Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 399
Filtrar
1.
J Clin Epidemiol ; : 111438, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909756

RESUMO

OBJECTIVE: To define the minimum knowledge required for guideline panel members (healthcare professionals and consumers) involved in developing recommendations about healthcare related testing. STUDY DESIGN AND SETTING: A developmental study with a multi-staged approach. We derived a first set of knowledge components from literature and subsequently performed semi-structured interviews with nine experts. We refined the set of knowledge components and checked it with the interviewees for final approval. RESULTS: Understanding the test-management pathway, e.g., how test results should be used in context of decisions about interventions, is the key knowledge component. The final list includes 26 items on the following topics: health question, test-management pathway, target population, test, test result, interpretation of test results & subsequent management, and impact on people important outcomes. For each item, the required level of knowledge is defined. CONCLUSION: We developed a list of knowledge components required for guideline panels to formulate recommendations on healthcare related testing. The list could be used to design specific training programs for guideline panel members when developing recommendations about tests and testing strategies in healthcare.

3.
Mult Scler J Exp Transl Clin ; 6(2): 2055217320928101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728476

RESUMO

BACKGROUND: Breastfeeding as an infant appears protective against later development of some autoimmune diseases, but research into its influence on multiple sclerosis (MS) risk has yielded inconclusive results. OBJECTIVE: We investigated the possible impact of breastfeeding on MS risk. METHODS: We used two population-based case-control studies comprising 3670 cases and 6737 matched controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between MS and exposure to prolonged breastfeeding (4 months or longer) versus reduced breastfeeding (less than 4 months). A meta-analysis of case-control studies that assessed the impact of breastfeeding on MS risk among women and men was conducted. RESULTS: Prolonged breastfeeding was associated with reduced MS risk among men (OR 0.7, 95% CI 0.5-0.9) but not among women (OR 0.9, 95% CI 0.8-1.1). Among men, a synergistic effect was observed between HLA-DRB1*15:01 carrier status and reduced breastfeeding. CONCLUSIONS: Findings from the current study add to accumulating evidence that breastfeeding may be a modifiable protective factor for reducing the risk of MS in offspring. When possible, mothers should be supported to breastfeed their infants; however, the mechanism of a sex-specific biologic effect of breastfeeding on MS risk is unclear.

4.
BJOG ; 126(13): 1560-1567, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31310697

RESUMO

OBJECTIVE: Risk of fetotoxicity after paracetamol exposure in the third trimester. DESIGN: Observational cohort study and retrospective case assessment. SETTING: Germany, 2008-2017. POPULATION: Pregnant women exposed to paracetamol. METHODS: Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. MAIN OUTCOME MEASURES: The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. RESULTS: In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. CONCLUSIONS: Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. TWEETABLE ABSTRACT: Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Permeabilidade do Canal Arterial/induzido quimicamente , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Acetaminofen/efeitos adversos , Adulto , Analgésicos não Narcóticos/efeitos adversos , Permeabilidade do Canal Arterial/embriologia , Feminino , Humanos , Recém-Nascido , Rim/anormalidades , Rim/embriologia , Nefropatias/embriologia , Gravidez , Terceiro Trimestre da Gravidez , Estudos Retrospectivos , Medição de Risco
5.
AJNR Am J Neuroradiol ; 40(8): 1422-1426, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31296522

RESUMO

BACKGROUND AND PURPOSE: Spinal muscular atrophy, a genetic disease resulting in loss of motor function, presents from in utero to adulthood. Depending on progression and secondary scoliosis, spinal stabilization may be necessary. When planning intrathecal access in these patients, spinal anatomy is the most important factor. Therefore, when planning intrathecal nusinersen injections, we subdivided patients with spinal muscular atrophy into simple-versus-complex spine subgroups. Our purpose was to present our experience with our first 42 transforaminal intrathecal nusinersen injections. MATERIALS AND METHODS: We reviewed 31 consecutive patients with spinal muscular atrophy types 1-3 who presented for intrathecal nusinersen injections from March 2017 to September 2018. Nine children had complex spines (ie, spinal instrumentation and/or fusion) and required preprocedural imaging for route planning for subarachnoid space access via transforaminal or cervical approaches. RESULTS: A total of 164 intrathecal nusinersen injections were performed in 31 children 4-226 months of age, with 100% technical success in accessing the subarachnoid space. Nine patients with complex spinal anatomy underwent 45 intrathecal nusinersen injections; 42 of 45 procedures were performed via a transforaminal approach with the remaining 3 via cervical techniques. There were no complications. CONCLUSIONS: Our initial experience has resulted in a protocol-driven approach based on simple or complex spinal anatomy. Patients with simple spines do not need preprocedural imaging or imaging-guided intrathecal nusinersen injections. In contrast, the complex spine subgroup requires preprocedural imaging for route planning and imaging guidance for therapy, with the primary approach being the transforaminal approach for intrathecal nusinersen injections.


