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1.
Nonlinear Dynamics Psychol Life Sci ; 28(2): 261-287, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506137

RESUMO

We develop a foreign exchange market model in which a market maker adjusts the exchange rate with respect to the trading behavior of chartists, fundamentalists and a central bank. While chartists bet on the persistence of bull and bear markets, fundamentalists speculate on mean reversion. The central bank seeks to stabilize the foreign exchange market by placing buy (sell) orders when the undervaluation (overvaluation) of the exchange rate exceeds a certain threshold. Since a one-dimensional piecewise-linear discontinuous map with three branches determines the evolution of the exchange rate, we use a combination of analytical and numerical tools to explore the extent to which the central bank is able to tame the behavior of the foreign exchange market.

2.
AJNR Am J Neuroradiol ; 43(12): 1749-1755, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36357152

RESUMO

BACKGROUND AND PURPOSE: Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and fistulas. Because reliable visibility of these liquid embolic agents is essential for intraprocedural visual control to prevent complications, novel angiographic systems are equipped with material-specific roadmap modes. The aim of this study was the systematic in vitro comparison of conventional and material-specific roadmap modes regarding the visibility of the most used liquid embolic agents. MATERIALS AND METHODS: A recently introduced in vitro model, resembling cerebral vessels, was embolized with Onyx 18, Squid 18, PHIL 25%, and n-BCA mixed with iodized oil (n = 4 for each liquid embolic agent), as well as with contrast medium and saline, both serving as a reference. Imaging was performed in conventional and material-specific roadmap modes. The visibility of the liquid embolic agents in both modes was compared quantitatively and qualitatively. RESULTS: Significant differences between conventional and material-specific roadmap modes regarding the visibility of the liquid embolic agents were observed for all study groups. All liquid embolic agents were better visible in the material-specific roadmap modes compared with the conventional mode in qualitative and quantitative analyses (eg, Onyx in conventional-versus-material-specific modes along the 1.0-mm sector: mean contrast-to-noise ratio, 5.69 [SD, 0.85] versus 47.18 [SD, 5.72]; P < .001, respectively). CONCLUSIONS: In this in vitro study, we demonstrated a better visibility of all investigated liquid embolic agents by using material-specific roadmap modes compared with the conventional roadmap technique. Especially in complex anatomic situations, these novel roadmap modes could improve the visual control and thus the safety and efficacy of embolization procedures in clinical practice.


Assuntos
Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Humanos , Dimetil Sulfóxido/uso terapêutico , Embolização Terapêutica/métodos , Resultado do Tratamento , Malformações Arteriovenosas Intracranianas/terapia , Polivinil/uso terapêutico , Angiografia
3.
Eur Radiol ; 32(4): 2246-2254, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34773465

RESUMO

OBJECTIVES: Artif icial intelligence (AI)-based image analysis is increasingly applied in the acute stroke field. Its implementation for the detection and quantification of hemorrhage suspect hyperdensities in non-contrast-enhanced head CT (NCCT) scans may facilitate clinical decision-making and accelerate stroke management. METHODS: NCCTs of 160 patients with suspected acute stroke were analyzed regarding the presence or absence of acute intracranial hemorrhages (ICH) using a novel AI-based algorithm. Read was performed by two blinded neuroradiology residents (R1 and R2). Ground truth was established by an expert neuroradiologist. Specificity, sensitivity, and area under the curve were calculated for ICH and intraparenchymal hemorrhage (IPH) detection. IPH-volumes were segmented and quantified automatically by the algorithm and semi-automatically. Intraclass correlation coefficient (ICC) and Dice coefficient (DC) were calculated. RESULTS: In total, 79 of 160 patients showed acute ICH, while 47 had IPH. Sensitivity and specificity for ICH detection were 0.91 and 0.89 for the algorithm; 0.99 and 0.98 for R1; and 1.00 and 0.98 for R2. Sensitivity and specificity for IPH detection were 0.98 and 0.89 for the algorithm; 0.83 and 0.99 for R1; and 0.91 and 0.99 for R2. Interreader reliability for ICH and IPH detection showed strong agreements for the algorithm (0.80 and 0.84), R1 (0.96 and 0.84), and R2 (0.98 and 0.92), respectively. ICC indicated an excellent (0.98) agreement between the algorithm and the reference standard of the IPH-volumes. The mean DC was 0.82. CONCLUSION: The AI-based algorithm reliably assessed the presence or absence of acute ICHs in this dataset and quantified IPH volumes precisely. KEY POINTS: • Artificial intelligence (AI) is able to detect hyperdense volumes on brain CTs reliably. • Sensitivity and specificity are highest for the detection of intraparenchymal hemorrhages. • Interreader reliability for hemorrhage detection shows strong agreement for AI and human readers.


