Miniaturization of hiPSC-derived 3D neural cultures in stirred-tank bioreactors for parallelized preclinical assessment of rAAV.

Introduction: Engineered 3D models employing human induced pluripotent stem cell (hiPSC) derivatives have the potential to recapitulate the cell diversity and structure found in the human central nervous system (CNS). Therefore, these complex cellular systems offer promising human models to address the safety and potency of advanced therapy medicinal products (ATMPs), such as gene therapies. Specifically, recombinant adeno-associated viruses (rAAVs) are currently considered highly attractive for CNS gene therapy due to their broad tropism, low toxicity, and moderate immunogenicity. To accelerate the clinical translation of rAAVs, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. The integration of hiPSC-derived CNS models in rAAV development will require, amongst other factors, robust, small-scale, high-throughput culture platforms that can feed the preclinical trials. Methods: Herein, we pioneer the miniaturization and parallelization of a 200 mL stirred-tank bioreactor-based 3D brain cell culture derived from hiPSCs. We demonstrate the applicability of the automated miniaturized Ambr® 15 Cell Culture system for the maintenance of hiPSC-derived neurospheroids (iNSpheroids), composed of neuronal and glial cells. Critical process parameters were optimized, namely, cell density and agitation mode. Results: Under optimized conditions, stable iNSpheroid cultures were attained in the microbioreactors for at least 15 days, with high cell viability and astrocytic and neuronal phenotype maintenance. This culture setup allowed the parallelization of different rAAVs, in different multiplicity of infections (MOIs), to address rAAV-host interactions at a preclinical scale. The iNSpheroids were exposed to rAAV2- and rAAV9-eGFP in the microbioreactors. Transgene expression was detected 14 days post-transduction, revealing different astrocyte/neuron tropism of the two serotypes. Discussion: We advocate that the iNSpheroid cultures in miniaturized bioreactors are reliable and reproducible screening tools for addressing rAAV transduction and tropism, compatible with preclinical demands.

Associations of Mental Health Issues with Health Literacy and Vaccination Readiness against COVID-19 in Long-Term Care Facilities-A Cross-Sectional Analysis.

Vaccinations against COVID-19 are of the utmost importance in long-term care facilities. During the pandemic, mental health issues increased significantly. This cross-sectional analysis aimed to assess the associations of depression and anxiety with health literacy in people in need of care and the association of depression and burnout with vaccination readiness against COVID-19 in health care workers (HCWs). Within our cross-sectional study, people in need of care were assessed for symptoms of depression (PHQ-9), anxiety (GAD-7), and health literacy (HLS-EU-Q16). Among HCWs, we assessed symptoms of depression (PHQ-9) and burnout (MBI-HSS), as well as psychological antecedents of vaccination (5C) to measure vaccination readiness against COVID-19. A multivariate regression analysis was performed. Symptoms of a major depression were significantly associated with reduced health literacy (p = 0.010) in people in need of care. Among HCWs, symptoms of depression and burnout reduced vaccination readiness against COVID-19 significantly. In particular, collective responsibility was reduced in HCWs suffering from burnout symptoms (p = 0.001). People in need of care and their HCWs could benefit from intensified target group-specific vaccination counseling. Additionally, more attention should be paid to the protection of mental health in long-term care facilities.

[" Not Even in The Corridor!" - Subjective Perception Of Institutional Measures During The Covid-19 Pandemic Of Nursing Home Residents: A Qualitative Study]. / " nicht mal auf den Gang!" ­ Das subjektive Empfinden institutioneller Maßnahmen während der Covid-19 Pandemie von Pflegeheimbewohnern. Eine qualitative Studie.

