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1.
BMC Med Educ ; 23(1): 224, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37029404

RESUMEN

BACKGROUND: Person-centered care is needed to effectively support workers with chronic health conditions. Person-centered care aims to provide care tailored to an individual person's preferences, needs and values. To achieve this, a more active, supportive, and coaching role of occupational and insurance physicians is required. In previous research, two training programs and an e-learning training with accompanying tools that can be used in the context of person-centered occupational health care were developed to contribute to this changing role. The aim was to investigate the feasibility of the developed training programs and e-learning training to enhance the active, supportive, and coaching role of occupational and insurance physicians needed for person-centered occupational health care. Information about this is important to facilitate implementation of the tools and training into educational structures and occupational health practice. METHODS: A qualitative study was conducted, with N = 29 semi-structured interviews with occupational physicians, insurance physicians, and representatives from occupational educational institutes. The aim was to elicit feasibility factors concerning the implementation, practicality and integration with regard to embedding the training programs and e-learning training in educational structures and the use of the tools and acquired knowledge and skills in occupational health care practice after following the trainings and e-learning training. Deductive analysis was conducted based on pre-selected focus areas for a feasibility study. RESULTS: From an educational perspective, adapting the face-to-face training programs to online versions, good coordination with educational managers and train-the-trainer approaches were mentioned as facilitating factors for successful implementation. Participants underlined the importance of aligning the occupational physicians' and insurance physicians' competences with the educational content and attention for the costs concerning the facilitation of the trainings and e-learning training. From the professional perspective, factors concerning the content of the training and e-learning training, the use of actual cases from practice, as well as follow-up training sessions were reported. Professionals expressed good fit of the acquired skills into their consultation hour in practice. CONCLUSION: The developed training programs, e-learning training and accompanying tools were perceived feasible in terms of implementation, practicality, and integration by occupational physicians, insurance physicians and educational institutes.


Asunto(s)
Salud Laboral , Humanos , Estudios de Factibilidad , Aprendizaje , Personal de Salud/educación , Atención Dirigida al Paciente
2.
Bioact Mater ; 19: 127-138, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35475029

RESUMEN

Calcium phosphates (CaP) are widely used synthetic bone graft substitutes, having bioactivity that is regulated by a set of intertwined physico-chemical and structural properties. While some CaPs have shown to be as effective in regenerating large bone defects as autologous bone, there is still the need to understand the role of individual material properties in CaP performance. Here, we aimed to decouple the effects of chemical composition and surface-microstructure of a beta-tricalcium phosphate (TCP) ceramic, with proven osteoinductive potential, on human mesenchymal stromal cells (hMSCs) differentiation. To this end, we replicated the surface structure of the TCP ceramic into polylactic acid without inorganic additives, or containing the chemical constituents of the ceramic, i.e., a calcium salt, a phosphate salt, or TCP powder. The microstructure of the different materials was characterized by confocal laser profilometry. hMSCs were cultured on the materials, and the expression of a set of osteogenic genes was determined. The cell culture medium was collected and the levels of calcium and phosphate ions were quantified by inductively-coupled plasma mass spectrometry. The results revealed that none of the tested combinations of properties in polymer/composite replicas was as potent in supporting the osteogenic differentiation of hMSCs as the original ceramic. Nevertheless, we observed some effects of the surface structure in the absence of inorganics, as well as combined effects of surface structure and the added salts, in particular calcium, on osteogenic differentiation. The approach presented here can be used to study the role of independent properties in other CaP-based biomaterials.

