More than the clock: distinct regulation of muscle function and metabolism by PER2 and RORα.

Circadian rhythms, governed by the dominant central clock, in addition to various peripheral clocks, regulate almost all biological processes, including sleep-wake cycles, hormone secretion and metabolism. In certain contexts, the regulation and function of the peripheral oscillations can be decoupled from the central clock. However, the specific mechanisms underlying muscle-intrinsic clock-dependent modulation of muscle function and metabolism remain unclear. We investigated the outcome of perturbations of the primary and secondary feedback loops of the molecular clock in skeletal muscle by specific gene ablation of Period circadian regulator 2 (Per2) and RAR-related orphan receptor alpha (Rorα), respectively. In both models, a dampening of core clock gene oscillation was observed, while the phase was preserved. Moreover, both loops seem to be involved in the homeostasis of amine groups. Highly divergent outcomes were seen for overall muscle gene expression, primarily affecting circadian rhythmicity in the PER2 knockouts and non-oscillating genes in the RORα knockouts, leading to distinct outcomes in terms of metabolome and phenotype. These results highlight the entanglement of the molecular clock and muscle plasticity and allude to specific functions of different clock components, i.e. the primary and secondary feedback loops, in this context. The reciprocal interaction between muscle contractility and circadian clocks might therefore be instrumental to determining a finely tuned adaptation of muscle tissue to perturbations in health and disease. KEY POINTS: Specific perturbations of the primary and secondary feedback loop of the molecular clock result in specific outcomes on muscle metabolism and function. Ablation of Per2 (primary loop) or Rorα (secondary loop) blunts the amplitude of core clock genes, in absence of a shift in phase. Perturbation of the primary feedback loop by deletion of PER2 primarily affects muscle gene oscillation. Knockout of RORα and the ensuing modulation of the secondary loop results in the aberrant expression of a large number of non-clock genes and proteins. The deletion of PER2 and RORα affects muscle metabolism and contractile function in a circadian manner, highlighting the central role of the molecular clock in modulating muscle plasticity.

Automated Heart Rate Detection in Seismocardiograms Using Electrocardiogram-Based Algorithms-A Feasibility Study.

In recent decades, much work has been implemented in heart rate (HR) analysis using electrocardiographic (ECG) signals. We propose that algorithms developed to calculate HR based on detected R-peaks using ECG can be applied to seismocardiographic (SCG) signals, as they utilize common knowledge regarding heart rhythm and its underlying physiology. We implemented the experimental framework with methods developed for ECG signal processing and peak detection to be applied and evaluated on SCGs. Furthermore, we assessed and chose the best from all combinations of 15 peak detection and 6 preprocessing methods from the literature on the CEBS dataset available on Physionet. We then collected experimental data in the lab experiment to measure the applicability of the best-selected technique to the real-world data; the abovementioned method showed high precision for signals recorded during sitting rest (HR difference between SCG and ECG: 0.12 ± 0.35 bpm) and a moderate precision for signals recorded with interfering physical activity-reading out a book loud (HR difference between SCG and ECG: 6.45 ± 3.01 bpm) when compared to the results derived from the state-of-the-art photoplethysmographic (PPG) methods described in the literature. The study shows that computationally simple preprocessing and peak detection techniques initially developed for ECG could be utilized as the basis for HR detection on SCG, although they can be further improved.

Beyond technology acceptance-a focused ethnography on the implementation, acceptance and use of new nursing technology in a German hospital.