BACKGROUND: In the context of the Covid-19 pandemic, institutional measures were decreed to protect nursing home residents from infection. Their appropriateness has been a subject of controversy. The aim of this work was to better understand the subjective perception of the protective measures during the Covid-19 pandemic by the nursing home residents in Bavaria and to shed light on the role of nursing staff and general practitioners in coping with the crisis. METHODS: Semi-structured interviews were conducted with residents of inpatient long-term care facilities. Data analysis was carried out by means of structured content analysis according to Kuckartz. RESULTS: A total of ten nursing home residents with various degrees of care were interviewed, five of whom had already been infected with Covid-19 at the time of the survey. The respondents reported, on the one hand, their need for protection and, on the other hand, the isolation they experienced during the pandemic. Trust in the care provided by the nursing staff was emphasized. A reliable personal contact to already known general practitioners was missing. CONCLUSION: The role of nurses and general practitioners deserves more attention and may be a key to better acceptance and management of such crisis situations.

Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody.

Monoclonal antibody-based therapy has shown efficacy against cancer, autoimmune, infectious, and inflammatory diseases. Multispecific antibodies (MsAbs), including trispecifics (tsAbs), offer enhanced therapeutic potential by targeting different epitopes. However, when co-expressed from three or more different polypeptide chains, MsAb production can lead to incorrect chain assembly and co-production of mispaired species with impaired biological activity. Moreover, mispairing carries significant challenges for downstream purification, decreasing yields and increasing the cost of bioprocess development. In this study, quantitative transcriptomics and proteomics analyses were employed to investigate which signaling pathways correlated with low and high mispairing clone signatures. Gene and protein expression profiles of Chinese hamster ovary (CHO) clones producing an tsAb were analyzed in the exponential growth and stationary (tsAb production) phase of fed-batch culture. Functional analysis revealed activated endoplasmic reticulum stress in high mispairing clones in both culture phases, while low mispairing clones exhibited expression profiles indicative of activated protein translation, as well as higher endocytosis and target protein degradation, suggesting the clearance of unfolded proteins through ubiquitin-mediated mechanisms. In addition, through transcriptomic profiling, we identified a group of genes that have the potential to be used as a biomarker panel tool for identifying high mispairing levels in the early stages of bioprocess development.

Physicians' assessment of the Bavarian drug-expenditure control system: a qualitative study.

BACKGROUND: In 2014 a new system for drug expenditures, the Wirkstoffvereinbarung (WSV, English: Active substance agreement) was implemented in Bavaria. In pre-defined indication groups, economic prescription of medications shall be enabled based on the selection, quantity, and proportion of an individual drug. Ambulatory care physicians receive quarterly trend reports on their prescribing behavior. This study examines physicians' perceptions of the WSV. METHODS: Qualitative interviews (n = 20) and seven focus groups (n = 36) were conducted with ambulatory care physicians (e.g. general practitioners, cardiologists, pulmonologists). The methodology followed Qualitative Content Analysis. RESULTS: Physicians generally accepted the necessity of prescribing economically. The majority of them rated the WSV positively and better than the previous system. As an improvement, they especially named timely feedback in form of easily understandable trend reports, encouraging self-reflection as well as allowing early control options. Problems perceived were drug discount contracts that were strongly criticized as leading to patients mixing up medications. Some perceived constraints of therapeutic freedom. CONCLUSIONS: The implementation of the WSV is mostly viewed positively by physicians. The restrictions of therapeutic freedom partially perceived might be met by improved information on the reasons why some drugs are rated as less economical than others. TRIAL REGISTRATION NUMBER: Main ID: DRKS00019820 (German Register of Clinical Studies and World Health Organization).

Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study.

BACKGROUND: In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines. METHODS: A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors. RESULTS: In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations. CONCLUSION: The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety. TRIAL REGISTRATION: DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.

Development of a subset of the international classification of functioning, disability and health as a basis for a questionnaire for community-dwelling older adults aged 75 and above in primary care: a consensus study.