Assuntos
Inteligência Artificial , Acidente Vascular Cerebral , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
4.
AJNR Am J Neuroradiol ; 42(1): 126-131, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33214178

RESUMO

BACKGROUND AND PURPOSE: Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and dural arteriovenous fistulas. The aim of this study was to assess the degree of artifact inducement by the most frequently used liquid embolic agents in conventional CT in an experimental in vitro model. MATERIALS AND METHODS: Dimethyl-sulfoxide-compatible tubes were filled with the following liquid embolic agents (n = 10, respectively): Onyx 18, all variants of Squid, PHIL 25%, PHIL LV, and n-BCA mixed with iodized oil. After inserting the tubes into a CT imaging phantom, we acquired images. Artifacts were graded quantitatively by the use of Hounsfield units in a donut-shaped ROI using a customized software application that was specifically designed for this study and were graded qualitatively using a 5-point scale. RESULTS: Quantitative and qualitative analyses revealed the most artifacts for Onyx 18 and the least artifacts for n-BCA, PHIL 25%, and PHIL LV. Squid caused more artifacts compared with PHIL, both for the low-viscosity and for the extra-low-viscosity versions (eg, quantitative analysis, Squid 18: mean ± SD, 30.3 ± 9.7 HU versus PHIL 25%: mean ± SD, 10.6 ± 0.8 HU; P < .001). Differences between the standard and low-density variants of Squid were observed only quantitatively for Squid 12. There were no statistical differences between the different concentrations of Squid and PHIL. CONCLUSIONS: In this systematic in vitro analysis investigating the most commonly used liquid embolic agents, relevant differences in CT imaging artifacts could be demonstrated. Ethylene-vinyl alcohol-based liquid embolic agents induced more artifacts compared with liquid embolic agents that use iodine as a radiopaque component.


Assuntos
Artefatos , Embolização Terapêutica , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Dimetil Sulfóxido , Combinação de Medicamentos , Embolização Terapêutica/métodos , Técnicas In Vitro , Polivinil , Tantálio , Tomografia Computadorizada por Raios X/métodos
5.
Sci Rep ; 8(1): 12333, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120303

RESUMO

Humpback whale (Megaptera novaeangliae) populations typically undertake seasonal migrations, spending winters in low latitude breeding grounds and summers foraging in high latitude feeding grounds. Until recently, a broad scale understanding of whale movement has been derived from whaling records, Discovery marks, photo identification and genetic analyses. However, with advances in satellite tagging technology and concurrent development of analytical methodologies we can now detail finer scale humpback whale movement, infer behavioural context and examine how these animals interact with their physical environment. Here we describe the temporal and spatial characteristics of migration along the east Australian seaboard and into the Southern Ocean by 30 humpback whales satellite tagged over three consecutive austral summers. We characterise the putative Antarctic feeding grounds and identify supplemental foraging within temperate, migratory corridors. We demonstrate that Antarctic foraging habitat is associated with the marginal ice zone, with key predictors of inferred foraging behaviour including distance from the ice edge, ice melt rate and variability in ice concentration two months prior to arrival. We discuss the highly variable ice season within the putative foraging habitat and the implications that this and other environmental factors may have on the continued strong recovery of this humpback whale population.

6.
Acta Physiol (Oxf) ; 222(3)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28888063

RESUMO

AIM: The voltage-gated potassium channel KV 11.1 is the molecular basis for the IKr current, which plays an important role in cardiac physiology. Its malfunction is associated with both inherited and acquired cardiac arrhythmias. Native currents differ from those in experimental models, suggesting additional regulatory mechanisms. We hypothesized that the post-translational modification sumoylation fine-tunes channel activity. METHODS: The functional effects of sumoylation on KV 11.1 were addressed by employing two-electrode voltage-clamp (TEVC) experiments in Xenopus laevis oocytes. Site-directed mutagenesis enabled a further analysis of the SUMO-target amino acids. We assessed protein expression levels and used confocal imaging for localization studies. RESULTS: Co-expression with Ubc9 and SUMO alters the electrophysiological properties of KV 11.1 leading to a decrease in steady-state current amplitude largely due to faster inactivation and alteration of deactivation kinetics. We identified three lysines (K21, K93 and K116) in the PAS domain as the putative SUMO-targets. CONCLUSION: This study indicates KV 11.1 as a sumoylation target and offers three main targets: K21, K93, and K116. Furthermore, it proposes an underlying mechanism for the observed kinetic impact of the PAS domain.


