Evaluating a woman-centred web-based breastfeeding educational intervention in Saudi Arabia: A before-and-after quasi-experimental study.

BACKGROUND: Although digital educational resources are used worldwide to educate new parents, the impact of digital resources tailored specifically to women's needs on breastfeeding practices is not well explored. AIM: The study aimed to evaluate the effectiveness of using a women-centred Web-Based Breastfeeding Educational Resource (WEBBER) in increasing the rate of exclusive breastfeeding at one month after birth. METHODS: A quasi-experimental study with before and after intervention was conducted in one metropolitan hospital in Saudi Arabia. Participants were primiparous women (n=290) aged 18 or above who intended to breastfeed. The intervention involved introducing the WEBBER to pregnant women and reinforcing its uses as a routine breastfeeding educational resource. Women's characteristics and infant feeding data were collected at one month after birth via an online survey. FINDINGS: The rate of exclusive breastfeeding at one month postpartum among the women who received the WEBBER intervention was nearly three times higher compared to the women prior to the introduction of the intervention (66 % vs. 26 %, p-value <.001). Furthermore, other predictors of exclusive breastfeeding at one month were the mother being unemployed, the baby not receiving infant formula in the hospital, and the mother having postnatal intention to continue breastfeeding for 6 months or more. DISCUSSION AND CONCLUSION: Using WEBBER as a routine breastfeeding educational resource increased the rate of exclusive breastfeeding one month after birth. Embedding woman-centred digital resources into routine breastfeeding education is an effective intervention for women in Saudi Arabia.

Acceptability of Gynecologic e-Health Modalities by Hispanic/Latina Women of Reproductive Age.

Introduction: Electronic health (e-Health) modalities effectively address healthcare access limitations; however, there are limited data on their adoption by Hispanic/Latina women who are disproportionally affected by health disparities. Methods: We conducted a cross-sectional study by disseminating an anonymous electronic questionnaire via social media to assess the perception of Hispanic/Latina women of reproductive age regarding facilitators and barriers for using e-Health modalities, including telemedicine and mobile apps, to monitor gynecologic health. Results: The questionnaire was completed by 351 Hispanic/Latina participants with high levels (98.3%) of advanced technological expertise. Current use of a gynecologic mobile app was reported by 63.8%, primarily for menstruation (85.1%) and ovulation (46.3%) tracking. While only 17.6% of participants were offered the option of a gynecologic consultation via telemedicine, the majority (90.5%) would agree to one. Higher education and advanced technological expertise correlated with acceptance of telemedicine for gynecological consults. Being younger (<29 y/o), a student, not having a preferred gynecologist and having a lower income significantly correlated with gynecologic mobile app acceptability. Conclusions: We showed that e-Health modalities are highly acceptable for Hispanic/Latina women of reproductive age to facilitate gynecological care and documented factors that are significantly associated with e-Health acceptability. These findings are relevant to public health emergencies that cause access to care limitations disproportionally affecting this already underserved population.

Negotiating Hegemonic Masculinities and Mutual Exoticization within Grindr Tourism Interactions: "Everyone in Tel Aviv is a Muscle God".

Dating apps are spaces where masculinities are communicated digitally, affecting inequalities around gender expressions. This study aims to identify the masculinities communicated within Grindr tourism interactions in Tel Aviv and analyze how masculinities shape relations among international tourists and locals. Methods consist of interviews and audio diaries with nineteen tourist, local, and immigrant Grindr users in Tel Aviv. Theories of affordances, hegemonic masculinities, and relational sociology are used to analyze the data. In discussion of the results, the concept of mutual exoticization is put forth to interpret the social dynamics valued within Grindr tourism interactions, thereby revealing oppositional fantasies tied to nationalities and masculinities. The study also explores ethnicity's association with social and erotic capital in digital circulations of a localized Mizrahi masculinity. Findings reveal that while hegemonic masculinities are circulated on Grindr, resistance is also a part of Grindr tourism relations around masculinities. This research concludes by shedding light on masculinity inequalities within digital spaces where different nationalities co-congregate, revealing everyday negotiations of gender regimes. Grindr is the site of both reproduction of and resistance to social inequalities around masculinities.

App-Based Addiction Prevention at German Vocational Schools: Implementation and Reach for a Cluster-Randomized Controlled Trial.