OBJECTIVES: Functioning of older adults needs to be adequately described before it can become the focus of care. The International Classification of Functioning, Disability and Health (ICF) provides a basis for describing functioning. As the ICF is too extensive for daily practice in primary care, there is a need for a reduced number of categories. The aim is to develop an ICF-subset for community-dwelling older adults aged 75 and above in primary care. DESIGN: The scientific basis for decision-making in our consensus study was laid by four preparatory studies, identifying potentially relevant ICF categories from four perspectives (research, patients', experts' and clinical perspective). The results of the preparatory phase were discussed by an international expert panel in a consensus study following the Nominal Group Technique (NGT). SETTING: An international 1-day online consensus conference. PARTICIPANTS: International experts (n=7) participated in the consensus conference, meeting the following criteria: extensive expertise in the field of the ICF and/or caring for older adults, and being fluent in English. RESULTS: Each preparatory study yielded a different number of categories with some overlaps but also differences. The expert panel decided to: (1) restrict the subset to second-level categories and reduce the number of categories from the preparatory phase, (2) limit the subset to the component activities and participation and (3) weight the patients' perspective as the most relevant one. CONCLUSIONS: By using consensus techniques and the NGT, the process led to 51 second-level ICF categories to describe the functioning of community-dwelling older adults. The decisions made in the consensus conference emphasised the importance of considering the individual life situation from a more holistic perspective and addressing functioning as a focus of care. Next, the 51 categories will contribute to the development of an ICF-based questionnaire.

Reactogenicity and safety of COVID-19 primary immunisation and booster vaccination regimens: a comparative observational cohort study.

BACKGROUND: Since the beginning of the COVID-19 vaccination campaigns, recommendations regarding the vaccination have been very dynamic. Although the safety and efficacy of different vaccines have been analysed, data were scarce for vaccine regimens combining different vaccines. We therefore aimed to evaluate and compare the perceived reactogenicity and need for medical consultation after the most frequently applied homologous and heterologous COVID-19 vaccination regimens. METHODS: In an observational cohort study, reactogenicity and safety were assessed within a maximum follow-up time of 124 days using web-based surveys. Reactogenicity was assessed for different vaccination regimens 2 weeks after a vaccination (short-term survey). The following surveys, long-term and follow-up surveys, focused on the utilisation of medical services, including those that were not suspected to be vaccine-related. RESULTS: Data of 17,269 participants were analysed. The least local reactions were seen after a ChAdOx1 - ChAdOx1 regimen (32.6%, 95% CI [28.2, 37.2]) and the most after the first dose with mRNA-1273 (73.9%, 95% CI [70.5, 77.2]). Systemic reactions were least frequent in participants with a BNT162b2 booster after a homologous primary immunisation with ChAdOx1 (42.9%, 95% CI [32.1, 54.1]) and most frequent after a ChAdOx1 - mRNA-1273 (85.5%, 95% CI [82.9, 87.8]) and mRNA-1273/mRNA-1273 regimen (85.1%, 95% CI [83.2, 87.0]). In the short-term survey, the most common consequences were medication intake and sick leave (after local reactions 0% to 9.9%; after systemic reactions 4.5% to 37.9%). In the long-term and follow-up surveys, between 8.2 and 30.9% of participants reported consulting a doctor and between 0% and 5.4% seeking hospital care. The regression analyses 124 days after the first and after the third dose showed that the odds for reporting medical consultation were comparable between the vaccination regimens. CONCLUSIONS: Our analysis revealed differences in reactogenicity between the COVID-19 vaccines and vaccination regimens in Germany. The lowest reactogenicity as reported by participants was seen with BNT162b2, especially in homologous vaccination regimens. However, in all vaccination regimens reactogenicity rarely led to medical consultations. Small differences in seeking any medical consultation after 6 weeks diminished during the follow-up period. In the end, none of the vaccination regimens was associated with a higher risk for medical consultation. TRIAL REGISTRATION: DRKS DRKS00025881 ( https://drks.de/search/de/trial/DRKS00025373 ). Registered on 14 October 2021. DRKS DRKS00025373 ( https://drks.de/search/de/trial/DRKS00025881 ). Registered on 21 May 2021. Registered retrospectively.