Assuntos
Forame Magno/diagnóstico por imagem , Atrofias Musculares Espinais da Infância/diagnóstico por imagem , Atrofias Musculares Espinais da Infância/terapia , Coluna Vertebral/diagnóstico por imagem , Adolescente , Adulto , Vértebras Cervicais/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Injeções Espinhais , Masculino , Procedimentos Neurocirúrgicos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/uso terapêutico , Cuidados Pré-Operatórios , Espaço Subaracnóideo/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
6.
HNO ; 67(Suppl 2): 46-50, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927015

RESUMO

BACKGROUND: Tinnitus frequently occurs alongside psychological comorbidities whose assessment is important for treatment planning and -success. The selection of suitable questionnaires is thus crucial. The present study aims to investigate the ICD-10 Symptom Rating (ISR) to this regard. METHODS: The current study investigated tinnitus burden and psychological comorbidities in a sample of N = 311 patients with chronic tinnitus. All participants completed an intensive 7­day multimodal tinnitus-specific therapy. Tinnitus burden was measured using the German version of the Tinnitus Questionnaire (TQ). Psychological comorbidities were measured using the ISR (total score, depressive disorder, anxiety disorder, obsessive-compulsive disorder, somatoform disorder, and eating disorder), the Perceived Stress Questionnaire (PSQ; total score, tension, worries, joy, and demands), and the General Depression Scale (Allgemeine Depressionsskala, ADS). RESULTS: Sixty-five percent of participants suffered from psychological comorbidities. Treatment response comprised improvements in the TQ, ISQ, PSQ and ADS. At baseline, tinnitus-burden correlated with the ISR-total, ISR-obsessive-compulsive disorder and PSQ-tension scores. Post treatment, the-now reduced-tinnitus burden was additionally predicted by ISR-depressive and eating disorder scores. CONCLUSION: The ISR is a useful tool for measuring psychological comorbidities in patients with chronic tinnitus as well as short-term treatment response. Therapeutic approaches for chronic tinnitus should address stress-related tension, depressive symptomatology and coping strategies such as maladaptive eating behaviours.


Assuntos
Classificação Internacional de Doenças , Zumbido , Comorbidade , Depressão/psicologia , Humanos , Escalas de Graduação Psiquiátrica , Transtornos Somatoformes/psicologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Zumbido/diagnóstico , Zumbido/psicologia
7.
HNO ; 67(3): 178-183, 2019 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-30806717

RESUMO

BACKGROUND: Psychological comorbidities are frequent in tinnitus patients and their diagnosis is important for both interventions as well as treatment success. The selection of suitable questionnaires is thus crucial. The present study aimed to investigate the ICD-10 Symptom Rating (ISR) questionnaire for the diagnosis of psychological comorbidities. METHODS: The current study investigated tinnitus burden and psychological comorbidities in a sample of n = 311 patients with chronic tinnitus. All participants completed an intensive 7­day multimodal tinnitus-specific therapy. Tinnitus burden was measured using the German version of the Tinnitus Questionnaire (TQ). Psychological comorbidities were measured using the ISR (total score, depressive disorder, anxiety disorder, obsessive-compulsive disorder, somatoform disorder, and eating disorder), the Perceived Stress Questionnaire (PSQ; total score, tension, worries, joy, and demands), and the General Depression Scale (Allgemeine Depressionsskala, ADS). RESULTS: Psychological comorbidities were suffered by 65% of participants. Treatment response comprised improvements in TQ, ISR, PSQ, and ADS. At baseline, tinnitus burden correlated with the ISR total, ISR obsessive-compulsive disorder, and PSQ tension scores. Post-treatment, the now reduced tinnitus burden was also predicted by the ISR depressive and eating disorder scores. CONCLUSION: The ISR is a useful tool for measuring psychological comorbidities in patients with chronic tinnitus as well as for assessing short-term treatment response. Therapeutic approaches for chronic tinnitus should also consider stress-related tension, depressive symptomatology, and coping strategies such as maladaptive eating behaviors.


