User Experience of a Just-in-Time Smartphone Resonance Breathing Application for Substance Use Disorder: Acceptability, Appropriateness, and Feasibility.

BACKGROUND: Addressing the negative impact of substance use disorders (SUDs) on individuals, families, and communities is a public health priority. Most treatments and interventions require engagement with a healthcare provider or someone who can offer recovery support. The need for interventions that facilitate self-management of relapse triggers at the moment they occur is also critical. Our study aimed to explore the user experience of individuals using a just-in-time smartphone episodic resonance breathing (eRPB) intervention to address stress, anxiety, and drug cravings. METHODS: We conducted an 8-week pilot study of the eRPB with 30 individuals in recovery from SUD. Data on 3 indicators of user experience-acceptability, appropriateness, and feasibility-were collected using survey questions (n = 30) and semi-structured interviews (n = 11). We performed univariate analysis on the survey data and deductive thematic analysis on the qualitative data. RESULTS: A majority of the survey respondents agreed that the application (app) was acceptable (> 77%), appropriate (> 82%), and feasible (> 89%). Several interview participants stated that the app helped them relax and manage stress and cravings and expressed appreciation for the simplicity of its design. Participants also reported barriers to feasibility (such as forgetting to use the app) and recommendations for improvement (such as the addition of motivational messages). CONCLUSIONS: Our findings show that individuals in recovery from SUD had highly positive experiences with the eRPB app. A positive user experience may improve adherence to the intervention and, ultimately, the self-management of stress, anxiety, and craving relapse triggers.

Omaveloxolone Ameliorates Cognitive Deficits by Inhibiting Apoptosis and Neuroinflammation in APP/PS1 Mice.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with aging, characterized by progressive cognitive impairment and memory loss. However, treatments that delay AD progression or improve its symptoms remain limited. The aim of the present study was to investigate the therapeutic effects of omaveloxolone (Omav) on AD and to explore the underlying mechanisms. Thirty-week-old APP/PS1 mice were selected as an experimental model of AD. The spatial learning and memory abilities were tested using the Morris water maze. Amyloid-beta (Aß) deposition in the brains was measured using immunohistochemistry. Network pharmacological analyses and molecular docking were conducted to gain insights into the therapeutic mechanisms of Omav. Finally, validation analyses were conducted to detect changes in the associated pathways and proteins. Our finding revealed that Omav markedly rescued cognitive dysfunction and reduced Aß deposition in the brains of APP/PS1 mice. Network pharmacological analysis identified 112 intersecting genes, with CASP3 and MTOR emerging as the key targets. In vivo validation experiments indicated that Omav attenuated neuronal apoptosis by regulating apoptotic proteins, including caspase 3, Bax, and Bcl-2. Moreover, Omav suppressed neuroinflammation and induced autophagy by inhibiting the phosphorylation of mTOR. These findings highlight the therapeutic efficacy of Omav in AD and that its neuroprotective effects were associated with inhibiting neuronal apoptosis and regulating neuroinflammation.

Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aß) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aß plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aß plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.

Nondietary psychological app program leads to sustained weight loss due to trained physiological satiety perception.

Obese people are mostly unable to maintain successful weight loss after the end of a dietary change. One reason is that conventional weight reduction concepts neglect physiological hunger and satiety perception, leading to a relapse to previous eating habits on the long run. We examined the long-term efficacy of a psychological smartphone weight loss program, which avoids any dietary instructions and aims at relearning of satiety perception. Parameters of body weight alterations and psychological features, for example, satiety perception, food cravings, and emotional eating, were explored in a nonrandomized experimental study comprising 75 obese participants. Measurements occurred at baseline, two times during program application, as well as at 6- and 12-month follow-up. Participants displayed significant weight loss during the entire study period (p = .029) and showed an improved body composition at the 6-month follow-up (p = .018). These effects were associated with increased satiety perception, as well as reduced food cravings, and emotional eating habits. Notably, all improvements in measured parameters significantly sustained between the end of the program and the 12-month follow-up (p < .005 for all). Psychological relearning of satiety perception may outclass dietary approaches in terms of long-term efficiency.

Therapeutic modulation of APP-CD74 axis can activate phagocytosis of TAMs in GBM.