Impact of the COVID-19 pandemic on people in need of care or support: protocol for a SARS-CoV-2 registry.

INTRODUCTION: People in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical and psychosocial impact of the COVID-19 pandemic on people in need of care or support in Bavaria, Germany. To describe the persons' life conditions comprehensively, we assess the perspectives and needs of the respective care teams too. Results will serve as evidence-based source to manage the pandemic and long-term prevention strategies. METHODS AND ANALYSIS: The 'Bavarian ambulatory COVID-19 Monitor' is a multicentre registry including a purposive sample of up to 1000 patient-participants across three study sites in Bavaria. The study group consists of 600 people in need of care with a positive SARS-CoV-2 PCR test. Control group 1 comprises 200 people in need of care with a negative SARS-CoV-2 PCR test, while control group 2 comprises 200 people with a positive SARS-CoV-2 PCR test but are not in need of care. We assess the clinical course of infection, psychosocial aspects and care needs using validated measures. Follow-up is every 6 months for up to 3 years. Additionally, we assess up to 400 people linked to these patient-participants (caregivers, general practitioners (GPs)) for their health and needs. Main analyses are stratified by level of care I-V (I=minor/V=most severe impairment of independence), inpatient/outpatient care setting, sex and age. We use descriptive and inferential statistics to analyse cross-sectional data and changes over time. In qualitative interviews with 60 stakeholders (people in need of care, caregivers, GPs, politicians), we explore interface problems of different functional logics, of everyday and professional perspectives. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Hospital LMU Munich (#20-860) and the study sites (Universities of Wurzburg and Erlangen) approved the protocol. We disseminate the results by peer-reviewed publications, international conferences, governmental reports, etc.

Detecting Medication Risks among People in Need of Care: Performance of Six Instruments.

INTRODUCTION: Numerous tools exist to detect potentially inappropriate medication (PIM) and potential prescribing omissions (PPO) in older people, but it remains unclear which tools may be most relevant in which setting. OBJECTIVES: This cross sectional study compares six validated tools in terms of PIM and PPO detection. METHODS: We examined the PIM/PPO prevalence for all tools combined and the sensitivity of each tool. The pairwise agreement between tools was determined using Cohen's Kappa. RESULTS: We included 226 patients in need of care (median (IQR age 84 (80-89)). The overall PIM prevalence was 91.6 (95% CI, 87.2-94.9)% and the overall PPO prevalence was 63.7 (57.1-69.9%)%. The detected PIM prevalence ranged from 76.5%, for FORTA-C/D, to 6.6% for anticholinergic drugs (German-ACB). The PPO prevalences for START (63.7%) and FORTA-A (62.8%) were similar. The pairwise agreement between tools was poor to moderate. The sensitivity of PIM detection was highest for FORTA-C/D (55.1%), and increased to 79.2% when distinct items from STOPP were added. CONCLUSION: Using a single screening tool may not have sufficient sensitivity to detect PIMs and PPOs. Further research is required to optimize the composition of PIM and PPO tools in different settings.

Unveiling Human Proteome Signatures of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent but still poorly understood clinical entity. Its current pathophysiological understanding supports a critical role of comorbidities and their chronic effect on cardiac function and structure. Importantly, despite the replication of some HFpEF phenotypic features, to this day, experimental models have failed to bring new effective therapies to the clinical setting. Thus, the direct investigation of HFpEF human myocardial samples may unveil key, and possibly human-specific, pathophysiological mechanisms. This study employed quantitative proteomic analysis by advanced mass spectrometry (SWATH-MS) to investigate signaling pathways and pathophysiological mechanisms in HFpEF. Protein-expression profiles were analyzed in human left ventricular myocardial samples of HFpEF patients and compared with a mixed control group. Functional analysis revealed several proteins that correlate with HFpEF, including those associated with mitochondrial dysfunction, oxidative stress, and inflammation. Despite the known disease heterogeneity, proteomic profiles could indicate a reduced mitochondrial oxidative phosphorylation and fatty-acid oxidation capacity in HFpEF patients with diabetes. The proteomic characterization described in this work provides new insights. Furthermore, it fosters further questions related to HFpEF cellular pathophysiology, paving the way for additional studies focused on developing novel therapies and diagnosis strategies for HFpEF patients.