Assuntos
Transtornos Mentais , Zumbido , Comorbidade , Transtorno Depressivo , Humanos , Classificação Internacional de Doenças , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Zumbido/epidemiologia , Zumbido/psicologia
8.
J Asthma ; 56(4): 350-359, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29668337

RESUMO

OBJECTIVE: There is limited knowledge about the potential relationship between asthma and heart function. Aim of our present study was to examine if asthma may be associated with manifest or subclinical heart dysfunction. METHODS: Seventy-two allergic mild-to-moderate and severe asthma patients and 20 matched controls were enrolled in the study. Depending on the anti-asthmatic therapy, four subgroups of asthma patients were created: patients under long-acting beta2-agonists (LABA) and inhaled cortisone without oral cortisone treatment with (1a) versus without (1b) additional omalizumab therapy; patients with LABA, inhaled cortisone and omalizumab treatment with (2a) versus without (2b) oral cortisone. Standard echocardiographic parameters as well as global longitudinal left and right ventricular strains as determined by ultrasound-based speckle-tracking method were evaluated. Furthermore, NT-pro-brain natriuretic peptide (NT-pro-BNP), immunoglobulin E (IgE), C-reactive protein (CRP), and blood count were assessed in asthma and control groups. RESULTS: There were no relevant differences in standard echocardiographic measures between both asthma groups and the control collective. Longitudinal left ventricular strain values were reduced significantly in severe and mild-to-moderate asthma groups (-12.91 ± 0.84% and -13.92 ± 1.55%, respectively), whereas longitudinal right ventricular strain values were additionally relevantly decreased in severe asthma (-10.35 ± 1.04%) compared to the control (-16.55 ± 0.49% and -18.48 ± 1.90%, respectively). Cardiac strains were similar in subgroups 1a and 1b. In contrast, patients from subgroup 2a presented reduced heart strains and decreased lung function compared to those from 2b. CRP, IgE, and eosinophils were significantly increased in asthma versus control individuals. CONCLUSIONS: Allergic asthma, especially severe asthma is associated with subclinical impaired left and right ventricular function as determined by speckle-tracking analysis.


Assuntos
Asma/tratamento farmacológico , Asma/epidemiologia , Processamento de Imagem Assistida por Computador , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Direita/epidemiologia , Administração por Inalação , Adulto , Análise de Variância , Antiasmáticos , Asma/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Quimioterapia Combinada , Ecocardiografia/métodos , Feminino , Seguimentos , Humanos , Incidência , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem
9.
Rev Sci Instrum ; 89(10): 10J103, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399916

RESUMO

Two new magnetic probes have been deployed on the Pegasus spherical tokamak to study the dynamics of local helicity injection non-solenoidal plasma start-up and current drive. The magnetic radial array probe consists of 15 pickup coils (∼5 × 8 mm each) that measure B ̇ z ( R ) over a 15 cm linear extent. The coils consist of traces embedded in a printed circuit board. Three coil designs are utilized to balance frequency response and coil sensitivity. Helmholtz coil measurements are used to measure coil and full assembly bandwidths (∼2 MHz and ∼200 kHz, respectively) and sensitivities (0.18/0.35/0.96 mV T-1 s). The magnetic radial scanning probe is an array of Hall effect sensors that measure field strength ( | B | ≤ 177 mT) and direction at 8 spatial points (ΔR = 1.5 cm), supporting the studies of equilibrium field structure and low-frequency (≤5 kHz) current dynamics. It uses commercial surface-mount Hall effect sensors with chip-integrated amplifiers and compensators that are mounted in a 3-D printed frame. Helmholtz coil measurements indicate negligible cross-field gain nonlinearity and provide absolute calibration of the diagnostic. Both probes are constructed as an electrostatically shielded insertable air-side assembly that mounts within a radially translatable ultrahigh vacuum assembly from an existing probe.