Introduction: Hospitalised patients could benefit from the emergence of novel technologies for nursing care. There are numerous technical products available, but these rarely find their way into practice. Further knowledge is required about the circumstances under which technology in nursing is accepted and used. In the research project "Centre for Implementing Nursing Care Innovations", technical innovations are implemented on a trauma surgery inpatient ward in Germany. After implementation, it was investigated: Which implemented technologies are accepted/rejected, and which factors influence the acceptance/rejection of technology for nurses? Material and methods: A focused ethnography was used, containing two approaches: First, participant observation was conducted to examine nurses' and patients' interaction with technologies. Observations were fixed in a field research diary and analysed using evaluative qualitative content analysis. Second, a questionnaire was used by nurses to provide information about the use frequency and technology suitability. The results of the study were consolidated and analysed using the UTAUT model. Results: Seven studied technologies can be summarised in four result categories: (1) A Mobilising mattress, a Special projector and a Sound pillow are accepted and used by nurses and patients, because they offer a way to provide high quality care with little additional effort. (2) A Fall prevention system is consistently used in patient care as a work obligation, but since nurses consider the system error-prone, acceptance is low. (3) An Interactive therapy ball is accepted but nurses cannot use it due to the high workload. (4) An App for nurse-patient communication and a work-equipment tracking system are not used or accepted because nurses do not see a practical benefit in the systems. Discussion: Acceptance or rejection of a product does not necessarily equate to use or non-use of the technology. Before implementation, technology acceptance among users occurs as prejudice-when users are given time to experiment with technology, intention-to-use can stabilize into sustained use. Accepted and used technologies can serve to mask problems (such as staff shortages) and encourage problematic developments, such as the reduction of contact time at the bedside. Therefore, technology acceptance should be qualified in asking to what accepted technology contributes.

Prolonged mHealth-Based Arrhythmia Monitoring in Patients With Hypertrophic Cardiomyopathy (HCM-PATCH): Protocol for a Single-Center Cohort Study.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias and other arrhythmias. Screening for arrhythmias is mandatory to assess the individual SCD risk, but long-term electrocardiography (ECG) is rarely performed in routine clinical practice. Intensified monitoring may increase the detection rate of ventricular arrhythmias and identify more patients with an increased SCD risk who are potential candidates for the primary prophylactic implantation of an implantable cardioverter-defibrillator. To date, reliable data on the clinical benefit of prolonged arrhythmia monitoring in patients with HCM are rare. OBJECTIVE: This prospective study aims to measure the prevalence of ventricular arrhythmias in patients with HCM observed by mobile health (mHealth)-based continuous rhythm monitoring over 14 days compared to standard practice (a 24- and 48-h long-term ECG). The frequency of ventricular arrhythmias in this 14-day period is compared with the frequency in the first 24 or 48 hours for the same patient (intraindividual comparison). METHODS: Following the sample size calculation, 34 patients with a low or intermediate risk for SCD, assessed by the HCM Risk-SCD calculator, will need to be recruited in this single-center cohort study between June 2023 and February 2024. All patients will receive an ECG patch that records their heart activity over 14 days. In addition, cardiac magnetic resonance imaging and genetic testing data will be integrated into risk stratification. All patients will be asked to complete questionnaires about their symptoms; previous therapy; family history; and, at the end of the study, their experience with the ECG patch-based monitoring. RESULTS: The Hypertrophic Cardiomyopathy: Clinical Impact of a Prolonged mHealth-Based Arrhythmia Monitoring by Single-Channel ECG (HCM-PATCH) study investigates the prevalence of nonsustained ventricular tachycardia (ie, ≥3 consecutive ventricular beats at a rate of 120 beats per minute, lasting for <30 seconds) in low- to intermediate-risk patients with HCM (according to the HCM Risk-SCD calculator) with additional mHealth-based prolonged rhythm monitoring. The study was funded by third-party funding from the Department of Cardiology and Intensive Care Medicine, University Hospital Ostwestfalen-Lippe of Bielefeld University in June 2023 and approved by the institutional review board in May 2023. Data collection began in June 2023, and we plan to end the study in February 2024. Of the 34 patients, 26 have been recruited. Data analysis has not yet taken place. Publication of the results is planned for the fall of 2024. CONCLUSIONS: Prolonged mHealth-based rhythm monitoring could lead to differences in the prevalence of arrhythmias compared to 24- and 48-hour long-term ECGs. This may lead to improved identification of patients at high risk and trigger therapeutic interventions that may provide better protection from SCD or atrial fibrillation-related complications such as embolic stroke. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00032144; https://tinyurl.com/498bkrx8. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52035.

Digital health applications from a government-regulated directory of reimbursable health apps in Germany-a systematic review for evidence and bias.