Active monitoring of adverse reactions following COVID-19 and other vaccinations: a feasibility study as part of the CoVaKo project.

BACKGROUND: The Corona-Vakzin-Konsortium project (CoVaKo) analyses the efficacy and safety of COVID-19 vaccines in a real-world setting, as well as breakthrough infections in Bavaria, Germany. A subproject of CoVaKo aims to identify adverse reactions of the COVID-19 vaccine and compare these to adverse reactions of other vaccines in an online survey. In a preceding feasibility study, the study materials were tested for comprehensibility, visual design, and motivation to participate, as well as for their ability to be implemented and carried out in primary care practices and vaccination centres. METHODS: We used a mixed-methods research design. First, three focus groups consisting of general population participants were organised to evaluate the study materials and survey. Second, a test roll-out was conducted in vaccination centres and primary care practices that involved implementing and quantitatively evaluating the online survey. Third, interviews were conducted with participating general practitioners and heads of vaccination centres four weeks after the test roll-out. RESULTS: Parts of the information and registration form proved incomprehensible, specifically regarding the recruitment material and/or online survey. For example, headings were misleading given that, relative to other vaccinations, the COVID-19 vaccination was overemphasised in the title. Participants requested additional information regarding the procedure and completion time. Within 31 days, 2199 participants, who received either a COVID-19 vaccination (99%) or at least one of the control vaccinations (1%), registered for the study. Participants (strongly) agreed that the registration process was easy to understand, that the completion time was reasonable, and that the technical setup was straightforward. Physicians and heads of the vaccination centres perceived the study as easy to integrate into their workflow. The majority expressed willingness to participate in the main study. CONCLUSIONS: Our study indicated that identifying and documenting adverse reactions following vaccinations using an online survey is feasible. Testing materials and surveys provided valuable insight, enabling subsequent improvements. Participation from health professionals proved essential in ensuring the practicality of procedures. Lastly, adapting the study's organisation to external fluctuating structures and requirements confirmed necessary for a successful implementation, especially due to dynamic changes in the nation's COVID-19 vaccination strategies. TRIAL REGISTRATION: The trial was retrospectively registered at the "Deutsches Register Klinischer Studien" (DRKS-ID: DRKS00025881 ) on Oct 14, 2021.

[Prescribing behavior of Bavarian general practitioners at the inpatient-outpatient interface within the context of the Bavarian active substance agreement-qualitative results of the WirtMed Study]. / Verordnungsverhalten von bayerischen Hausärzt*innen an der stationär-ambulanten Schnittstelle vor dem Hintergrund der Bayerischen Wirkstoffvereinbarung ­ Qualitative Ergebnisse der WirtMed-Studie.

BACKGROUND AND OBJECTIVES: In 2014, the Association of Statutory Health Insurance Physicians of Bavaria introduced the active substance agreement (WSV) for the transparent control of pharmaceutical expenditure within the framework of the efficiency principle (§ 12 of the Fifth Book of the German Social Code [SGB V]). It replaced the prescribing target scheme. Regarding the role of the WSV, the article presents the reasons of the general practitioners (GPs) for or against a further prescription of drugs from the hospital. MATERIALS AND METHODS: In a qualitative study design, individual interviews (n = 18) and two focus groups (n = 10) were conducted with Bavarian GPs between November 2019 and March 2020 and evaluated according to qualitative content analysis. RESULTS: With the introduction of the WSV, recourse concerns decreased for GPs overall. Patient-oriented care and the professional correctness of therapy decisions are of great importance in prescribing, ahead of cost-effectiveness. Economic challenges arise with discharge medication, especially with the lead substance target of oral anticoagulants, the generic targets for antidiabetics, and for therapeutics for the cardiovascular system. Generally criticized are drug discount contracts, which often lead to drug changes after hospital discharge. There are individual reports of a "predominance" of hospital physicians when prescribing, which is contrary to their own economic actions as GPs. According to the GPs, there is a lack of cross-sectoral cost responsibility. CONCLUSIONS: In the view of GPs, a smooth interface transition is not yet available in the outpatient sector despite a framework agreement on discharge management and the new control system of the WSV. An economical supply of drugs continues to require political discussion across sectors, but also across federal states.

