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1.
Support Care Cancer ; 31(5): 281, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37074497

RESUMO

PURPOSE: Supervised exercise is a potentially promising supportive care intervention for people with metastatic breast cancer (MBC), but research on the patients' perspective is limited. The aim of the current focus group study was to gain an in-depth understanding of MBC patients' perceived barriers, facilitators, and preferences for supervised exercise programs. METHODS: Eleven online focus groups with, in total, 44 MBC patients were conducted in four European countries (Germany, Poland, Spain, Sweden). Main topics of the semi-structured discussions covered attitudes towards participation in supervised exercise programs, perceived facilitators, experienced barriers, and exercise preferences. Interviews were transcribed verbatim, translated into English, and coded based on a preliminary coding framework, supplemented by themes emerging during the sessions. The codes were subsequently examined for interrelations and re-organized into overarching clusters. RESULTS: Participants had positive attitudes towards exercise, but experienced physical limitations and insecurities that inhibited their participation. They expressed a strong desire for exercise tailored to their needs, and supervision by an exercise professional. Participants also highlighted the social nature of group training as an important facilitator. They had no clear preference for exercise type, but rather favored a mixture of different activities. Flexible training modules were considered helpful to increase exercise program adherence. CONCLUSIONS: MBC patients were generally interested in supervised exercise programs. They preferred group exercise that facilitates social interaction, but also expressed a need for individualized exercise programs. This suggests the relevance to develop flexible exercise programs that are adjusted to the individual's needs, abilities, and preferences.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Exercício Físico , Pesquisa Qualitativa , Terapia por Exercício , Grupos Focais
2.
Qual Life Res ; 32(2): 447-459, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36273365

RESUMO

PURPOSE: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. METHODS: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach's α, and intra-class correlation coefficient). RESULTS: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68-0.92) and test-retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. CONCLUSION: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.


Assuntos
COVID-19 , Qualidade de Vida , Adulto , Humanos , Qualidade de Vida/psicologia , Estudos Prospectivos , Reprodutibilidade dos Testes , COVID-19/epidemiologia , Inquéritos e Questionários , Psicometria
3.
Support Care Cancer ; 30(8): 6593-6602, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35486229

RESUMO

PURPOSE: Informed consent procedures in clinical trials often differ in length and complexity to those in clinical routine care. Little is known about the benefit of extensive procedures as intended in clinical trials compared to procedures in routine cancer treatment. METHODS: In two different clinical studies performed at a comprehensive cancer center, we compared patients' comprehension and satisfaction of current informed consent procedures in routine clinical care with the level of comprehension and satisfaction of patients treated within clinical trials. Patients with a new cancer diagnosis and recent informed consent received a questionnaire about satisfaction, comprehension, time management, and physician-patient relationship of the informed consent process. Patients in cohort 1 consented to cancer treatment within a clinical trial and were additionally interviewed in a structured way; patients in cohort 2 consented to "standard" chemotherapy and received a follow-up questionnaire after 6 months. RESULTS: In cohort 1, 82 patients completed the questionnaire and had an additional structured interview. They were treated in 41 different trials, receiving up to 40 pages of educational material. In cohort 2, 89 patients completed the first and 52 completed the follow-up questionnaire after receiving a standard informed consent form of 6 pages. Subjective understanding and satisfaction with the information provided was equally very high. However, deficits in objective understanding were observed in both cohorts. CONCLUSION: Extensive informed consent procedures for clinical cancer trials have not been associated with a higher level of satisfaction or measurable objective understanding; therefore, the benefit seems to be limited.


