12 results
Search Results
2. The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data – A case study with caffeine.
- Author
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Bessems, Jos G.M., Paini, Alicia, Gajewska, Monika, and Worth, Andrew
- Subjects
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EXPOSURE dose , *EFFECT of radiation on skin , *HEALTH risk assessment , *PHYSIOLOGICAL effects of caffeine , *SKIN physiology - Abstract
Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
3. Orai3 channel is the 2-APB-induced endoplasmic reticulum calcium leak.
- Author
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Leon-Aparicio, Daniel, Pacheco, Jonathan, Chavez-Reyes, Jesus, Galindo, Jose M., Valdes, Jesus, Vaca, Luis, and Guerrero-Hernandez, Agustin
- Abstract
We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca 2+ leak using synthetic Ca 2+ indicators that report changes in both the cytoplasmic ([Ca 2+ ] i ) and the luminal ER ([Ca 2+ ] ER ) Ca 2+ concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca 2+ leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca 2+ ] ER but did not decrease the ER Ca 2+ leak after thapsigargin (TG). Orai3 channel, but neither Orai1 nor Orai2, colocalizes with expressed IP 3 R and only Orai3 channel supported the 2-APB-induced ER Ca 2+ leak, while Orai1 and Orai2 inhibited this type of ER Ca 2+ leak. Decreasing the expression of Orai3 inhibited the 2-APB-induced ER Ca 2+ leak but did not modify the ER Ca 2+ leak revealed by inhibition of SERCA pumps with TG. However, reducing the expression of Orai3 channel resulted in larger [Ca 2+ ] i response after TG but only when the ER store had been overloaded with Ca 2+ by eliminating the acidic internal Ca 2+ store with bafilomycin. These data suggest that Orai3 channel does not participate in the TG-revealed ER Ca 2+ leak but forms an ER Ca 2+ leak channel that is limiting the overloading with Ca 2+ of the ER store. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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4. Using risk prediction models and species sensitivity maps for large-scale identification of infrastructure-related wildlife protection areas: The case of bird electrocution.
- Author
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Pérez-García, Juan Manuel, DeVault, Travis L., Botella, Francisco, and Sánchez-Zapata, José Antonio
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WILDLIFE conservation , *BIRD mortality , *ELECTROCUTION , *SPECIES diversity , *PREDICTION models , *DECISION making in environmental policy - Abstract
The use of systematic area-selection procedures to design protected areas can help optimize conservation actions. However, this process has rarely been used to identify high-risk mortality areas to protect wildlife from human impacts. Electrocution on power lines is one the most important human-related causes of bird mortality worldwide, especially for raptors. Identifying and correcting dangerous individual pylons can significantly reduce the number of electrocution victims, but applying this procedure at a large spatial scale is impractical. In this paper we describe a new selection process that allows for identification of high-risk mortality areas at large scales, combining spatial electrocution risk models with maps of species sensitivity to such an impact. We used the Valencia Region (eastern Spain) as our study system. The risk prediction map was built using bird electrocution records on 1 km × 1 km grids from 2000 to 2009 and the species sensitivity map was built using data on presence and use of four raptor species. The combination of both maps was compared to the distribution of Special Protected Areas and validated by local experts to identify prediction errors or gaps. The final proposal of high priority areas to protect birds from electrocution covered 16.3% of the Valencia Region. Our work supports the use of predictive models and sensitivity maps in the decision-making process to locate high priority infrastructure-related wildlife protection areas at a large scale. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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5. Artificial Intelligence in Precision Cardiovascular Medicine.
- Author
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Krittanawong, Chayakrit, Zhang, HongJu, Wang, Zhen, Aydar, Mehmet, and Kitai, Takeshi
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CARDIOVASCULAR agents , *ARTIFICIAL intelligence , *PHENOTYPES , *MACHINE learning , *COST effectiveness , *THERAPEUTICS , *ALGORITHMS , *CARDIOLOGY - Abstract
Artificial intelligence (AI) is a field of computer science that aims to mimic human thought processes, learning capacity, and knowledge storage. AI techniques have been applied in cardiovascular medicine to explore novel genotypes and phenotypes in existing diseases, improve the quality of patient care, enable cost-effectiveness, and reduce readmission and mortality rates. Over the past decade, several machine-learning techniques have been used for cardiovascular disease diagnosis and prediction. Each problem requires some degree of understanding of the problem, in terms of cardiovascular medicine and statistics, to apply the optimal machine-learning algorithm. In the near future, AI will result in a paradigm shift toward precision cardiovascular medicine. The potential of AI in cardiovascular medicine is tremendous; however, ignorance of the challenges may overshadow its potential clinical impact. This paper gives a glimpse of AI's application in cardiovascular clinical care and discusses its potential role in facilitating precision cardiovascular medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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6. The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities.
