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Objective: The instrument THERapy-related InterACTion (THER-I-ACT) was developed to document therapeutic interactions comprehensively in the human therapist–patient setting. Here, we investigate whether the instrument can also reliably be used to characterise therapeutic interactions when a digital system with a humanoid robot as a therapeutic assistant is used.
Methods: Participants and therapy: Seventeen stroke survivors receiving arm rehabilitation (i.e., arm basis training (ABT) for moderate-to-severe arm paresis [n = 9] or arm ability training (AAT) for mild arm paresis [n = 8]) using the digital therapy system E-BRAiN over a course of nine sessions. Analysis of the therapeutic interaction: A total of 34 therapy sessions were videotaped. All therapeutic interactions provided by the humanoid robot during the first and the last (9th) session of daily training were documented both in terms of their frequency and time used for that type of interaction using THER-I-ACT. Any additional therapeutic interaction spontaneously given by the supervising staff or a human helper providing physical assistance (ABT only) was also documented. All ratings were performed by two trained independent raters.
Statistical analyses: Intraclass correlation coefficients (ICCs) were calculated for the frequency of occurrence and time used for each category of interaction observed.
Results: Therapeutic interactions could comprehensively be documented and were observed across the dimensions provision of information, feedback, and bond-related interactions. ICCs for therapeutic interaction category assessments from 34 therapy sessions by two independent raters were high (ICC ≥0.90) for almost all categories of the therapeutic interaction observed, both for the occurrence frequency and time used for categories of therapeutic interactions, and both for the therapeutic interaction performed by the robot and, even though much less frequently observed, additional spontaneous therapeutic interactions by the supervisory staff and a helper being present. The ICC was similarly high for an overall subjective rating of the concentration and engagement of patients (0.87).
Conclusion: Therapeutic interactions can comprehensively and reliably be documented by trained raters using the instrument THER-I-ACT not only in the traditional patient–therapist setting, as previously shown, but also in a digital therapy setting with a humanoid robot as the therapeutic agent and for more complex therapeutic settings with more than one therapeutic agent being present.
Objective: To characterize a socially active humanoid robot’s therapeutic interaction as a therapeutic assistant when providing arm rehabilitation (i.e., arm basis training (ABT) for moderate-to-severe arm paresis or arm ability training (AAT) for mild arm paresis) to stroke survivors when using the digital therapeutic system Evidence-Based Robot-Assistant in Neurorehabilitation (E-BRAiN) and to compare it to human therapists’ interaction.
Methods: Participants and therapy: Seventeen stroke survivors receiving arm rehabilitation (i.e., ABT [n = 9] or AAT [n = 8]) using E-BRAiN over a course of nine sessions and twenty-one other stroke survivors receiving arm rehabilitation sessions (i.e., ABT [n = 6] or AAT [n = 15]) in a conventional 1:1 therapist–patient setting. Analysis of therapeutic interaction: Therapy sessions were videotaped, and all therapeutic interactions (information provision, feedback, and bond-related interaction) were documented offline both in terms of their frequency of occurrence and time used for the respective type of interaction using the instrument THER-I-ACT. Statistical analyses: The therapeutic interaction of the humanoid robot, supervising staff/therapists, and helpers on day 1 is reported as mean across subjects for each type of therapy (i.e., ABT and AAT) as descriptive statistics. Effects of time (day 1 vs. day 9) on the humanoid robot interaction were analyzed by repeated-measures analysis of variance (rmANOVA) together with the between-subject factor type of therapy (ABT vs. AAT). The between-subject effect of the agent (humanoid robot vs. human therapist; day 1) was analyzed together with the factor therapy (ABT vs. AAT) by ANOVA.
Main results and interpretation: The overall pattern of the therapeutic interaction by the humanoid robot was comprehensive and varied considerably with the type of therapy (as clinically indicated and intended), largely comparable to human therapists’ interaction, and adapted according to needs for interaction over time. Even substantially long robot-assisted therapy sessions seemed acceptable to stroke survivors and promoted engaged patients’ training behavior.