Assuntos
Ensaios Clínicos como Assunto , Consentimento Livre e Esclarecido , Neoplasias , Estudos de Coortes , Humanos , Neoplasias/tratamento farmacológico , Relações Médico-Paciente , Inquéritos e Questionários
4.
Psychother Psychosom Med Psychol ; 71(9-10): 363-369, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34255329

RESUMO

AIM: The aim of the study is to look at the specific contribution of outpatient cancer counselling centers (OCCC) from the perspective of both the person seeking advice and the referring health care professionals. METHODS: Qualitative design by means of guideline-based face-to-face interviews with cancer patients/relatives and individual telephone interviews with referring health care professionals. RESULTS: A total of 43 persons seeking advice and 30 referring health care professionals were interviewed. With regard to the contents of counselling, psycho-oncological support and help for self-help in combination with social-legal information about additional support services are perceived as central features. In the group of referring physicians, however, there seems to be some uncertainty about what OCCCs (can) provide. CONCLUSION: On the one hand, the results point to a specific core of the services offered by OCCCs, and on the other hand to ambiguous perceptions on the part of the respondents. They may contribute to further sharpening the profile of OCCC and to clarifying their place in the health care system.


Assuntos
Aconselhamento , Neoplasias , Atenção à Saúde , Pessoal de Saúde , Humanos , Neoplasias/terapia , Psico-Oncologia
5.
Future Oncol ; 14(8): 727-735, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29578364

RESUMO

AIM: The aim was to evaluate cost-effectiveness of yttrium-90 transarterial radioembolization (TARE) in comparison to sorafenib treatment. PATIENTS & METHODS: A single-center, retrospective, observational study was performed, 166 patients with intermediate-/advanced-stage hepatocellular carcinoma were treated with sorafenib and 19 with TARE. The patients out of the sorafenib group matching the inclusion criteria for TARE, were reassigned to a subgroup SOR3. RESULTS: Mean costs for SOR3 patients amounted to €27,992 per patient, instead for TARE treatment, mean expense per patient was €17,761 (p = 0.028). Overall survival was similar between the two groups, while midterm survival rates (p = 0.012) were significantly higher with TARE treatment. CONCLUSION: TARE causes significantly lower treatment costs than sorafenib with better outcome in midterm survival.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Idoso , Carcinoma Hepatocelular/economia , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/economia , Quimioembolização Terapêutica/métodos , Análise Custo-Benefício/economia , Feminino , Humanos , Neoplasias Hepáticas/economia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/economia , Compostos de Fenilureia/economia , Estudos Retrospectivos , Sorafenibe , Radioisótopos de Ítrio/economia
6.
Biochim Biophys Acta ; 1842(9): 1406-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24859227

RESUMO

Mutations in the only known mammalian iron exporter ferroportin cause a rare iron overload disorder termed ferroportin disease. Two distinct clinical phenotypes are caused by different disease mechanisms: mutations in ferroportin either cause loss of iron export function or gain of function due to resistance to hepcidin, the peptide hormone that normally downregulates ferroportin. The aim of the present study was to examine the disease mechanisms of the thus far unclassified A69T and D181V ferroportin mutations. We overexpressed wild-type and mutant ferroportin fused to green fluorescent protein in human embryonic kidney cells and used a (59)Fe-assay, intracellular ferritin concentrations, confocal microscopy and flow cytometry to study iron export function, subcellular localization and the responsiveness to hepcidin. While the A69T ferroportin mutation seems not to affect the iron export function it causes dose-dependent hepcidin resistance. We further found that D181V mutated ferroportin is iron export defective and hepcidin resistant, similar to the loss of function mutations A77D and C367X. This indicates that intact iron export might be necessary for hepcidin-induced downregulation of ferroportin. This hypothesis was investigated by studying the hepcidin response under modulation of iron availability. Incubation of wild-type ferroportin overexpressing cells with holo-transferrin increases the hepcidin effect whereas chelating extracellular ferrous iron causes hepcidin resistance. In this study we present data that postulates to classify the D181V ferroportin mutation as loss of function and the A69T mutation as dose-dependent hepcidin resistant and outline a possible causal link between iron export function and the hepcidin effect.