Background: The Digital Healthcare Act, passed in November 2019, authorizes healthcare providers in Germany to prescribe digital health applications (DiGA) to patients covered by statutory health insurance. If DiGA meet specific efficacy requirements, they may be listed in a special directory maintained by the German Federal Institute for Drugs and Medical Devices. Due to the lack of well-founded app evaluation tools, the objectives were to assess (I) the evidence quality situation for DiGA in the literature and (II) how DiGA manufacturers deal with this issue, as reflected by the apps available in the aforementioned directory. Methods: A systematic review of the literature on DiGA using PubMed, Scopus, and Web of Science was started on February 4, 2023. Papers addressing the evidence for applications listed in the directory were included, while duplicates and mere study protocols not reporting on data were removed. The remaining publications were used to assess the quality of the evidence or potential gaps in this regard. Results were aggregated in tabular form. Results: The review identified fourteen relevant publications. Six studies suggested inadequate scientific evidence, five mentioned shortcomings of tools for validating DiGA-related evidence, and four publications described a high potential for bias, potentially influencing the validity of the results. Concerns about limited external generalizability were also raised. Conclusions: The literature review found evidence-related gaps that must be addressed with adequate measures. Our findings can serve as a basis for a plea for a more detailed examination of the quality of evidence in the DiGA context.

Expectations of new technologies in nursing care among hospital patients in Germany - an interview study.

Introduction: New technologies will be increasingly available for nursing care, including robots, patient mobilisation devices, digital event detection or prevention equipment. Technologies are expected to support nurses, increase patients' safety and reduce costs. Yet, although these technologies will significantly shape patients' experience, we need to learn more about patients' perspectives regarding new technology in care. This study aims to investigate attitudes, expectations, worries and anticipated implementation effects of new assistive technology in nursing care by patients. Methods: Qualitative, guided, semi-open interviews were conducted. The recruitment was carried out in a trauma surgery ward of a university hospital in Germany. Eight different technologies were presented via video clips and additional information to the patients, followed by in-depth discussions. The interviews were analysed using qualitative evaluative content analysis. The Consolidated Criteria for Reporting Qualitative Research (COREQ) Checklist was used to ensure study quality. Results: Study participants anticipate different outcomes for the implementation of new nursing technology: (1) For patients, they consider the potential for improvement in health and well-being as well as for their hospital stay experience, but also fear possible health risks or social or emotional factors like loss of autonomy or loneliness. (2) For professional nurses, participants expect relief from physically stressful work routines; however, they might be replaced by machines and lose their employment (3) For the nursing process, safety and quality improvements for care delivery may encounter a negative quantification of human life and risks of constant surveillance. Conclusion: Patients identify opportunities, challenges and shortcomings of nursing technology implementation. They describe nuanced and mixed accounts of patients' perspectives that are structured in a 'continuum of anticipated effects' of implementing technology in our article. The results can inform future implementation strategies.

ASIC1a affects hypothalamic signaling and regulates the daily rhythm of body temperature in mice.

The body temperature of mice is higher at night than during the day. We show here that global deletion of acid-sensing ion channel 1a (ASIC1a) results in lower body temperature during a part of the night. ASICs are pH sensors that modulate neuronal activity. The deletion of ASIC1a decreased the voluntary activity at night of mice that had access to a running wheel but did not affect their spontaneous activity. Daily rhythms of thyrotropin-releasing hormone mRNA in the hypothalamus and of thyroid-stimulating hormone ß mRNA in the pituitary, and of prolactin mRNA in the hypothalamus and pituitary were suppressed in ASIC1a-/- mice. The serum thyroid hormone levels were however not significantly changed by ASIC1a deletion. Our findings indicate that ASIC1a regulates activity and signaling in the hypothalamus and pituitary. This likely leads to the observed changes in body temperature by affecting the metabolism or energy expenditure.

Evaluation of a semiautomated App Store analysis for the identification of health apps for cardiac arrhythmias.