Conclusion: Humanoid robot interaction as implemented in the digital system E-BRAiN matches the human therapeutic interaction and its modification across therapies well and promotes engaged training behavior by patients. These characteristics support its clinical use as a therapeutic assistant and, hence, its application to support specific and intensive restorative training for stroke survivors.
Generation of Inducible BCL11B Knockout in TAL1/LMO1 Transgenic Mouse T Cell Leukemia/Lymphoma Model
(2022)
The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.
Titin is a multifunctional filamentous protein anchored in the M-band, a hexagonally organized supramolecular lattice in the middle of the muscle sarcomere. Functionally, the M-band is a framework that cross-links myosin thick filaments, organizes associated proteins, and maintains sarcomeric symmetry via its structural and putative mechanical properties. Part of the M-band appears at the C-terminal end of isolated titin molecules in the form of a globular head, named here the “M-complex”, which also serves as the point of head-to-head attachment of titin. We used high-resolution atomic force microscopy and nanosurgical manipulation to investigate the topographical and internal structure and local mechanical properties of the M-complex and its associated titin molecules. We find that the M-complex is a stable structure that corresponds to the transverse unit of the M-band organized around the myosin thick filament. M-complexes may be interlinked into an M-complex array that reflects the local structural and mechanical status of the transversal M-band lattice. Local segments of titin and the M-complex could be nanosurgically manipulated to achieve extension and domain unfolding. Long threads could be pulled out of the M-complex, suggesting that it is a compact supramolecular reservoir of extensible filaments. Nanosurgery evoked an unexpected volume increment in the M-complex, which may be related to its function as a mechanical spacer. The M-complex thus displays both elastic and plastic properties which support the idea that the M-band may be involved in mechanical functions within the muscle sarcomere.
Background
Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN.
Methods
This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition.
Discussion
The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER.
Trial registration
The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326.
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are involved in the modulation of the DNA-damage response (DDR) and upon exposure to ionizing radiation (IR), their expression fluctuates. In this study, we propose a workflow that enables the creation of regulatory networks by integrating transcriptomics data as well as regulatory data in order to better understand the interplay between genes, transcription factors (TFs), miRNAs, and lncRNAs in the cellular response to IR. We preprocessed and analyzed publicly available gene expression profiles and then applied our consensus and integration approach using open source data and tools. To exemplify the benefits of our proposed workflow, we identified a total of 32 differentially expressed transcripts corresponding to 20 unique differentially expressed genes (DEGs) and using these DEGs, we constructed a regulatory network consisting of 106 interactions and 100 nodes (11 DEGs, 78 miRNAs, 1 DEG acting as a TF, and 10 lncRNAs). Overrepresentation analyses (ORAs) furthermore linked our DEGs and miRNAs to annotations pertaining to the DDR and to IR. Our results show that MDM2 and E2F7 function as network hubs, and E2F7, miR-25-3p, let-7a-5p, and miR-497-5p are the four nodes with the highest betweenness centrality. In brief, our workflow, that is based on open source data and tools, and that generates a regulatory network, provides novel insights into the regulatory mechanisms involving miRNAs and lncRNAs in the cellular response to IR.
Background: Little is known about how substance use affects health-related quality of life (HRQOL) in depressed individuals. Here, associations between alcohol consumption and HRQOL in hospital and ambulatory care patients with past-year depressive symptoms are analyzed. Method: The sample consisted of 590 participants (26.8% non-drinkers) recruited via consecutive screenings. Individuals with alcohol use disorders were excluded. HRQOL was assessed with the Veterans Rand 12-item health survey (VR-12). Multivariable fractional polynomials (MFP) regression analyses were conducted (1) to test for non-linear associations between average daily consumption and HRQOL and (2) to analyze associations between alcohol consumption and the physical and mental health component summaries of the VR-12 and their subdomains. Results: Alcohol consumption was positively associated with the physical health component summary of the VR-12 (p = 0.001) and its subdomains general health (p = 0.006), physical functioning (p < 0.001), and bodily pain (p = 0.017), but not with the mental health component summary (p = 0.941) or any of its subdomains. Average daily alcohol consumption was not associated with HRQOL. Conclusion: Alcohol consumption was associated with better physical HRQOL. Findings do not justify ascribing alcohol positive effects on HRQOL. Data indicate that non-drinkers may suffer from serious health disorders. The results of this study can inform the development of future alcohol- and depression-related interventions.