Assuntos
Proteínas de Transporte de Cátions/genética , Hemocromatose/genética , Hepcidinas/metabolismo , Ferro/metabolismo , Mutação/genética , Receptores de Superfície Celular/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Feminino , Ferritinas/metabolismo , Genótipo , Hemocromatose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
7.
Am J Hum Genet ; 84(2): 188-96, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19185281

RESUMO

Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na(+)/H(+) exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions--i.e., a syndromic form of CSD--occurring in ten families from an isolated form--i.e., classic CSD--presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593-1G-->A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A-->T, c.337+2T-->C, c.553+2T-->A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues.


Assuntos
Diarreia/genética , Síndromes de Malabsorção/genética , Glicoproteínas de Membrana/genética , Mutação , Sódio/metabolismo , Sequência de Aminoácidos , Anus Imperfurado/genética , Anus Imperfurado/mortalidade , Anus Imperfurado/patologia , Sequência de Bases , Mapeamento Cromossômico , Estudos de Coortes , Análise Mutacional de DNA , Diarreia/mortalidade , Diarreia/patologia , Fezes/química , Feminino , Genes Recessivos , Humanos , Lactente , Recém-Nascido , Síndromes de Malabsorção/mortalidade , Síndromes de Malabsorção/patologia , Masculino , Dados de Sequência Molecular , Linhagem , RNA Mensageiro/genética , Análise de Sobrevida
8.
HPB (Oxford) ; 14(2): 122-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22221573

RESUMO

AIMS: The diagnosis of autoimmune pancreatitis (AIP) and immunoglobulin subclass 4 (IgG(4) )-associated cholangitis (IAC) is based on imaging studies, serology, histology and a response to steroid therapy. The major serological finding is an elevation of the serum IgG(4) concentration. Previous studies have shown that its sensitivity is about 70% and its specificity exceeds 90% at a cut-off of 140 mg/dl in selected patient populations. The aim of the present study was to assess the performance of serum IgG(4) as a diagnostic parameter in an unselected liver and pancreas clinic population. METHODS AND RESULTS: IgG(4) was prospectively determined in 1412 patients and clinical diagnoses were recorded from a review of patient charts. The prevalence of AIP or IAC in the entire cohort was 1.1% (n= 15). The sensitivity of IgG(4) for the diagnosis of AIP and IAC was 80% and the specificity was 86% at a cut-off value of ≥135 mg/dl. The positive predictive value and the negative predictive value were 6% and 99.7%, respectively. The most common differential diagnosis in patients with elevated IgG(4) was liver cirrhosis. CONCLUSION: IgG(4) has a reasonable sensitivity and specificity in a liver and pancreas clinic population, where liver cirrhosis appears to be the most frequent differential diagnosis for elevated IgG(4) concentrations.


Assuntos
Doenças Autoimunes/diagnóstico , Colangite/diagnóstico , Imunoglobulina G/sangue , Pancreatite/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Colangite/sangue , Colangite/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina G/classificação , Cirrose Hepática/diagnóstico , Cirrose Hepática/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatite/sangue , Pancreatite/imunologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Regulação para Cima , Adulto Jovem
9.
J Cancer Res Ther ; 18(Supplement): S501-S506, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36511016

RESUMO

Skin reactions after transarterial chemoembolization (TACE) with anthracyclines are rare and mostly limited to small areas. We describe a 56-year-old male with hepatocellular carcinoma treated with epirubicin chemoembolization. Immediately the procedure, pain on the right side and an extended livedo reticularis-like skin reaction appeared. Since dexrazoxane, a topoisomerase-II catalytic-cycle inhibitor, has been shown to be effective in preventing or reducing skin necrosis and ulceration following anthracycline extravasation, the drug was administered 8 h after TACE and repeated in the following 2 days. Due to marked extrahepatic diffusion of epirubicin as evidenced by computed tomography imaging, the patient showed signs of systemic organ involvement. The critically ill patient required close follow-up and intensified treatment including blood supply and pulmonary drainage of a pleural effusion. The patient presented a significant clinical improvement of the skin lesions and resolution of organ involvement with normalization of laboratory parameters after dexrazoxane. In conclusion, adverse extended skin reactions and severe systemic effects related to anthracyclines diffusion could be properly treated with dexrazoxane infusion.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Epirubicina/efeitos adversos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Antibióticos Antineoplásicos/efeitos adversos , Antraciclinas , Inibidores da Topoisomerase II
10.
J Patient Rep Outcomes ; 6(1): 26, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35348945

