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1.
Prev Med Rep ; 29: 101964, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36161129

RESUMO

Smoking prevention in schoolchildren to inform and prevent smoking initiation has been widely studied; however, the potential effect of interventions provided in a hospital setting is unknown. An intervention program named "Schoolchildren smoking prevention in the hospital" was developed in which the health aspects of smoking and its individual consequences were presented in an interactive informational event provided by a thoracic surgeon and a pulmonologist. We aimed to assess the feasibility and the short-term effect of smoking-related knowledge improvement in schoolchildren in a hospital setting. Scholars of 45 classes in Canton of Zurich in Switzerland filled in an anonymous 5-item questionnaire with questions on general knowledge about smoking. The answers were evaluated in this prospective observational cohort study. The primary endpoint was to compare the knowledge improvement by interpretation of answers before-and-after the smoking prevention intervention. Additionally, the performance of children was compared after setting up an overall score and specific subgroups according to gender and school-level. Between Jan 2010, and Oct 2019, schoolchildren aged 10 to 16 years participated in this intervention program and completed the questionnaire before (N = 1270) and after (N = 1264) the intervention. The amount of correctly answered questions increased from 40% (±20) before to 81% (±17), p < 0·0001 after the educational session. An intervention program on health effects of smoking provided by lung specialists in the hospital is feasible, well received, leads to a substantial increase of knowledge, and hopefully can be further explored in the development of smoking prevention programs for schoolchildren.

3.
Ultrasound Obstet Gynecol ; 56(5): 678-683, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763720

RESUMO

OBJECTIVES: Fetal surgery for repair of open neural tube defect (ONTD) typically results in decreased need for a ventriculoperitoneal shunt (VPS). Our objectives were to determine the trend in ventricle size (VS) during pregnancy and whether VS and change in VS, as assessed by ultrasound, were predictive of the need for VPS in pregnancy with ONTD. METHODS: This was a retrospective analysis of prospectively collected data of consecutive pregnancies with ONTD, evaluated in a single center from January 2012 to May 2018. Two groups were identified: the first consisted of pregnancies that underwent in-utero repair (IUR) and the second those that had postnatal repair (PNR). Penalized B splines were used to determine the trend in VS, across 2-week gestational-age (GA) epochs, between 24 and 36 weeks of gestation. VS at each GA epoch and the change in VS between each GA epoch were compared between the IUR and PNR groups. To determine whether VS at any GA was predictive of VPS, receiver-operating-characteristics (ROC) curves were used and the optimal cut-off at each GA epoch was identified. Univariate analysis and multiple logistic regression were used for further analysis. RESULTS: ONTD was diagnosed in 110 fetuses, of whom 69 underwent IUR and 41 had PNR. Fetuses in the IUR group were more likely to have Chiari II malformation (100.0% vs 82.9%; P < 0.01), lower GA at delivery (34.9 ± 3.2 vs 37.1 ± 2.1 weeks; P < 0.01) and lower rates of VPS within the first year postpartum (36.2% vs 61.0%; P = 0.02) compared with the PNR group. In both groups, VS increased steadily with GA from the initial evaluation to delivery. In the IUR group, there was a significant change in VS between the 24 + 0 to 25 + 6-week and the 26 + 0 to 27 + 6-week epochs (2.3 (95% CI, 0.4-4.1) mm; P = 0.02). There was a positive trend in the change in VS at later GAs, but this was not significant. Although there was no significant change in VS in the PNR group before 30 weeks, there was a positive trend after that time. On multivariate analysis, each week of advancing GA was associated with a mean increase of 0.74 mm in VS (P < 0.0001) in both groups. VS was not associated with the level or type of lesion, but presence of Chiari II malformation was associated with a mean increase of 5.88 mm (P < 0.0001) in VS in both the IUR and PNR groups. VS was modestly predictive of need for VPS in both groups, with area under ROC curves between 0.68 and 0.76 at the different GA epochs. Change in VS between the first and last measurements was also modestly predictive of the need for VPS, with better performance in the PNR group. CONCLUSIONS: VS increased with advancing GA in all fetuses with ONTD, although in the IUR group this increase occurred immediately after fetal surgery and in the PNR group it occurred after 30 weeks of gestation. In-utero surgery was associated with a decreased rate of VPS and was more predictive of need for VPS than was VS. Postnatal factors resulting in increased need for VPS in the PNR group need to be assessed further. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Ventrículos Cerebrais/diagnóstico por imagem , Defeitos do Tubo Neural/diagnóstico por imagem , Defeitos do Tubo Neural/cirurgia , Ultrassonografia Pré-Natal/estatística & dados numéricos , Derivação Ventriculoperitoneal/estatística & dados numéricos , Adulto , Ventrículos Cerebrais/embriologia , Feminino , Terapias Fetais/estatística & dados numéricos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Defeitos do Tubo Neural/embriologia , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
4.
Sci Total Environ ; 659: 1382-1386, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096348

