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1.
Transfusion ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770549

RESUMO

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)-1a. Recent studies indicate that two anti-HPA subtypes exist: Type I reacts with epitopes residing on the plexin-semaphorin-integrin (PSI) and type II with plexin-semaphorin-integrin/integrin epidermal growth factor 1 (I-EGF1) domains of the ß3 integrin. Here, we evaluated whether a Cys460Trp mutation in the I-EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti-HPA-1a. METHODS: Stable HEK293 cell lines expressing wild-type and mutant αIIbß3 and αvß3 were generated to prove the reactivity of different antibodies against HPA-1a. RESULTS: Flow cytometry analysis of wild-type (Cys460) and mutant (Trp460) expressed on HEK293 cells showed equal surface expression of αIIbß3 and αvß3. When tested with mutant αIIbß3 cells, reduced binding was observed in Type II but not in Type I anti-HPA-1a. These results could be confirmed with platelets carrying Cys460Trp mutation. Interestingly, reduced binding of Type I antibodies was detected with mutant αvß3 cells. Both antibody types were found in maternal sera from FNAIT cases by an antigen-capture assay with use of HEK293 transfected cells. CONCLUSIONS: These observations confirm the existence of Type I and Type II anti-HPA-1a. Furthermore, this study underlines different immunogenicity of HPA-1a antigen(s) residing on either αIIbß3 or αvß3. Further analysis of FNAIT cases from mothers having a fetus with and without intracranial bleedings with use of such an approach may highlight the functional relevance of different anti-HPA-1a subtypes.

3.
Biochim Biophys Acta Bioenerg ; 1861(11): 148263, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32663477

RESUMO

rnf genes are widespread in anaerobic bacteria and hypothesized to encode a respiratory enzyme that couples exergonic reduction of NAD with reduced ferredoxin as a reductant to vectorial ion (Na+, H+) translocation across the cytoplasmic membrane. However, despite its importance for the physiology of these bacteria, little is known about the subunit composition and the function of subunits. Here, we have purified the entire Rnf complex from the acetogen Acetobacterium woodii or after its production in Escherichia coli. These studies revealed covalently bound flavin in RnfB and RnfD. Unfortunately, the complex did not catalyze electron transfer from reduced ferredoxin to NAD. We, therefore, concentrated on the two cytosolic subunits RnfC and RnfB. RnfC was produced in E. coli, purified and shown to have 8.3 mol iron and 8.6 mol sulfur per mol of the subunit, consistent with the presence of two [4Fe-4S] centers, which were verified by EPR analysis. Flavins could not be detected, but RnfC catalyzed NADH-dependent FMN reduction. These data confirm RnfC as NADH-binding subunit and FMN as an intermediate in the electron transport chain. RnfB could only be produced as a fusion to the maltose-binding protein. It contained 25 mol iron and 26 mol sulfur, consistent with the predicted six [4Fe4S] centers. The FeS centers in RnfB were reduced with reduced ferredoxin as reductant. These data are consistent with RnfB as the ferredoxin-binding subunit of the complex.

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5.
PLoS One ; 15(4): e0230659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315371

RESUMO

OBJECTIVES: The current study aims to examine the construct of empowerment in the context of a transition education program. Patient education programs strive to empower adolescents with chronic conditions to take responsibility for their own health care to manage their transition from pediatric to adult medicine. Our study aimed to identify the core components of patient empowerment and examined whether its components are responsive to a patient education program. METHODS: Data was collected in two longitudinal studies involving N = 723 adolescents with chronic conditions. We used Latent Difference Score models (LDSm) of: 1) self-efficacy (GSE), 2) transition competence (TCS), and 3) patient activation (PAM) to quantify the latent variable of patient empowerment (PE). Additionally, the LDSm were extended to analyze the effects of group affiliation (intervention vs. control) and participants' age on empowerment. RESULTS: PE was identifiable by the three components. The intervention group developed significantly higher scores of PE compared to the control group. Age (13-21 years) did not moderate the relation between group affiliation and PE. CONCLUSIONS: We quantified PE successfully using a psychometric modeling of change. Patient empowerment is measureable and utilizable in the specific context of transition of adolescents with chronic conditions.