3.
Persoonia ; 49: 171-194, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38234384

RESUMEN

During surveys in central Florida of the zombie-ant fungus Ophiocordyceps camponoti-floridani, which manipulates the behavior of the carpenter ant Camponotus floridanus, two distinct fungal morphotypes were discovered associated with and purportedly parasitic on O. camponoti-floridani. Based on a combination of unique morphology, ecology and phylogenetic placement, we discovered that these morphotypes comprise two novel lineages of fungi. Here, we propose two new genera, Niveomyces and Torrubiellomyces, each including a single species within the families Cordycipitaceae and Ophiocordycipitaceae, respectively. We generated de novo draft genomes for both new species and performed morphological and multi-loci phylogenetic analyses. The macromorphology and incidence of both new species, Niveomyces coronatus and Torrubiellomyces zombiae, suggest that these fungi are mycoparasites since their growth is observed exclusively on O. camponoti-floridani mycelium, stalks and ascomata, causing evident degradation of their fungal hosts. This work provides a starting point for more studies into fungal interactions between mycopathogens and entomopathogens, which have the potential to contribute towards efforts to battle the global rise of plant and animal mycoses. Citation: Araújo JPM, Lebert BM, Vermeulen S, et al. 2022. Masters of the manipulator: two new hypocrealean general, Niveomyces (Cordycipitaceae) and Torrubiellomyces (Ophiocordycipitaceae), parasitic on the zombie ant fungus Ophiocordyceps camponoti-floridani. Persoonia 49: 171-194. https://doi.org/10.3767/persoonia.2022.49.05.

4.
BMC Public Health ; 21(1): 1091, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098911

RESUMEN

BACKGROUND: The aim was to identify the most important determinants of practice for the implementation of person-centered tools which enhance work participation for patients with chronic health conditions. METHODS: A mixed-method study was conducted consisting of semi-structured interviews, a focus group and a survey. Various stakeholders were involved including (representatives of) workers with chronic health conditions, insurance physicians, occupational physicians, other healthcare professionals, researchers, employers, and policymakers. The semi-structured interviews were performed to identify implementation determinants, followed by a focus group to validate resulting determinants. To conclude, a survey was conducted to select the most important implementation determinants through prioritization by ranking the order of importance. The Tailored Implementation of Chronic Diseases checklist (TICD) was used as concept-driven coding frame for the qualitative analysis of the interviews and focus group. The self-developed survey was based on the domains of the TICD. The survey was analyzed by frequency count of first ranking of determinants per and between domains of the TICD. RESULTS: Various stakeholders participated (N = 27) in the interviews and focus group. The qualitative data retrieved yielded a list of determinants with additional in-depth themes according to the TICD. For the selection of the most important determinants, a survey with 101 respondents was conducted, consisting of occupational physicians, insurance physicians and workers with a chronic health condition. From the seven domains of the TICD, respondents emphasized the importance of taking into account the needs and factors associated with workers with a chronic health condition as this determinant ranked highest. Taking into account the individual needs and wishes of workers was mentioned to enable successful implementation, whereas stress of the workers was indicated to impede implementation. Other important determinants included 'being able to work with the tools' in terms of time and usability or 'cognitions, beliefs and attitudes of occupational and insurance physicians' to be able to use the tools. CONCLUSION: This study identified the most important determinants from the perspective of various stakeholders involved in the implementation of client-centered tools in occupational health for workers with chronic health conditions. Furthermore, by prioritizing the most important determinants, targeted implementation strategies can be developed.


Asunto(s)
Lista de Verificación , Proyectos de Investigación , Enfermedad Crónica , Grupos Focales , Personal de Salud , Humanos , Investigación Cualitativa
5.
PLoS One ; 16(3): e0248293, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33735291

RESUMEN

The distribution of signaling molecules following mechanical or chemical stimulation of a cell defines cell polarization, with regions of high active Cdc42 at the front and low active Cdc42 at the rear. As reaction-diffusion phenomena between signaling molecules, such as Rho GTPases, define the gradient dynamics, we hypothesize that the cell shape influences the maintenance of the "front-to-back" cell polarization patterns. We investigated the influence of cell shape on the Cdc42 patterns using an established computational polarization model. Our simulation results showed that not only cell shape but also Cdc42 and Rho-related (in)activation parameter values affected the distribution of active Cdc42. Despite an initial Cdc42 gradient, the in silico results showed that the maximal Cdc42 concentration shifts in the opposite direction, a phenomenon we propose to call "reverse polarization". Additional in silico analyses indicated that "reverse polarization" only occurred in a particular parameter value space that resulted in a balance between inactivation and activation of Rho GTPases. Future work should focus on a mathematical description of the underpinnings of reverse polarization, in combination with experimental validation using, for example, dedicated FRET-probes to spatiotemporally track Rho GTPase patterns in migrating cells. In summary, the findings of this study enhance our understanding of the role of cell shape in intracellular signaling.