RESUMO

Biotransformation of methane at landfill sites can be estimated by applying compound specific stable isotope analysis of methane from the anaerobic and the cover layer surface zone. Next to these two input parameters, merely the knowledge of the carbon isotopic fractionation of the bacterial methane oxidation in terms of the enrichment factor (ε) is required. However, many factors and conditions have been described to affect ε. These include temperature, the applied landfill cover, the type of expressed methane monooxygenase (MMO), and cell density. In this work we investigated the microbial methane oxidation with respect to temperature and type of methanotrophic enrichment culture. A newly designed setup was used to overcome potential CH4-substrate limitations such as diffusion that could affect the determined values of ε by improper and inhomogeneous mixing. The isotopic fractionation was determined based on the stable carbon isotope analysis of methane and carbon dioxide. The obtained value for isotopic fractionation was ε22°C = -0.0136 ±â€¯0.0036. Also for the first time, bulk stable isotope analysis of bacterial cell mass was performed by flow injection analysis isotope ratio mass spectrometry.


Assuntos
Biodegradação Ambiental , Monitoramento Ambiental/métodos , Metano/análise , Microbiologia do Solo , Instalações de Eliminação de Resíduos , Metano/metabolismo , Oxigenases , Eliminação de Resíduos
5.
Sci Total Environ ; 665: 1064-1072, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30893738

RESUMO

Biological stability of treated wastewater is currently determined by methods such as biological oxygen demand, ATP-quantification, or flow-cytometric cell counting. However, the continuous increase in water reclamation for wastewater reuse requires new methods for quantifying degradation of biodegradable dissolved organic carbon (BDOC) ranging from very small to high concentrations of dissolved organic carbon (DOC). Furthermore, direct activity measures or absolute concentrations of BDOC are needed that produce comparable and reproducible results in all laboratories. Measuring carbon mineralization by CO2 evolution presents a suitable approach for directly measuring the microbial degradation activity. In this work, we investigated the extent of BDOC in water samples from effluent of a wastewater treatment plant and after purification by ultrafiltration over 204 days. BDOC monitoring was performed with the recently introduced reverse stable isotope labeling (RIL) analysis using mid-infrared spectroscopy for the monitoring of microbial CO2 production. Average BDOC degradation rates ranged from 0.11 to 0.32 mg L-1 d-1 for wastewater treatment plant effluent and from 0.03 to 0.22 mg L-1 d-1 after ultrafiltration. BDOC was degraded over >90 days indicating the long-term instability of the DOC. Degradation experiments over 88 days revealed first order kinetic rate constants for BDOC which corresponded to 12.7 ·â€¯10-3 d-1 for wastewater treatment plant effluent and 2.7 ·â€¯10-3 d-1 after ultrafiltration, respectively. A thorough sensitivity analysis of the RIL showed that the method is very accurate and sensitive with method detection limits down to 10 µg·â€¯L-1 of measured CO2.