Glioblastoma multiforme (GBM) remains the most lethal central nervous system cancer with poor survival and few targeted therapies. The GBM tumor microenvironment is complex and closely associated with outcomes. Here, we analyzed the cell-cell communication within the microenvironment and found the high level of cell communication between GBM tumor cells and tumor-associated macrophages (TAMs). We found that the amyloid protein precursor (APP)-CD74 axis displayed the highest levels of communication between GBM tumor cells and TAMs, and that APP and CD74 expression levels were significantly corelated with poorer patient outcomes. We showed that the expression of APP on the surface of GBM inhibited phagocytosis of TAMs through the binding of APP to the CD74/CXCR4 cell surface receptor complex. We further demonstrated that disrupting the APP-CD74 axis could upregulated the phagocytosis of TAMs in vitro and in vivo. Finally, we demonstrated that APP promotes the phosphorylation of SHP-1 by binding to CD74. Together, our findings revealed that the APP-CD74 axis was a highly expressed anti-phagocytic signaling pathway that may be a potential immunotherapeutic target for GBM.

Univie: An App for Managing Digital Health Data of Refugees.

The refugee crisis has reached historic proportions, with more than 82 million people on the run. Access to healthcare is often difficult for them due to a lack of medical records and language barriers. This paper examines a digital medical documentation system for refugees that captures, stores, and translates records. International data protection standards are considered. The contribution consists of designing a system that manages and translates medical data across borders and integrates a prediction model for epidemics in refugee camps.

Insights into the Quality of Mobile Health Apps: Preliminary Results of an Analysis of MARS Scores.

Many mHelath applications have been developed, and the Mobile App Rating Scale (MARS) is a common tool for assessing them. This study aims to provide mean values for MARS scores found in recent literature. We systematically searched for literature in which MARS was used and analyzed them. MARS values for 5,920 applications from 215 studies were compiled. The mean MARS Quality Score is 3.51. The highest average score was achieved in the Functionality category (3.98), followed by Aesthetics (3.52), Information (3.33), Engagement (3.18) and Subjective (2.72). To the best of our knowledge, this is the first study to calculate average values for the five categories of the MARS and the MARS score based on such an extensive collection of data. The study shows that the overall quality of the applications is above the average value of 2.5.

Revolutionizing Physical Activity: How Private Sector Physicians Harness Mobile Apps for Enhanced Health Outcomes.

INTRODUCTION: The vital importance of engaging in physical activity for the maintenance and improvement of health is undeniable. The advent of digital technology has significantly enhanced the encouragement of physical activity (PA) through numerous interventions. Our study's goal is to examine the usage and prescription practices of mobile applications and fitness trackers by doctors operating in the private sector. METHODS: cross-sectional study, which targeted doctors in the private sector, whether general practitioners or specialists was carried out in January and February 2024, A paper questionnaire was distributed to the doctors' offices. RESULTS: the mean age was 44.3±11.7 years, 77% of doctors are physically active, the prevalence of use of mobile applications and fitness trackers among private sector physicians for improving and monitoring their physical activity was 32% with a CI ranging from [26-40] % and only 15% recommend mobile apps to patients. This reluctance was attributed to the applications' lack of customization and the challenges patients faced in using them. CONCLUSION: In our research, we found that doctors rarely utilized mobile applications to enhance their practice of physical activity and were hesitant to recommend them to their patients.

Evaluating the Effectiveness of a Novel Personalized Health Education Approach for Hemodialysis Patients: A Four-Week Study Using a Widely-Used Communication App in Taiwan.

Dialysis patients often have inadequate health literacy, affecting self-care and outcomes. This study used LINE app to provide personalized health education to Taiwanese dialysis patients and collected physiological data via wearables. While physical activity levels remained unchanged, participants' disease literacy significantly improved post-intervention. Patients' health literacy will evaluate by Health Literacy Questionnaire for Taiwanese Hemodialysis patients (HLQHD). The findings highlight technology-driven interventions' potential to enhance health literacy and disease management among dialysis patients.

Designing a Social Snus Cessation Mobile Application with an Integrated AI Function.