Assuntos
Doença Crônica/psicologia , Empoderamento , Educação em Saúde , Adolescente , Feminino , Humanos , Masculino , Autoeficácia
6.
Orphanet J Rare Dis ; 15(1): 100, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321554

RESUMO

BACKGROUND: Wolcott-Rallison syndrome (WRS) is characterized by permanent early-onset diabetes, skeletal dysplasia and several additional features, e.g. recurrent liver failure. This is the first multicentre approach that focuses on diabetes management in WRS. We searched the German/Austrian Diabetes-Patienten-Verlaufsdokumentation (DPV) registry and studied anthropometric characteristics, diabetes treatment, glycaemic control and occurrence of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in 11 patients with WRS. Furthermore, all local treatment centres were personally contacted to retrieve additional information on genetic characteristics, migration background and rate of consanguinity. RESULTS: Data were analysed at diabetes onset and after a median follow-up period of 3 (1.5-9.0) years (time from diagnosis to latest follow-up). Median age at diabetes onset was 0.2 (0.1-0.3) years, while onset was delayed in one patient (aged 16 months). Seventy percent of patients manifested with DKA. At follow-up, 90% of patients were on insulin pump therapy requiring 0.7 [0.5-1.0] IU of insulin/kg/d. More than two third of patients had HbA1c level ≥ 8%, 40% experienced at least one episode of SH in the course of the disease. Three patients died at 0.6, 5 and 9 years of age, respectively. To the best of our knowledge three patients carried novel mutations in EIF2AK3. CONCLUSION: Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.

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9.
J Biol Chem ; 295(18): 5970-5983, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184353

RESUMO

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7 -/- mice. Although palmitoylation of barttin in kidneys of Zdhhc7 -/- animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7 -/- mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

10.
Annu Rev Pathol ; 15: 439-466, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31657966

RESUMO

Legionella species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of Legionella pneumophila in 1977, four decades of research on Legionella biology and Legionnaires' disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, Legionella species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. This review aims to discuss current knowledge of Legionella infection mechanisms and future research directions to be taken that might answer the many remaining open questions. This research will without a doubt be a terrific scientific journey worth taking.

11.
J Affect Disord ; 260: 45-52, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493638

RESUMO

BACKGROUND: Self-compassion may be shaped by early attachment experiences, and has been linked to mental health and well-being. This study examined the role of two distinct features of self-compassion, self-warmth and self-coldness, in the relationship between attachment insecurity and depression as well as quality of life in a general population sample in Germany. METHODS: Participants (N = 2,253; 53.4% female, Mage 50 years) completed the Self-Compassion Scale (SCS), Adult Attachment Scale (AAS), Beck Depression Inventory-Fast Screen (BDI-FS), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Mediation analysis was used to examine whether insecure attachment predicted increased symptoms of depression and decreased quality of life through decreased self-warmth and increased self-coldness. RESULTS: Attachment-related anxiety and avoidance had a significant direct effect on depressive symptoms and significant indirect effect via self-warmth and self-coldness. The indirect effect via self-warmth appears to be of negligible magnitude. Attachment-related anxiety and avoidance had a significant direct effect on quality of life, and significant indirect effect via self-coldness. The indirect effect via self-warmth was not statistically significant, speaking against self-warmth as a relevant mediator. LIMITATIONS: Causal conclusions cannot be drawn based on cross-sectional research design. All measures were based on participant self-report. CONCLUSIONS: This study contributes to a more differentiated understanding of how attachment insecurity and self-compassion may contribute to affective disorders. Findings suggest that self-coldness may be particularly relevant in affective disorders and when addressing relational struggles, with both theoretical and clinical implications for psychotherapy and future research.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31641830