Assuntos
Canal de Potássio ERG1/metabolismo , Proteína SUMO-1/metabolismo , Animais , Feminino , Humanos , Oócitos , Sumoilação , Xenopus laevis
7.
J Mass Spectrom ; 52(7): 480-491, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28558143

RESUMO

Conformational change and modification of proteins are involved in many cellular functions. However, they can also have adverse effects that are implicated in numerous diseases. How structural change promotes disease is generally not well-understood. This perspective illustrates how mass spectrometry (MS), followed by toxicological and epidemiological validation, can discover disease-relevant structural changes and therapeutic strategies. We (with our collaborators) set out to characterize the structural and toxic consequences of disease-associated mutations and post-translational modifications (PTMs) of the cytosolic antioxidant protein Cu/Zn-superoxide dismutase (SOD1). Previous genetic studies discovered >180 different mutations in the SOD1 gene that caused familial (inherited) amyotrophic lateral sclerosis (fALS). Using hydrogen-deuterium exchange with mass spectrometry, we determined that diverse disease-associated SOD1 mutations cause a common structural defect - perturbation of the SOD1 electrostatic loop. X-ray crystallographic studies had demonstrated that this leads to protein aggregation through a specific interaction between the electrostatic loop and an exposed beta-barrel edge strand. Using epidemiology methods, we then determined that decreased SOD1 stability and increased protein aggregation are powerful risk factors for fALS progression, with a combined hazard ratio > 300 (for comparison, a lifetime of smoking is associated with a hazard ratio of ~15 for lung cancer). The resulting structural model of fALS etiology supported the hypothesis that some sporadic ALS (sALS, ~80% of ALS is not associated with a gene defect) could be caused by post-translational protein modification of wild-type SOD1. We developed immunocapture antibodies and high sensitivity top-down MS methods and characterized PTMs of wild-type SOD1 using human tissue samples. Using global hydrogen-deuterium exchange, X-ray crystallography and neurotoxicology, we then characterized toxic and protective subsets of SOD1 PTMs. To cap this perspective, we present proof-of-concept that post-translational modification can cause disease. We show that numerous mutations (N➔D; Q➔E), which result in the same chemical structure as the PTM deamidation, cause multiple diseases. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Esclerose Lateral Amiotrófica/genética , Superóxido Dismutase-1/metabolismo , Esclerose Lateral Amiotrófica/epidemiologia , Sítios de Ligação , Simulação por Computador , Cristalografia por Raios X/métodos , Métodos Epidemiológicos , Humanos , Espectrometria de Massas/métodos , Modelos Moleculares , Mutação , Estudo de Prova de Conceito , Ligação Proteica , Conformação Proteica , Processamento de Proteína Pós-Traducional , Proteólise , Eletricidade Estática , Superóxido Dismutase-1/genética
9.
Ann Oncol ; 27(12): 2257-2262, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27733374

RESUMO

BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). CONCLUSIONS: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted. REGISTERED CLINICAL TRIAL NUMBER: NCT00798655.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Panitumumabe , Carcinoma de Células Escamosas de Cabeça e Pescoço
10.
Acta Physiol (Oxf) ; 218(1): 28-37, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26914447

RESUMO

AIM: Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurones. METHODS: Effects of fatty acids and fatty acid analogues on mouse dorsal root ganglion neurones and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology. RESULTS: Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 µm) and increased the threshold current to evoke action potentials in dorsal root ganglion neurones. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-vs.-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 µm). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. CONCLUSIONS: These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability.


Assuntos
Ácidos Graxos Insaturados/farmacologia , Canal de Potássio KCNQ2/agonistas , Canal de Potássio KCNQ3/agonistas , Animais , Ácidos Graxos Ômega-3/farmacologia , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Xenopus laevis
11.
Ann Oncol ; 26(1): 40-47, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24997207