The application of artificial intelligence (AI) in healthcare is expected to be increased in the coming years. There has been little attention paid on exploring how social aspects and AI can be integrated into mobile applications to support the people who want to quit snus. Our research aims to design a prototype of a social snus cessation mobile application for university students in Sweden, incorporating an AI function. This paper presents a work-in-progress of our research.

Development of an mHealth App by Experts for Queer Individuals' Sexual-Reproductive Health Care Services and Needs: Nominal Group Technique Study.

BACKGROUND: Queer individuals continue to be marginalized in South Africa; they experience various health care challenges (eg, stigma, discrimination, prejudice, harassment, and humiliation), mental health issues (eg, suicide and depression), and an increased spread of HIV or AIDS and sexually transmitted illnesses (STIs; chlamydia, gonorrhea, and syphilis). Mobile health (mHealth) apps have the potential to resolve the health care deficits experienced by health care providers when managing queer individuals and by queer individuals when accessing sexual-reproductive health care services and needs, thus ensuring inclusivity and the promotion of health and well-being. Studies have proven that the nominal group technique (NGT) could be used to solve different social and health problems and develop innovative solutions. This technique ensures that different voices are represented during decision-making processes and leads to robust results. OBJECTIVE: This study aims to identify important contents to include in the development of an mHealth app for addressing the sexual-reproductive health care services and needs of queer individuals. METHODS: We invited a group of 13 experts from different fields, such as researchers, queer activists, sexual and reproductive health experts, private practicing health care providers, innovators, and private health care stakeholders, to take part in a face-to-face NGT. The NGT was conducted in the form of a workshop with 1 moderator, 2 research assistants, and 1 principal investigator. The workshop lasted approximately 2 hours 46 minutes and 55 seconds. We followed and applied 5 NGT steps in the workshop for experts to reach consensus. The main question that experts were expected to answer was as follows: Which content should be included in the mHealth app for addressing sexual-reproductive health care services and needs for queer individuals? This question was guided by user demographics and background, health education and information, privacy and security, accessibility and inclusivity, functionality and menu options, personalization and user engagement, service integration and partnerships, feedback and improvement, cultural sensitivity and ethical considerations, legal and regulatory compliance, and connectivity and data use. RESULTS: Overall, experts voted and ranked the following main icons: menu options (66 points), privacy and security (39 points), user engagement (27 points), information hub (26 points), user demographics (20 points), connectivity (16 points), service integration and partnerships (10 points), functionalities (10 points), and accessibility and inclusivity (7 points). CONCLUSIONS: Conducting an NGT with experts from different fields, possessing vast skill sets, knowledge, and expertise, enabled us to obtain targeted data on the development of an mHealth app to address sexual-reproductive health care services and needs for queer individuals. This approach emphasized the usefulness of a multidisciplinary perspective to inform the development of our mHealth app and demonstrated the future need for continuity in using this approach for other digital health care innovations and interventions.

Deciphering the needs of patients with hereditary breast and ovarian Cancer in the Process of Genetic Counseling to Inform the Development of a Mobile Support App: a qualitative study in Germany.

Patients with hereditary breast and ovarian cancer (HBOC) are not only concerned about their own health but also about that of their children, grandchildren, and other relatives. Therefore, they have specific needs for information and support. During genetic counseling guidance is provided to HBOC patients and other individuals who may be at risk for familial cancer. The purpose of the study was to identify the needs of HBOC patients during the genetic counseling process that could be addressed by digital solutions. Nine semi-structured qualitative interviews were conducted. Overall, the patients appreciated the personal contact with human geneticists as an especially positive factor in the genetic counseling process. However, patients noted the following needs (1) support in the time following genetic counseling, (2) support before genetic counseling by collecting own and familial medical information, (3) Need for contact options to support services, (4) Need for patient-friendly medical information, (5) Wish for administration-related components in a support app. The results will inform the development of a patient-centered mobile support app.

Cytokine and acute-phase proteins response following vaccination against infectious bronchitis in broilers.