Asunto(s)
Polaridad Celular/fisiología , Forma de la Célula/fisiología , Modelos Biológicos , Proteína de Unión al GTP cdc42/metabolismo , Simulación por Computador , Difusión , Transducción de Señal/fisiología
6.
Behav Genet ; 49(3): 270-285, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30659475

RESUMEN

We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas del Tejido Nervioso/genética , Proteínas R-SNARE/genética , ARN Largo no Codificante/genética , Adulto , Animales , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Estudios de Cohortes , ADN sin Sentido/genética , ADN sin Sentido/metabolismo , Femenino , Predisposición Genética a la Enfermedad/genética , Genética de Población/métodos , Estudio de Asociación del Genoma Completo , Genotipo , Células HEK293 , Humanos , Masculino , Ratones , Fenotipo , Polimorfismo de Nucleótido Simple/genética , ARN Largo no Codificante/metabolismo , Factores de Riesgo
7.
Toxicol Lett ; 303: 72-77, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30605749

RESUMEN

PURPOSE: Cd is considered as a genotoxic carcinogen for which a threshold can be identified. This threshold has, however, not been established and the shape of the relationship between Cd exposure and genotoxic effects is unknown. The aim of the present study was to analyse the shape of the dose-response relationship for the genotoxic effects of Cd in occupational settings. METHODS: The study has a cross-sectional design and includes 60 healthy male and female workers with known Cd exposure selected from two plants manufacturing or recycling nickel-Cd batteries. The frequency of MN was measured in circulating lymphocytes, and related to internal Cd doses (Cd-B, Cd-U). Determinants of MN frequency were traced by multivariate regression analysis. RESULTS: Cd exposure covered a wide range as measured by Cd-B (0.02-1.26 µg/dL), Cd-U (0.26-15.80 µg/g creat) and seniority in the plant (1-42 years). Gender was the only parameter significantly associated with MN frequency, women having on average 8.5 additional MN/1000 BN cells compared to men. Cd-B, Cd-U or Ni-U did not influence MN frequency when adjusted for gender and other potential confounders. CONCLUSION: This finding is consistent with the existing knowledge on the mechanisms governing the genotoxic activity of Cd, which are all non-stochastic and thresholded. The threshold for systemic genotoxic effects of Cd is thus beyond the range of internal exposure considered in the present investigation.


Asunto(s)
Cadmio/toxicidad , Daño del ADN , Linfocitos/efectos de los fármacos , Pruebas de Micronúcleos , Exposición Profesional/efectos adversos , Adulto , Carcinógenos/toxicidad , Creatinina/sangre , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Níquel/toxicidad
10.
Artículo en Inglés | MEDLINE | ID: mdl-26603683

RESUMEN

Over 50% of cancer survivors lose their job or quit working. Cancer survivors who experience job loss may face different challenges regarding return to work, compared to cancer survivors with employers. This qualitative study aimed to explore barriers and facilitators for return to work in cancer survivors with job loss and in insurance physicians who assist cancer survivors in their return to work. We conducted five focus groups and one interview (cancer survivors, N = 17; insurance physicians, N = 23). Topics included, among others, experience of job loss and barriers and facilitators for return to work. Data were audio recorded and analysed using thematic analysis. Our main finding was that cancer survivors experienced a double loss: loss of job on top of loss of health. As a result, cancer survivors feared for job applications, lacked opportunities to gradually increase work ability, and faced reluctance from employers in hiring them. Insurance physicians expressed a need for more frequent and longer consultations with cancer survivors with job loss. We conclude that cancer survivors who experience double loss encounter specific barriers in the return to work process. This calls for a tailored approach regarding return to work support.


Asunto(s)
Supervivientes de Cáncer , Médicos , Reinserción al Trabajo , Desempleo , Adulto , Femenino , Grupos Focales , Humanos , Seguro de Salud , Solicitud de Empleo , Masculino , Persona de Mediana Edad , Países Bajos , Investigación Cualitativa
11.
Br J Dermatol ; 176(5): 1288-1296, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27564082

RESUMEN

BACKGROUND: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. OBJECTIVES: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. METHODS: We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2 -test or Fisher's exact test (PASI 75, secondary analysis). RESULTS: We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis. CONCLUSIONS: We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.