Assuntos
Carbono/análise , Monitoramento Ambiental/métodos , Substâncias Húmicas/análise , Águas Residuárias/análise , Monitoramento Ambiental/instrumentação , Marcação por Isótopo/métodos , Reciclagem , Espectrofotometria Infravermelho/métodos
6.
Parasit Vectors ; 10(1): 90, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212669

RESUMO

BACKGROUND: Stable isotope analysis of carbon and nitrogen can deliver insights into trophic interactions between organisms. While many studies on free-living organisms are available, the number of those focusing on trophic interactions between hosts and their associated parasites still remains scarce. In some cases information about taxa (e.g. acanthocephalans) is completely missing. Additionally, available data revealed different and occasionally contrasting patterns, depending on the parasite's taxonomic position and its degree of development, which is most probably determined by its feeding strategy (absorption of nutrients through the tegument versus active feeding) and its localization in the host. METHODS: Using stable isotope analysis of carbon and nitrogen we provided first data on the trophic position of an acanthocephalan species with respect to its fish host. Barbels (Barbus barbus) infected only with adult acanthocephalans Pomphorhynchus laevis as well as fish co-infected with the larval (L4) nematodes Eustrongylides sp. from host body cavity were investigated in order to determine the factors shaping host-parasite trophic interactions. Fish were collected in different seasons, to study also potential isotopic shifts over time, whereas barbels with single infection were obtained in summer and co-infected ones in autumn. RESULTS: Acanthocephalans as absorptive feeders showed lower isotope discrimination values of δ 15N than the fish host. Results obtained for the acanthocephalans were in line with other parasitic taxa (e.g. cestodes), which exhibit a similar feeding strategy. We assumed that they feed mainly on metabolites, which were reprocessed by the host and are therefore isotopically lighter. In contrast, the nematodes were enriched in the heavier isotope δ 15N with respect to their host and the acanthocephalans, respectively. As active feeders they feed on tissues and blood in the body cavity of the host and thus showed isotope discrimination patterns resembling those of predators. We also observed seasonal differences in the isotope signatures of fish tissues and acanthocephalans, which were attributed to changes in food composition of the host and to seasonality in the transmission and development of acanthocephalans. CONCLUSIONS: This study provided first data on trophic interaction between an acanthocephalan species and its associated host, which support the tendency already described for other taxa with similar nutrition strategy (e.g. cestodes). Actively feeding taxa such as larval Eustrongylides sp., appear to act like predators as it can be seen from their isotope discrimination values. However, future research on additional host-parasite systems and especially on acanthocephalans is needed in order to corroborate these conclusions.


Assuntos
Acantocéfalos/fisiologia , Carbono/metabolismo , Cyprinidae/parasitologia , Doenças dos Peixes/parasitologia , Helmintíase Animal/parasitologia , Interações Hospedeiro-Parasita , Nitrogênio/metabolismo , Animais , Ascaridídios/fisiologia , Infecções por Ascaridida/parasitologia , Infecções por Ascaridida/veterinária , Isótopos de Carbono , Cadeia Alimentar , Isótopos de Nitrogênio , Estado Nutricional
7.
Urologe A ; 56(3): 336-341, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-28102436