This article examines the implementation, participation rates, and potential determinants of participation in the digital addiction prevention program "ready4life." A two-arm cluster-randomized trial recruited German vocational students via class-based strategies. Intervention group received 16 weeks of in-app coaching; the control group received health behavior information, with coaching offered after 12 months. Potential determinants of participation were analyzed based on class and individual characteristics. Out of 525 contacted schools, 35 participated, enrolling 376 classes. Implementation during the pandemic required flexible adjustments, with 49.7% of introductions conducted in person, 43.1% digitally via online streaming, and 7.2% received a video link via email. Despite challenges, 72.3% of the vocational students downloaded the app, and 46.7% gave informed consent. Participation rates were highest among (associate) professionals, vocational grammar school classes, classes introduced by females, younger individuals, members of the project team, and classes introduced face-to-face. Female gender, lower social competencies, lifetime cannabis use, higher problematic internet use, and higher perceived stress were associated with higher individual participation. The study highlights the importance of proactive outreach and personalized interventions for addiction prevention programs in vocational schools. While reached students aligned with the aims of the app, tailored recruitment strategies could enhance engagement among under-represented groups. The trial was registered in the German Clinical Trials Register (DRKS): DRKS00022328; registration date 09.10.2020.

Mobile App-Based Mindfulness Intervention for Addressing Psychological Distress Among Survivors of Hospitalization for COVID-19 Infection.

BACKGROUND: Psychological distress symptoms are present and persistent among many patients who survive a critical illness like COVID-19. RESEARCH QUESTION: Could a self-directed mobile app-delivered mindfulness intervention be feasibly and rapidly implemented within a clinical trials network to reduce distress symptoms? STUDY DESIGN AND METHODS: A randomized clinical trial was conducted between January 2021 and May 2022 at 29 US sites and included survivors of hospitalization due to COVID-19-related illness with elevated symptoms of depression at discharge. Participants were randomized to intervention or usual care control. The intervention consisted of four themed weeks of daily audio, video, and text content. All study procedures were virtual. The primary outcome was depression symptoms assessed with the Patient Health Questionnaire 9 at 3 months. Secondary outcomes included anxiety (Generalized Anxiety Disorder 7-item scale), quality of life (EQ-5D), and adherence. We used general linear models to estimate treatment arm differences in outcomes over time. RESULTS: Among 56 randomized participants (mean age ± SD, 51.0 ± 13.2 years; 38 female [67.9%]; 14 Black participants [25%]), 45 (intervention: n = 23 [79%]; control: n = 22 [81%]) were retained at 6 months. There was no difference in mean improvement between intervention and control participants at 3 months in Patient Health Questionnaire 9 (-0.5 vs 0.1), Generalized Anxiety Disorder 7-item scale (-0.3 vs 0.1), or EQ-5D (-0.03 vs 0.02) scores, respectively; 6-month results were similar. Only 15 participants (51.7%) initiated the intervention, whereas the mean number ± SD of the 56 prescribed intervention activities completed was 12.0 ± 15.2. Regulatory approvals delayed trial initiation by nearly a year. INTERPRETATION: Among survivors of COVID-19 hospitalization with elevated psychological distress symptoms, a self-directed mobile app-based mindfulness intervention had poor adherence. Future psychological distress interventions mobilized at broad scale should focus efforts on patient engagement and regulatory simplification to enhance success. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04581200; URL: www.clinicaltrials.gov.

Fish 3D Locomotion app: a user-friendly computer application package for automatic data calculation and endpoint extraction for novel tank behavior in fish.