RESUMO

BACKGROUND: We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. METHODS: Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. RESULTS: The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. CONCLUSION: The resulting COVID-19 questionnaire covers health-related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients' acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).

11.
J Cancer Res Clin Oncol ; 147(7): 2117-2126, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33420813

RESUMO

PURPOSE: Informed consent is required prior to any medical procedure. In the context of cancer treatment, special efforts are needed to inform cancer patients properly about treatment, potential sequelae and alternative therapies. Little is known about the effectiveness of current informed consent strategies and patients' individual satisfaction. Given the heterogeneity in terms of age, education, sex and other factors, detailed understanding of patients' comprehension and perception is the basis for further optimization of the informed consent process, which was the aim of the current investigation. METHODS: Patients with a new cancer diagnosis and recent informed consent were asked to complete a questionnaire about satisfaction, comprehension, time management, physician-patient relationship and other items of the informed consent process. Patients were followed for 6 months and invited to complete a follow-up questionnaire. RESULTS: In total, 89 patients completed the first questionnaire and 52 the follow-up questionnaire. Subjective understanding was assumed high, however, this did not correlate with objective understanding. Age and education were identified as influencing factors for comprehension. 85% of the patients were satisfied with the information provided. A major gap was the information on alternative therapies. Moreover, not all patients perceived the consent dialog as such, and particularly the individual treatment intention partially remained unclear for some patients. CONCLUSIONS: To ensure that informed consent is based on solid understanding, informed consenting must be patient-centered and consider the individual expectations, needs and abilities of cancer patients. Further studies are required to develop tailored informed consent strategies.


Assuntos
Institutos de Câncer/organização & administração , Comunicação , Consentimento Livre e Esclarecido/normas , Neoplasias/terapia , Relações Médico-Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Compreensão , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
12.
J Hepatol ; 53(5): 941-9, 2010 11.
Artigo em Inglês | MEDLINE | ID: mdl-20691492

RESUMO

BACKGROUND & AIMS: Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies. METHODS: We conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease. RESULTS: Of the 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms. CONCLUSIONS: In contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron.


Assuntos
Proteínas de Transporte de Cátions/genética , Ferritinas/sangue , Sobrecarga de Ferro/genética , Mutação , Transferrina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Proteínas de Transporte de Cátions/química , Criança , Pré-Escolar , Feminino , Hemocromatose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo Genético
13.
J Hepatol ; 53(6): 1101-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20801540

RESUMO

BACKGROUND & AIMS: Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facilitates cellular iron export and iron binding to transferrin. RESULTS: A novel homozygous ceruloplasmin gene mutation, c.2554+1G>T, was identified as the cause of aceruloplasminemia in three affected siblings. Two siblings presented with movement disorders and diabetes. Complementary DNA sequencing showed that this mutation causes skipping of exon 14 and deletion of amino acids 809-852 while preserving the open reading frame. Western blotting of liver extracts and sera of affected patients showed retention of the abnormal protein in the liver. Aceruloplasminemia was associated with severe brain and liver iron overload, where hepatic mRNA expression of the iron hormone hepcidin was increased, corresponding to the degree of iron overload. Hepatic iron concentration normalized after 3 and 5months of iron chelation therapy with deferasirox, which was also associated with reduced insulin demands. During short term treatment there was no clinical or imaging evidence for significant effects on brain iron overload. CONCLUSIONS: Aceruloplasminemia can show an incomplete clinical penetrance but is invariably associated with iron accumulation in the liver and in the brain. Iron accumulation in aceruloplasminemia is a result of defective cellular iron export, where hepcidin regulation is appropriate for the degree of iron overload. Iron chelation with deferasirox was effective in mobilizing hepatic iron but has no effect on brain iron.


