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1.
Rev Med Interne ; 45(6): 335-342, 2024 Jun.
Artigo em Francês | MEDLINE | ID: mdl-38216390

RESUMO

INTRODUCTION: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care. PATIENTS AND METHODS: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria. RESULTS: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ. CONCLUSION: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients.


Assuntos
Arterite de Células Gigantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/complicações , Feminino , Idoso , Masculino , Estudos Retrospectivos , Seguimentos , Idoso de 80 Anos ou mais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos de Coortes , Artérias Temporais/patologia
2.
Neurogenetics ; 22(3): 221-224, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34013494

RESUMO

TRIO is a Dbl family guanine nucleotide exchange factor (GEF) and an important regulator of neuronal development. Most truncating and missense variants affecting the Dbl homology domain of TRIO are associated with a neurodevelopmental disorder with microcephaly (MIM617061). Recently, de novo missense variants affecting the spectrin repeat region of TRIO were associated with a novel phenotype comprising severe developmental delay and macrocephaly (MIM618825). Here, we provide more evidence on this new TRIO-associated phenotype by reporting two severely affected probands with de novo missense variants in TRIO affecting the spectrin repeat region upstream of the typically affected GEF1 domain of the protein.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Megalencefalia/genética , Mutação de Sentido Incorreto/genética , Proteínas Serina-Treonina Quinases/genética , Espectrina/genética , Humanos , Microcefalia/genética , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Espectrina/metabolismo
3.
Dalton Trans ; 47(40): 14184-14188, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29995055

RESUMO

Polymers that exhibit changes of their luminescence colour in response to external stimuli are attractive candidates for sensing systems. We herein report the preparation of europium-based metallosupramolecular polymers, which can be processed into films and coatings that display readily detectable luminescence colour changes in response to various types of analytes.

4.
Z Gerontol Geriatr ; 50(7): 653-654, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28980019

RESUMO

Correction to: Z Gerontol Geriat 2017 https://doi.org/10.1007/s00391-017-1290-7 The article "The MINDMAP project: mental well-being in urban environments. Design and first results of a survey on healthcare planning policies, strategies and programmes that address mental health promotion and mental disorder prevention for older people in …The original article was corrected.

5.
J Nutr Health Aging ; 21(9): 1016-1023, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29083443

RESUMO

OBJECTIVES: An RCT of a health promotion and preventive care intervention was done in 2001-2002. Here, long-term analyses based on 12 years of follow-up of survival and of change in functional competence between intervention and control group are presented. Positive 1-year results (significantly higher use of preventive services and better health behaviour) were presented earlier. DESIGN: Parallel group randomised controlled trial (RCT) with 878 participants in the intervention and 1,702 participants in the control group. SETTING: The study took place in Hamburg, Germany and made use of health care structures and professionals of a geriatrics centre. PARTICIPANTS: Study participants were initially community-dwelling, aged 60 years and older and without B-ADL-restrictions, cognitive impairment, or need of nursing care, with sufficient command of the German language. INTERVENTIONS: Health promotion and preventive care interventions relied on an extensive health questionnaire and the subsequent offer to participate in multi-topic personal reinforcement performed in small group sessions or at preventive home visits. MEASUREMENTS: Primary outcome: Survival time; in some analyses, adjustments were made for gender, age and self-perceived health. Secondary outcome: Functional competence (LUCAS Functional Ability Index) based on responses to self-administered questionnaires at 1-year follow-up and 12 years after 1-year follow-up (2013/2014). RESULTS: Mean time under observation was 10.3 years. 38.3% (987/2,580) of the participants died; intervention group (IG): 35.7% (313/878), control group (CG): 39.6% (674/1,702); HR=0.89; p=0.09. Functional competence at 1-year follow-up: IG: ROBUST 67.4% (391/580), FRAIL 11.9% (69/580) vs. CG: ROBUST 62.9% (861/1,368), FRAIL 14.8% (203/1,368); p=0.12. 12-years after 1-year follow-up: IG: ROBUST 50.0% (160/320), FRAIL 30.9% (99/320) vs. CG: ROBUST 48.9% (307/628), FRAIL 34.1% (214/628); p=0.56. CONCLUSIONS: Insignificant but consistent effects on survival and the dynamics of functional competence suggest effectivity of the complex intervention. We plan to take a closer look at the effect of each reinforcement separately.