This paper introduces the Fish 3D Locomotion app (F3LA), a Python-based, Graphical User Interface (GUI)-equipped tool designed to automate behavioral endpoint extraction in zebrafish locomotion assays. Building on our previous work, which utilized a specialized aquatic tank with a mirror and a single camera for fish movement tracking in three dimensions, F3LA significantly enhances data processing efficiency. Its accuracy was tested by reanalyzing and comprehensively comparing the calculated data with the previously published data from prior publications. From the comparison results, 90% of endpoints showed a similar statistical difference result. These minor differences were due to the different starting points for the dataset and updated calculation formulas that are implemented in F3LA. In addition, shoaling area or shoaling volume calculations are also included in F3LA as a new feature that can serve as sensitive indicators of social cohesion, group dynamics, or stress responses, offering insights into neuropsychological conditions or the effects of pharmacological interventions. Furthermore, F3LA offers a marked improvement over manual operations, being at least five times faster, while maintaining consistent accuracy as it reduces human-induced errors, ensuring a higher degree of reliability in the results. Finally, the potency of F3LA was tested to evaluate the toxicities of 14 rare earth elements (REEs) to the adult zebrafish behaviors. Based on the results, our findings suggested that each tested REE altered fish behaviors in different patterns and magnitudes to each other. However, among the tested light rare earth elements (LREEs), neodymium was demonstrated to cause more relatively severe behavior alterations than other LREEs, indicated by the statistically higher value of entropy (0.2695 ± 0.04977 (mean with a standard deviation)) than the control group (0.2352 ± 0.05896). Meanwhile, in terms of heavy rare earth elements (HREEs), erbium seemed to lead to more distinct behavior toxicities than other HREEs, which was shown by the statistically lower level of fractal dimension (2.022 ± 0.3412) than the untreated group (2.255 ± 0.1661). Taken together, F3LA's development marks a significant advance in high-throughput toxicological and pharmacological assessments in zebrafish, leveraging three-dimensional locomotion data for a more comprehensive analysis of fish behavior performance, providing a significant contribution to research in various fields.

Resilience eDBT: Development and Usability Evaluation of a Dialectical Behavior Therapy Skills Training App for Eating Disorders.

OBJECTIVE: Dialectical behavior therapy (DBT) is an evidence-based treatment for disorders characterized by recurrent binge eating. Yet, access to specialized treatment like DBT remains limited. To increase the accessibility of DBT, we developed a DBT skills training app (Resilience: eDBT) for the management of eating disorder (ED) symptoms. This paper delineates the developmental process of Resilience and tests its usability. METHODS: Descriptive information on the development and features of Resilience is provided, including its framework, content structure and delivery formats, functionality, data storage procedure, and privacy protocols. Usability was assessed via a mixed methods approach in 10 symptomatic individuals. Qualitative data were organized based on an existing framework, which included six themes: usability, visual design, user engagement, content, therapeutic persuasiveness, and therapeutic alliance. RESULTS: Resilience demonstrated good usability via a Systems Usability Scale score of 85.5, which exceeded the recommended cutoff of 68. Positive aspects of the app, according to interview data, were the ease of use and the visual design, while the addition of peer support was suggested as an opportunity for improvement. DISCUSSION: A novel DBT-based app may serve as an acceptable, low-intensity option or adjunct to traditional treatment for targeting ED symptoms that emerge in daily life. However, notable limitations include the small sample size and the single time point at which the usability assessment was conducted.

Development of a Web App to Enhance Physical Activity in People With Cystic Fibrosis: Co-Design and Acceptability Evaluation by Patients and Health Professionals.

BACKGROUND: Cystic fibrosis (CF) is a genetic disease affecting the respiratory and digestive systems, with recent treatment advances improving life expectancy. However, many people with CF lack adequate physical activity (PA). PA can enhance lung function and quality of life, but barriers exist. The Cystic Fibrosis Decisional Balance of Physical Activity questionnaire assesses the decisional balance for PA in adults with CF, but it is not optimal for clinical use. A digital app might overcome this limitation by improving the efficiency of administration, interpretation of results, and communication between patients and health care professionals. OBJECTIVE: This paper presents the development process and reports on the acceptability of a web app designed to measure and monitor the decisional balance for PA in people with CF. METHODS: This study comprised two stages: (1) the co-design of a digital app and (2) the evaluation of its acceptability among health care professionals and people with CF. A participatory approach engaged stakeholders in the app's creation. The app's acceptability, based on factors outlined in the Unified Theory of Acceptance and Use of Technology 2, is vital for its successful adoption. Participants volunteered, gave informed consent, and were aged >18 years and fluent in French. Data collection was performed through qualitative interviews, video presentations, surveys, and individual semistructured interviews, followed by quantitative and qualitative data analyses. RESULTS: In total, 11 health care professionals, 6 people with CF, and 5 researchers were involved in the co-design phase. Results of this phase led to the coconstruction of an app named MUCO_BALAD, designed for people with CF aged ≥18 years, health care professionals, and researchers to monitor the decisional balance for PA in people with CF. In the acceptability evaluation phase, the sample included 47 health care professionals, 44 people with CF, and 12 researchers. The analysis revealed that the acceptability measures were positive and that app acceptability did not differ according to user types. Semistructured interviews helped identify positive and negative perceptions of the app and the interface, as well as missing functionalities. CONCLUSIONS: This study assessed the acceptability of an app and demonstrated promising qualitative and quantitative results. The digital tool for measuring the decisional balance in PA for people with CF is encouraging for health care professionals, people with CF, and researchers, according to the valuable insights gained from this study.