- Author
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Pruessner, Marita, Cullen, Alexis E., Aas, Monica, and Walker, Elaine F.
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SCHIZOPHRENIA , *DIATHESIS-stress model (Psychology) , *DISEASE progression , *HYPOTHALAMIC-pituitary-adrenal axis , *NEUROBIOLOGY - Abstract
Over the past decade, our understanding of the role of stress in serious mental illness has become more sophisticated. In this paper, we revisit the neural diathesis-stress model of schizophrenia that was initially proposed in 1997 and updated in 2008. In light of cumulative research findings, we must now encompass evidence on the premorbid periods of psychosis, and our more nuanced understanding of hypothalamic-pituitary-adrenal (HPA) axis function and its association with neurodevelopmental, epigenetic, neurotransmitter, and inflammatory processes, as well as brain structure and function. Giving consideration to the methodological complexities that have become more apparent as research in this area has burgeoned, the various indices of HPA axis function, and the different stages of illness, we review relevant research published since the 2008 update of the model. We conclude by proposing an extended neural diathesis-stress model that addresses the broader neurobiological context of stress psychobiology in psychosis progression. Implications of this model for best practice, with regards to both future research and treatment strategies, are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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7. Peri-conception maternal lipid profiles predict pregnancy outcomes.
- Author
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Ogundipe, Enitan, Johnson, Mark R., Wang, Yiqun, and Crawford, Michael A.
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In this study, healthy women and those at high-risk of adverse pregnancy outcomes (pre-eclampsia, fetal growth restriction, gestational diabetes) were selected to assess the effect of fatty acid supplementation. The purpose of this paper is to report two novel findings (i) at recruitment the receiver operating characteristic (ROC) for erythrocyte oleic acid predicted spontaneous delivery at 34 weeks gestation (ROC=0.926 n=296) for all women entering the study. Further analysis revealed oleic and all monounsaturated fatty acids were similarly predictive with or without a supplement during the pregnancy. (ii) At delivery, we observed a biomagnification of saturated fatty acids from mother to fetus with the reverse for monounsaturates. The major conclusions are (i) the status of the mother in the months prior to conception is a stronger predictor of preterm delivery than the events during the pregnancy. (ii) Saturated fats may be playing an important function in supporting fetal membrane growth. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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8. Evaluation of the nutrition screening tool for childhood cancer (SCAN).
- Author
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Murphy, Alexia J., White, Melinda, Viani, Karina, and Mosby, Terezie T.
- Abstract
Summary Background & aims Malnutrition is a serious concern for children with cancer and nutrition screening may offer a simple alternative to nutrition assessment for identifying children with cancer who are at risk of malnutrition. The present paper aimed to evaluate the nutrition screening tool for childhood cancer (SCAN). Methods SCAN was developed after an extensive review of currently available tools and published screening recommendation, consideration of pediatric oncology nutrition guidelines, piloting questions, and consulting with members of International Pediatric Oncology Nutrition Group. In Study 1, the accuracy and validity of SCAN against pediatric subjective global nutrition assessment (pediatric SGNA) was determined. In Study 2, subjects were classified as ‘at risk of malnutrition’ and ‘not at risk of malnutrition’ according to SCAN and measures of height, weight, body mass index (BMI) and body composition were compared between the groups. Results The validation of SCAN against pediatric SGNA showed SCAN had ‘excellent’ accuracy (0.90, 95% CI 0.78–1.00; p < 0.001), 100% sensitivity, 39% specificity, 56% positive predictive value and 100% negative predictive value. When subjects in Study 2 were classified into ‘at risk of malnutrition’ and ‘not at risk of malnutrition’ according to SCAN, the ‘at risk of malnutrition’ group had significantly lower values for weight Z score (p = 0.001), BMI Z score (p = 0.001) and fat mass index (FMI) (p = 0.04), than the ‘not at risk of malnutrition’ group. Conclusions This study shows that SCAN is a simple, quick and valid tool which can be used to identify children with cancer who are at risk of malnutrition. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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9. Procalcitonin and community-acquired pneumonia (CAP) in children.
