RepoMed (Medizinische Hochschule Hannover)
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Quantitative und qualitative Analyse von Präferenzen ausländischer Patient/ innen und Leistungserbringern in deutschen herzchirurgischen Universitätskliniken
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HSPB1 Is Essential for Inducing Resistance to Proteotoxic Stress in Beta-Cells.
No full textDuring type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant's outcome, several strategies are being studied. We have previously shown that prolactin induces protection against proinflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat-shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1 attenuated levels of pro-apoptotic proteins such as CHOP and BIM, as well as increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and, thus, enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aimed at the optimization of beta-cell replacement therapies
Cardiorespiratory Events Following the Second Routine Immunization in Preterm Infants: Risk Assessment and Monitoring Recommendations.
No full textDue to frequent cardiorespiratory events (CREs) in response to the first routine immunization (rIM), current guidelines recommend readmitting and monitoring extremely preterm infants after the second rIM, though evidence on CREs in response to the second rIM is weak. In a prospective observational study, preterm infants with an increase in CREs after the first rIM were monitored for CREs before and after the second rIM. Seventy-one infants with a median gestational age of 26.4 weeks and a median weight of 820 g at birth were investigated at a median postnatal age of 94 days. All but seven infants showed an increase in CREs after the second rIM. The frequency of hypoxemias (p < 0.0001), apneas (p = 0.0003) and cardiorespiratory events requiring tactile stimulation (CRE-ts) (p = 0.0034) increased significantly. The 25 infants (35%) presenting with CRE-ts were significantly more likely to have been continuously hospitalized since birth (p = 0.001) and to receive analeptic therapy at the first rIM (p = 0.002) or some kind of respiratory support at the first (p = 0.005) and second rIM (p < 0.0001). At a postmenstruational age of 43.5 weeks, CRE-ts ceased. Our data support the recommendation to monitor infants who fulfil the above-mentioned criteria during the second rIM up to a postmenstruational age of 44 weeks
Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders
No full textIntroduction The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). Methods Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. Results The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%-25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%-22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41-1.70, severe depression 1.33, 95% CI 1.18-1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27-1.38, PIM 1.18, 95% CI: 1.14-1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11-1.46, PIM 1.27, 95% CI: 1.11-1.44), respectively. Conclusion This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles
Comparison of dual-energy computer tomography and dynamic contrast-enhanced MRI for evaluating lung perfusion defects in chronic thromboembolic pulmonary hypertension.
No full textObjectives To evaluate the agreement in detecting pulmonary perfusion defects in patients with chronic thromboembolic pulmonary hypertension using dual-energy CT and dynamic contrast-enhanced MRI. Second, to compare both imaging modalities in monitoring lung perfusion changes in these patients after undergoing pulmonary endarterectomy. Methods 20 patients were examined with CT and MRI before and/or after pulmonary endarterectomy. Estimated perfusion defect percentage from both modalities was compared in a lobe-based analysis. Spatial agreement of perfusion defect maps was also assessed. Results A significant correlation between CT and MRI based perfusion defect percentage was calculated in all lung lobes (r > 0.78; p < 0.001). In addition, a good spatial agreement between perfusion defect maps was found (mean spatial overlap for the whole lung was 68.2%; SD = 6.9). Both CT and MRI detected improvements in pulmonary perfusion after pulmonary endarterectomy: 8% and 7% decrease in whole lung perfusion defect percentage (p = 0.007 and 0.004), respectively. In a lobe-wise analysis, improvements were statistically significant only in lower lobes using both modalities (reduction in defect percentage ranged from 16-29%; p < 0.02). Conclusions Dual-energy CT is an alternative to MRI in monitoring chronic thromboembolic pulmonary hypertension. Both imaging modalities provided comparable estimations of perfusion defects and could detect similar improvement in lung perfusion after pulmonary endarterectomy
Relationship Satisfaction in People with Parkinson's Disease and Their Caregivers: a Cross-Sectional Observational Study
No full textParkinson's disease (PD) is a neurodegenerative disorder, which leads to reduced health-related quality of life (HR-QoL) and autonomy in advanced stages of the disease. Hence, people with PD (PwPD) are in need of help, which is often provided by informal caregivers, especially spouses. This might influence the relationship satisfaction in patients and their spousal caregivers. Additionally, previous studies have shown that a reduced relationship satisfaction may result in mental disorders and reduced physical health. The aim of this study is to identify factors influencing PwPD and their caregivers' relationship satisfaction in a cross-sectional observational study. Analyses revealed an overall satisfying relationship, measured by the Quality of Marriage Index, in PwPD (n = 84) and their caregivers (n = 79). Relationship satisfaction in PwPD mildly decreased with reduced HR-QoL and more severe depressive symptoms. Reduced relationship satisfaction in caregivers was significantly associated with decreased HR-QoL, higher caregiver burden, more severe depressive symptoms and increased neuropsychiatric symptoms in PwPD. Further studies are needed to investigate the influence of the identified factors over time and if relationship satisfaction has a reciprocal impact on caregiver burden, HR-QoL as well as mental and physical health
Structural and Biochemical Characterization of a Dye-Decolorizing Peroxidase from Dictyostelium discoideum.
No full textA novel cytoplasmic dye-decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds, and general peroxidase substrates such as ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H2O2 during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described
Validation of the Parkinson's Disease Caregiver Burden Questionnaire in Progressive Supranuclear Palsy.
No full textProgressive supranuclear palsy (PSP) is an atypical Parkinson syndrome with axial akinetic-rigid symptoms, early postural instability, and ocular motor impairments. Patients experience a rapid loss of autonomy and care dependency; thus, caregivers must assist in the activities of daily living early in the course of the disease. Caregiver burden is an extremely important factor in disease management. However, there are no specific questionnaires for assessment of caregiver burden in PSP. This study aims to validate the Parkinson's disease caregiver burden questionnaire (PDCB) as a specific measure of caregiver burden in PSP. PSP patients were assessed by the PSP rating scale, PSP quality-of-life questionnaire (PSP-QoL), Montreal cognitive assessment test (MoCA), and geriatric depression scale (GDS-15). Caregivers filled out the short form 36-health survey, GDS-15, PDCB, and the caregiver burden inventory (CBI). 22 patient caregiver pairs completed the study. PDCB showed a highly significant correlation with the CBI (r 0.911; p < 0.001). Internal reliability of the PDCB measured by Cronbach's alpha was favourable at 0.803. These data support the specificity of the PDCB in PSP caregivers. Future studies with larger sample sizes of PSP patients and caregivers and a multicentric longitudinal design should be performed to gain further insight of caregiver burden in PSP