RESUMO

PURPOSE: Personal and perceived stigma can hinder persons in appraising their symptoms as constituting part of a mental illness (self-labeling), an important early step in the help-seeking process. This study examines the impact of personal and perceived stigma on self-labeling and provides prospective data on the possible connections between self-labeling and help-seeking behavior. METHODS: Personal stigmatizing attitudes, perceived stigma and self-labeling behavior as well as their statistical connections were cross-sectionally investigated in a community sample of 207 participants with a present untreated mental health problem. We further conducted prospective analyses to investigate possible associations between self-labeling and help-seeking behavior at 3 and 6 month follow-ups. Socio-demographics, previous treatment and depression symptoms were also measured as potential confounders. RESULTS: Personal stigmatizing attitudes were significantly more pronounced in respondents who self-labeled as physically compared to mentally ill, while group differences in levels of perceived stigma were not. Self-labeling as physically or mentally ill increased the likelihood of seeking help from the health service provider deemed most suitable for that label (physical: GP, p <0.05; mental: MHP, p < 0.1) compared to persons who applied no self-label. CONCLUSIONS: The findings suggest that personal stigmatizing attitudes-rather than perceived stigma-impact on self-labeling, and highlight the need for interventions that assist persons with mental illness in overcoming those attitudes. They also underscore the possible impact of self-labeling in the help-seeking process and underline the important role of GPs in mental health care. Further, preferably epidemiological research into the matter would be desirable.

16.
J Relig Health ; 58(6): 2219-2240, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446605

RESUMO

Spiritual well-being is a major issue in health care, but instruments for measuring this construct in adolescents are lacking. This study adapted the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-being Scale (FACIT-Sp-12) for use with Brazilian adolescents with chronic diseases and developed a parental observer-rated version, using an expert panel, back-translation, and cognitive interviews with 72 participants. The psychometric properties of both versions were verified with two- and three-factor models by testing with 212 participants. The self- and parental-reported versions showed face validity, content validity, and acceptable levels of internal consistency for the overall scale and the two-factor model. The convergent validity was satisfactory for most items in both two- and three-factor models, but there was a lack of discrimination in the three-factor model using multitrait-multimethod analysis. This study presents the first instrument to assess the spiritual well-being of adolescents from their point of view and to allow their parents to serve as evaluators. However, we recommend further psychometric testing of the self- and parental-report scales to assess spiritual well-being in adolescents with chronic diseases in Brazil.


Assuntos
Doença Crônica/psicologia , Psicometria/estatística & dados numéricos , Qualidade de Vida/psicologia , Religião e Medicina , Espiritualidade , Inquéritos e Questionários/normas , Adolescente , Brasil , Criança , Doença Crônica/etnologia , Feminino , Nível de Saúde , Humanos , Masculino , Pais , Procurador , Reprodutibilidade dos Testes , Autorrelato , Tradução
17.
Environ Health Perspect ; 127(6): 69003, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31219709
19.
Neuroimage ; 191: 470-480, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30790673

RESUMO

Health-related quality of life is likely associated with the brain via processes relating to physiology, behavior, cognition, emotion and stress. Previous studies with small student or clinical samples have identified associations with gray matter volume in the anterior cingulate cortex, prefrontal cortex, insular cortex, (para)hippocampal area, amygdala, and precuneus. The present study investigated the association of gray matter volume of these brain areas with mental and physical components of health, as well as general health perception, measured with the 12-item Short Form Health Survey, in a large sample of 3027 participants from the Study of Health in Pomerania, using voxel-based morphometry for T1-weighted magnetic resonance imaging. Higher physical, but not mental, health-related quality of life and general health perception were associated with larger gray matter volume of the anterior cingulate cortex, medial prefrontal cortex, insular cortex, and the precuneus with a substantial decrease when controlling for lifestyle, comorbidity and symptoms. Age-stratified analyses revealed significantly higher partial correlations of physical health and left insular gray matter volume in the oldest age group. Our study emphasizes the importance of high medial prefrontal and anterior insula gray matter volume for health-related quality of life on the basis of a large sample size.


Assuntos
Envelhecimento/patologia , Envelhecimento/psicologia , Córtex Cerebral/patologia , Substância Cinzenta/patologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Community Ment Health J ; 55(3): 507-518, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694419

RESUMO

This study aims to develop and implement brief implicit association tests (BIATs) assessing stigmatizing attitudes towards mental illness, awareness of mental distress and self-identification as having a mental illness. We recruited 229 people (age range 18-80 years) with currently untreated depressive symptoms. In addition to BIATs, explicit measures assessed depression severity, contact experience and self-identification as having a mental illness. BIATs showed good feasibility. Age and educational differences were observed for each BIAT. Regarding depression severity, people with mild depression severity showed stronger implicit label-avoidance. Novel BIATs proved feasible and future research should investigate the predictive value of implicit measures on help seeking in people with mental illness.


Assuntos
Depressão/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Estigma Social , Estereotipagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos
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