Assuntos
Promoção da Saúde/métodos , Vida Independente/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Geriatria , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
6.
Z Gerontol Geriatr ; 50(7): 588-602, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28819693

RESUMO

BACKGROUND: The MINDMAP consortium (2016-2019) aims to identify opportunities provided by the urban environment for the promotion of mental well-being and functioning of older people in Europe by bringing together European cities with urban longitudinal ageing studies: GLOBE, HAPIEE, HUNT, LASA, LUCAS, RECORD, Rotterdam Study, Turin Study. A survey on mental healthcare planning policies and programmes dedicated to older persons covering the range from health promotion to need of nursing care was performed for profound data interpretation in Amsterdam, Eindhoven, Hamburg, Helsinki, Kaunas, Krakow, London, Nord-Trøndelag, Paris, Prague, Rotterdam and Turin. OBJECTIVES: To collect detailed information on healthcare planning policies and programmes across these European cities to evaluate variations and to delineate recommendations for sciences, policies and planners using experience from evidence-based practice feedback from the MINDMAP cities. MATERIALS AND METHODS: The MINDMAP partners identified experts in the 12 cities with the best background knowledge of the mental health sector. After pretesting, semi-structured telephone interviews (1-2 h) were performed always by the same person. A structured evaluation matrix based on the geriatric functioning continuum and the World Health Organization (WHO) Public Health Framework for Healthy Ageing was applied. RESULTS: A complete survey (12 out of 12) was performed reporting on 41 policies and 280 programmes on the city level. It appeared from extensive analyses that the focus on older citizens, specific target groups, and multidimensional programmes could be intensified. CONCLUSION: There is a broad variety to cope with the challenges of ageing in health, and to address both physical and mental capacities in older individuals and their dynamic interactions in urban environments.


Assuntos
Promoção da Saúde , Transtornos Mentais , Saúde Mental , Idoso , Idoso de 80 Anos ou mais , Cidades , Europa (Continente) , Feminino , Humanos , Estudos Longitudinais , Masculino , Inquéritos e Questionários , Saúde da População Urbana
7.
Anaesthesia ; 72(10): 1230-1236, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28762464

RESUMO

Current descriptions of thoracic paravertebral block techniques require the needle tip to be anterior to the superior costotransverse ligament. We hypothesised that an injection point midway between the posterior border of the transverse process and the pleura would result in spread to the paravertebral space. We completed bilateral injections of 5 ml methylene blue 0.2% midway between the posterior border of the transverse process and the pleura at T2, T4, T6, T8 and T10 in three unembalmed cadavers. The presence of methylene blue dye at the nerve root in the paravertebral space, the corresponding intercostal nerve and sympathetic chain at the level of injection, and at additional levels, was examined. We identified the superior costotransverse ligament, pleural displacement and spread to the erector spinae plane. We describe two case reports using this technique in patients. Our cadaver results and clinical cases demonstrate that, with the exception of cadaver 1, an injection point midway between the posterior border of the transverse process and pleura consistently achieved spread of dye at least to the paravertebral space at the level of injection, and frequently to adjacent levels. This may be a plausible explanation for the landmark technique's inability to reliably achieve a multilevel block. We describe a new ultrasound-guided technique for a single level paravertebral block.


Assuntos
Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Idoso , Anestésicos Locais/administração & dosagem , Cadáver , Corantes/farmacocinética , Feminino , Humanos , Nervos Intercostais/diagnóstico por imagem , Azul de Metileno/farmacocinética , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Ropivacaina/administração & dosagem , Vértebras Torácicas/diagnóstico por imagem
8.
Clin Genet ; 89(1): 74-81, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25652421

RESUMO

Cornelia de Lange syndrome (CdLS) and KBG syndrome are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, and some craniofacial and limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified in at least 70% of the patients with CdLS. Consequently, additional causative genes, either unknown or responsible of partially merging entities, possibly account for the remaining 30% of the patients. In contrast, KBG has only been associated with mutations in ANKRD11. By exome sequencing we could identify heterozygous loss-of-function mutations in ANKRD11 in two patients with the clinical diagnosis of CdLS. Both patients show features reminiscent of CdLS such as characteristic facies as well as a small head circumference which is not described for KBG syndrome. Patient A, who carries the mutation in a mosaic state, is a 4-year-old girl with features reminiscent of CdLS. Patient B, a 15-year-old boy, shows a complex phenotype which resembled CdLS during infancy, but has developed to a more KBG overlapping phenotype during childhood. These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes.