RESUMO

BACKGROUND: A urethral stricture is a scar of the urethral epithelium which can cause obstructive voiding dysfunction with consequential damage of the upper urinary tract. Almost 45% of all strictures are iatrogenic; they develop in 2-9% of patients after radical prostatectomy, but can also occur after prostate cancer radiotherapy. This study provides 5­year data of a certified prostate cancer center (PKZ) in terms of urethral strictures. MATERIALS AND METHODS: Between 01/2008 and 12/2012 a total of 519 men were irradiated for prostate cancer (LDR and HDR brachytherapy as well as external beam radiation). The entire cohort was followed-up prospectively according to a standardized protocol (by type of irradiation). Short segment urethral strictures were treated by urethrotomy, recurrent and long segment stenosis with buccal mucosa urethroplasty. RESULTS: A total of 18 of 519 (3.4%) patients developed a urethral stricture post-therapeutically, which recurred in 66% of cases after the first operative treatment. The largest risk for developing a urethral stricture is attributed to the HDR brachytherapy (8.9%). CONCLUSION: Urethral strictures after prostate cancer radiotherapy should be diagnosed and treated in time for long-term preservation of renal function. The rate of radiogenic urethral strictures (3.4%) is equivalent to those after radical prostatectomy. Due to a high rate of recurrences, urethrotomy has a limited importance after irradiation.


Assuntos
Braquiterapia/estatística & dados numéricos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/epidemiologia , Radioterapia Conformacional/estatística & dados numéricos , Estreitamento Uretral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Fracionamento da Dose de Radiação , Alemanha/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/patologia , Fatores de Risco , Estreitamento Uretral/patologia
8.
Chem Commun (Camb) ; 51(70): 13485-7, 2015 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-26214384

RESUMO

While cyclic ether forming terpene synthases are known, the basis for such heterocyclisation is unclear. Here it is reported that numerous (di)terpene synthases, particularly including the ancestral ent-kaurene synthase, efficiently produce isomers of manoyl oxide from the stereochemically appropriate substrate. Accordingly, such heterocyclisation is easily accomplished by terpene synthases. Indeed, the use of single residue changes to induce production of the appropriate substrate in the upstream active site leads to efficient bifunctional enzymes producing isomers of manoyl oxide, representing novel enzymatic activity.


Assuntos
Alquil e Aril Transferases/metabolismo , Técnicas de Química Analítica/métodos , Ciclização , Cromatografia Gasosa-Espectrometria de Massas , Modelos Biológicos , Modelos Moleculares
9.
Food Chem Toxicol ; 81: 129-136, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25910834

RESUMO

Astaxanthin, a naturally occurring xanthophyll, is commercially used as a coloring agent in salmon feed, but also marketed as a dietary supplement. The objective of this study was to investigate the subchronic toxicity of synthetic [3S, 3'S]-Astaxanthin in rats. A powder formulation containing approximately 20% [3S, 3'S]-Astaxanthin was administered via the diet to groups of 10 male and 10 female Wistar rats at concentrations of 5000, 15,000 and 50,000 ppm for a period of 13 weeks. A formulation of comparable composition but without [3S, 3'S]-Astaxanthin served as a placebo control. There were no effects observed on survival, clinical examinations, clinical pathology, estrous cycle as well as on sperm parameters. At terminal necropsy, a macroscopically visible brown-blue discoloration of the gastrointestinal contents was noted which was considered to be secondary to the violet-brown color of the test material. No other significant or dose-related abnormalities were found in the tissues collected at termination. Our observations support that ingestion of [3S, 3'S]-Astaxanthin of up to 700-920 mg/kg bw/day in rats in a gelatin/carbohydrate formulation is without adverse effects.


Assuntos
Testes de Toxicidade Subcrônica/métodos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Glicemia/metabolismo , Peso Corporal , Colesterol/sangue , Creatinina/sangue , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Albumina Sérica/metabolismo , Triglicerídeos/sangue , Xantofilas/sangue , Xantofilas/toxicidade
10.
J Thromb Haemost ; 12(2): 220-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24641308