Asunto(s)
Productos Biológicos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Psoriasis/tratamiento farmacológico , Adalimumab/uso terapéutico , Etanercept/uso terapéutico , Femenino , Marcadores Genéticos , Humanos , Subunidad p40 de la Interleucina-12/genética , Masculino , Persona de Mediana Edad , Psoriasis/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Resultado del Tratamiento , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Ustekinumab/uso terapéutico
12.
Aliment Pharmacol Ther ; 45(3): 391-402, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27943397

RESUMEN

BACKGROUND: Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. AIM: To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment. METHODS: The cohort study consisted of the first 270 IBD patients starting thiopurine treatment as part of the Dutch randomised-controlled trial evaluating pre-treatment thiopurine S-methyltransferase genotype testing (ClinicalTrials.gov NCT00521950). Blood samples for metabolite assessment were collected at T1. Hepatotoxicity was defined by alanine aminotransaminase elevations >2 times the upper normal limit or a ratio of alanine aminotransaminase/alkaline phosphatase ≥5. RESULTS: Forty-seven patients (17%) presented hepatotoxicity during the first 20 weeks of thiopurine treatment. A T1 6-MMPR threshold of 3615 pmol/8 × 108 erythrocytes was defined. Analysis of patients on stable thiopurine dose (n = 174) showed that those exceeding the 6-MMPR threshold were at increased risk of hepatotoxicity: OR = 3.8 (95% CI: 1.8-8.0). Age, male gender and BMI were significant determinants. A predictive algorithm was developed based on these determinants and the 6-MMPR threshold to assess hepatotoxicity risk [AUC = 0.83 (95% CI: 0.75-0.91)]. 6-MMPR concentrations above the threshold also correlated with gastrointestinal complaints: OR = 2.4 (95% CI: 1.4-4.3), and general malaise: OR = 2.0 (95% CI: 1.1-3.7). CONCLUSIONS: In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure.


Asunto(s)
Azatioprina/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mercaptopurina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Genotipo , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/metabolismo , Masculino , Mercaptopurina/análogos & derivados , Metiltransferasas/metabolismo , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tioinosina/análogos & derivados , Tioinosina/metabolismo , Tionucleótidos/metabolismo , Resultado del Tratamiento , Adulto Joven
13.
Br J Cancer ; 112(3): 594-600, 2015 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-25429525

RESUMEN

BACKGROUND: Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case-control studies worldwide. METHODS: Information on (i) history and age at onset of regular cystitis ('regular low-UTI') and (ii) number and age at onset of UTI treated with antibiotics ('UTI-ab') from 1809 UBC patients and 4370 controls was analysed. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, education, smoking, and use of aspirin/ibuprofen were generated, for men and women separately. RESULTS: Regular low-UTI was associated with an increased UBC risk (men: OR (95% CI) 6.6 (4.2-11); women: 2.7 (2.0-3.5)), with stronger effects in muscle-invasive UBC. Statistically significant decreased risks (ORs ∼0.65) were observed for up to five UTI-ab, specifically in those who (had) smoked and experienced UTI-ab at a younger age. In women, UTI experienced after menopause was associated with a higher UBC risk, irrespective of the number of episodes. CONCLUSIONS: Regular cystitis is positively associated with UBC risk. In contrast, a limited number of episodes of UTI treated with antibiotics is associated with decreased UBC risk, but not in never-smokers and postmenopausal women.


Asunto(s)
Neoplasias de la Vejiga Urinaria/epidemiología , Infecciones Urinarias/epidemiología , Anciano , Estudios de Casos y Controles , Cistitis/complicaciones , Cistitis/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Recurrencia , Factores de Riesgo
14.
Ann Rheum Dis ; 74(3): e15, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24532677

RESUMEN

INTRODUCTION: Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. METHODS: We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. RESULTS: The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. CONCLUSIONS: Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.