Reactogenicity after heterologous and homologous COVID-19 prime-boost vaccination regimens: descriptive interim results of a comparative observational cohort study.

BACKGROUND: Due to safety signals after vaccination with COVID-19 vector vaccines, several states recommended to complete the primary immunization series in individuals having received one dose of ChAdOx1 (AstraZeneca) with an mRNA vaccine. However, data on safety and reactogenicity of this heterologous regimen are still scarce. The aim of this study was therefore to compare the reactogenicity and the frequency of medical consultations after boost vaccination in a heterologous regimen with ChAdOx1 and mRNA-vaccines (BNT162b2, BioNTech/Pfizer or mRNA-1273, Moderna) to homologous regimens with ChAdOx1 or mRNA-vaccines, respectively. METHODS: In an observational cohort study reactogenicity and safety were assessed 14-19 days (short-term) and 40 to 56 days (long-term) after the boost vaccination using web-based surveys. In the short-term survey solicited and unsolicited reactions were assessed, while the long-term survey focussed on health problems leading to medical consultation after the vaccination, including those that were not suspected to be vaccine-related. RESULTS: In total, 9146 participants completed at least one of the surveys (ChAdOx1/ChAdOx1: n = 552, ChAdOx1/mRNA: n = 2382, mRNA/mRNA: n = 6212). In the short-term survey, 86% with ChAdOx1/mRNA regimen reported at least one reaction, in the ChAdOx1/ChAdOx1 and mRNA/mRNA cohorts 58% and 76%, respectively (age and sex adjusted p < 0.0001). In the long-term survey, comparable proportions of individuals reported medical consultation (ChAdOx1/ChAdOx1 vs. ChAdOx1/mRNA vs. mRNA/mRNA: 15% vs. 18% vs. 16%, age and sex adjusted p = 0.398). Female gender was associated with a higher reactogenicity and more medical consultations. Younger age was associated with a higher reactogenicity, whereas elderly people reported more medical consultations. CONCLUSION: Although the short-term reactogenicity was higher with the heterologous regimen than with the homologous regimens, other factors such as higher efficacy and limited resources during the pandemic may prevail in recommending specific regimens.

[What support does a mobile, assistive app provide for informal caregivers? A qualitative analysis of the MoCaB app user experience]. / Unterstützung pflegender Angehöriger durch eine mobile, assistive App. Eine qualitative Analyse der Perspektive von Nutzerinnen und Nutzern der App MoCaB.

BACKGROUND: In the joint project "Mobile Care Backup" funded by the German Federal Ministry of Education and Research, the smartphone-based app "MoCaB" was developed in close cooperation with informal caregivers. It provides individualized, algorithm-based information and can accompany and support caring relatives in everyday life. After a multi-step development, informal caregivers tested the MoCaB app in a home setting at the end of the research project. The goal was to find out how the test persons evaluate MoCaB and in which form the app can provide support to informal caregivers. METHODS: Eighteen test persons caring for relatives participated in a four-week test of MoCaB. Guideline-based qualitative interviews to record usage behavior and experiences with the app were conducted after two and four weeks of testing, transcribed and analyzed using qualitative content analysis. RESULTS: The test persons described the care-related information as helpful. The individualized, algorithm-based mode of information delivery and the exercises provided for family caregivers were generally rated as helpful, but their use depends on the individual usage style. Three dimensions can describe the effects of MoCaB: 1) expansion of care-relevant knowledge, 2) stimulation of self-reflection, and 3) behavior towards the care recipients. DISCUSSION: With few exceptions, the testing caregivers felt that the MoCaB app was enriching. The support dimensions have an effect at different points in everyday life and vary in intensity, depending on the duration of the existing care activity and the individual preferences of the users. CONCLUSION: The way in which caregivers used the app was not always consistent with the expected behaviors. This demonstrates the relevance of open-ended, qualitative research methods in the evaluation of health apps.