RESUMO

BACKGROUND: Recombinant factor VIIa (rFVIIa) is approved for use in controlling bleeding episodes in people with hemophilia who have developed inhibitors to replacement therapy. Due to its short half-life (t½), frequent injections are required, limiting its use as a prophylactic treatment. A novel, recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP) has been developed to extend the t(½) of rFVIIa. OBJECTIVES: The aim of our studies was to investigate the pharmacokinetic/pharmacodynamic characteristics of rVIIa-FP in preclinical animal species. METHODS: Pharmacokinetic (PK) parameters were derived after single intravenous dosing in hemophilia A mice, rats, rabbits and monkeys. PK analysis was based on human FVII plasma levels determined by measuring FVII antigen levels by ELISA in mice and rats, and FVIIa activity using STACLOT® VIIa-rTF in rabbits and monkeys. Induction of thrombin generation was investigated in mice, while hemostatic activity was assessed by thrombus formation in rabbits. RESULTS: Compared with rFVIIa, rVIIa-FP displayed a prolonged t(½), enhanced in vivo recovery and reduced clearance in all species investigated. In mice, 16 h after treatment with rVIIa-FP, thrombin levels were quantifiable, indicating prolonged efficacy, whereas values had approached baseline at this time after treatment with rFVIIa. After 12 h, hemostatic efficacy was negligible in rFVIIa-treated rabbits, but sustained in animals receiving rVIIa-FP. CONCLUSIONS: These studies indicate that the longer t(½) of rVIIa-FP compared with rFVIIa translates into extended activity. These findings suggest that rVIIa-FP has the potential to be administered less frequently than rFVIIa-containing concentrates in clinical use.


Assuntos
Albuminas/farmacologia , Fator VIIa/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Albuminas/química , Albuminas/farmacocinética , Animais , Fator VIIa/química , Fator VIIa/farmacocinética , Hemofilia A/tratamento farmacológico , Macaca fascicularis , Camundongos , Tempo de Protrombina , Coelhos , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacocinética
11.
Thromb Haemost ; 110(5): 931-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24178510

RESUMO

The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa), respectively. The extension of the half-lives of rFIX and rFVIIa could allow for longer intervals between infusions and could thereby improve adherence and clinical outcomes and may improve quality of life. Albumin fusion is one of a number of different techniques currently being examined to prolong the half-life of rFIX and rFVIIa. Results from a phase I clinical trial demonstrated that the recombinant fusion protein linking FIX to albumin (rIX-FP) has a five-times longer half-life than rFIX, and preclinical studies with the recombinant fusion protein linking FVIIa to albumin (rVIIa-FP) suggest that rVIIa-FP possesses a significantly extended half-life versus rFVIIa. In this review, we describe albumin fusion technology and examine the recent progress in the development of rIX-FP and rVIIa-FP.


Assuntos
Albuminas/metabolismo , Fator IX/metabolismo , Fator VIIa/metabolismo , Hemofilia A/tratamento farmacológico , Engenharia de Proteínas/métodos , Proteínas Recombinantes de Fusão/uso terapêutico , Albuminas/genética , Albuminas/uso terapêutico , Animais , Fator IX/genética , Fator IX/uso terapêutico , Fator VIIa/genética , Fator VIIa/uso terapêutico , Hemofilia A/sangue , Humanos , Adesão à Medicação , Engenharia de Proteínas/tendências , Qualidade de Vida
12.
Klin Padiatr ; 225(6): 303-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24166094

RESUMO

Treatment for neuroblastoma, the most common extracranial childhood tumor, spans a broad range of aggressiveness that mirrors the risk profiles of disease subtypes, with high-risk neuroblastoma still presenting a clinical challenge. Currently, most patients with relapsed neuro-blastoma die of disease and present a major challenge for treatment. New therapeutic options are urgently needed to improve patient survival. Activating mutations in the gene encoding the anaplastic lymphoma kinase (ALK) remain the most frequent druggable mutations identified in neuroblastomas to date. Preclinical data support an oncogene addiction of neuroblastoma cells to mutated ALK and demonstrate that ALK inhibitory therapy strongly combats tumor models. Most recently, pediatric phase I testing has been completed for the first approved ALK inhibitor, Crizotinib, showing very encouraging antitumoral results in neuroblastoma patients. Subsequently, an international phase I study with the second generation ALK inhibitor, LDK-378, will be launched that makes ALK inhibitory therapy also available to pediatric patients in Germany.