Background
Person-Centered-Care (PCC) requires knowledge about patient preferences. Among People-living-with-Dementia (PlwD) data on quantitative, choice-based preferences, which would allow to quantify, weigh and rank patient-relevant elements of dementia-care, and identify most/least preferred choices, are limited. The Analytic-Hierarchy-Process (AHP) may be one approach to elicit quantitative, choice-based preferences with PlwD, due to simple pairwise comparisons of individual criteria from a complex decision-problem, e.g. health care decisions. Furthermore, data on congruence of patient preferences with physicians’ judgements for PCC are missing. If patient preferences and physicians’ judgements differ, provision of PCC becomes unlikely. An understanding of patient preferences compared to physician’s judgements will support the implementation of truly PCC, i.e. state of the art dementia-care aligned with patient preferences.
Methods
This mixed-methods-study will be based on the results from a previous systematic review and conducted in three phases: (I) literature-based key intervention-categories of PCC will be investigated during qualitative interviews with Dementia-Care-Managers (DCMs) and PlwD to identify actually patient-relevant (sub) criteria of PCC; (II) based on findings from phase I, an AHP-survey will be designed and pre-tested for face- and content-validity, and consistency during face-to-face “thinking-aloud”-interviews with PlwD and two expert panels (DCMs and physicians); (III) the developed survey will elicit patient preferences and physicians’ judgements for PCC. To assess individual importance weights for (sub) criteria in both groups, the Principal-Eigenvector-Method will be applied. Weights will be aggregated per group by Aggregation-of-Individual-Priorities-mode. Descriptive and interferential statistical analyses will be conducted to assess congruence of importance-weights between groups. Subgroup-analyses shall investigate participant-heterogeneities, sensitivity of AHP-results shall be tested by inclusion/exclusion of inconsistent respondents.
Discussion
Little research is published on quantitative, choice-based preferences in dementia care. We expect that (1) PlwD have preferences and can express these, (2) that the AHP is a suitable technique to elicit quantitative, choice-based preferences among PlwD, and (3) to identify a divergence between patient preferences and physicians’ judgements for PCC. With the help of the AHP-technique, which supports systematic decision-making including multiple criteria, it may be possible to involve PlwD in future care decisions (patient participation) and ensure implementation of truly Person-Centered-Dementia-Care.
Trial registration
Approval of the study was granted by the Ethics Committee at the University Medicine Greifswald the 09Apr2021 (Reg.-Nr.: BB 018–21, BB 018-21a, BB 018-21b).
Primary tooth trauma occurs commonly during the development of motor coordination. Its consequences do not only affect the traumatized primary tooth but may affect the underlying permanent successor as well. Its management may involve very high costs on patients and insurance companies and complicated injuries can have negative effects on the quality of life of preschool children. Investigating the causes and patterns of trauma in primary teeth are highly needed to aim for preventive measures. This retrospective study compared the patterns of dental trauma injuries at the trauma center at Greifswald University/Germany for a recent pediatric cohort (2014-16, 103 children) with a historic one before the German unification and the health care system reformation (1974-1989, n=120). The data contained details on etiology, injury types and treatment delivered for 450 injured teeth (247 historic, 203 recent). In both cohorts, the occurrence was more common in males than females (63%/55%, resp.) with an age peak from 2 to 6 years. Maxillary incisors were most affected (89.6%/88.6%, resp.) and periodontal ligament injuries dominated (77.8%/90.3%, resp.).
Almost half of the injuries occurred at home (46.6%), mostly due to falling (48.5%) or during playing (37.8%) in the recent pediatric cohort which provided better forensic data due to insurance issues and potential concern about child abuse. Advice and follow up was the most common approach in the recent pediatric cohort (76%).
