and it is believed that the adverse events are related to its effects, as well as potentiating effects of other stimulants in these drinks. Education, regulation, and further studies are required.
Eriksson, Ulrika K.; van Bodegom, David; May, Linda; Boef, Anna G. C.; Westendorp, Rudi G. J.
2013-01-01
Background C-reactive protein (CRP) levels are reported to be elevated in populations of African descent living in affluent environments compared to populations of European ancestry. However, the natural history of CRP levels in populations of African descent living under adverse environments remains largely unknown. Methods CRP levels were measured with a high sensitivity assay in 624 apparently healthy individuals who contributed blood as part of a study on innate immune responsiveness in a traditional Ghanaian population living under adverse environmental conditions in a malaria endemic area. As a comparison, we included CRP measurements from 2931 apparently healthy individuals from the Dutch population that were included in the same batch of CRP analyses. Associations between CRP and body mass index (BMI), immune responsiveness, and P. falciparum parasitaemia were investigated. Results In an age- and sex-adjusted model, CRP levels were 0.54 mg/L lower in the Ghanaian compared to the Dutch cohort (1.52 vs. 0.98 mg/L, p<0.001). When accounting for the substantially higher average BMI in the Dutch compared to the Ghanaians (25.6 vs. 18.4 kg/m2) the difference in CRP levels disappeared. BMI associated positively with CRP in the Dutch but not in the Ghanaians. In individuals with an acute phase response, CRP levels were higher in the Ghanaian compared to the Dutch cohort (24.6 vs. 17.3 mg/L, p = 0.04). Levels of CRP were positively related to immune responsiveness and P. falciparum parasitaemia (all p<0.001) among Ghanaians. Conclusions Our study demonstrates that West-Africans do not exhibit an inherently high inflammatory state. The role of genes, environment and gene-environment interaction in explaining reports of elevated CRP levels in populations of African ancestry when compared to other ethnicities living in affluent environments thus merits further investigation. PMID:23922912
Eriksson, Ulrika K; van Bodegom, David; May, Linda; Boef, Anna G C; Westendorp, Rudi G J
2013-01-01
C-reactive protein (CRP) levels are reported to be elevated in populations of African descent living in affluent environments compared to populations of European ancestry. However, the natural history of CRP levels in populations of African descent living under adverse environments remains largely unknown. CRP levels were measured with a high sensitivity assay in 624 apparently healthy individuals who contributed blood as part of a study on innate immune responsiveness in a traditional Ghanaian population living under adverse environmental conditions in a malaria endemic area. As a comparison, we included CRP measurements from 2931 apparently healthy individuals from the Dutch population that were included in the same batch of CRP analyses. Associations between CRP and body mass index (BMI), immune responsiveness, and P. falciparum parasitaemia were investigated. In an age- and sex-adjusted model, CRP levels were 0.54 mg/L lower in the Ghanaian compared to the Dutch cohort (1.52 vs. 0.98 mg/L, p<0.001). When accounting for the substantially higher average BMI in the Dutch compared to the Ghanaians (25.6 vs. 18.4 kg/m(2)) the difference in CRP levels disappeared. BMI associated positively with CRP in the Dutch but not in the Ghanaians. In individuals with an acute phase response, CRP levels were higher in the Ghanaian compared to the Dutch cohort (24.6 vs. 17.3 mg/L, p = 0.04). Levels of CRP were positively related to immune responsiveness and P. falciparum parasitaemia (all p<0.001) among Ghanaians. Our study demonstrates that West-Africans do not exhibit an inherently high inflammatory state. The role of genes, environment and gene-environment interaction in explaining reports of elevated CRP levels in populations of African ancestry when compared to other ethnicities living in affluent environments thus merits further investigation.
Restani, Patrizia; Di Lorenzo, Chiara; Garcia-Alvarez, Alicia; Badea, Mihaela; Ceschi, Alessandro; Egan, Bernadette; Dima, Lorena; Lüde, Saskia; Maggi, Franco M.; Marculescu, Angela; Milà-Villarroel, Raimon; Raats, Monique M.; Ribas-Barba, Lourdes; Uusitalo, Liisa; Serra-Majem, Lluís
2016-01-01
Background The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. Objectives To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. Subjects/Setting From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. Results Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. Conclusions Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals. PMID:26928206
NASA Astrophysics Data System (ADS)
Shao, Yue; Shi, Frank G.
