| 1. |
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 7. |
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| 8. |
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| 9. |
- Morales, J. C., et al.
(författare)
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A giant exoplanet orbiting a very-low-mass star challenges planet formation models
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6460, s. 1441-1445
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Tidskriftsartikel (refereegranskat)abstract
- Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.
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| 10. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 11. |
- Gerkin, RC, et al.
(författare)
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The best COVID-19 predictor is recent smell loss: a cross-sectional study
- 2020
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset.ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10), which can be deployed when viral lab tests are impractical or unavailable.
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| 12. |
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| 13. |
- Teixeira, P. J., et al.
(författare)
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A Classification of Motivation and Behavior Change Techniques Used in Self-Determination Theory-Based Interventions in Health Contexts
- 2020
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Ingår i: Motivation Science. - : American Psychological Association (APA). - 2333-8113 .- 2333-8121. ; 6:4, s. 438-455
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Tidskriftsartikel (refereegranskat)abstract
- While evidence suggests that interventions based on self-determination theory have efficacy in motivating adoption and maintenance of health-related behaviors, and in promoting adaptive psychological outcomes, the motivational techniques that comprise the content of these interventions have not been comprehensively identified or described. The aim of the present study was to develop a classification system of the techniques that comprise self-determination theory interventions, with satisfaction of psychological needs as an organizing principle. Candidate techniques were identified through a comprehensive review of self-determination theory interventions and nomination by experts. The study team developed a preliminary list of candidate techniques accompanied by labels, definitions, and function descriptions of each. Each technique was aligned with the most closely related psychological need satisfaction construct (autonomy, competence, or relatedness). Using an iterative expert consensus procedure, participating experts (N = 18) judged each technique on the preliminary list for redundancy, essentiality, uniqueness, and the proposed link between the technique and basic psychological need. The procedure produced a final classification of 21 motivation and behavior change techniques (MBCTs). Redundancies between final MBCTs against techniques from existing behavior change technique taxonomies were also checked. The classification system is the first formal attempt to systematize self-determination theory intervention techniques. The classification is expected to enhance consistency in descriptions of self-determination theory-based interventions in health contexts, and assist in facilitating synthesis of evidence on interventions based on the theory. The classification is also expected to guide future efforts to identify, describe, and classify the techniques that comprise self-determination theory-based interventions in multiple domains.
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| 14. |
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| 15. |
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| 16. |
- Guardia-Escote, L., et al.
(författare)
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Sex and Exposure to Postnatal Chlorpyrifos Influence the Epigenetics of Feeding-Related Genes in a Transgenic APOE Mouse Model: Long-Term Implications on Body Weight after a High-Fat Diet
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Developmental exposure to toxicants and diet can interact with an individual's genetics and produce long-lasting metabolic adaptations. The different isoforms of the apolipoprotein E (APOE) are an important source of variability in metabolic disorders and influence the response to the pesticide chlorpyrifos (CPF). We aimed to study the epigenetic regulation on feeding control genes and the influence of postnatal CPF exposure, APOE genotype, and sex, and how these modifications impact on the metabolic response to a high-fat diet (HFD). Both male and female apoE3- and apoE4-TR mice were exposed to CPF on postnatal days 10-15. The DNA methylation pattern of proopiomelanocortin, neuropeptide Y, leptin receptor, and insulin-like growth factor 2 was studied in the hypothalamus. At adulthood, the mice were given a HFD for eight weeks. The results highlight the importance of sex in the epigenetic regulation and the implication of CPF treatment and APOE genotype. The body weight progression exhibited sex-dimorphic differences, apoE4-TR males being the most susceptible to the effects induced by CPF and HFD. Overall, these results underscore the pivotal role of sex, APOE genotype, and developmental exposure to CPF on subsequent metabolic disturbances later in life and show that sex is a key variable in epigenetic regulation.
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| 17. |
- Peris-Sampedro, Fiona, et al.