10.
Pharm Res ; 36(1): 7, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30411161

RESUMO

PURPOSE: The identification of novel cell lines which combine the most important properties of mucosal membranes in terms of drug absorption, transmembrane transport and mucus secretion can help to establish improved and meaningful test systems for pharmacological and infectiological studies. METHODS: We have established a novel mucus secreting tumor cell line (Cx-03) derived from a female patient who underwent radical hysterectomy after diagnosis of a large malignant carcino sarcoma (Muellerian mixed tumor). Via xenotransplantation in SCID beige mice, recultivation and subcloning a stable cell line was established from primary tumor cells. RESULTS: Human origin and novelty of the cell line was determined by karyotype analysis and STR fingerprint. During growth cells produce considerable amounts of a PAS positive viscoelastic mucus. Immunostaining revealed expression of mucins and the mucin modifier CLCA1. We demonstrate in initial electrophysiological experiments that confluent, polarized monolayers of Cx-03 are formed (on PCF-filter supports) that exhibit stable electrical resistance (> 600 Ω cm2). Confluent Cx-03 monolayers express barrier-forming tight junction proteins claudin-1 and -4 which co-localize with zonula occludens protein-1 (ZO-1) at cell-cell contacts. CONCLUSIONS: Mucus secretion is a rare property among mammalian cell lines. In combination with its ability to form polarized monolayers Cx-03 might contribute as a novel cell based model for drug absorption, transport and barrier studies.


Assuntos
Linhagem Celular Tumoral , Mucinas/metabolismo , Muco/metabolismo , Sarcoma/metabolismo , Neoplasias Uterinas/metabolismo , Animais , Impedância Elétrica , Células Epiteliais/patologia , Feminino , Humanos , Camundongos SCID , Sarcoma/patologia , Neoplasias Uterinas/patologia , Proteína da Zônula de Oclusão-1/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-29735739

RESUMO

Using the simple 'allosteron' model, we show that it is possible, in principle, to elicit pathways by which fluctuation allostery affects self-assembly of protein complexes. We treat the cases of (i) protein fibrils and nucleation, (ii) n-mer protein complexes, and (iii) weakly attractive allosteric interactions in protein-like soft nanoscale objects that can be tuned to define exclusive self-associating families.This article is part of a discussion meeting issue 'Allostery and molecular machines'.


Assuntos
Regulação Alostérica , Entropia , Proteínas/química , Modelos Moleculares
12.
Phys Rev Lett ; 120(3): 036001, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29400489

RESUMO

Fluids with spatial density variations of single or mixed molecules play a key role in biophysics, soft matter, and materials science. The fluid structures usually form via spinodal decomposition or nucleation following an instantaneous destabilization of the initially disordered fluid. However, in practice, an instantaneous quench is often not viable, and the rate of destabilization may be gradual rather than instantaneous. In this work we show that the commonly used phenomenological descriptions of fluid structuring are inadequate under these conditions. We come to that conclusion in the context of surface catalysis, where we employ kinetic Monte Carlo simulations to describe the unimolecular adsorption of gaseous molecules onto a metal surface. The adsorbates diffuse at the surface and, as a consequence of lateral interactions and due to an ongoing increase of the surface coverage, phase separate into coexisting low- and high-density regions. The typical size of these regions turns out to depend much more strongly on the rate of adsorption than predicted from recently reported phenomenological models. We discuss how this finding contributes to the fundamental understanding of the crossover from liquid-liquid to liquid-solid demixing of solution-cast polymer blends.

13.
Nat Commun ; 9(1): 423, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29379024

RESUMO

Often, the interpretation of experiments concerning the manipulation of the energy distribution of laser-accelerated ion bunches is complicated by the multitude of competing dynamic processes simultaneously contributing to recorded ion signals. Here we demonstrate experimentally the acceleration of a clean proton bunch. This was achieved with a microscopic and three-dimensionally confined near critical density plasma, which evolves from a 1 µm diameter plastic sphere, which is levitated and positioned with micrometer precision in the focus of a Petawatt laser pulse. The emitted proton bunch is reproducibly observed with central energies between 20 and 40 MeV and narrow energy spread (down to 25%) showing almost no low-energetic background. Together with three-dimensional particle-in-cell simulations we track the complete acceleration process, evidencing the transition from organized acceleration to Coulomb repulsion. This reveals limitations of current high power lasers and viable paths to optimize laser-driven ion sources.