2017-07-01
The effective passive radiation cooling that is enabled by silicone-based composites is investigated for its dependence on coating thickness and filler size in the range of nanometers to micrometers. It is established, contrary to prior reports, that the effective passive radiation cooling does not exhibit a filler size dependence, i.e., there is no optimal size at which a maximum cooling would be reached. However, the apparent cooling effect is filler type dependent and among the fillers investigated, Al2O3 exhibits the best apparent cooling effect. In addition, the apparent cooling effect is dependent on coating thickness: the thickness dependence is non-monotonic, and the maximum cooling occurs at an optimal thickness of 70 μm, regardless of filler type. Potential significant implications of the findings are also discussed.
Deployment Health Centers Review, 2016-2017
2017-08-21
the short and long-term adverse effects of military service on the physical and mental health of veterans. We recommend that the DHB continue to...adverse effects of military service on the physical and mental health of veterans” by expanding on current clinical, surveillance, and research efforts...the ability to identify, treat, and minimize the short- and long-term adverse effects of military service on the mental and physical health of
[Eye cosmetics--the beauty and the beast].
Blumenfeld, Oren; Nathansohn, Nir; Yeshurun, Itamar; Ashkenazi, Isaac
2005-05-01
The use of eye cosmetics is a popular practice in modern times that dates back to ancient civilizations. This practice, however, is not without hazards. The most common adverse effect of eye cosmetics is eyelid dermatitis, although an array of other adverse effects has been reported. This article reviews the different types of eye cosmetics in current use, their composition and the adverse effects of both commercial and traditional products.
NASA Astrophysics Data System (ADS)
Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.
2015-10-01
Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.
Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.
2015-01-01
Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. PMID:26482413
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
Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.
Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng
2012-12-01
Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.
Mining adverse drug reactions from online healthcare forums using hidden Markov model.
Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo
2014-10-23
Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also identified. The results from the HMM based Text Miner are encouraging to pursue further enhancements to this approach. The mined novel side-effects can act as early indicators for health authorities to help focus their efforts in post-marketing drug surveillance.
Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong
2012-07-25
To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P < 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.
Mersha, Mahlet D; Patel, Bansri M; Patel, Dipen; Richardson, Brittany N; Dhillon, Harbinder S
2015-09-17
Bisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA. Experiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA. Building upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.
Chen, Jianmin; Saggar, Jasdeep K; Ward, Wendy E; Thompson, Lilian U
2011-01-01
Previous studies showed that flaxseed lignan (secoisolariciresinol diglucoside, SDG) and oil (FO) inhibit established breast tumor growth in athymic mice with or without tamoxifen (TAM) treatment. TAM was found to increase bone mineral content (BMC) and density (BMD) in breast cancer patients. It is not known whether SDG or FO alone or combined with TAM affects bone health. Hence, the effects of SDG and FO, alone or in combination, on BMC, BMD, and biomechanical bone strength in ovariectomized athymic mice with established human breast tumors (MCF-7) treated with or without TAM were studied. In a factorial design, mice were divided into four non-TAM and four TAM groups. Each group consisted of mice fed a basal diet (BD), SDG (1 g/kg), FO (38.5 g/kg) or SDG + FO (combination) diets. The TAM group had TAM implants that provide a 5-mg TAM dose released over 60 d. TAM exerted an overall significant effect in increasing BMC, BMD, and biomechanical strength in femurs and lumbar vertebra. Without TAM treatment, SDG produced significant lower femur BMD (6%) while FO produced lower vertebrae BMC (8%) and BMD (6%). With TAM treatment, SDG and FO did not exert an effect on BMC and BMD at the femur or vertebra. SDG and FO produced no marked effect on biomechanical bone strength with or without TAM treatment. In conclusion, FS components did not significantly attenuate the positive effects on bone induced by TAM in this model system, indicating no apparent adverse effects on bone health.
Zhang, Xu; Li, Haobang; Jiang, Guitao; Wang, Xiangrong; Huang, Xuan; Li, Chuang; Wu, Duanqin; Dai, Qiuzhong
2018-04-11
The objective of this study was to evaluate the effects of enzyme supplementation on the nutrient, amino acid, and energy utilization efficiency of citrus pulp and hawthorn pulp as unusual feedstuffs in Linwu ducks. Forty ducks were assigned to each treatment group and fed diets with or without complex enzyme supplementation. All birds received the same quantity of raw material (60 g) via the force-feeding procedure. With the exception of leucine and phenylalanine, amino acid concentrations in hawthorn pulp were twice those in citrus pulp. Enzyme supplementation significantly increased apparent dry matter digestibility (ADM) of citrus pulp (P < 0.05), but had no significant effects (P > 0.05) on the apparent and true utilization rates of other nutrients, apparent metabolizable energy (AME), or true metabolizable energy (TME), from citrus pulp and hawthorn pulp by Linwu ducks. However, enzyme supplementation significantly increased (P < 0.05) apparent gross energy, true gross energy, AME, and TME of hawthorn pulp for Linwu ducks. There were no differences in the apparent and true utilization rates of amino acids from citrus pulp (P > 0.56) between the groups, with the exception of arginine (P < 0.05). There was an increasing trend in the apparent and true utilization rates of alanine (P = 0.06) and tyrosine (P = 0.074) from citrus pulp with enzyme supplementation. The apparent and true utilization rates of threonine in hawthorn pulp were increased significantly (P < 0.05) following enzyme supplementation. The addition of exogenous enzymes improved the forage quality of citrus pulp and hawthorn pulp, which represent potential feed resources for husbandry production.