Assuntos
Síndrome de Cornélia de Lange/diagnóstico , Síndrome de Cornélia de Lange/genética , Exoma , Estudos de Associação Genética , Fenótipo , Proteínas Repressoras/genética , Adolescente , Pré-Escolar , Fácies , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino
9.
J Nutr Health Aging ; 19(10): 1012-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26624213

RESUMO

OBJECTIVES: Prevention of in-hospital falls contributes to improvement of patient safety. However, the identification of high-risk patients remains a challenge despite knowledge of fall-risk factors. Hence, objective was to prospectively validate the performance of the LUCAS (Longitudinal Urban Cohort Ageing Study) fall-risk screening, based on routine data (fall history, mobility, mental status) and applied by nurses. DESIGN: Observational study comparing two groups of patients who underwent different fall-risk screenings; the LUCAS screening (2010 - 2011) and the STRATIFY (St. Thomas's Risk Assessment Tool In Falling Elderly Inpatients) (2004 - 2006). SETTING: Urban teaching hospital. PARTICIPANTS: Consecutively hospitalized patients (≥ 65 years old) were screened on admission; LUCAS n = 2,337, STRATIFY n = 4,735. MEASUREMENTS: The proportions of fallers were compared between the STRATIFY and the LUCAS time periods. The number of fallers expected was compared to that observed in the LUCAS time period. Standardized fall-incidence recording included case-note checks for unreported falls. Plausibility checks of fall-risk factors and logistic regression analysis for variable fall-risk factors were performed. RESULTS: The proportions of fallers during the two time periods were LUCAS n = 291/2,337 (12.5%) vs. STRATIFY n = 508/4,735 (10.7%). After adjustment for risk-factor prevalence, the proportion of fallers expected was 14.5% (334/2,337), the proportion observed was 12.5% (291/2,337) (p = 0.038). CONCLUSIONS: In-hospital fall prevention including systematic use of the LUCAS fall-risk screening reduced the proportion of fallers compared to that expected from the patients' fall-risk profile. Raw proportions of fallers are not suitable to evaluate fall prevention in hospital because of variable prevalence of patients' fall-risk factors over time. Continuous communication, education and training is needed to sustain in-hospital falls prevention.


Assuntos
Acidentes por Quedas/prevenção & controle , Avaliação Geriátrica/métodos , Hospitalização , Segurança do Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais , Hospitais Urbanos , Humanos , Incidência , Pacientes Internados , Masculino , Prevalência , Medição de Risco , Fatores de Risco
10.
Mol Oral Microbiol ; 29(6): 307-20, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24943676

RESUMO

Conserved C-terminal domains (CTD) have been shown to act as a signal for the translocation of certain proteins across the outer membrane of Bacteroidetes via a type IX secretion system (T9SS). The genome sequence of the periodontal pathogen Tannerella forsythia predicts the presence of the components for a T9SS in conjunction with a suite of CTD proteins. T. forsythia is covered with a two-dimensional crystalline surface (S-) layer composed of the glycosylated CTD proteins TfsA and TfsB. To investigate, if T9SS is functional in T. forsythia, T9SS-deficient mutants were generated by targeting either TF0955 (putative C-terminal signal peptidase) or TF2327 (PorK ortholog), and the mutants were analyzed with respect to secretion, assembly and glycosylation of the S-layer proteins as well as proteolytic processing of the CTD and biofilm formation. In either mutant, TfsA and TfsB were incapable of translocation, as evidenced by the absence of the S-layer in transmission electron microscopy of ultrathin-sectioned bacterial cells. Despite being entrapped within the periplasm, mass spectrometry analysis revealed that the S-layer proteins were modified with the complete, mature glycan found on the secreted proteins, indicating that protein translocation and glycosylation are two independent processes. Further, the T9SS mutants showed a denser biofilm with fewer voids compared with the wild-type. This study demonstrates the functionality of T9SS and the requirement of CTD for the outer membrane passage of extracellular proteins in T. forsythia, exemplified by the two S-layer proteins. In addition, T9SS protein translocation is decoupled from O-glycan attachment in T. forsythia.


Assuntos
Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/fisiologia , Bacteroidetes/metabolismo , Glicoproteínas de Membrana/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Bacteroidetes/genética , Bacteroidetes/ultraestrutura , Biofilmes/crescimento & desenvolvimento , Técnicas de Inativação de Genes , Glicosilação , Glicoproteínas de Membrana/química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Mutação , Fenótipo , Estrutura Terciária de Proteína , Transporte Proteico , Espectrometria de Massas por Ionização por Electrospray
11.
Curr Med Chem ; 21(17): 1938-55, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24606495

RESUMO

The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2 subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.