(författare)
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New mechanistic insights on the metabolic-disruptor role of chlorpyrifos in apoE mice: a focus on insulin- and leptin-signalling pathways
- 2018
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 92:5, s. 1717-1728
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we have provided evidence, suggesting that mice expressing the human apolipoprotein E3 (apoE3) are more prone to develop an obesity-like phenotype and a diabetic profile when subchronically fed a chlorpyrifos (CPF)-supplemented diet. The aim of the current study was to examine the underlying mechanisms through which CPF alters both insulin- and leptin-signalling pathways in an APOE-dependent manner. Both adult apoE3- and E4-targeted replacement and C57BL/6 mice were exposed to CPF at 0 or 2 mg/kg body weight/day through the diet for 8 consecutive weeks. We determined the expression of JAK2, p-JAK2, STAT3, p-STAT3, SOCS3, IRS-1, p-IRS-1, AKT, p-AKT, GSK3 beta, p-GSK3 beta, and apoE in the liver, as well as hepatic mRNA levels of pon1, pon2, and pon3. CPF markedly disrupted both leptin and insulin homeostasis, particularly in apoE3 mice. Indeed, only CPF-fed apoE3 mice exhibited an increased phosphorylation ratio of STAT3, as well as increased total SOCS3 protein levels. Similarly, the exposure to CPF drastically reduced the phosphorylation ratio of both AKT and GSK3 beta, especially in apoE3 mice. Overall, CPF reduced the expression of the three pon genes, principally in C57BL/6 and apoE3 mice. These results provide notable mechanistic insights on the metabolic effects of the pesticide CPF, and attest the increased vulnerability of apoE3 carriers to its metabolic-disruptor role.
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| 18. |
- Bui, Christine L, et al.
(författare)
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Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users
- 2014
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Ingår i: Current Drug Safety. - : Bentham Science Publishers Ltd.. - 1574-8863 .- 2212-3911. ; 9:1, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis.Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%).Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.
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| 19. |
- Guardia-Escote, L., et al.
(författare)
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APOE genetic background and sex confer different vulnerabilities to postnatal chlorpyrifos exposure and modulate the response to cholinergic drugs
- 2019
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 376
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF) is an extensively used organophosphate pesticide. Exposure to CPF has been related to neurobehavioral disorders, particularly during neurodevelopment. Apolipoprotein E (apoE) is a lipid and cholesterol carrier and a susceptibility factor for cognitive impairment which can influence the response to toxic exposures. The study was aimed at assessing the effects of postnatal exposure to CPF on object recognition memory and its modulation by sex and APOE genotype. Human apoE3 and apoE4 targeted replacement mice and C57BL/6 mice were postnatally exposed to 0 or 1 mg/kg/day of CPF. Recognition memory was evaluated in an Object Recognition Test (ORT). In order to study the contribution of cholinergic and GABAergic neurotransmitter systems to recognition memory, a pharmacological challenge was included. Sex, genotype and postnatal exposure to CPF were key factors throughout the testing period. Specifically, CPF increased exploratory behavior and impaired discrimination performance. We observed that administering scopolamine, a cholinergic antagonist, was detrimental to recognition memory. However, discrimination in C57BL/6 and apoE4 males improved with the administration of the cholinergic agonist rivastigmine, but the same drug worsened retention in apoE4 females. Finally, the GABAergic agonist alprazolam altered performance in a sex- and genotype-dependent manner. Overall, these results suggest complex interactions between sex, APOE genotype and postnatal CPF exposure and indicate a different functioning of both the cholinergic and GABAergic neurotransmitter system between groups. © 2019 Elsevier B.V.
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| 20. |
- Kaye, James A, et al.
(författare)
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Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials : a retrospective, population-based cohort study
- 2014
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Ingår i: Pharmacotherapy. - : Wiley. - 0277-0008 .- 1875-9114. ; 34:4, s. 336-349
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials.DESIGN: Retrospective, observational cohort study with a nested case-control analysis.DATA SOURCE: HealthCore Integrated Research Database.PATIENTS: Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use.MEASUREMENTS AND MAIN RESULTS: Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7).CONCLUSION: The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.
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| 21. |
- Teixeira, Pedro J., et al.