BACKGROUND: Smartphone apps are increasingly utilised by patients and physicians for medical purposes. Thus, numerous applications are provided on the App Store platforms. OBJECTIVES: The aim of the study was to establish a novel, expanded approach of a semiautomated retrospective App Store analysis (SARASA) to identify and characterise health apps in the context of cardiac arrhythmias. MATERIALS AND METHODS: An automated total read-out of the "Medical" category of Apple's German App Store was performed in December 2022 by analysing the developer-provided descriptions and other metadata using a semiautomated multilevel approach. Search terms were defined, based on which the textual information of the total extraction results was automatically filtered. RESULTS: A total of 435 of 31,564 apps were identified in the context of cardiac arrhythmias. Of those, 81.4% were found to deal with education, decision support, or disease management, and 26.2% (additionally) provided the opportunity to derive information on heart rhythm. The apps were intended for healthcare professionals in 55.9%, students in 17.5%, and/or patients in 15.9%. In 31.5%, the target population was not specified in the description texts. In all, 108 apps (24.8%) provided a telemedicine treatment approach; 83.7% of the description texts did not reveal any information on medical product status; 8.3% of the apps indicated that they have and 8.0% that they do not have medical product status. CONCLUSION: Through the supplemented SARASA method, health apps in the context of cardiac arrhythmias could be identified and assigned to the target categories. Clinicians and patients have a wide choice of apps, although the app description texts do not provide sufficient information about the intended use and quality.

COVID-19 Mobile Apps Trends Derived from Long-Term Google Play Analysis.

In this paper, we describe the 5-year trends of COVID-related mobile apps in the Google Play platform obtained by retrospectively analyzing app descriptions. Out of 21764 and 48750 unique apps available free of charge in the "medical" and "health and fitness", there were 161 and 143 COVID-related apps, respectively. The prominentrise in apps' prevalence occurred in January 2021.

Conciliation and Approval of Quality Principles for the Self-Declaration of the Quality of Health Apps.

This poster describes the conciliation and approval process of the unified set of criteria for self-declaration of health app quality. The timeline underlines the necessity of transparency and open communication in regulations.

Do Health Apps Stigmatize People with Obesity?

Apps in the "Medicine" category of Apple's App Store were examined concerning the potential stigmatization of people with obesity through word and image language. Only 5/71 potentially stigmatizing apps related to obesity were identified. Stigmatization in this context can occur, for example, through the excessive promotion of very slim people in connection with weight loss-related apps.

[Secure app usage-Evaluation benchmarks for medical apps : Quality aspects for health apps based on 9 key criteria]. / "Secure app usage" ­ Bewertungsmaßstäbe für klinische Applikationen : Qualitätsaspekte für Gesundheits-Apps anhand von 9 Qualitätskriterien.

Smartphones and health apps are an integral part of everyday life. They are increasingly being used for medical purposes. However, there is no fundamental basis or consensus on the evidence on which decisions are made towards a unified digital strategy. Consequently, the understanding of the quality of health apps is only inconsistent and fuzzily defined. The 9 quality criteria presented by the Association of Medical Societies (AWMF)-transparency, appropriateness, risk appropriateness, ethical harmlessness, legal conformity, content validity, technical appropriateness, usability, resource efficiency-serve as a guide for individual and institutionalized quality assessment. The principles are based on a comprehensive compilation of existing (inter-) national standards and evaluation benchmarks. Analogously to usual medical practice, it is also obligatory to conduct one's own research for a suitable app and to weigh up the risks and benefits when using an app.

On-Site Visualization of Ballistocardiography Data.

We describe the background, features and functions of a custom application for the acquisition, live presentation, and convenient recording of ballistocardiography data acquired by external accelerometric sensors.

Medical Apps for Android and iOS: Differences and Similarities.

Google Play and Apple's App Store dominate the mobile health app market. We analyzed the metadata and descriptive texts of apps in the medical category using semi-automated retrospective app store analysis (SARASA) and compared the store offerings in terms of their number, descriptive texts, user ratings, medical device status, diseases, and conditions (both keyword-based). Relatively speaking, the store listings for the selected items were comparable.

Evidence of Digital Health Applications from a State-Regulated Repository for Reimbursable Health Applications in Germany.