RESUMO

The tumor antigen (TA)-targeted monoclonal antibodies (mAb) cetuximab and panitumumab target the human epidermal growth factor receptor and have been integrated into treatment regimens for advanced squamous cell carcinoma of the head and neck (SCCHN). The therapeutic efficacy of these mAbs has been found to be enhanced when combined with radiotherapy and chemotherapy. However, clinical trials indicate that these findings are limited to fewer than 20% of treated patients. Therefore, identifying patients who are likely to benefit from these agents is crucial to improving therapeutic strategies. Interestingly, it has been noted that TA-targeted mAbs mediate their effects by contributing to cell-mediated cytotoxicity in addition to inhibition of downstream signaling pathways. Here, we describe the potential immunogenic mechanisms underlying these clinical findings, their role in the varied clinical response and identify the putative biomarkers of antitumor activity. We review potential immunological biomarkers that affect mAb therapy in SCCHN patients, the implications of these findings and how they translate to the clinical scenario, which are critical to improving patient selection and ultimately outcomes for patients undergoing therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antígenos de Neoplasias/imunologia , Biomarcadores , Carcinoma de Células Escamosas/radioterapia , Cetuximab , Terapia Combinada , Receptores ErbB/imunologia , Neoplasias de Cabeça e Pescoço/radioterapia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Macrófagos/imunologia , Panitumumabe , Infecções por Papillomavirus , Receptores de IgG/genética , Fator de Transcrição STAT3/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T Reguladores/imunologia , Evasão Tumoral/imunologia
12.
Pharm Stat ; 11(5): 394-402, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22740352

RESUMO

For normally distributed data analyzed with linear models, it is well known that measurement error on an independent variable leads to attenuation of the effect of the independent variable on the dependent variable. However, for time-to-event variables such as progression-free survival (PFS), the effect of the measurement variability in the underlying measurements defining the event is less well understood. We conducted a simulation study to evaluate the impact of measurement variability in tumor assessment on the treatment effect hazard ratio for PFS and on the median PFS time, for different tumor assessment frequencies. Our results show that scan measurement variability can cause attenuation of the treatment effect (i.e. the hazard ratio is closer to one) and that the extent of attenuation may be increased with more frequent scan assessments. This attenuation leads to inflation of the type II error. Therefore, scan measurement variability should be minimized as far as possible in order to reveal a treatment effect that is closest to the truth. In disease settings where the measurement variability is shown to be large, consideration may be given to inflating the sample size of the study to maintain statistical power.


Assuntos
Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Intervalo Livre de Doença , Humanos , Modelos Lineares , Neoplasias/patologia , Modelos de Riscos Proporcionais , Tamanho da Amostra , Fatores de Tempo
13.
Theriogenology ; 77(1): 53-64, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22015155

RESUMO

Motility of Pinctada margaritifera (Linnaeus, 1758); var: cumingii (Jameson, 1901) (P. margaritifera) spermatozoa collected from gonads are not immediately activated at spawning in seawater (SW) but motility occurs when spermatozoa are transferred into alkaline seawater (pH ranging from 9.0 to 11.4). This motility-activating effect of alkaline pH is reversed when pH is shifted back to more acidic values. In both cases, activity of sperm (% motile cells) increases gradually after alkaline pH activation then lasts for several minutes. The characteristics of these fully motile spermatozoa are described in details at the level of flagella: the wave amplitude and wave-length range 5 to 6 µm and 15 µm respectively, while the flagellar beat frequency is approximately 49 Hz. The velocity of sperm displacement is from 220 to 230 µm/sec. The general swimming pattern is almost circular: the head trajectories describe portions of circles intercalated with small linear segments. Spermatozoa saved in natural seawater at 4°C retain potent motility for several days and can be subsequently activated by alkaline seawater. Respiration and ATP concentration were measured in 3 conditions: regular seawater (pH 7.8), artificial diluent (pH 8.2), and alkaline Tris-buffered seawater (pH 10.5). Results show that sperm respiration rates are higher whereas ATP levels are lower in the latter two media.


Assuntos
Pinctada/fisiologia , Motilidade dos Espermatozoides , Espermatozoides/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Concentração de Íons de Hidrogênio , Masculino , Água do Mar/química , Espermatozoides/metabolismo
14.
Rev Sci Instrum ; 82(9): 093906, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21974599

RESUMO

Simple test equipment has been developed for studying the elastic limit and plastic deformation of thin metal wires and thin foils (down to 10 µm) under torsion, tension, and bending. Using load-unload methods and gauge lengths up to 1 m, plastic strain as low as 10(-6) can be measured accurately.