Asunto(s)
Artritis Reumatoide/genética , Antígenos HLA/genética , Alelos , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Citrulina/inmunología , Estudio de Asociación del Genoma Completo , Antígenos HLA/inmunología , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Humanos , Modelos Logísticos , Péptidos/inmunología , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Población Blanca/genética
15.
J Asthma ; 51(7): 743-50, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24654705

RESUMEN

OBJECTIVE: This study will investigate the reproducibility and influencing factors of exhaled breath temperature measured with the tidal breathing technique in asthmatic patients and healthy children. METHODS: Exhaled breath temperature, fractional exhaled nitric oxide, and spirometry were assessed in 124 children (63 healthy and 61 asthmatic), aged 11.2 ± 2.5 year, M/F 73/51. A modified version of the American Thoracic Society questionnaire on the child's present and past respiratory history was obtained from parents. Parents were also asked to provide detailed information on their child's medication use during the previous 4 weeks. Ear temperature, ambient temperature, and relative-ambient humidity were also recorded. RESULTS: Exhaled breath temperature measurements were highly reproducible; the second measurement was higher than the first measurement, consistent with a test-retest situation. In 13 subjects, between-session within-day reproducibility of exhaled breath temperature was still high. Exhaled breath temperature increased with age and relative-ambient humidity. Exhaled breath temperature was comparable in healthy and asthmatic children; when adjusted for potential confounders (i.e. ambient conditions and subject characteristics), thermal values of asthmatic patients exceeded those of the healthy children by 1.1 °C. Normalized exhaled breath temperature, by subtracting ambient temperature, was lower in asthmatic patients treated with inhaled corticosteroids than in those who were corticosteroid-naive. CONCLUSION: Measurements of exhaled breath temperature are highly reproducible, yet influenced by several factors. Corrected values, i.e. normalized exhaled breath temperature, could help us to assess the effect of therapy with inhaled corticosteroids. More studies are needed to improve the usefulness of the exhaled breath temperature measured with the tidal breathing technique in children.


Asunto(s)
Asma/fisiopatología , Temperatura Corporal , Pruebas Respiratorias , Espiración , Estudios de Casos y Controles , Niño , Humanos , Óxido Nítrico/análisis , Reproducibilidad de los Resultados , Temperatura , Volumen de Ventilación Pulmonar
16.
Pharmacogenomics J ; 14(2): 115-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23648444

RESUMEN

Methotrexate (MTX), one of the important pillars in the treatment of different forms of cancer, is associated with the development of hepatotoxicity. The 677C>T variant (rs1801133) in the methylenetetrahydrofolate reductase (MTHFR) gene might affect the development of hepatotoxicity. Results in literature are, however, contradictive. The aim of this study was to evaluate the role of the MTHFR 677C>T polymorphism in MTX-induced hepatotoxicity by analyzing a Dutch cohort of pediatric patients treated with high doses of MTX and subsequently performing a meta-analysis. Ninety-eight patients receiving 542 courses of high-dose MTX were genotyped for the MTHFR 677C>T variant. Hepatotoxicity was evaluated retrospectively according to common terminology criteria for adverse events-National Cancer Institute criteria. The influence of MTHFR 677C>T on hepatotoxicity was examined using a generalized estimating equation (GEE) analysis. A fixed-effect meta-analysis based on this and previous studies investigating the association between the MTHFR 677C>T polymorphism and uniformly coded hepatotoxicity was performed. The GEE analysis showed an increased risk of developing hepatotoxicity for T versus C allele (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.0-3.2, P=0.04). This finding was not supported by the meta-analysis including seven studies and 1044 patients; the OR for the 677T versus C allele was 1.1 (95% CI 0.84-1.5, P=0.25). Heterogeneity between studies was observed, possibly related to differences in MTX dose and leucovorin rescue. In conclusion, in patients with cancer, the MTHFR 677T allele has only a minor role in the development of MTX-induced hepatotoxicity. Observed heterogeneity between studies warrants further study into (tailored) leucovorin rescue.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Metotrexato/efectos adversos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Niño , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Metotrexato/administración & dosificación , Polimorfismo de Nucleótido Simple
18.
B-ENT ; 8(3): 219-23, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23113387

RESUMEN

A solitary fibrous tumour (SFT) is a rare tumour that originates from the mesenchyme and arises mainly in the pleura. In this report, we present a rare case of a 77-year-old man with a SFT in the left nasal cavity. On CT and MRI, a large mass is seen in the left nasal cavity, extending to the choana. The mass was radically resected via functional endoscopic sinus surgery (FESS). Histological examination showed a fibroblastic mesenchymal tumour with a prominent hemangiopericytic vascular branching pattern that stained diffusely positive for the immunohistochemical markers CD34, Bcl-2, and CD99, which was compatible with the histopathological diagnosis of a SFT. Imaging and histological features are discussed, along with the reports in literature, clinical management, and follow-up of this pathology.