17 RCTs for 15 digital health applications (DiGA) permanently listed in the state-regulated register were analyzed descriptively for methodological study aspects relevant to evidence analysis. The analysis revealed that several underlying studies had limitations, at least worthy of discussion, in terms of their power concerning sample size, intervention and control group specifications, drop-out rates, and blinding.

Deletion of the Circadian Clock Gene Per2 in the Whole Body, but Not in Neurons or Astroglia, Affects Sleep in Response to Sleep Deprivation.

The sleep-wake cycle is a highly regulated behavior in which a circadian clock times sleep and waking, whereas a homeostatic process controls sleep need. Both the clock and the sleep homeostat interact, but to what extent they influence each other is not understood. There is evidence that clock genes, in particular Period2 (Per2), might be implicated in the sleep homeostatic process. Sleep regulation depends also on the proper functioning of neurons and astroglial cells, two cell-types in the brain that are metabolically dependent on each other. In order to investigate clock-driven contributions to sleep regulation we non-invasively measured sleep of mice that lack the Per2 gene either in astroglia, neurons, or all body cells. We observed that mice lacking Per2 in all body cells (Per2Brdm and TPer2 animals) display earlier onset of sleep after sleep deprivation (SD), whereas neuronal and astroglial Per2 knock-out animals (NPer2 and GPer2, respectively) were normal in that respect. It appears that systemic (whole body) Per2 expression is important for physiological sleep architecture expressed by number and length of sleep bouts, whereas neuronal and astroglial Per2 weakly impacts night-time sleep amount. Our results suggest that Per2 contributes to the timing of the regulatory homeostatic sleep response by delaying sleep onset after SD and attenuating the early night rebound response.

Development of Open Backend Structures for Health Care Professionals to Improve Participation in App Developments: Pilot Usability Study of a Medical App.

BACKGROUND: Efficient digitization in medicine still is in its infancy but undeniably has great potential for current and future challenges in health care. Thus far, the rollout of medical apps has not resulted in widespread use of smartphones in the German health care sector-the reasons for this have not been clarified so far. Nevertheless, the lack of user involvement in the development process and content creation might contribute to low acceptance of these products. OBJECTIVE: This study aims to outline an approach to involve medical expertise without any coding knowledge for developing medical app content and functions. METHODS: An end user-operable backend was built. Its usability was evaluated using a usability evaluation test protocol. The results of the usability tests were evaluated by the app development team, and the usability test was repeated for optimizing backend usability. In total, 40 criteria to measure the ease of app usage were defined a priori. The usability test comprised 20 tasks that had to be fulfilled. Usability tasks were analyzed for completion, dropout, and test duration. Due to the COVID-19 pandemic, digital videoconferencing platforms (Zoom and QuickTime Player) were used to complete usability questionnaires. Finally, several backend-based apps for several specialties (infectiology, plastic and reconstructive surgery, and orthopedics) were developed by health care professionals as prototypes. RESULTS: Initial usability testing was conducted with 5 participants (4 men and 1 woman; mean age 39.2, SD 5.97 years). All of them could complete the assigned backend tasks with only a few workflow interruptions and some minor errors. After usability optimization, the workflow completion time decreased from 5.03 minutes to 3.50 minutes, indicating a time saving. The basic backend structure was clear to all test users and the handling was intuitive to learn. Some minor errors in the backend occurred during the test rounds. The apps developed using the aforementioned approach are in clinical use as a proof of concept. CONCLUSIONS: Backends offering operability for medical professionals might have great potential for app development in the mobile health sector. Sophisticated and time-saving usability are pivotal for the acceptance of medical software, as illustrated by the backend-based apps presented herein, which are in clinical use as a proof of concept. Basic interventions are essential and sufficient for adequate usability optimization. Practicable, well-structured software usability evaluation is possible based on the usability evaluation test protocol.

Orthopaedic and trauma surgeons' prioritisation of app quality principles based on their demographic background.