(författare)
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Classification of Techniques Used in Self-Determinationheory-Based Interventions in Health Contexts : An Expert Consensus Study
- 2020
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Ingår i: Motivation Science. - Washington, DC : American Psychological Association (APA). - 2333-8113 .- 2333-8121. ; 6:4, s. 438-445
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Tidskriftsartikel (refereegranskat)abstract
- While evidence suggests that interventions based on self-determination theory can be effective in motivating adoption and maintenance of health-related behaviors, and in promoting adaptive psychological outcomes, the motivational techniques that comprise the content of these interventions have not been comprehensively identified or described. The aim of the present study was to develop a classification system of the techniques that comprise self-determination theory interventions, with satisfaction of psychological needs as an organizing principle. Candidate techniques were identified through a comprehensive review of self-determination theory interventions and nomination by experts. The study team developed a preliminary list of candidate techniques accompanied by labels, definitions, and function descriptions of each. Each technique was aligned with the most closely-related psychological need satisfaction construct (autonomy, competence, or relatedness). Using an iterative expert consensus procedure, participating experts (N = 18) judged each technique on the preliminary list for redundancy, essentiality, uniqueness, and the proposed link between the technique and basic psychological need. The procedure produced a final classification of 21 motivation and behavior change techniques (MBCTs). Redundancies between final MBCTs against techniques from existing behavior change technique taxonomies were also checked. The classification system is the first formal attempt to systematize self-determination theory intervention techniques. The classification is expected to enhance consistency in descriptions of self-determination theory-based interventions in health contexts, and assist in facilitating synthesis of evidence on interventions based on the theory. The classification is also expected to guide future efforts to identify, describe, and classify the techniques that comprise self-determination theory-based interventions in multiple domains. © 2020, American Psychological Association.
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| 22. |
- Basaure, P., et al.
(författare)
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Learning, memory and the expression of cholinergic components in mice are modulated by the pesticide chlorpyrifos depending upon age at exposure and apolipoprotein E (APOE) genotype
- 2019
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 93:3, s. 693-707
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms of the apolipoprotein E (APOE) gene differentially affect neurobiological functions and cognitive performance and confer different vulnerabilities to subclinical exposures to chlorpyrifos (CPF), a pesticide used worldwide. The data reported on this topic suggest a complex interaction between cholinergic signaling and the APOE genotype. To gain greater functional insight into this interaction, we evaluated spatial learning and memory and hippocampal cholinergic expression in young apoE3 and apoE4 transgenic mice exposed to CPF. Male and female mice were exposed to CPF at 0 or 1 mg/kg on postnatal days 10-15 and then, exposed to CPF at 0 or 2 mg/kg for 60 days at 5 months of age. At 6 months of age, mice were tested for spatial skills in a Barnes maze. At the end of the task, animals were killed and gene expression of cholinergic components was assessed in the hippocampus. Our results show that apoE4 female mice performed worse in the spatial task, while postnatal CPF impaired escape strategies and spatial memory in apoE3 mice. In turn, CPF in adulthood improved spatial abilities in apoE4 female mice. Regarding gene expression, choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) expression were increased in apoE4 mice. Postnatal exposure to CPF increased ChAT mRNA levels in apoE4 mice, whereas adult exposure to CPF induced changes in acetylcholinesterase-S, alpha 7- and alpha 4-subunit nicotinic receptor expression in apoE4 females. The current findings provide new insights into APOE-dependent cholinergic signaling, which directly affects the response to CPF cholinergic insult, especially in APOE4 subjects.
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| 23. |
- Basaure, P., et al.
(författare)
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Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice
- 2018
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 118, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides in the world. Our previous results described that apolipoprotein E (APOE) polymorphisms are a source of individual differences in susceptibility to CPF. The aim of this study was to assess the physical and biochemical effects of postnatal exposure to CPF in the apoE targeted replacement mouse model. Mice were exposed to CPF at 0 or 1 mg/kg/day from postnatal day 10–15. Physical development, plasma and forebrain cholinesterase (ChE) activity and gene expression in liver and forebrain were evaluated. CPF exposure delays physical maturation and decreases the expression of choline acetyltransferase, α4-subunit and the α7 receptor. CPF decreases the expression of vesicular acetylcholine transporter (VAChT) mRNA in the forebrain only in apoE3 mice. The expression of paraoxonase-2 in the forebrain was also influenced by APOE genotype and CPF. Differences between genotypes were observed in litter size, ChE activity, expression of butyrylcholinesterase and paraoxonase-1 in liver and variants of acetylcholinesterase, VAChT and the α7 receptor in the forebrain. These results support that there are different vulnerabilities to postnatal CPF exposure according to the APOE polymorphism, which in turn affects the cholinergic system and defenses to oxidative stress. © 2018 Elsevier Ltd
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