The Acceptability, Engagement, and Feasibility of Mental Health Apps for Marginalized and Underserved Young People: Systematic Review and Qualitative Study.

BACKGROUND: Smartphone apps may provide an opportunity to deliver mental health resources and interventions in a scalable and cost-effective manner. However, young people from marginalized and underserved groups face numerous and unique challenges to accessing, engaging with, and benefiting from these apps. OBJECTIVE: This study aims to better understand the acceptability (ie, perceived usefulness and satisfaction with an app) and feasibility (ie, the extent to which an app was successfully used) of mental health apps for underserved young people. A secondary aim was to establish whether adaptations can be made to increase the accessibility and inclusivity of apps for these groups. METHODS: We conducted 2 sequential studies, consisting of a systematic literature review of mental health apps for underserved populations followed by a qualitative study with underserved young male participants (n=20; age: mean 19). Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, an electronic search of 5 databases was conducted in 2021. The search yielded 18,687 results, of which 14 articles met the eligibility criteria. RESULTS: The included studies comprised a range of groups, including those affected by homelessness, having physical health conditions, living in low- and middle-income countries, and those with sexual and gender minority identities. Establishing and maintaining user engagement was a pervasive challenge across mental health apps and populations, and dropout was a reported problem among nearly all the included studies. Positive subjective reports of usability, satisfaction, and acceptability were insufficient to determine users' objective engagement. CONCLUSIONS: Despite the significant amount of funding directed to the development of mental health apps, juxtaposed with only limited empirical evidence to support their effectiveness, few apps have been deliberately developed or adapted to meet the heterogeneous needs of marginalized and underserved young people. Before mental health apps are scaled up, a greater understanding is needed of the types of services that more at-risk young people and those in limited-resource settings prefer (eg, standard vs digital) followed by more rigorous and consistent demonstrations of acceptability, effectiveness, and cost-effectiveness. Adopting an iterative participatory approach by involving young people in the development and evaluation process is an essential step in enhancing the adoption of any intervention, including apps, in "real-world" settings and will support future implementation and sustainability efforts to ensure that marginalized and underserved groups are reached. TRIAL REGISTRATION: PROSPERO CRD42021254241; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254241.

Development of a Novel Mobile Health App to Empower Young People With Type 1 Diabetes to Exercise Safely: Co-Design Approach.

BACKGROUND: Blood glucose management around exercise is challenging for youth with type 1 diabetes (T1D). Previous research has indicated interventions including decision-support aids to better support youth to effectively contextualize blood glucose results and take appropriate action to optimize glucose levels during and after exercise. Mobile health (mHealth) apps help deliver health behavior interventions to youth with T1D, given the use of technology for glucose monitoring, insulin dosing, and carbohydrate counting. OBJECTIVE: We aimed to develop a novel prototype mHealth app to support exercise management among youth with T1D, detail the application of a co-design process and design thinking principles to inform app design and development, and identify app content and functionality that youth with T1D need to meet their physical activity goals. METHODS: A co-design approach with a user-centered design thinking framework was used to develop a prototype mHealth app "acT1ve" during the 18-month design process (March 2018 to September 2019). To better understand and respond to the challenges among youth with diabetes when physically active, 10 focus groups were conducted with youth aged 13-25 years with T1D and parents of youth with T1D. Thereafter, we conducted participatory design workshops with youth to identify key app features that would support individual needs when physically active. These features were incorporated into a wireframe, which was critically reviewed by participants. A beta version of "acT1ve" was built in iOS and android operating systems, which underwent critical review by end users, clinicians, researchers, experts in exercise and T1D, and app designers. RESULTS: Sixty youth with T1D, 14 parents, 6 researchers, and 10 clinicians were engaged in the development of "acT1ve." acT1ve included key features identified by youth, which would support their individual needs when physically active. It provided advice on carbohydrates and insulin during exercise, information on hypoglycemia treatment, pre- and postexercise advice, and an educational food guide regarding exercise management. "acT1ve" contained an exercise advisor algorithm comprising 240 pathways developed by experts in diabetes and exercise research. Based on participant input during exercise, acT1ve provided personalized insulin and carbohydrate advice for exercise lasting up to 60 minutes. It also contains other features including an activity log, which displays a complete record of the end users' activities and associated exercise advice provided by the app's algorithm for later reference, and regular reminder notifications for end users to check or monitor their glucose levels. CONCLUSIONS: The co-design approach and the practical application of the user-centered design thinking framework were successfully applied in developing "acT1ve." The design thinking processes allowed youth with T1D to identify app features that would support them to be physically active, and particularly enabled the delivery of individualized advice. Furthermore, app development has been described in detail to help guide others embarking on a similar project. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619001414101; https://tinyurl.com/mu9jvn2d.