BACKGROUND: Although apps are becoming increasingly relevant in healthcare, there is limited knowledge about how healthcare professionals perceive "quality" in this context and how quality principles that can aid them in assessing health-related apps may be prioritised. The objective was to investigate physicians' views of predefined (general) quality principles for health apps and to determine whether a ranking algorithm applied to the acquired data can provide stable results against various demographic influences and may thus be appropriate for prioritisation. METHODS: Participants of an online survey of members of two German professional orthopaedics associations conducted between 02/12/2019 and 02/01/2020 were asked about their perception of a set of quality principles for health apps (i.e., "practicality," "risk adequacy," "ethical soundness," "legal conformity," "content validity," "technical adequacy," "usability," "resource efficiency," and "transparency"). Structured as a Kano survey, for each principle, there were questions about its perceived relevance and opinions regarding the presence or absence of corresponding characteristics. The available data were evaluated descriptively, and a newly developed method for prioritisation of the principles was applied overall and to different demographic strata (for validation). RESULTS: Three hundred eighty-two datasets from 9503 participants were evaluated. Legal conformity, content validity, and risk adequacy filled ranks one to three, followed by practicability, ethical soundness, and usability (ranks 4 to 6). Technical adequacy, transparency, and resource efficiency ranked last (ranks 7 to 9). The ranking based on the proposed method was relatively stable, irrespective of demographic factors. The principles were seen as essential, with one exception ("resource efficiency"). Only those with little to no interest in digitisation (22/382, 5.8%) rated the nine principles indifferently. CONCLUSIONS: The specified quality principles and their prioritisation can lay a foundation for future assessments of apps in the medical field. Professional societies build upon this to highlight opportunities for digital transformations in medicine and encourage their members to participate.

Proposal of a New Rating Concept for Digital Health Applications in Orthopedics and Traumatology.

BACKGROUND: Health-related mobile applications (apps) are rapidly increasing in number. There is an urgent need for assessment tools and algorithms that allow the usability and content criteria of these applications to be objectively assessed. The aim of this work was to establish and validate a concept for orthopedic societies to rate health apps to set a quality standard for their safe use. METHODS: An objective rating concept was created, consisting of nine quality criteria. A self-declaration sheet for app manufacturers was designed. Manufacturers completed the self-declaration, and the app was examined by independent internal reviewers. The pilot validation and analysis were performed on two independent health applications. An algorithm for orthopedic societies was created based on the experiences in this study flow. RESULTS: "Sprunggelenks-App" was approved by the reviewers with 45 (98%) fulfilled criteria and one (2%) unfulfilled criterion. "Therapie-App" was approved, with 28 (61%) met criteria, 6 (13%) unfulfilled criteria and 12 (26%) criteria that could not be assessed. The self-declaration completed by the app manufacturer is recommended, followed by a legal and technical rating performed by an external institution. When rated positive, the societies' internal review using independent raters can be performed. In case of a positive rating, a visual certification can be granted to the manufacturer for a certain time frame. CONCLUSION: An objective rating algorithm is proposed for the assessment of digital health applications. This can help societies to improve the quality assessment, quality assurance and patient safety of those apps. The proposed concept must be further validated for inter-rater consistency and reliability.

Suprachiasmatic to paraventricular nuclei interaction generates normal food searching rhythms in mice.

Searching for food follows a well-organized decision process in mammals to take up food only if necessary. Moreover, scavenging is preferred during their activity phase. Various time-dependent regulatory processes have been identified originating from the suprachiasmatic nuclei (SCN), which convert external light information into synchronizing output signals. However, a direct impact of the SCN on the timing of normal food searching has not yet been found. Here, we revisited the function of the SCN to affect when mice look for food. We found that this process was independent of light but modified by the palatability of the food source. Surprisingly, reducing the output from the SCN, in particular from the vasopressin releasing neurons, reduced the amount of scavenging during the early activity phase. The SCN appeared to transmit a signal to the paraventricular nuclei (PVN) via GABA receptor A1. Finally, the interaction of SCN and PVN was verified by retrograde transport-mediated complementation. None of the genetic manipulations affected the uptake of more palatable food. The data indicate that the PVN are sufficient to produce blunted food searching rhythms and are responsive to hedonistic feeding. Nevertheless, the search for normal food during the early activity phase is significantly enhanced by the SCN.