BACKGROUND: Infectious bronchitis (IB) is an important disease of poultry, and vaccination is the best method of preventing IB in the poultry industry worldwide. OBJECTIVES: This study was designed to evaluate cytokine and acute-phase protein (APP) responses and their correlations with antibody titres following vaccination regimes against IB in the broiler. MATERIALS AND METHODS: Broilers were vaccinated with H120 and 1/96 vaccine strains, and MIX (H120 + 1/96) vaccine strains on Days 0 and 14. Heterophils/lymphocyte (H/L) ratio, APPs including chicken serum amyloid A (SAA), chicken pentraxin 3 (chPTX3), chicken interleukin 1ß (IL-1ß), chicken interleukin 6 (IL-6) levels and antibody titres were measured. RESULTS: An increase in the H/L ratio, SAA, chPTX3, IL-1ß and IL-6 levels in vaccinated groups was observed 1 day after the first (highest rates) and second (lower levels) vaccination up to 3 days in three different patterns and then started to decrease. The results showed an immediate, short-lived response and moderate increases in all criteria. Changing patterns of APPs were different but in similar pattern after the first and second immunization in vaccinated groups. A positive correlation between all criteria values on Days 1 and 15 with antibody titres on Day 28 may indicate agonistic cross-regulation. CONCLUSION: Different types of IB vaccines could induce different patterns of APPs responses, which can be used to evaluate immune response outcomes in vaccine design, development and administration. The IL-6 with the highest increase can be a sensitive parameter and chPTX3 with the high increase could be an important criterion.

Exploring User Experiences of the Mom2B mHealth Research App During the Perinatal Period: Qualitative Study.

BACKGROUND: Perinatal depression affects a significant number of women during pregnancy and after birth, and early identification is imperative for timely interventions and improved prognosis. Mobile apps offer the potential to overcome barriers to health care provision and facilitate clinical research. However, little is known about users' perceptions and acceptability of these apps, particularly digital phenotyping and ecological momentary assessment apps, a relatively novel category of apps and approach to data collection. Understanding user's concerns and the challenges they experience using the app will facilitate adoption and continued engagement. OBJECTIVE: This qualitative study explores the experiences and attitudes of users of the Mom2B mobile health (mHealth) research app (Uppsala University) during the perinatal period. In particular, we aimed to determine the acceptability of the app and any concerns about providing data through a mobile app. METHODS: Semistructured focus group interviews were conducted digitally in Swedish with 13 groups and a total of 41 participants. Participants had been active users of the Mom2B app for at least 6 weeks and included pregnant and postpartum women, both with and without depression symptomatology apparent in their last screening test. Interviews were recorded, transcribed verbatim, translated to English, and evaluated using inductive thematic analysis. RESULTS: Four themes were elicited: acceptability of sharing data, motivators and incentives, barriers to task completion, and user experience. Participants also gave suggestions for the improvement of features and user experience. CONCLUSIONS: The study findings suggest that app-based digital phenotyping is a feasible and acceptable method of conducting research and health care delivery among perinatal women. The Mom2B app was perceived as an efficient and practical tool that facilitates engagement in research as well as allows users to monitor their well-being and receive general and personalized information related to the perinatal period. However, this study also highlights the importance of trustworthiness, accessibility, and prompt technical issue resolution in the development of future research apps in cooperation with end users. The study contributes to the growing body of literature on the usability and acceptability of mobile apps for research and ecological momentary assessment and underscores the need for continued research in this area.

Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Combining one-session treatment with a homework program including app-based technology to enhance the treatment of childhood specific phobias: A study protocol of a multicenter pragmatic randomized controlled trial.

Introduction: Childhood specific phobias are among the most common and earliest onset mental disorders with a lifetime prevalence of more than ten percent. Brief intensive cognitive behavioral therapy (CBT) programs such as the One-Session Treatment (OST) are found to be effective in the remission of the specific phobias following treatment, but there is still room for improvement. The goal of the current study is to examine whether the long-term efficacy of OST increases by using a homework program supported by an app specifically designed for children; the Kids Beat Anxiety (KibA) homework program. Methods: Children aged between 7 and 14 years with a specific phobia receive OST preceded by a three-week baseline phase to control for time-effects. Directly following OST, children are randomized to either a four-week homework period supported by an app (OST + app), or standard One-Session Treatment with a four-week homework period that is only supported by therapist instructions (OST-only). Primary outcome variables are diagnosis and severity of the specific phobia. Secondary outcomes include behavioral avoidance, self-reported fear, and functional impairment. Data will be analyzed based on intention-to-treat and per protocol samples using mixed-effects multilevel linear models. Ethics and dissemination: The current study was approved by the METC of the Academic Medical Center, Amsterdam, The Netherlands (number: NL72697.018.20) and the Ethical Committee of the Ruhr University, Bochum, Germany (number: 663). Results of this trial will be published in peer-reviewed journals. Trial registration: The study was pre-registered at the Dutch Trial Register, number: NL 9216.