Assuntos
Benzoatos/uso terapêutico , Ceruloplasmina/genética , Quelantes de Ferro/uso terapêutico , Ferro/metabolismo , Mutação , Triazóis/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/genética , Encéfalo/metabolismo , Ceruloplasmina/deficiência , Ceruloplasmina/metabolismo , Consanguinidade , Deferasirox , Feminino , Hepcidinas , Homozigoto , Humanos , Distúrbios do Metabolismo do Ferro/tratamento farmacológico , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/metabolismo , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Linhagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Metab Brain Dis ; 25(3): 285-95, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20852922

RESUMO

Hepatic encephalopathy is a common complication of cirrhosis. The degree of neuro-psychiatric impairment is highly variable and its clinical staging subjective. We investigated whether eye movement response times-saccadic latencies-could serve as an indicator of encephalopathy. We studied the association between saccadic latency, liver function and paper- and pencil tests in 70 patients with cirrhosis and 31 patients after liver transplantation. The tests included the porto-systemic encephalopathy (PSE-) test, critical flicker frequency, MELD score and ammonia concentration. A normal range for saccades was established in 31 control subjects. Clinical and biochemical parameters of liver, blood, and kidney function were also determined. Median saccadic latencies were significantly longer in patients with liver cirrhosis when compared to patients after liver transplantation (244 ms vs. 278 ms p < 0.001). Both patient groups had prolonged saccadic latency when compared to an age matched control group (175 ms). The reciprocal of median saccadic latency (µ) correlated with PSE tests, MELD score and critical flicker frequency. A significant correlation between the saccadic latency parameter early slope (σ(E)) that represents the prevalence of early saccades and partial pressure of ammonia was also noted. Psychometric test performance, but not saccadic latency, correlated with blood urea and sodium concentrations. Saccadic latency represents an objective and quantitative parameter of hepatic encephalopathy. Unlike psychometric test performance, these ocular responses were unaffected by renal function and can be obtained clinically within a matter of minutes by non-trained personnel.


Assuntos
Medições dos Movimentos Oculares/normas , Encefalopatia Hepática/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Movimentos Sacádicos/fisiologia , Idoso , Feminino , Encefalopatia Hepática/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/etiologia , Projetos Piloto , Tempo de Reação/fisiologia , Índice de Gravidade de Doença
15.
Front Robot AI ; 7: 36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33501204

RESUMO

In swarm robotics multiple robots collectively solve problems by forming advantageous structures and behaviors similar to the ones observed in natural systems, such as swarms of bees, birds, or fish. However, the step to industrial applications has not yet been made successfully. Literature is light on real-world swarm applications that apply actual swarm algorithms. Typically, only parts of swarm algorithms are used which we refer to as basic swarm behaviors. In this paper we collect and categorize these behaviors into spatial organization, navigation, decision making, and miscellaneous. This taxonomy is then applied to categorize a number of existing swarm robotic applications from research and industrial domains. Along with the classification, we give a comprehensive overview of research platforms that can be used for testing and evaluating swarm behavior, systems that are already on the market, and projects that target a specific market. Results from this survey show that swarm robotic applications are still rare today. Many industrial projects still rely on centralized control, and even though a solution with multiple robots is employed, the principal idea of swarm robotics of distributed decision making is neglected. We identified mainly following reasons: First of all, swarm behavior emerging from local interactions is hard to predict and a proof of its eligibility for applications in an industrial context is difficult to provide. Second, current communication architectures often do not match requirements for swarm communication, which often leads to a system with a centralized communication infrastructure. Finally, testing swarms for real industrial applications is an issue, since deployment in a productive environment is typically too risky and simulations of a target system may not be sufficiently accurate. In contrast, the research platforms present a means for transforming swarm robotics solutions from theory to prototype industrial systems.