Assuntos
Sistemas de Liberação de Medicamentos , Neuroblastoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Quinase do Linfoma Anaplásico , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Criança , Ensaios Clínicos Fase I como Assunto , Crizotinibe , Análise Mutacional de DNA , Aprovação de Drogas , Alemanha , Humanos , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Sulfonas/efeitos adversos , Sulfonas/uso terapêutico
13.
Oncogene ; 32(8): 1059-65, 2013 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-22484425

RESUMO

Neuroblastoma is an embryonal tumor with a heterogeneous clinical course. The tumor is presumed to be derived from the neural crest, but the cells of origin remain to be determined. To date, few recurrent genetic changes contributing to neuroblastoma formation, such as amplification of the MYCN oncogene and activating mutations of the ALK oncogene, have been identified. The possibility to model neuroblastoma in mice allows investigation of the cell of origin hypothesis in further detail. Here we present the evidence that murine neural crest progenitor cells can give rise to neuroblastoma upon transformation with MYCN or ALK(F1174L). For this purpose we used JoMa1, a multipotent neural crest progenitor cell line, which is kept in a viable and undifferentiated state by a tamoxifen-activated c-Myc transgene (c-MycER(T)). Expression of MYCN or ALK(F1174L), one of the oncogenic ALK variants identified in primary neuroblastomas, enabled these cells to grow independently of c-MycER(T) activity in vitro and caused formation of neuroblastoma-like tumors in vivo in contrast to parental JoMa1 cells and JoMa1 cells-expressing TrkA or GFP. Tumorigenicity was enhanced upon serial transplantation of tumor-derived cells, and tumor cells remained susceptible to the MYC-inhibitor, NBT-272, indicating that cell growth depended on functional MYCN. Our findings support neural crest progenitor cells as the precursor cells of neuroblastoma, and indicate that neuroblastomas arise as their malignant progeny.


Assuntos
Células-Tronco Neoplásicas/patologia , Crista Neural/patologia , Neuroblastoma/genética , Neuroblastoma/patologia , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Células-Tronco/patologia , Quinase do Linfoma Anaplásico , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Humanos , Camundongos , Camundongos Nus , Camundongos Transgênicos , Proteína Proto-Oncogênica N-Myc , Células-Tronco Neoplásicas/metabolismo , Crista Neural/metabolismo , Neuroblastoma/metabolismo , Proteínas Nucleares/biossíntese , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/metabolismo , Células-Tronco/metabolismo , Transfecção , Transplante Heterólogo
14.
IEEE Trans Vis Comput Graph ; 18(12): 2216-25, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26357129

RESUMO

Geoscientific modeling and simulation helps to improve our understanding of the complex Earth system. During the modeling process, validation of the geoscientific model is an essential step. In validation, it is determined whether the model output shows sufficient agreement with observation data. Measures for this agreement are called goodness of fit. In the geosciences, analyzing the goodness of fit is challenging due to its manifold dependencies: 1) The goodness of fit depends on the model parameterization, whose precise values are not known. 2) The goodness of fit varies in space and time due to the spatio-temporal dimension of geoscientific models. 3) The significance of the goodness of fit is affected by resolution and preciseness of available observational data. 4) The correlation between goodness of fit and underlying modeled and observed values is ambiguous. In this paper, we introduce a visual analysis concept that targets these challenges in the validation of geoscientific models - specifically focusing on applications where observation data is sparse, unevenly distributed in space and time, and imprecise, which hinders a rigorous analytical approach. Our concept, developed in close cooperation with Earth system modelers, addresses the four challenges by four tailored visualization components. The tight linking of these components supports a twofold interactive drill-down in model parameter space and in the set of data samples, which facilitates the exploration of the numerous dependencies of the goodness of fit. We exemplify our visualization concept for geoscientific modeling of glacial isostatic adjustments in the last 100,000 years, validated against sea levels indicators - a prominent example for sparse and imprecise observation data. An initial use case and feedback from Earth system modelers indicate that our visualization concept is a valuable complement to the range of validation methods.