15.
Br J Pharmacol ; 160(8): 2028-44, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20649599

RESUMO

BACKGROUND AND PURPOSE: The compound NS5806 increases the transient outward current (I(to)) in canine ventricular cardiomyocytes and slows current decay. In human and canine ventricle, I(to) is thought to be mediated by K(V)4.3 and various ancillary proteins, yet, the exact subunit composition of I(to) channels is still debated. Here we characterize the effect of NS5806 on heterologously expressed putative I(to) channel subunits and other potassium channels. EXPERIMENTAL APPROACH: Cloned K(V)4 channels were co-expressed with KChIP2, DPP6, DPP10, KCNE2, KCNE3 and K(V)1.4 in Xenopus laevis oocytes or CHO-K1 cells. KEY RESULTS: NS5806 increased K(V)4.3/KChIP2 peak current amplitudes with an EC(50) of 5.3 +/- 1.5microM and significantly slowed current decay. KCNE2, KCNE3, DPP6 and DPP10 modulated K(V)4.3 currents and the response to NS5806, but current decay was slowed only in complexes containing KChIP2. The effect of NS5806 on K(V)4.2 was similar to that on K(V)4.3, and current decay was only slowed in presence of KChIP2. However, for K(V)4.1, the slowing of current decay by NS5806 was independent of KChIP2. K(V)1.4 was strongly inhibited by 10 microM NS5806 and K(V)1.5 was inhibited to a smaller extent. Effects of NS5806 on kinetics of currents generated by K(V)4.3/KChIP2/DPP6 with K(V)1.4 in oocytes could reproduce those on cardiac I(to) in canine ventricular myocytes. K(V)7.1, K(V)11.1 and K(ir)2 currents were unaffected by NS5806. CONCLUSION AND IMPLICATIONS: NS5806 modulated K(V)4 channel gating depending on the presence of KChIP2, suggesting that NS5806 can potentially be used to address the molecular composition as well as the physiological role of cardiac I(to).


Assuntos
Ativação do Canal Iônico/efeitos dos fármacos , Proteínas Interatuantes com Canais de Kv/metabolismo , Compostos de Fenilureia/farmacologia , Potássio/metabolismo , Canais de Potássio Shal/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Células CHO , Clonagem Molecular , Cricetinae , Cricetulus , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Humanos , Cinética , Proteínas Interatuantes com Canais de Kv/genética , Canal de Potássio Kv1.4/metabolismo , Potenciais da Membrana , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Canais de Potássio Shal/genética , Canais de Potássio Shal/metabolismo , Transfecção , Xenopus laevis
16.
Hautarzt ; 60(4): 320-7, 2009 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-19225743

RESUMO

BACKGROUND: Data on health services utilization by children and adults due to atopic eczema (AE) are scarce, as well as data concerning the epidemiology of AE in adults. METHODS: Utilizing a population-based administrative health care database from Saxony, Germany, that covers comprehensive information on outpatient health care of 2.1 million individuals in 2003 and 2004, this study describes the relevance of AE as the proportion of children and adults with outpatient visits due to AE (ICD10 L20). Age- and sex-stratified prevalences of AE were estimated as the proportion of individuals insured by the Saxony Compulsory Health Insurance (AOK Sachsen), who were diagnosed as having AE at least twice within the study period. RESULTS: Being diagnosed in 15.6% of all children (age<18), AE was the most prevalent chronic-inflammatory condition at all in this age group. The prevalence of AE was 22.8% in one year old children, 8% in adolescents, and 2 to 4% in adults. CONCLUSION: AE is of utmost public health importance in children and adolescents, and also relevant for outpatient healthcare beyond the discipline of dermatology in adults. Despite the higher prevalence in children, approximately 60% of all patients with AE were adults.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Sistema de Registros , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dermatite Atópica/terapia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
18.
Int J Obes (Lond) ; 31(11): 1642-51, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17607325