NiADA (Non-invasive Anemia Detection App), a Smartphone-Based Application With Artificial Intelligence to Measure Blood Hemoglobin in Real-Time: A Clinical Validation.

Background  Anemia is a severe public health problem in India affecting more than half of the population. To reduce its burden on the population, the Government of India under the Anemia Mukt Bharat program has adopted a monitoring strategy for the diagnosis and treatment of anemia. Point-of-care testing (POCT) devices play a pivotal role in testing hemoglobin at a community level where sophisticated laboratory instruments are not available. The majority of the currently available POCT devices are invasive in nature which have their own limitations. A non-invasive method of hemoglobin estimation will address many of the limitations of an invasive POCT instrument, which will further improve people's acceptability for hemoglobin testing. The Non-Invasive Anemia Detection App (NiADA) (Monere AI Private Limited, Kolkata, West Bengal, India), a non-invasive POCT application, uses artificial intelligence (AI) to predict the hemoglobin level from lower eyelid images. This real-time, point-of-care, low-cost solution uses a custom computer vision deep-learning algorithm to determine blood hemoglobin value.  Method  The study validates an AI-based smartphone application NiADA against laboratory hemoglobin estimation and a widely used point-of-care hemoglobin estimation instrument (HemoCue Hb 301; HemoCue AB, Angelholm, Skane County, Sweden). The study was conducted in a tertiary care hospital in Eastern India and recruited a total of 556 participants. These included 58 pediatric patients, 51 pregnant women, 214 adult females, and 224 adult males. Statistical analysis was performed using Python (Python Software Foundation, Wilmington, Delaware, United States). A p-value of < 0.05 was taken to be significant.  Result  The mean difference observed between NiADA and laboratory-estimated hemoglobin values came out to be -0.29 g/dL and -0.89 g/dL for adult females and males respectively, and 0.61 g/dL for pregnant women and -0.69g/dL for the pediatric population. The limits of agreement for NiADA were narrow at 2.77 to -2.18 g/dL for adult females, 3.76 to -1.96 g/dL for adult males, 1.89 to -3.29 g/dL for pregnant women, and 3.28 to -2.08 g/dL for the pediatric population. The sensitivity and specificity of the NiADA application against the laboratory estimation method were 75.8% and 53.8% for adult females, 70.0% and 48.3% for adult males, 23.8% and 90% for pregnant females, and 75% and 57% for the pediatric population.  Conclusion  As a non-invasive application, NiADA's performance is satisfactory and comparable with minimally invasive tools like HemoCue Hb 301 and other POCT devices.

Breathing Life Into Meta-Analytic Methods.

Meta-analyses have become indispensable in the behavioral sciences, combining and summarizing data from multiple studies. While they offer many advantages (e.g., increased power, higher generality, and resolving conflicting findings), they currently only provide a snapshot at a given point. In active research areas, frequent meta-analytic updates are necessary to incorporate new evidence. We propose guidelines for live, dynamic meta-analyses and introduce an accessible tool using the R environment. Our app, powered by the Shiny package, enables the meta-analyst to integrate evidence interactively as an update of an existing meta-analysis or from scratch (i.e., a new meta-analysis). By embracing dynamic meta-analyses and leveraging modern tools, researchers can ensure up-to-date meta-analyses in their respective fields.

TFTF: An R-Based Integrative Tool for Decoding Human Transcription Factor-Target Interactions.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF-target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application and package utilizing the R program, which predicts TF-target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF-target gene networks. Despite its current limitation to human data, it provides a platform to explore gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species.