15.
Phys Rev Lett ; 107(5): 051301, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21867059

RESUMO

We report results of a search for light (≲10 GeV) particle dark matter with the XENON10 detector. The event trigger was sensitive to a single electron, with the analysis threshold of 5 electrons corresponding to 1.4 keV nuclear recoil energy. Considering spin-independent dark matter-nucleon scattering, we exclude cross sections σ(n)>7×10(-42) cm(2), for a dark matter particle mass m(χ)=7 GeV. We find that our data strongly constrain recent elastic dark matter interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as well as the DAMA annual modulation signal.


Assuntos
Radiação Cósmica , Interpretação Estatística de Dados , Elétrons , Física Nuclear , Humanos , Luz , Fótons , Espalhamento de Radiação
16.
Toxicol Sci ; 123(1): 264-80, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21642632

RESUMO

Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.


Assuntos
Nanopartículas Metálicas/toxicidade , Pele/efeitos dos fármacos , Queimadura Solar/tratamento farmacológico , Protetores Solares/toxicidade , Titânio/toxicidade , Óxido de Zinco/toxicidade , Animais , Eritema/etiologia , Eritema/patologia , Eritema/prevenção & controle , Técnicas In Vitro , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Pele/patologia , Pele/efeitos da radiação , Pele/ultraestrutura , Queimadura Solar/etiologia , Queimadura Solar/patologia , Protetores Solares/farmacocinética , Suínos/fisiologia , Titânio/farmacocinética , Titânio/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Óxido de Zinco/farmacocinética , Óxido de Zinco/efeitos da radiação
17.
Eur Addict Res ; 16(2): 78-84, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20110712

RESUMO

BACKGROUND: Dually diagnosed clients are described as one of the most challenging treatment populations, often leading to staff frustration, helplessness and negative attitudes. As yet it is unclear whether dual diagnosis (DD)-specific competency and therapeutic optimism among staff are related to client outcomes. METHODS: The study used a 3-month follow-up design involving 124 DD clients starting treatment at 6 UK addiction services. Practitioners (n = 46) treating these clients were assessed regarding their DD specialisation levels. Cox regression analyses were performed to examine predictors of clients' 3-month retention rates. RESULTS: Staff reported a median of 7 years work experience with DD clients, and 80% had received co-morbidity-specific training. Practitioners provided high average ratings on both the DD competency and the therapeutic optimism scale. Nevertheless, 78% of the sample indicated additional support needs in dealing with this client group. Higher levels of DD competencies among staff predicted better client retention. CONCLUSION: The increased provision of support packages for practitioners is vital for improving competency levels in dealing with DD clients, which in turn may lead to improved client outcomes.


Assuntos
Competência Clínica/normas , Diagnóstico Duplo (Psiquiatria) , Corpo Clínico/educação , Transtornos Mentais/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Reino Unido
18.
Eur J Vasc Endovasc Surg ; 39(3): 308-13, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19906547