Trauma patterns in the primary dentition seem to be rather universal due to the activities of small children and their anatomic conditions. Trauma to primary dentition occurred mostly at home or in the nurseries and possibly is hard to avoid due to falls or accidents during normal playing. Even after 30 years and a change in the health care system due to German unification, the patterns remain similar.
2
In catastrophic situations such as pandemics, patients' healthcare including admissions to hospitals and emergency services are challenged by the risk of infection and by limitations of healthcare resources. In such a setting, the use of telemedicine interventions has become extremely important. New technologies have proved helpful in pandemics as a solution to improve the quality of life in vulnerable patients such as persons with neurological diseases. Moreover, telemedicine interventions provide at-home solutions allowing clinicians to telemonitor and assess patients remotely, thus minimizing risk of infection. After a review of different studies using telemedicine in neurological patients, we propose a telemedicine process flow for healthcare of subjects with chronic neurological disease to respond to the new challenges for delivering quality healthcare during the transformation of public and private healthcare organizations around the world forced by COVID-19 pandemic contingency. This telemedicine process flow represents a replacement for in-person treatment and thereby the provision equitable access to the care of vulnerable people. It is conceptualized as comprehensive service including (1) teleassistance with patient counseling and medical treatment, (2) telemonitoring of patients' health conditions and any changes over time, as well as (3) telerehabilitation, i.e., interventions to assess and promote body functions, activities, and consecutively participation. The hereby proposed telemedicine process flow could be adopted on a large scale to improve the public health response during healthcare crises like the COVID-19 pandemic but could equally promote equitable health care independent of people's mobility or location with respect to the specialized health care center.
Over the past decades, the human life span has dramatically increased, and therefore, a steady increase in diseases associated with age (such as Alzheimer’s disease and Parkinson’s disease) is expected. In these neurodegenerative diseases, there is a cognitive decline and memory loss, which accompany increased systemic inflammation, the inflamm-aging, and the insulin resistance. Despite numerous studies of age-related pathologies, data on the contribution of brain insulin resistance and innate immunity components to aging are insufficient. Recently, much research has been focused on the consequences of nutrients and adiposity- and nutrient-related signals in brain aging and cognitive decline. Moreover, given the role of metainflammation in neurodegeneration, lifestyle interventions such as calorie restriction may be an effective way to break the vicious cycle of metainflammation and have a role in social behavior. The various effects of calorie restriction on metainflammation, insulin resistance, and neurodegeneration have been described. Less attention has been paid to the social determinants of aging and the possible mechanism by which calorie restriction might influence social behavior. The purpose of this review is to discuss current knowledge in the interdisciplinary field of geroscience—immunosenescence, inflamm-aging, and metainflammation—which makes a significant contribution to aging. A substantial part of the review is devoted to frontiers in the brain insulin resistance in relation to neuroinflammation. In addition, we summarize new data on potential mechanisms of calorie restriction that influence as a lifestyle intervention on the social brain. This knowledge can be used to initiate successful aging and slow the onset of neurodegenerative diseases.
Quality of healthcare can be improved when the best external evidence available is integrated in clinical decision-making in a systematic explicit manner. With the rapid expansion of clinical evidence, the opportunities for evidence-based high-quality healthcare increase. Paradoxically, the likelihood of any one person to get a complete and balanced picture of the evidence available decreases. This is especially true for rehabilitation interventions that are complex in nature and where clinical research is rather diverse. Given the complex nature of the evidence, there is a substantial risk of misinterpreting the complex information both at the level of individual sources (e.g., reports of clinical trials) and for aggregated data syntheses (e.g., systematic reviews and meta-analyses). These risks are inherent in these sources themselves and are in addition related to the methodological expertise necessary to make valid use of the evidence for clinical decision-making. Taken together, there is a great demand for systematic structured guidance from evidence to clinical decision. This methodology paper describes a structured process for the development and report of evidence-based clinical practice recommendations that uses systematic reviews and meta-analyses as evidence source. It provides a comprehensive framework with specific requirements for the development group, the formulation of the healthcare question addressed, the systematic search for the evidence, its critical appraisal, the extraction and the outcome-centered presentation of the evidence, the rating of its quality, strengths and weaknesses, any further considerations relevant for decision-making, and an explicit recommendation statement along with its justification, implementation, and resource aspects. The suggested methodology uses international standards in evidence synthesis, critical appraisal of systematic reviews, rating the quality of evidence, characteristics of recommendations, and guideline development as developed by Cochrane, GRADE (Grading of Recommendations Assessment, Development and Evaluation), AMSTAR (A MeaSurement Tool to Assess systematic Reviews), and AGREE (Appraisal of Guidelines for REsearch & Evaluation). An added distinctive feature of the methodology is to focus on the most up-to-date, most valid evidence and hence to support the development of valid practice recommendations in an efficient way. Practice recommendations generated by such a valid methodology would be generally applicable and promote evidence-based clinical practice globally.