How Safe Are Common Analgesics for the Treatment of Acute Pain for Children? A Systematic Review.
Hartling, Lisa; Ali, Samina; Dryden, Donna M; Chordiya, Pritam; Johnson, David W; Plint, Amy C; Stang, Antonia; McGrath, Patrick J; Drendel, Amy L
2016-01-01
Background . Fear of adverse events and occurrence of side effects are commonly cited by families and physicians as obstructive to appropriate use of pain medication in children. We examined evidence comparing the safety profiles of three groups of oral medications, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, to manage acute nonsurgical pain in children (<18 years) treated in ambulatory settings. Methods . A comprehensive search was performed to July 2015, including review of national data registries. Two reviewers screened articles for inclusion, assessed methodological quality, and extracted data. Risks (incidence rates) were pooled using a random effects model. Results . Forty-four studies were included; 23 reported on adverse events. Based on limited current evidence, acetaminophen, ibuprofen, and opioids have similar nausea and vomiting profiles. Opioids have the greatest risk of central nervous system adverse events. Dual therapy with a nonopioid/opioid combination resulted in a lower risk of adverse events than opioids alone. Conclusions . Ibuprofen and acetaminophen have similar reported adverse effects and notably less adverse events than opioids. Dual therapy with a nonopioid/opioid combination confers a protective effect for adverse events over opioids alone. This research highlights challenges in assessing medication safety, including lack of more detailed information in registry data, and inconsistent reporting in trials.
2011-01-01
Background The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta-estradiol was used as a positive control for 'estrogen-like' effects. Methods Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta-zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. Results Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM) after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha-zearalenol >17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity-associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility. Conversely, zearalenone and 17beta-estradiol did not induce the acrosome reaction but induced hyperactive motility albeit to a different extent. Conclusions Apparently, the mycotoxin zearalenone has 17beta-estradiol-like estrogenic activity that enables it to induce hyperactivated motility of equine sperm cells, whereas the zearalenol derivatives induce premature completion of the acrosome reaction and thereby adversely affect stallion sperm physiology. The alpha form of zearalenol still possessed the estrogenic ability to induce hyperactivated motility, whereas its beta stereo-isomere had lost this property. PMID:21970729
Ogulmus, Cansu; Karacaoglu, Merve; Kafaligonul, Hulusi
2018-03-01
The coordination of intramodal perceptual grouping and crossmodal interactions plays a critical role in constructing coherent multisensory percepts. However, the basic principles underlying such coordinating mechanisms still remain unclear. By taking advantage of an illusion called temporal ventriloquism and its influences on perceived speed, we investigated how audiovisual interactions in time are modulated by the spatial grouping principles of vision. In our experiments, we manipulated the spatial grouping principles of proximity, uniform connectedness, and similarity/common fate in apparent motion displays. Observers compared the speed of apparent motions across different sound timing conditions. Our results revealed that the effects of sound timing (i.e., temporal ventriloquism effects) on perceived speed also existed in visual displays containing more than one object and were modulated by different spatial grouping principles. In particular, uniform connectedness was found to modulate these audiovisual interactions in time. The effect of sound timing on perceived speed was smaller when horizontal connecting bars were introduced along the path of apparent motion. When the objects in each apparent motion frame were not connected or connected with vertical bars, the sound timing was more influential compared to the horizontal bar conditions. Overall, our findings here suggest that the effects of sound timing on perceived speed exist in different spatial configurations and can be modulated by certain intramodal spatial grouping principles such as uniform connectedness.
Long term effects of early adversity on cognitive function.
Richards, M; Wadsworth, M E J
2004-10-01
To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.
The effects of phase on the perception of 3D shape from texture: psychophysics and modeling.
Thaler, Lore; Todd, James T; Dijkstra, Tjeerd M H
2007-02-01
Two experiments are reported in which observers judged the apparent shapes of elliptical cylinders with eight different textures that were presented with scrambled and unscrambled phase spectra. The results revealed that the apparent depths of these surfaces varied linearly with the ground truth in all conditions, and that the overall magnitude of surface relief was systematically underestimated. In general, the apparent depth of a surface is significantly attenuated when the phase spectrum of its texture is randomly scrambled, though the magnitude of this effect varies for different types of texture. A new computational model of 3D shape from texture is proposed in which apparent depth is estimated from the relative density of edges in different local regions of an image, and the predictions of this model are highly correlated with the observers' judgments.