Assuntos
Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Mutação , Ligação Proteica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo
12.
J Nutr Health Aging ; 17(3): 264-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23459980

RESUMO

OBJECTIVES: In-hospital falls in older patients are frequent, but the identification of patients at risk of falling is challenging. Aim of this study was to improve the identification of high-risk patients. Therefore, a simplified screening-tool was developed, validated, and compared to the STRATIFY predictive accuracy. DESIGN: Retrospective analysis of 4,735 patients; evaluation of predictive accuracy of STRATIFY and its single risk factors, as well as age, gender and psychotropic medication; splitting the dataset into a learning and a validation sample for modelling fall-risk screening and independent, temporal validation. SETTING: Geriatric clinic at an academic teaching hospital in Hamburg, Germany. PARTICIPANTS: 4,735 hospitalised patients ≥65 years. MEASUREMENTS: Sensitivity, specificity, positive and negative predictive value, Odds Ratios, Youden-Index and the rates of falls and fallers were calculated. RESULTS: There were 10.7% fallers, and the fall rate was 7.9/1,000 hospital days. In the learning sample, mental alteration (OR 2.9), fall history (OR 2.1), and insecure mobility (Barthel-Index items 'transfer' + 'walking' score = 5, 10 or 15) (OR 2.3) had the most strongest association to falls. The LUCAS Fall-Risk Screening uses these risk factors, and patients with ≥2 risk factors contributed to the high-risk group (30.9%). In the validation sample, STRATIFY SENS was 56.8, SPEC 59.6, PPV 13.5 and NPV 92.6 vs. LUCAS Fall-Risk Screening was SENS 46.0, SPEC 71.1, PPV 14.9 and NPV 92.3. CONCLUSIONS: Both the STRATIFY and the LUCAS Fall-Risk Screening showed comparable results in defining a high-risk group. Impaired mobility and cognitive status were closely associated to falls. The results do underscore the importance of functional status as essential fall-risk factor in older hospitalised patients.


Assuntos
Acidentes por Quedas/prevenção & controle , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Hospitais , Humanos , Pacientes Internados , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
13.
Clin Genet ; 84(6): 531-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23425300

RESUMO

Acrodysostosis is characterized by a peripheral dysostosis that is accompanied by short stature, midface hypoplasia, and developmental delay. Recently, it was shown that heterozygous point mutations in the PRKAR1A gene cause acrodysostosis with hormone resistance. By mutational analysis of the PRKAR1A gene we detected four different mutations (p.Arg368Stop, p.Ala213Thr, p.Tyr373Cys, and p.Arg335Cys) in four of seven affected patients with acrodysostosis. The combination of clinical results, endocrinological parameters and in silico mutation analysis gives evidence to suppose a pathogenic effect of each mutation. This assumption is supported by the de novo origin of these mutations. Apart from typical radiological abnormalities of the hand bones, elevated thyroid stimulating hormone and parathyroid hormone values as well as short stature are the most common findings. Less frequent features are characteristic facial dysmorphisms, sensorineural hearing loss and mild intellectual disability. These results lead to the conclusion that mutations of PKRAR1A are the major molecular cause for acrodysostosis with endocrinological abnormalities. In addition, in our cohort of 44 patients affected with brachydactyly type E (BDE) we detected only one sequence variant of PRKAR1A (p.Asp227Asn) with an unclear effect on protein function. Thus, we conclude that PRKAR1A mutations may play no major role in the pathogenesis of BDE.


Assuntos
Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Disostoses/genética , Deficiência Intelectual/genética , Mutação , Osteocondrodisplasias/genética , Adolescente , Adulto , Alelos , Criança , Análise Mutacional de DNA , Disostoses/diagnóstico , Disostoses/metabolismo , Feminino , Ossos da Mão/diagnóstico por imagem , Ossos da Mão/patologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Masculino , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/metabolismo , Fenótipo , Radiografia , Adulto Jovem
14.
J Appl Microbiol ; 114(1): 25-35, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22943489