T cells are the key players of the adaptive immune response. They coordinate the activation of other immune cells and kill malignant and virus-infected cells. For full activation T cells require at least two signals. Signal 1 is induced after recognition of MHC/peptide complexes presented on antigen presenting cells (APCs) by the clonotypic TCR (T-cell receptor)/CD3 complex whereas Signal 2 is mediated via the co-stimulatory receptor CD28, which binds to CD80/CD86 molecules that are present on APCs. These signaling events control the activation, proliferation and differentiation of T cells. In addition, triggering of the TCR/CD3 complex induces the activation of the integrin LFA-1 (leukocyte function associated antigen 1) leading to increased ligand binding (affinity regulation) and LFA-1 clustering (avidity regulation). This process is termed “inside-out signaling”. Subsequently, ligand bound LFA-1 transmits a signal into the T cells (“outside-in signaling”) which enhances T-cell interaction with APCs (adhesion), T-cell activation and T-cell proliferation. After triggering of signal transducing receptors, adapter proteins organize the proper processing of membrane proximal and intracellular signals as well as the activation of downstream effector molecules. Adapter proteins are molecules that lack enzymatic or transcriptional activity and are composed of protein-protein and protein-lipid interacting domains/motifs. They organize and assemble macromolecular complexes (signalosomes) in space and time. Here, we review recent findings regarding three cytosolic adapter proteins, ADAP (Adhesion and Degranulation-promoting Adapter Protein), SKAP1 and SKAP2 (Src Kinase Associated Protein 1 and 2) with respect to their role in TCR/CD3-mediated activation, proliferation and integrin regulation.
BackgroundIn crisis communication, warning messages are key to informing and galvanizing the public to prevent or mitigate damage. Therefore, this study examines how risk appraisal and individual characteristics influence the intention to comply with behavioral recommendations of a warning message regarding three hazard types: the COVID-19 pandemic, violent acts, and severe weather.
MethodsA cross-sectional survey examined 403 German participants from 18 to 89 years (M = 29.24; 72% female). Participants were allocated to one of three hazard types (COVID-19 pandemic, violent acts, severe weather) and presented with warning messages that were previously issued via an official warning app. Four components of risk appraisal—perceived severity (PS), anticipated negative emotions (AE), anticipatory worry (AW), and risk perception (RP)—were assessed before and after presenting the warning message. Path models were calculated to predict the intention to comply with the warning message, controlling for age, gender, and previous hazard experience.
ResultsFor the COVID-19 pandemic, higher age (β = 0.18) predicted warning compliance (R2 = 0.05). AE (β = 0.20) predicted compliance in the case of violent acts (R2 = 0.09). For severe weather, PS (β = 0.28), age (β = 0.29), and female gender (β = 0.34) lead to higher compliance (R2 = 0.27). Changes across risk appraisal components were not consistent, as some facets decreased after the receipt of a warning message.
DiscussionRisk appraisal has shown a marginal yet differential influence on warning message compliance in different types of hazards. Regarding the COVID-19 pandemic, the impact of sociodemographic factors on compliance should be studied more intensively. Moreover, integrating intermediary variables, such as self-efficacy, is necessary.