Stem cells characterization: OMICS reinforcing analytics.

Stem cells hold outstanding potential to model and treat disease and are valuable tools in pharmacology and toxicology. Characterization of stem cells and derivatives still poses many challenges to ensure safe, efficacious, and reliable therapies. Regulatory agencies have defined key mandatory attributes related to identity, purity, sterility, and genomic integrity, however robust analytics to determine cell's potency are still a major challenge, in most cases assessed case-by-case. Importantly, the application of high-throughput 'omic tools is opening new perspectives on stem cell's research and development. Here, analytical methodologies currently employed to characterize stem cells' quality attributes are discussed, with special focus on 'omics as relevant tools for definition of cell's mechanism of action, and for potency assay development and assessment.

Analysing the Selection of Appropriate Technical Solutions for Nurses in a Clinical Setting.

This work focuses the selection of technical solutions for professional nursing in a clinical setting. For a participatory approach the needs of the nursing staff are queried and analysed. Supplemented by data of patients a baseline for the selection of technical solutions is created.

Proteomic and Glyco(proteo)mic tools in the profiling of cardiac progenitors and pluripotent stem cell derived cardiomyocytes: Accelerating translation into therapy.

Research in stem cells paved the way to an enormous amount of knowledge, increasing expectations on cardio regenerative therapeutic approaches in clinic. While the first generation of clinical trials using cell-based therapies in the heart were performed with bone marrow and adipose tissue derived mesenchymal stem cells, second generation cell therapies moved towards the use of cardiac-committed cell populations, including cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes. Despite all these progresses, translating the aptitudes of R&D and pre-clinical data into effective clinical treatments is still highly challenging, partially due to the demanding regulatory and safety concerns but also because of the lack of knowledge on the regenerative mechanisms of action of these therapeutic products. Thus, the need of analytical methodologies that enable a complete characterization of such complex products and a deep understanding of their therapeutic effects, at the cell and molecular level, is imperative to overcome the hurdles of these advanced therapies. Omics technologies, such as proteomics and glyco(proteo)mics workflows based on state of the art mass-spectrometry, have prompted some major breakthroughs, providing novel data on cell biology and a detailed assessment of cell based-products applied in cardiac regeneration strategies. These advanced 'omics approaches, focused on the profiling of protein and glycan signatures are excelling the identification and characterization of cell populations under study, namely unveiling pluripotency and differentiation markers, as well as paracrine mechanisms and signaling cascades involved in cardiac repair. The leading knowledge generated is supporting a more rational therapy design and the rethinking of challenges in Advanced Therapy Medicinal Products development. Herein, we review the most recent methodologies used in the fields of proteomics, glycoproteomics and glycomics and discuss their impact on the study of cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes biology. How these discoveries will impact the speed up of novel therapies for cardiovascular diseases is also addressed.

[Into the Garbage? - Reasons for the Non-use of Technical Innovations in Inpatient Care]. / "In den Müll?!" ­ Ursachenforschung zur Nicht-Nutzung technischer Innovationen in der stationären Pflege.

Despite the potentially positive effects of new technologies, innovations are often not well accepted by nurses. The aim of this study was to explore the reasons for not using a distributed alarm system and to derive recommendations for future projects. Three group discussions were held with 14 nurses. Content analysis was used to explore the data. The nursing staff was not involved in the selection and introduction of the technology. A lack of knowledge or interest was not the reason for not using the system. The technology rather interrupted work processes, led to additional workload and exposure to more noise pollution for employees and patients. Technologies must fit into daily work routines. Ideally, nurses should be involved in the development, but at the least, they should be consulted at the time of introduction.