RESUMO

AIMS: Engineered metal nanoparticles are increasingly used in consumer products, in part as additives that exhibit advantageous antimicrobial properties. Conventional nanoparticle susceptibility testing is based largely on determination of nontemporal growth profiles such as measurements of inhibition zones in common agar diffusion tests, counting of colony-forming units, or endpoint or regular-interval growth determination via optical density measurements. For better evaluation of the dynamic effects from exposure to nanoparticles, a cultivation-based assay was established in a 96-well format and adapted for time-resolved testing of the effects of nanoparticles on micro-organisms. METHODS AND RESULTS: The modified assay allowed simultaneous cultivation and on-line analysis of microbial growth inhibition. The automated high-throughput assay combined continuous monitoring of microbial growth with the analysis of many replicates and was applied to Cupriavidus necator H16 test organisms to study the antimicrobial effects of spherical silver [Ag(0)] nanoparticles (primary particle size distribution D90 < 15 nm). Ag(0) concentrations above 80 µg ml(-1) resulted in complete and irreversible inhibition of microbial growth, whereas extended lag phases and partial growth inhibition were observed at Ag(0) concentrations between 20 and 80 µg ml(-1) . Addition of Ag(0) nanoparticles at different growth stages led to either complete inhibition (addition of 40 µg ml(-1) Ag(0) from 0 h to 6 h) or resulted in full recovery (40 µg ml(-1) Ag(0) addition ≥9 h). CONCLUSIONS: Contrary to the expected results, our data indicate growth stimulation of C. necator at certain Ag(0) nanoparticle concentrations, as well as varying susceptibility to nanoparticles at different growth stages. SIGNIFICANCE AND IMPACT OF THE STUDY: These results underscore the need for time-resolved analyses of microbial growth inhibition by Ag(0) nanoparticles. Due to the versatility of the technique, the assay will likely complement existing microbiological methods for cultivation and diagnostics of microbes, in addition to tests of other antimicrobial nanoparticles.


Assuntos
Antibacterianos/farmacologia , Técnicas Bacteriológicas/métodos , Cupriavidus necator/efeitos dos fármacos , Nanopartículas Metálicas , Prata/farmacologia , Cupriavidus necator/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Tamanho da Partícula
15.
Artigo em Alemão | MEDLINE | ID: mdl-22842893

RESUMO

What kind of health targets should be pursued concerning the health care of elderly people? What kind of activities should be implemented to ensure good health care with regard to future challenges? The Association for the Continuous Development of the National Health Target Process, health-targets.de, deals with these issues under the new national health target "Healthy Ageing". We develop concrete objectives and proposals for practical implementation in the areas of "outpatient and inpatient care", "nursing" and "rehabilitation in old age". health-targets.de supports a common health target process and initiates interventions in the field of health care for elderly people.


Assuntos
Envelhecimento/psicologia , Doença Crônica/enfermagem , Avaliação Geriátrica , Qualidade de Vida/psicologia , Ajustamento Social , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/psicologia , Comportamento Cooperativo , Avaliação da Deficiência , Feminino , Controle de Acesso , Alemanha , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Humanos , Comunicação Interdisciplinar , Masculino , Admissão do Paciente , Equipe de Assistência ao Paciente
16.
Internist (Berl) ; 53(3): 341-4, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22189462

RESUMO

We report the case of a 47-year-old man who was admitted because of syncope. Upon hospital admission, he rapidly developed circulatory shock with generalized edema and a severe hemoconcentration with a hematocrit of 70%. The condition was stabilized with infusion of 17 l of cristalloid fluids over a period of 24 h. After ruling out possible secondary causes, the diagnosis of a systemic capillary leak syndrome--a severe transient endothelial barrier dysfunction of unknown origin--was made. A triad of hypotension, hemoconcentration (hematocrit >60%) and macromolecular extravasation is the typical finding; furthermore, a strong association with monoclonal gammopathy of unknown significance (MGUS) is described.


Assuntos
Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/terapia , Edema/diagnóstico , Edema/terapia , Choque/diagnóstico , Choque/terapia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Mol Syndromol ; 1(6): 301-306, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22190900

RESUMO

Ellis-van Creveld (EvC) syndrome is a rare autosomal recessive malformation syndrome with the main features cardiac defects, postaxial hexadactyly, mesomelic shortening of the limbs, short ribs, dysplastic nails and teeth, oral frenula and various other abnormalities while mental function is normal. We describe 2 adult EvC patients with the cardinal skeletal features of mesomelic short stature and severe, progressive genu valgum deformity, resulting from loss of function mutations in the EVC genes. While the genu valgum was the predominating and disabling feature in patient 1, patient 2 showed acroosteolyses in the distal phalanges and a symmetrical synostosis of metacarpals in his hands. Moreover, patient 2 developed synostoses in the additional fingers in adolescence which had not been present at the age of 12 years, suggesting a further progression of skeletal disease. Joint fusion of phalanges so far has not been reported in EvC syndrome. Our data further expand the phenotypic spectrum of EvC related skeletal malformations and contribute important new information on the clinical course of EvC syndrome with increasing age.