RESUMO

OBJECTIVE: The magnitude of the contribution of childbearing to the development of obesity is not entirely understood. Published studies on postpartum weight retention focus on risk factors and clinical interventions. Pooled estimates of postpartum weight retention have not been reported. We summarized the existing evidence of the natural history of postpartum weight retention and estimated the extent of time after delivery that weight retention is attributable to pregnancy. DESIGN: Systematic review and meta-analysis of qualitatively homogeneous studies. DATA SOURCES: Medline search of published studies between January 1995 and August 2005; bibliography of candidate studies. REVIEW METHODS: Eligibility: Observational studies and control groups of randomized controlled trials. Independent review and data abstraction including study design, subject characteristics, women's weight and study quality by two reviewers. Meta-analysis of average postpartum weight retention at different points in time after delivery. Sensitivity analysis for study specific covariates using meta-regression. RESULTS: Twenty-five studies describing 21 cohorts met eligibility criteria. Sixteen studies appeared homogeneous enough to be included in the meta-analysis. Average postpartum weight retention decreased continuously until 12 months postpartum (6 weeks: 2.42 (95% confidence interval (95% CI): 2.32-2.52) Body mass index (BMI), 6 months: 1.14 (95% CI: 1.04-1.25) BMI, 12 months: 0.46 (95% CI: 0.38-0.54) BMI). Postpartum weight retention was 0.46 BMI lower in studies with follow-up rate > or =80% at 6 weeks postpartum compared to studies with lower follow-up rate (P<0.01). CONCLUSION: Published studies consistently showed a decline in mean body weight within the first year postpartum. Data on body weight later than 12 months postpartum are scarce. The published evidence suggests a re-increase in body weight. As there are rather lifestyle-related than biological reasons for an increase in body weight after one year postpartum, we suggest using the term 'postpartum weight retention' exclusively within a limited period (for example, up to 12-18 months) postpartum.


Assuntos
Obesidade/etiologia , Complicações na Gravidez , Índice de Massa Corporal , Feminino , Humanos , Período Pós-Parto , Gravidez , Fatores de Risco , Fatores de Tempo , Aumento de Peso
19.
J Eur Acad Dermatol Venereol ; 21(5): 606-19, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17447974

RESUMO

OBJECTIVE: To systematically assess the effectiveness of systemic cyclosporin in patients with severe atopic eczema. STUDY DESIGN: Systematic review and meta-analysis of controlled and uncontrolled trials. Electronic (MEDLINE, Cochrane databases) and hand search of published work. Independent standardized assessment of eligibility and data abstraction by two reviewers. METHODS: For the qualitative review data on study design, study population, methodology, results, tolerability and methodological quality was independently extracted by two reviewers. Qualitatively homogeneous studies were pooled using a random-effects model. The mean relative change in objective disease severity was chosen as the main outcome measure for the quantitative analysis. Publication bias was explored by regressing treatment effect on sample size. Sensitivity analysis included meta-regression of study-specific covariates (inclusion of children, study type, concomitant topical therapy, study quality). RESULTS: Fifteen studies including 602 patients met the eligibility criteria. In all studies analysed, cyclosporin consistently decreased the severity of atopic eczema. Twelve studies appeared homogeneous enough to be pooled. After 2 weeks of treatment we found a dose-related response with a pooled mean decrease in disease severity of 22% (95%-CI 8-36%) under low-dose cyclosporin ( 3 mg/kg) and 40% (95%-CI 29-51%) at dosages >or=4 mg/kg. After 6-8 weeks the relative effectiveness was 55% (95%-CI 48-62%). CONCLUSIONS: Due to evidence of publication bias the quantitative results need to be interpreted with caution. Effectiveness of cyclosporin is similar in adults and children, but tolerability might be better in children. As data to adequately evaluate the long-term effectiveness and safety of cyclosporin in patients with atopic eczema are unavailable, long-term registries are encouraged.


Assuntos
Ciclosporina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Imunossupressores/uso terapêutico , Humanos
20.
Acta Neurochir (Wien) ; 146(9): 961-5; discussion 965, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15340805

RESUMO

BACKGROUND: A randomized prospective double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation. METHOD: In group I, 50 patients were treated by injection of 10 ml Ropivacaine 7,5% at the iliac crest bonegraft donor site. Local anaesthetic (LA) was injected through the wound drainage after closure of the muscle fascia, the suction drainage was opened after closure of the skin. Group II was treated with 0,9% saline. Operator and patient were blinded to the injected substance. Daily controls of pain intensity were made with the 10 cm visual analog scale from 0 (no pain) to 10 (severe pain) for 5 days. All patients were questioned regarding pain character and movement provoking pain. Additional pain medication was standardized. FINDINGS: Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups (p = 0,017, Chi-Square test). The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 (day 1: p = 0,54, not significant; day 2: p = 0,026; day 3: p = 0,008; day 4: p = 0,004; day 5: p = 0,002). INTERPRETATION: This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points. We conclude that wound infiltration with 7,5% Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain.


Assuntos
Amidas/uso terapêutico , Anestésicos Locais/uso terapêutico , Transplante Ósseo/métodos , Dor Pós-Operatória/prevenção & controle , Fusão Vertebral/métodos , Osteofitose Vertebral/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/administração & dosagem , Anestésicos Locais/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Ílio , Deslocamento do Disco Intervertebral/terapia , Masculino , Pessoa de Meia-Idade , Ropivacaina
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