- Author
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Giulia, Bivona, Luisa, Agnello, Concetta, Scazzone, Bruna, Lo Sasso, Chiara, Bellia, and Marcello, Ciaccio
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PNEUMONIA , *CHILDREN , *LUNG diseases , *AGE groups ,DEVELOPED countries - Abstract
The role of procalcitonin (PCT) as a biomarker for sepsis in adults is well documented, while its role in infections affecting neonatal children remains controversial. Among these infections, Community-Acquired pneumonia (CAP) has been studied extensively, because it's the second cause of death in children in developing countries, and one of the most frequent causes of hospitalization in industrialized countries. The PubMed database and the Cochrane Library were used to search for the following keywords: CAP, procalcitonin, and children. Thirteen articles were studied to determine the role of PCT in CAP management, specifically its usefulness for distinguishing pneumococcal infections from viral and unknown infections, for predicting severity and the correct antibiotic treatment. This paper focuses on the studies performed to identify the best inflammatory biomarker for CAP management. Although there is an increase in studies confirming the usefulness of PCT in CAP management in children, further studies are needed to have better understanding of its role for pediatric CAP management. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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10. Behind the scenes of vitamin D binding protein: More than vitamin D binding.
- Author
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Delanghe, Joris R., Speeckaert, Reinhart, and Speeckaert, Marijn M.
- Abstract
Although being discovered in 1959, the number of published papers in recent years reveals that vitamin D binding protein (DBP), a member of the albuminoid superfamily, is a hot research topic. Besides the three major phenotypes (DBP1F, DBP1S and DBP2), more than 120 unique variants have been described of this polymorphic protein. The presence of DBP has been demonstrated in different body fluids (serum, urine, breast milk, ascitic fluid, cerebrospinal fluid, saliva and seminal fluid) and organs (brain, heart, lungs, kidneys, placenta, spleen, testes and uterus). Although the major function is binding, solubilization and transport of vitamin D and its metabolites, the name of this glycoprotein hides numerous other important biological functions. In this review, we will focus on the analytical aspects of the determination of DBP and discuss in detail the multifunctional capacity [actin scavenging, binding of fatty acids, chemotaxis, binding of endotoxins, influence on T cell response and influence of vitamin D binding protein-macrophage activating factor (DBP-MAF) on bone metabolism and cancer] of this abundant plasma protein. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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11. Data processing of vibrational chemical imaging for pharmaceutical applications.
- Author
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Sacré, P.-Y., De Bleye, C., Chavez, P.-F., Netchacovitch, L., Hubert, Ph., and Ziemons, E.
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ELECTRONIC data processing , *IMAGING systems in chemistry , *DRUG analysis , *VIBRATIONAL spectra , *DRUG development - Abstract
Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools to analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational spectroscopy to imaging techniques and allows therefore the visualization of distribution of compounds or crystallization processes. However, these techniques provide a huge amount of data that must be processed to extract the relevant information. This review presents fundamental concepts of hyperspectral imaging, the basic theory of the most used chemometric tools used to pre-process, process and post-process the generated data. The last part of the present paper focuses on pharmaceutical applications of hyperspectral imaging and highlights the data processing approaches to enable the reader making the best choice among the different tools available. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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12. Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy.
- Author
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Bajaj, Jasmohan S., Heuman, Douglas M., Sterling, Richard K., Sanyal, Arun J., Siddiqui, Muhammad, Matherly, Scott, Luketic, Velimir, Stravitz, R. Todd, Fuchs, Michael, Thacker, Leroy R., Gilles, HoChong, White, Melanie B., Unser, Ariel, Hovermale, James, Gavis, Edith, Noble, Nicole A., and Wade, James B.
- Abstract
Background & Aims Detection of covert hepatic encephalopathy (CHE) is difficult, but point-of-care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test-retest reliability, and external validity. Methods Patients with cirrhosis (n = 167; 38% with overt HE [OHE]; mean age, 55 years; mean Model for End-Stage Liver Disease score, 12) and controls (n = 114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test-retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intrahepatic portosystemic shunt placement, and before and after correction for hyponatremia, to determine external validity. Results All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cutoffs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic value of 0.91; the area under the receiver operator characteristic value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test-retest reliability was high (intraclass coefficient, 0.83) among 30 patients retested 1–3 months apart. OffTime+OnTime increased significantly (206 vs 255 seconds, P = .007) among 10 patients retested 33 ± 7 days after transjugular intrahepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs 225 seconds, P = .03) in 7 patients tested before and after correction for hyponatremia (126 ± 3 to 132 ± 4 meq/L, P = .01) 10 ± 5 days apart. Conclusions A smartphone app called EncephalApp has good face validity, test-retest reliability, and external validity for the diagnosis of CHE. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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