Asunto(s)
Cavidad Nasal , Cirugía Endoscópica por Orificios Naturales/métodos , Neoplasias Nasales/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico , Anciano , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Nasales/cirugía , Tumores Fibrosos Solitarios/cirugía , Tomografía Computarizada por Rayos X
19.
Artículo en Inglés | MEDLINE | ID: mdl-21770846

RESUMEN

The aim of the current study was to evaluate and compare two representative samples of different classes of adsorbents intended for use as feed additives in the prevention or reduction of the adverse effects exerted by mycotoxins, specifically ochratoxin A (OTA) and zearalenone (ZEN). The adsorbents, an organically activated bentonite (OAB) and a humic acid polymer (HAP), were tested in a common in vitro model with a pH course comparing the maximum pH changes that can be expected in the digestive system of a monogastric animal, i.e. pH 7.4 for the oral cavity, pH 3.0 for the stomach, and pH 8.4 for the intestines. In the first experiment, the concentration-dependent adsorbent capacity of OAB and HAB were tested using a fixed concentration of either mycotoxin. Thereafter, adsorption was evaluated applying different isotherms models, such as Freundlich, Langmuir, Brunauer-Emmett-Teller (BET) and Redlich-Peterson, to characterize the adsorption process as being either homo- or heterogeneous and representing either mono- or multilayer binding. At the recommended statutory level for the mycotoxins of 0.1 mg kg(-1) OTA and 0.5 mg kg(-1) ZEN, OAB showed an adsorbed capacity of >96% towards both mycotoxins, regardless of the pH. The HAP product was also able to absorb >96% of both mycotoxins at pH 3.0, but extensive desorption occurred at pH 8.4. Based on χ-square (χ(2)) values, Langmuir and Redlich-Peterson equations proved to be the best models to predict monolayer equilibrium sorption of OTA and ZEN onto the organically activated bentonite and the humic acid polymer. The applied methodology has a sufficient robustness to facilitate further comparative studies with different mycotoxin-adsorbing agents.


Asunto(s)
Bentonita/química , Sustancias Húmicas , Modelos Teóricos , Micotoxinas/química , Polímeros/química , Termodinámica , Adsorción , Distribución de Chi-Cuadrado , Cromatografía Líquida de Alta Presión , Concentración de Iones de Hidrógeno , Estructura Molecular
20.
Am J Epidemiol ; 168(5): 541-7, 2008 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-18650222

RESUMEN

The prenatal environment plays an important role in many conditions, particularly those with onset early in life, such as childhood cancers and birth defects. Because both maternal and fetal genotypes can influence risk, investigators sometimes use a case-mother/control-mother design, with mother-offspring pairs as the unit of analysis, to study genetic factors. Risk models should account for both the maternal genotype and the correlated fetal genotype to avoid confounding. The usual logistic regression analysis, however, fails to fully exploit the fact that these are mothers and offspring. Consider an autosomal, diallelic locus, which could be related to disease susceptibility either directly or through linkage with a polymorphic causal locus. Three nested levels of assumptions are often natural and plausible. The first level simply assumes Mendelian inheritance. The second further assumes parental mating symmetry for the studied locus in the source population. The third additionally assumes parental allelic exchangeability. Those assumptions imply certain nonlinear constraints; the authors enforce those constraints by using Poisson regression together with the expectation-maximization algorithm. Calculations reveal that improvements in efficiency over the usual logistic analysis can be substantial, even if only the Mendelian assumption is honored. Benefits are even more marked if, as is typical, information on genotype is missing for some individuals.


Asunto(s)
Feto , Madres , Atención Prenatal/métodos , Efectos Tardíos de la Exposición Prenatal/genética , Adulto , Algoritmos , Alelos , Estudios de Casos y Controles , Exposición a Riesgos Ambientales , Femenino , Ligamiento Genético , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Modelos Logísticos , Modelos Genéticos , Países Bajos , North Carolina , Padres , Distribución de Poisson , Polimorfismo de Nucleótido Simple , Embarazo , Factores de Riesgo
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