18.
J Mol Biol ; 412(2): 251-66, 2011 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-21806996

RESUMO

Cyclin-dependent kinase (CDK) 8 associates with cyclin C (CycC) and belongs to the CDK module of the Mediator of transcription, together with MED12 and MED13. CDK8 is involved in the regulation of mRNA transcription and was identified as a potent oncogene in colon cancerogenesis. We have solved the 2.2-Å crystal structure of CDK8/CycC in complex with sorafenib, an anti-cancer drug of clinical relevance. The CDK8 structure reveals a unique CycC recognition helix that explains the specificity of the CDK8/CycC pair and discrimination among the highly promiscuous binding in the CDK/cyclin family. In contrast to all CDKs, the CDK8 activation loop appears not to be phosphorylated. Based on the structure, we discuss an alternate mode of CDK8 activation to the general CDK activation by T-loop phosphorylation. Sorafenib binds to the catalytic cleft of CDK8. It displays a deep pocket binding mode and is the first small molecule to induce a DFG-out conformation in the CDK family, which is actually DMG-out in CDK8.


Assuntos
Ciclina C/química , Quinase 8 Dependente de Ciclina/química , Sequência de Aminoácidos , Sítios de Ligação , Cristalografia por Raios X , Ciclina C/metabolismo , Quinase 8 Dependente de Ciclina/metabolismo , Ciclinas/química , Ativação Enzimática , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Homologia de Sequência de Aminoácidos
19.
Toxicol Lett ; 205(2): 97-104, 2011 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-21669261

RESUMO

The consumer exposure to the vast majority of cosmetic products is limited to dermal contact. Even spray applications tend to be topically exposed to skin or hair. Besides this skin contact, spray products require additional considerations in regard to potential inhalation for building a robust and reliable safety assessment. Over the years, cosmetic industry developed prediction models for the best estimate of inhalation exposure combining data from computer simulation programs available in the market, individual real measured data and last but not least the experience from the market. Such attempt is driven by the toxicological profile of individual used ingredients. The focus of this review is on the determination of inhalation exposure, and the derivation of safe exposure levels for cosmetic spray products. Many of the methods employed to ensure product safety of cosmetic sprays in accordance with the general requirements of the EC Cosmetics Directive are based on industry experience which are not necessarily consistent across companies. This paper presents an approach to compile common principles for risk assessment and thus contribute to standardisation of safety assessment methodologies utilized for spray product evaluation without interfering with the flexibility of the individual safety assessor. It is based on the experience within the author's companies and may be useful as a support document as well for SME (Small and Medium Enterprises) companies safety assessors. In this respect it can be seen as one fundamental step in a tiered approach of cosmetic spray safety evaluation.


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos/toxicidade , Exposição por Inalação/efeitos adversos , Aerossóis , Humanos , Medição de Risco
20.
Bioresour Technol ; 102(3): 2931-5, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21145230

RESUMO

The influence of compost as inoculum during continuous anaerobic digestion of fodder beet silage was studied over 330 days. Two simultaneously driven mesophilic fermentors (Inoc-1/Inoc-2) were inoculated with manure and sewage sludge. Only the digester Inoc-2 was inoculated additionally with compost. After 160 days fermentor Inoc-2 reached a hydraulic retention time (HRT) around 15 days whereas Inoc-1 remained at a HRT of 40d. After changing the substrate feed from one to three times a day both digesters stabilised at a shorter HRT; Inoc-2 at 10 days and Inoc-1 around 20 days. An additional inoculation of fermentor Inoc-1 by compost shortened the HRT to 10 days and revealed a minor increased gas production of about 6%. Fluorescence in situ hybridization indicated that probably an archaeal population shift was responsible for the observed stimulations. An addition of compost induced a methanogenic community change towards hydrogenotrophic methanogens.


Assuntos
Bactérias Anaeróbias/metabolismo , Beta vulgaris/microbiologia , Reatores Biológicos/microbiologia , Conservação de Recursos Energéticos/métodos , Produtos Agrícolas/microbiologia , Ecossistema , Microbiologia do Solo
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