Automated Pain Spots Recognition Algorithm Provided by a Web Service-Based Platform: Instrument Validation Study.

Background: Understanding the causes and mechanisms underlying musculoskeletal pain is crucial for developing effective treatments and improving patient outcomes. Self-report measures, such as the Pain Drawing Scale, involve individuals rating their level of pain on a scale. In this technique, individuals color the area where they experience pain, and the resulting picture is rated based on the depicted pain intensity. Analyzing pain drawings (PDs) typically involves measuring the size of the pain region. There are several studies focusing on assessing the clinical use of PDs, and now, with the introduction of digital PDs, the usability and reliability of these platforms need validation. Comparative studies between traditional and digital PDs have shown good agreement and reliability. The evolution of PD acquisition over the last 2 decades mirrors the commercialization of digital technologies. However, the pen-on-paper approach seems to be more accepted by patients, but there is currently no standardized method for scanning PDs. Objective: The objective of this study was to evaluate the accuracy of PD analysis performed by a web platform using various digital scanners. The primary goal was to demonstrate that simple and affordable mobile devices can be used to acquire PDs without losing important information. Methods: Two sets of PDs were generated: one with the addition of 216 colored circles and another composed of various red shapes distributed randomly on a frontal view body chart of an adult male. These drawings were then printed in color on A4 sheets, including QR codes at the corners in order to allow automatic alignment, and subsequently scanned using different devices and apps. The scanners used were flatbed scanners of different sizes and prices (professional, portable flatbed, and home printer or scanner), smartphones with varying price ranges, and 6 virtual scanner apps. The acquisitions were made under normal light conditions by the same operator. Results: High-saturation colors, such as red, cyan, magenta, and yellow, were accurately identified by all devices. The percentage error for small, medium, and large pain spots was consistently below 20% for all devices, with smaller values associated with larger areas. In addition, a significant negative correlation was observed between the percentage of error and spot size (R=-0.237; P=.04). The proposed platform proved to be robust and reliable for acquiring paper PDs via a wide range of scanning devices. Conclusions: This study demonstrates that a web platform can accurately analyze PDs acquired through various digital scanners. The findings support the use of simple and cost-effective mobile devices for PD acquisition without compromising the quality of data. Standardizing the scanning process using the proposed platform can contribute to more efficient and consistent PD analysis in clinical and research settings.

Data management plan and REDCap mobile data capture for a multi-country Household Air Pollution Intervention Network (HAPIN) trial.

Background: Household air pollution (HAP) is a leading environmental risk factor accounting for about 1.6 million premature deaths mainly in low- and middle-income countries (LMICs). However, no multicounty randomized controlled trials have assessed the effect of liquefied petroleum gas (LPG) stove intervention on HAP and maternal and child health outcomes. The Household Air Pollution Intervention Network (HAPIN) was the first to assess this by implementing a common protocol in four LMICs. Objective: This manuscript describes the implementation of the HAPIN data management protocol via Research Electronic Data Capture (REDCap) used to collect over 50 million data points in more than 4000 variables from 80 case report forms (CRFs). Methods: We recruited 800 pregnant women in each study country (Guatemala, India, Peru, and Rwanda) who used biomass fuels in their households. Households were randomly assigned to receive LPG stoves and 18 months of free LPG supply (intervention) or to continue using biomass fuels (control). Households were followed for 18 months and assessed for primary health outcomes: low birth weight, severe pneumonia, and stunting. The HAPIN Data Management Core (DMC) implemented identical REDCap projects for each study site using shared variable names and timelines in local languages. Field staff collected data offline using tablets on the REDCap Mobile Application. Results: Utilizing the REDCap application allowed the HAPIN DMC to collect and store data securely, access data (near real-time), create reports, perform quality control, update questionnaires, and provide timely feedback to local data management teams. Additional REDCap functionalities (e.g. scheduling, data validation, and barcode scanning) supported the study. Conclusions: While the HAPIN trial experienced some challenges, REDCap effectively met HAPIN study goals, including quality data collection and timely reporting and analysis on this important global health trial, and supported more than 40 peer-reviewed scientific publications to date.