14.
Br J Neurosurg ; 32(5): 574-576, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27967243

RESUMO

Presented is a case of a 64-year old male with a unique and yet unreported case of a spondylodiscitis caused by Clostridium perfringens. Becoming symptomatic with massive neurological deficits. Computed tomography (CT) revealed typical signs of spondylodiscitis involving the vertebral body L5 with extensive vacuum phenomenon.

15.
Macromolecules ; 50(15): 5914-5919, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-29056760

RESUMO

Solution-cast, thin-film polymer composites find a wide range of applications, such as in the photoactive layer of organic solar cells. The performance of this layer crucially relies on its phase-separated morphology. Efficient charge-carrier extraction requires each of the components to preferentially wet one of the two electrodes. It is often presumed that the experimentally observed surface enrichment required for this is caused by specific interactions of the active ingredients with each surface. By applying a generalized diffusion model, we find the dynamics to also play an important role in determining which component accumulates at which surface. We show that for sufficiently fast evaporation the component with the smallest cooperative diffusivity accumulates at the free interface. Counterintuitively, depending on the interactions between the various components, this may be the smaller solute. Our comprehensive numerical and analytical study provides a tool to predict and control phase-separated morphologies in thin-film polymer composites.

16.
Z Rheumatol ; 76(10): 838-847, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-28986633

RESUMO

BACKGROUND: The cervical spine is one of the main sites of manifestation in rheumatoid arthritis outside of the extremities. It can have a decisive influence on disease course via the occurrence of mechanical instabilities as well as neurologic symptoms. Both adequate diagnosis and the corresponding surgical treatment represent a challenge for the involved physicians. MATERIALS AND METHODS: This review presents relevant diagnostic strategies and possibilities for surgical intervention which aim to avoid potentially fatal neurologic symptoms. Basic literature and expert opinions are also discussed. RESULTS AND CONCLUSION: Through target-oriented surgical management, as well as tight clinical and radiologic monitoring during conservative and surgical therapy, potentially fatal disease courses can be avoided.


Assuntos
Artrite Reumatoide/diagnóstico , Vértebras Cervicais , Espondilite Anquilosante/diagnóstico , Artrite Reumatoide/cirurgia , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Diagnóstico Diferencial , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/cirurgia , Imageamento por Ressonância Magnética , Exame Neurológico , Platibasia/diagnóstico , Platibasia/cirurgia , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/cirurgia , Fusão Vertebral , Espondilite Anquilosante/cirurgia , Tomografia Computadorizada por Raios X
17.
Cell Mol Biol (Noisy-le-grand) ; 63(5): 119-126, 2017 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-28719356

RESUMO

Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only. Human neutrophil elastase (HNE) and respiratory Burst were measured. To evaluate the modulation of inflammatory crosstalk we applied inhibitors of COX (acetyl salicylic acid; ASA), NO-synthase (N-monomethyl-L-arginin; L-NMMA), and the PAF-receptor (WEB2086). Unstimulated, co-incubation of CaCo-2 cells and PMN led to significantly reduced Burst and elevated HNE as compared to PMN. After stimulation with A23187, co-incubation resulted in an inhibition of Burst and HNE. Using fMLP co-incubation failed to modulate Burst but increased HNE. Without stimulation, all three inhibitors abolished the effect of co-incubation on Burst but did not change HNE.  ASA partly prevented modulation of Burst L-NMMA and WEB2086 did not change Burst but abolished mitigation of HNE. Without stimulation, co-incubation reduced Burst and elevated HNE. Activation of PMN and CaCo-2 cells by fMLP as compared to A23187 resulted in a completely different pattern of Burst and HNE, possibly due to single vs. dual cell activation. Anti-inflammatory effect of co-incubation might in part be due to due to COX-signalling governing Burst whereas NO- and PAF-dependent signalling seemed to control HNE release.