RESUMO

BACKGROUND: To evaluate the therapeutic value of endovascular techniques for the treatment of profunda femoris artery obstructive disease (PFAOD) in critical limb ischaemia (CLI) patients, with technically demanding open profunda repair. DESIGN: Retrospective study of prospectively collected data of 15 consecutive CLI patients with technically demanding surgical treatment of PFAOD, that were treated by endovascular means in two European Centers of Vascular Surgery. MATERIALS: All patients had critical limb ischaemia with a history of at least two previous vascular reconstructions in the ipsilateral groin and severe co-morbid conditions. All patients had good common femoral artery flow, long occlusion of the superficial femoral and popliteal arteries and impairment of crural arteries. METHODS: Twelve patients underwent balloon angioplasty alone and, in the other three cases, an additional stent placement was necessary, due to flow-limiting dissection. The follow-up (mean 29.2+/-10 months) included a surveillance protocol with the best medical treatment and duplex scanning at 1, 3, 6, 12 months and yearly thereafter. RESULTS: The endovascular approach was technically successful in all cases and the procedure-related morbidity and mortality rates were 0% for the entire follow-up period. The 3-year primary and secondary patency rates of the treated segment were 80% and 86.7%, respectively. The limb salvage rate was 93.3%. CONCLUSIONS: The outcome of our series underscores the therapeutic value of balloon angioplasty in cases of severe PFAOD, as bailout treatment in critical limb ischaemia patients with technically demanding open profunda repair. This procedure can be repeated easily if significant restenosis occurs and provides a useful tool in selected cases.


Assuntos
Angioplastia com Balão/instrumentação , Arteriopatias Oclusivas/terapia , Artéria Femoral , Isquemia/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/fisiopatologia , Constrição Patológica , Estado Terminal , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Alemanha , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Isquemia/fisiopatologia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Radiografia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/efeitos adversos
19.
Skin Pharmacol Physiol ; 22(3): 166-76, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19365102

RESUMO

Uvinul T 150, a UVB absorber, was administered (concentration 5%) in a vehicle to the skin of hairless albino mice before ultraviolet radiation (UVR) exposure for 5 days per week in a photocarcinogenicity study. Uvinul T 150 prolonged the latency period to 50% skin tumor incidence (controls: 21-22 weeks; Uvinul T 150: 36 weeks in males and 31 weeks in females). When Uvinul T 150 was applied in an alternating-exposure procedure (3 days/week before and 2 days/week after UVR), the inhibition of photocarcinogenesis was less marked (latency period 28-30 weeks). The vehicle formulation had no effect (latency period 20-21 weeks). The sensitivity of the test system was demonstrated by a positive control (8-methoxy-psoralene). Although UVB absorption was shown to inhibit photocarcinogenesis, the results also suggest that UVA radiation makes a contribution to skin tumor formation.


Assuntos
Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Raios Ultravioleta , Animais , Relação Dose-Resposta à Radiação , Feminino , Masculino , Metoxaleno/toxicidade , Camundongos , Camundongos Pelados , Compostos Orgânicos/uso terapêutico , Veículos Farmacêuticos , Fármacos Fotossensibilizantes/toxicidade , Pele/patologia , Pele/efeitos da radiação , Úlcera Cutânea/patologia , Análise de Sobrevida
20.
Horm Metab Res ; 41(3): 250-4, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18975254

RESUMO

Blood neurotrophins like insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) are discussed to mediate health benefits of physical activity in humans. The aim of the study was to analyze the training effects of moderate endurance training (Em) and strength training with high loads (Sh) on blood plasma concentrations of IGF-1 and BDNF in humans. Venous blood samples were obtained from 27 healthy students, randomly assigned to an Em, Sh, and a control group, before and after a 12-week training intervention. Sh resulted in an increase in isometric (14.5%) and dynamic (8.3%) strength of the knee extensor muscles in the Sh group and Em led to a significant increase in the endurance performance in the Em group (p<0.05). IGF-1 basal plasma concentrations decreased (p<0.05) after the intervention in all groups. There were no significant changes for BDNF. Despite specific functional adaptations induced by Em and Sh there are no correspondingly different adaptations in the basal blood concentrations of the neurotrophins IGF-1 and BDNF. Additionally, exercise per se does not result in changes in basal plasma concentrations of BDNF, suggesting that the mode of the exercise programme is a decisive factor.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Força Muscular/fisiologia , Resistência Física/fisiologia , Exercício Físico , Nível de Saúde , Humanos , Cinética , Masculino , Esportes , Suporte de Carga , Adulto Jovem
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