Eta-secretase-like processing of the amyloid precursor protein (APP) by the rhomboid protease RHBDL4.

The amyloid precursor protein (APP) is a key protein in Alzheimer's disease synthesized in the endoplasmic reticulum (ER) and translocated to the plasma membrane where it undergoes proteolytic cleavages by several proteases. Conversely to other known proteases, we previously elucidated rhomboid protease RHBDL4 as a novel APP processing enzyme where several cleavages likely occur already in the ER. Interestingly, the pattern of RHBDL4-derived large APP C-terminal fragments resemble those generated by the η-secretase or MT5-MMP, which was described to generate so called Aη fragments. The similarity in large APP C-terminal fragments between both proteases raised the question whether RHBDL4 may contribute to η-secretase activity and Aη-like fragments. Here, we identified two cleavage sites of RHBDL4 in APP by mass spectrometry, which, intriguingly, lie in close proximity to the MT5-MMP cleavage sites. Indeed, we observed that RHBDL4 generates Aη-like fragments in vitro without contributions of α-, ß-, or γ-secretases. Such Aη-like fragments are likely generated in the ER since RHBDL4-derived APP-C-terminal fragments do not reach the cell surface. Inherited, familial APP mutations appear to not affect this processing pathway. In RHBDL4 knockout mice, we observed increased cerebral full length APP in comparison to wild type (WT) in support of RHBDL4 being a physiologically relevant protease for APP. Furthermore, we found secreted Aη fragments in dissociated mixed cortical cultures from WT mice, however significantly less Aη fragments in RHBDL4 knockout cultures. Our data underscores that RHBDL4 contributes to η-secretease-like processing of APP and that RHBDL4 is a physiologically relevant protease for APP.

Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.

AIMS: Tacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug-drug interactions (DDI). Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid-tacrolimus DDI differs by CYP3A4/5 genotypes. METHODS: Kidney transplant recipients (n = 2462) were classified by the number of loss of function alleles (LOF) (CYP3A5*3, *6 and *7 and CYP3A4*22) and steroid use at each tacrolimus trough in the first 6 months post-transplant. A population pharmacokinetic analysis was performed by nonlinear mixed-effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R. RESULTS: Steroids were associated with modestly higher (3%-11.8%) tacrolimus clearance. Patients with 0-LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2-LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1-LOF and 3/4-LOFs, respectively. CONCLUSIONS: Steroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses.

TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.

Reducing neuroendocrine psychosocial stress response through socio-emotional dyadic but not mindfulness online training.

Introduction: Stress-related diseases pose significant health risks and show wide prevalence. Empirical evidence suggests that contemplative practices, such as socio-emotional dyadic mental exercises, hold promise in mitigating the adverse effects of stress and promoting psychosocial well-being. This study aimed to investigate the differential effects of two online contemplative mental training programs on the psychosocial stress response: the first involved classic mindfulness practices, while the second incorporated a socio-emotional dyadic approach known as Affect Dyad. Methods: The study was conducted as part of the longitudinal CovSocial project's phase 2 in the context of the COVID-19 pandemic. 140 individuals participated in the Trier Social Stress Task (TSST), where the psychosocial stress response was assessed with cortisol saliva samples and subjective stress questionnaires in a cross-sectional design after the active training groups finished their intervention period. Participants were randomly assigned to the socio-emotional training group, mindfulness-based training group, or a control group that did not receive any training. Both training programs consisted of a ten-week intervention period with a daily 12-minute app-based mental training practice and weekly 2-hour online coaching sessions led by mental training teachers. Results: Results showed that the socio-emotional Dyad group but not the mindfulness-based group exhibited significantly lower cortisol levels at 10, 20, 30, and 40 minutes after the stressor as well as lower total cortisol output compared to the control group during the TSST, indicating a reduced hormonal stress response to a social stressor. Subjective markers did not show differences between the three groups. Discussion: These findings indicate that the daily socio-emotional dyadic practice, which emphasizes non-judgmental and empathic listening as well as the acceptance of challenging emotions in the presence of others within one's daily life context, may serve as a protective factor against the adverse effects of psychosocial stress triggered by the fear of negative social judgments. Given the high prevalence of stress-related diseases, such online mental training programs based on dyadic practices may thus represent an efficient and scalable approach for stress reduction.