Cortical neurodegeneration caused by Psen1 mutations is independent of Aß.

Mutations in the PSEN genes are the major cause of familial Alzheimer's disease, and presenilin (PS) is the catalytic subunit of γ-secretase, which cleaves type I transmembrane proteins, including the amyloid precursor protein (APP) to release Aß peptides. While PS plays an essential role in the protection of neuronal survival, PSEN mutations also increase the ratio of Aß42/Aß40. Thus, it remains unresolved whether PSEN mutations cause AD via a loss of its essential function or increases of Aß42/Aß40. Here, we test whether the knockin (KI) allele of Psen1 L435F, the most severe FAD mutation located closest to the active site of γ-secretase, causes age-dependent cortical neurodegeneration independent of Aß by crossing various Psen mutant mice to the App-null background. We report that removing Aß completely through APP deficiency has no impact on the age-dependent neurodegeneration in Psen mutant mice, as shown by the absence of effects on the reduced cortical volume and decreases of cortical neurons at the ages of 12 and 18 mo. The L435F KI allele increases Aß42/Aß40 in the cerebral cortex while decreasing de novo production and steady-state levels of Aß42 and Aß40 in the presence of APP. Furthermore, APP deficiency does not alleviate elevated apoptotic cell death in the cerebral cortex of Psen mutant mice at the ages of 2, 12, and 18 mo, nor does it affect the progressive microgliosis in these mice. Our findings demonstrate that Psen1 mutations cause age-dependent neurodegeneration independent of Aß, providing further support for a loss-of-function pathogenic mechanism underlying PSEN mutations.

Evaluation of a New Telemedicine System for Early Detection of Cardiac Instability in Patients With Chronic Heart Failure: Real-Life Out-of-Hospital Study.

BACKGROUND: For a decade, despite results from many studies, telemedicine systems have suffered from a lack of recommendations for chronic heart failure (CHF) care because of variable study results. Another limitation is the hospital-based architecture of most telemedicine systems. Some systems use an algorithm based on daily weight, transcutaneous oxygen measurement, and heart rate to detect and treat acute heart failure (AHF) in patients with CHF as early on as possible. OBJECTIVE: The aim of this study is to determine the efficacy of a telemonitoring system in detecting clinical destabilization in real-life settings (out-of-hospital management) without generating too many false positive alerts. METHODS: All patients self-monitoring at home using the system after a congestive AHF event treated at a cardiology clinic in France between March 2020 and March 2021 with at least 75% compliance on daily measurements were included retrospectively. New-onset AHF was defined by the presence of at least 1 of the following criteria: transcutaneous oxygen saturation loss, defined as a transcutaneous oxygen measurement under 90%; rise of cardiac frequency above 110 beats per minute; weight gain of at least 2 kg; and symptoms of congestive AHF, described over the phone. An AHF alert was generated when the criteria reached our definition of new-onset acute congestive heart failure (HF). RESULTS: A total of 111 consecutive patients (n=70 men) with a median age of 76.60 (IQR 69.5-83.4) years receiving the telemonitoring system were included. Thirty-nine patients (35.1%) reached the HF warning level, and 28 patients (25%) had confirmed HF destabilization during follow-up. No patient had AHF without being detected by the telemonitoring system. Among incorrect AHF alerts (n=11), 5 patients (45%) had taken inaccurate measurements, 3 patients (27%) had supraventricular arrhythmia, 1 patient (9%) had a pulmonary bacterial infection, and 1 patient (9%) contracted COVID-19. A weight gain of at least 2 kg within 4 days was significantly associated with a correct AHF alert (P=.004), and a heart rate of more than 110 beats per minute was more significantly associated with an incorrect AHF alert (P=.007). CONCLUSIONS: This single-center study highlighted the efficacy of the telemedicine system in detecting and quickly treating cardiac instability complicating the course of CHF by detecting new-onset AHF as well as supraventricular arrhythmia, thus helping cardiologists provide better follow-up to ambulatory patients.