Choi, Kwangseok; Taghavivand, Milad; Zhang, Lifeng
2017-03-15
Pharmaceutical powders are mainly organic materials and are likely to be charged due to repeated inter-particle and particle-wall contacts during industrial processes. This study experimentally investigated the effect of moisture content (ranging from approximately 1.8 to 30wt.%) on tribocharging behaviour of pharmaceutical granules, as well as their apparent volume resistivity. The tribocharging behaviour of pharmaceutical granules was investigated using a rotating device and apparent volume resistivity was measured in a conventional volume resistivity test cell. Additional measurements were performed on individual ingredients, each having the same moisture content as that of the granules, in order to investigate the effect of each single ingredient on the apparent volume resistivity of granules. In this work, the individual ingredients used for granules were: α-Lactose Monohydrate (α-LMH), Microcrystalline Cellulose (MCC), Hydroxypropyl Methylcellulose (HPMC), and Croscarmellose Sodium (CCS). The results showed that the specific charge of granules began to increase at the moisture contents below 5wt.%, which can be referred as critical moisture content of granules. The apparent volume resistivity showed the same behaviour, indicating that the specific charge could be due to an increase in apparent volume resistivity of granules at reduced moisture content. Finally, it was shown that the apparent volume resistivity measured for granules was mainly affected by that of the α-LMH, the major component of granules accounting for 40wt.%. Copyright © 2017 Elsevier B.V. All rights reserved.
Resilience in mental health: linking psychological and neurobiological perspectives
Rutten, B P F; Hammels, C; Geschwind, N; Menne-Lothmann, C; Pishva, E; Schruers, K; van den Hove, D; Kenis, G; van Os, J; Wichers, M
2013-01-01
Objective To review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies. Method Electronic and manual literature search of MEDLINE, EMBASE and PSYCHINFO, using a range of search terms around biological and psychological factors influencing resilience as observed in human and experimental animal studies, complemented by review articles and cross-references. Results The term resilience is used in the literature for different phenomena ranging from prevention of mental health disturbance to successful adaptation and swift recovery after experiencing life adversities, and may also include post-traumatic psychological growth. Secure attachment, experiencing positive emotions and having a purpose in life are three important psychological building blocks of resilience. Overlap between psychological and biological findings on resilience in the literature is most apparent for the topic of stress sensitivity, although recent results suggest a crucial role for reward experience in resilience. Conclusion Improving the understanding of the links between genetic endowment, environmental impact and gene–environment interactions with developmental psychology and biology is crucial for elucidating the neurobiological and psychological underpinnings of resilience. PMID:23488807
ERIC Educational Resources Information Center
Chartier, Mariette J.; Walker, John R.; Naimark, Barbara
2010-01-01
Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…
ERIC Educational Resources Information Center
Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.
2007-01-01
Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…
2013-01-01
Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed. PMID:23336848
Berninger, Jason P; LaLone, Carlie A; Villeneuve, Daniel L; Ankley, Gerald T
2016-04-01
The potential for pharmaceuticals in the environment to cause adverse ecological effects is of increasing concern. Given the thousands of active pharmaceutical ingredients (APIs) that can enter the aquatic environment through human and/or animal (e.g., livestock) waste, a current challenge in aquatic toxicology is identifying those that pose the greatest risk. Because empirical toxicity information for aquatic species is generally lacking for pharmaceuticals, an important data source for prioritization is that generated during the mammalian drug development process. Applying concepts of species read-across, mammalian pharmacokinetic data were used to systematically prioritize APIs by estimating their potential to cause adverse biological consequences to aquatic organisms, using fish as an example. Mammalian absorption, distribution, metabolism, and excretion (ADME) data (e.g., peak plasma concentration, apparent volume of distribution, clearance rate, and half-life) were collected and curated, creating the Mammalian Pharmacokinetic Prioritization For Aquatic Species Targeting (MaPPFAST) database representing 1070 APIs. From these data, a probabilistic model and scoring system were developed and evaluated. Individual APIs and therapeutic classes were ranked based on clearly defined read-across assumptions for translating mammalian-derived ADME parameters to estimate potential hazard in fish (i.e., greatest predicted hazard associated with lowest mammalian peak plasma concentrations, total clearance and highest volume of distribution, half-life). It is anticipated that the MaPPFAST database and the associated API prioritization approach will help guide research and/or inform ecological risk assessment. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.