16.
Trials ; 21(1): 434, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460811

RESUMO

BACKGROUND: Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap. METHODS/DESIGN: This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor-patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor-patient consultation; as well as the length of the doctor-patient consultation. DISCUSSION: Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient's distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases). TRIAL REGISTRATION: German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.


Assuntos
Glioma/psicologia , Glioma/reabilitação , Qualidade de Vida/psicologia , Estresse Psicológico/reabilitação , Assistência Ambulatorial , Atitude do Pessoal de Saúde , Análise por Conglomerados , Comunicação , Alemanha , Glioma/complicações , Glioma/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Multicêntricos como Assunto , Relações Médico-Paciente , Reabilitação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Encaminhamento e Consulta , Apoio Social , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários
17.
Blood Cells Mol Dis ; 43(2): 169-79, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19423366

RESUMO

The hormone hepcidin is produced mainly in the liver in response to iron loading and inflammation and secreted into the circulation as a 25-amino acid peptide. The 84-amino acid prohormone undergoes limited proteolytic cleavage at a conserved proprotein convertase (PC) recognition site. In addition to the 25-amino acid hepcidin, N-terminally truncated isoforms of lower biological activity are found in plasma and urine. Here we show that a redundant system of proprotein convertases cleaves prohepcidin at the predicted site releasing active hepcidin-25 from the proprotein. In addition to furin mediated cleavage of prohepcidin, we found prohepcidin peptidase activity of proprotein convertases PC5/6, PC7/LPC, PC1/3 and PC2 which was specific for the release of hepcidin-25 from prohepcidin as shown by mass spectrometry. In native tissue extracts, a calcium-dependent prohepcidin peptidase activity is present specifically releasing the 25-mer hepcidin isoform from the recombinant prohormone. In contrast, the 20-mer isoform of hepcidin is generated by a calcium-independent tissue activity which cleaves the 25-mer peptide but has no activity on the entire prohormone. This finding demonstrates the presence of an additional peptidase in this inactivation mechanism for hepcidin. An inhibitor of prohepcidin cleavage was designed and synthesized from d-amino acids (QRRRRR). Biochemical studies indicated that this is a potent and generic inhibitor of prohepcidin cleavage. Biochemical and inhibitor studies of endogenous tissue peptidase activities support the implication of proprotein convertases in the activation of hepcidin. Inactivation of the peptide hormone by N-terminal truncation is mediated by other distinct peptidases, which appear to act sequentially to initial release of hepcidin-25 from the proprotein.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeo Hidrolases/metabolismo , Pró-Proteína Convertases/metabolismo , Precursores de Proteínas/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/antagonistas & inibidores , Hepcidinas , Humanos , Camundongos , Peptídeos/farmacologia , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/antagonistas & inibidores , Proteínas Recombinantes de Fusão/antagonistas & inibidores , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo
19.
Praxis (Bern 1994) ; 104(25): 1393-7, 2015 Dec 09.
Artigo em Alemão | MEDLINE | ID: mdl-26649957

RESUMO

Chronic hepatitis B has a complex natural history. The age at infection, comorbidities, coinfections, and other, yet to be identified factors, determine the probability of developing a chronic infection. The HBV virus can never be completely eliminated and remains in the hepatocytes for life. However, to reach an inactive carrier status is a realistic goal of the therapy. For HBV treatment, pegylated interferon and direct antivirals are available. To screen persons at risk and to vaccinate all of the population are important prophylactic measures. Chronic hepatitis C infection leads, in 30% of cases, to liver cirrhosis. Treatment is recommended from fibrosis stage Metavir 2. New DAA allows short treatment, with a high response rate and very few adverse effects.


Assuntos
Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Medicina Geral , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/terapia , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez , Suíça , Adulto Jovem
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