Haploidentical stem cell transplantation (haplo SCT) in Stage IV neuroblastoma relapsed patients has been proven efficacious, while immunotherapy utilizing the anti-GD2 antibody dinutuximab beta has become a standard treatment for neuroblastoma. The combinatorial therapy of haplo SCT and dinutuximab may potentiate the efficacy of the immunotherapy. To gain further understanding of the synergistic effects, functional immunomonitoring was assessed during the clinical trial CH14.18 1021 Antibody and IL2 After haplo SCT in Children with Relapsed Neuroblastoma (NCT02258815). Rapid immune reconstitution of the lymphoid compartment was confirmed, with clinically relevant dinutuximab serum levels found in all patients over the course of treatment. Only one patient developed human anti-chimeric antibodies (HACAs). In-patient monitoring revealed highly functional NK cell posttransplant capable of antibody-dependent cellular cytotoxicity (ADCC). Degranulation of NK cell subsets revealed a significant response increased by dinutuximab. This was irrespective of the KIR receptor–ligand constellation within the NK subsets, defined by the major KIR receptors CD158a, CD158b, and CD158e. Moreover, complement-dependent cytotoxicity (CDC) was shown to be an extremely potent effector-cell independent mechanism of tumor cell lysis, with a clear positive correlation to GD2 expression on the cancer cells as well as to the dinutuximab concentrations. The ex vivo testing of patient-derived effector cells and the sera collected during dinutuximab therapy demonstrated both high functionality of the newly established lymphoid immune compartment and provided confidence that the antibody dosing regimen was sufficient over the duration of the dinutuximab therapy (up to nine cycles in a 9-month period). During the course of the dinutuximab therapy, proinflammatory cytokines and markers (sIL2R, TNFa, IL6, and C reactive protein) were significantly elevated indicating a strong anti-GD2 immune response. No impact of FcGR polymorphism on event-free and overall survival was found. Collectively, this study has shown that in-patient functional immunomonitoring is feasible and valuable in contributing to the understanding of anti-cancer combinatorial treatments such as haplo SCT and antibody immunotherapy.
Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies
(2021)
We decided to develop a short-form of the CHC-SUN/YHC-SUN, a questionnaire aiming at assessing health care satisfaction of children and adolescents with chronic health conditions. Data analysis was based on samples from three different studies. Item selection involved statistical analysis and expert consensus. For independent validation purposes, we calculated descriptive statistics on single-item and composite-scale levels and applied classic test theory, confirmatory factor analyses, and correlation analysis to investigate the psychometric properties of the final short-form by different types of reliability and validity. Internal consistency (Cronbach’s Alpha) reached values of a = 0.89 (self-report) and a = 0.92 (parents report), split-half reliability values reached 0.85 (self-report) and 0.91 (parents report). Confirmatory factor analysis indicated no sufficient fit for the single factor solution, whereas the solution with three factors and one higher order factor indicated the best overall fit amongst three competing models. Validity of the short-form measure can be assumed, e.g., as indicated by its association with a single-item measure on general health care satisfaction. The short-form measures of the CHC-SUN for parents (CHC-SUN-SF) and the YHC-SUN self-report version for adolescents (YHC-SUN-SF) feature excellent psychometric performances, provide economical assessments, and are easy-to-administer questionnaires. They should be used whenever brief measures are needed for economic reasons.
Abstract
Caveolae position CaV3.2 (T‐type Ca2+ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large‐conductance Ca2+‐activated K+ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca2+ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav3.2 channel inhibition by Ni2+ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca2+ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav1.2−/− mice, caffeine (RyR activator) and thapsigargin (Ca2+ transport ATPase inhibitor), we found that sufficient SR Ca2+ load is a prerequisite for the CaV3.2‐RyR axis to generate Ca2+ sparks. We identified a fraction of Ca2+ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd3+ (100 µM), but insensitive to CaV1.2 and CaV3.2 channel blockade. Our data demonstrate that the VSMC CaV3.2‐RyR axis is down‐regulated by aging. This defective CaV3.2‐RyR coupling is counterbalanced by a Gd3+ sensitive Ca2+ pathway providing compensatory Ca2+ influx for triggering Ca2+ sparks in aged VSMCs.