Promoção da saúde mental materna perinatal: Da evidência científica à construção de um protótipo de intervenção em cuidados de saúde primários / Promotion of maternal perinatal mental health: From scientific evidence to the construction of an intervention prototype in primary health care

Enquadramento Teórico/ Problemática: Os processos que envolvem a transição para a maternidade, presentes em todo o período perinatal, são bastante complexos, abrangendo um conjunto de dimensões experienciadas pela mulher, do ponto de vista biológico, psicológico e social, com significados muito relevantes para a saúde mental materna, com impactos na saúde da mulher e da criança e no sistema familiar e social. O presente estudo surge da necessidade de aprofundar a compreensão destes aspetos, no sentido de desenvolver uma resposta de saúde direcionada para a promoção da saúde mental materna em CSP, para uma prática baseada na evidência e no âmbito da ESMP. Objetivos: Descrever as vivências emocionais maternas no período perinatal de grávidas e mães em pós-parto até aos 12 meses, bem como, as percecionadas pelos seus companheiros e profissionais de saúde em contexto de CSP; Compreender os fatores de risco e protetores para a saúde mental materna perinatal, percecionados pelas grávidas, mães em pós-parto até aos 12 meses, seus companheiros e profissionais de saúde em contexto de CSP; Construír protótipo de intervenção para a promoção da saúde mental materna, em contexto de CSP e no âmbito da ESMP. Metodologia: Estudo com uma abordagem qualitativa, do tipo exploratório e descritivo. Compreendeu uma colheita de dados através de três focus groups: Grávidas e companheiros; Mães e companheiros com bebés até 12 meses e Profissionais de Saúde, num total de 29 participantes da área de abrangência da UCC de Abrantes, num processo de amostragem por conveniência. Os dados foram transcritos e analisados por meio de análise temática indutiva, com recurso ao NVivo 12. Cumpridos pressupostos éticos. Resultados: Da análise de dados, emergiram quatro dimensões e suas categorias: 1) Vivências emocionais maternas, com 9 categorias, com destaque para a ansiedade, medos, aumento da sensibilidade e fragilidade e desilusão e tristeza relacionada com o parto; 2) Fatores de risco percecionados para a saúde mental materna, com 31 categorias, com destaque para crenças erróneas, caraterísticas desfavoráveis da personalidade materna, privação do sono, falta ou fraco suporte do companheiro, vivência negativa da imagem corporal e as práticas dos profissionais de saúde percecionadas como dificultadoras; 3) Fatores protetores percecionados para a saúde mental materna, com 12 categorias, com destaque para o apoio e a presença do pai/companheiro em todo o processo, uma boa rede de suporte familiar, as competências maternas, a frequência de cursos de preparação para o parto e as práticas dos profissionais de saúde percecionadas como facilitadoras e 4) Sugestões Curso Promoção da Saúde Mental Materna, com 26 categorias, cujas áreas temáticas em destaque: a transição para a maternidade e os seus significados, alterações emocionais no período perinatal, estratégias e autocuidados em SM materna, gestão de expectativas e treino de competências na transição para a parentalidade. Conclusões: Neste estudo é evidenciada a relevância da SMMP e do papel da ESMP nesta área, sublinhando a necessidade de construção de práticas assentes na evidência científica. O modelo do Protótipo proposto surge da síntese de resultados do nosso estudo e de evidências encontradas na literatura de programas de SM Materna. As áreas temáticas que emergiram visam a aquisição de competências na transição para a maternidade, a promoção da literacia em saúde mental materna, a promoção dos fatores protetores e a minimização/controle dos fatores de risco para a saúde mental materna. Destaque para a recomendação do curso ocorrer em contexto comunitário e em equipa multidisciplinar e da necessidade de formação e treino dos profissionais de saúde, nesta área