Assuntos
Inflamação/patologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Aspirina/farmacologia , Azepinas/farmacologia , Células CACO-2 , Calcimicina/farmacologia , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/metabolismo , Explosão Respiratória/efeitos dos fármacos , Triazóis/farmacologia , ômega-N-Metilarginina/farmacologia
18.
Mol Psychiatry ; 22(9): 1359-1367, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28485404

RESUMO

Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects' alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10-72) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10-4) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10-20 for drinker status and beta=-0.19, P=1.91 × 10-35 for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10-7 and beta=-0.21, P=2.58 × 10-6, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10-10 for drinks/week and OR=0.96, P=4.08 × 10-5 for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10-8 for drinks/week and OR=1.04, P=5 × 10-4 for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Adulto , Negro ou Afro-Americano/genética , Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Povo Asiático/genética , Etnicidade/genética , Feminino , Loci Gênicos , Predisposição Genética para Doença , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Hispânico ou Latino/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Autorrelato , População Branca/genética
19.
Sci Total Environ ; 596-597: 124-135, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28431357

RESUMO

The ongoing trend of increasing air temperatures will potentially affect soil organic matter (SOM) turnover and soil C-CO2 emissions in terrestrial ecosystems of Maritime Antarctica. The effects of SOM quality on this process remain little explored. We evaluated (i) the quantity and quality of soil organic matter and (ii) the potential of C release through CO2 emissions in lab conditions in different soil types from Maritime Antarctica. Soil samples (0-10 and 10-20cm) were collected in Keller Peninsula and the vicinity of Arctowski station, to determine the quantity and quality of organic matter and the potential to emit CO2 under different temperature scenarios (2, 5, 8 and 11°C) in lab. Soil organic matter mineralization is low, especially in soils with low organic C and N contents. Recalcitrant C form is predominant, especially in the passive pool, which is correlated with humic substances. Ornithogenic soils had greater C and N contents (reaching to 43.15gkg-1 and 5.22gkg-1 for total organic carbon and nitrogen, respectively). C and N were more present in the humic acid fraction. Lowest C mineralization was recorded from shallow soils on basaltic/andesites. C mineralization rates at 2°C were significant lower than at higher temperatures. Ornithogenic soils presented the lowest values of C-CO2 mineralized by g of C. On the other hand, shallow soils on basaltic/andesites were the most sensitive sites to emit C-CO2 by g of C. With permafrost degradation, soils on basaltic/andesites and sulfates are expected to release more C-CO2 than ornithogenic soils. With greater clay contents, more protection was afforded to soil organic matter, with lower microbial activity and mineralization. The trend of soil temperature increases will favor C-CO2 emissions, especially in the reduced pool of C stored and protected on permafrost, or in occasional Histosols.

20.
Adv Exp Med Biol ; 980: 1-9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28132132

RESUMO

A common feature of sarcoidosis and atherosclerosis is a chronic systemic inflammatory reaction. Our hypothesis was that sarcoidosis may negatively influence the vessel status. We addressed the issue by examining preatherosclerotic vascular alternations using an ultrasound-based speckle-tracking method in 72 sarcoidosis patients and 15 matched controls. To find potential factors which may have a deleterious influence on arterial performance, different subgroups of sarcoidosis, such as sarcoidosis with or without cortisone therapy, pulmonary sarcoidosis in early and advanced stages, pulmonary sarcoidosis alone or combined with extrapulmonary sarcoidosis, and sarcoidosis with or without elevated blood levels of angiotensin converting enzyme (ACE)/soluble interleukin 2 receptor (sIL-2R) were investigated. We found in the general collective of sarcoidosis patients that circumferential strain (2.68 ± 0.19%), circumferential strain rate (0.21 ± 0.01 1/s), and radial displacement (0.10 ± 0.01 mm) were significantly decreased compared to controls (3.77 ± 0.35%, 0.28 ± 0.02 1/s, and 0.14 ± 0.02 mm, respectively). Vascular strains were more impaired in patients with cortisone therapy, pulmonary sarcoidosis in stages III-IV, and in pulmonary sarcoidosis accompanied by extrapulmonary involvement. The level of ACE/sIL-2R had no relevant influence on the angiological parameters. In conclusion, sarcoidosis is associated with increased vascular stiffness. Cortisone therapy and advanced stages of pulmonary sarcoidosis with extrapulmonary manifestations may account for the impaired vascular function in this patient collective.


Assuntos
Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/patologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/metabolismo , Receptores de Interleucina-2/metabolismo , Sarcoidose Pulmonar/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...