Early biomarkers in the presymptomatic phase of cognitive impairment: changes in the endocannabinoidome and serotonergic pathways in Alzheimer's-prone mice after mTBI.

BACKGROUND: Despite extensive studies on the neurobiological correlates of traumatic brain injury (TBI), little is known about its molecular determinants on long-term consequences, such as dementia and Alzheimer's disease (AD). METHODS: Here, we carried out behavioural studies and an extensive biomolecular analysis, including inflammatory cytokines, gene expression and the combination of LC-HRMS and MALDI-MS Imaging to elucidate the targeted metabolomics and lipidomics spatiotemporal alterations of brains from wild-type and APP-SWE mice, a genetic model of AD, at the presymptomatic stage, subjected to mild TBI. RESULTS: We found that brain injury does not affect cognitive performance in APP-SWE mice. However, we detected an increase of key hallmarks of AD, including Aß1-42 levels and BACE1 expression, in the cortices of traumatized transgenic mice. Moreover, significant changes in the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), occurred, including increased levels of the endocannabinoid 2-AG in APP-SWE mice in both the cortex and hippocampus, and N-acylserotonins, detected for the first time in the brain. The gene expression of enzymes for the biosynthesis and inactivation of eCBs and eCB-like mediators, and some of their main molecular targets, also underwent significant changes. We also identified the formation of heteromers between cannabinoid 1 (CB1) and serotonergic 2A (5HT2A) receptors, whose levels increased in the cortex of APP-SWE mTBI mice, possibly contributing to the exacerbated pathophysiology of AD induced by the trauma. CONCLUSIONS: Mild TBI induces biochemical changes in AD genetically predisposed mice and the eCBome may play a role in the pathogenetic link between brain injury and neurodegenerative disorders also by interacting with the serotonergic system.

Technology-Based Strategy to Improve Medication Compliance Among Patients With Schizophrenia Spectrum Disorders.

INTRODUCTION:  Non-compliance to medications remains a challenging problem in schizophrenia. Newer strategies with high feasibility and acceptability are always being researched. This study aimed to assess the effectiveness of technology-based intervention in improving medication compliance in individuals with schizophrenia. METHOD: This was a prospective intervention study where participants were required to use the SuperMD smartphone application (Digital-Health Technologies Pte Ltd, Kuala Lumpur, Malaysia) for a month. A change in the Medication Adherence Rating Scale-Malay Translation (MARS-M) and Malay Translation of Drug Adherence Inventory-9 (MDAI-9) scores indicated a change in compliance and attitude to medication. Positive and Negative Syndrome Scale (PANSS) was used to assess change in symptoms and insight. Medication compliance was also obtained from the SuperMD application. Paired T-test was used to evaluate the significance of changes in mean scores of research variables over the study period. Wilcoxon signed-rank test was used to analyze the subscale of MDAI-9 and the change in PANSS score. The Kruskal-Wallis test was used to determine the effect of the change of insight on the level of compliance with medication. RESULTS: There were 36 participants in this study. The results showed statistically significant improvement in compliance (0.65, p ≤ 0.01) but not in attitude towards medication (0.78, p = 0.065). There was also an improvement in PANNS score (-2.58, P ≤ 0.01). There was no significant change in insight (χ2(2) = 3.802, p = 0.15).  Conclusion:The use of technology-based strategies like SuperMD is effective in improving medication compliance for individuals with schizophrenia.

Type 2 diabetes foot inflammation prevention reminder socks.

It is not easy to determine the time between diagnosis and inflammation in patients with type 2 diabetes foot disease. In severe cases, it can lead to ulceration or even amputation. During the development of the inflammation, there will be changes in temperature and blood oxygen saturation in the sole of the foot. Therefore, early monitoring can be an effective prevention and reminder. By integrating flexible conductive fibres, conductive ink and fabric, six nodes on the sole of the foot are monitored. Blood oxygen is monitored above the thumb using photoelectric sensors. The monitoring data signals from these two areas are transmitted to the integrated sensor on the top of the socks and then to the mobile app via Bluetooth. Blood oxygen saturation and temperature can be displayed in real time, and the data is also uploaded to ports such as doctors, communities and hospitals for clinical diagnosis. This study can effectively monitor and remind the inflammatory changes after diabetic foot disease, and change the way of health monitoring by design. Although this study does not have the function of treatment, it is the greatest value of designing intervention medical health - prevention reminder.