Pilot monitoring study in patients with diabetic kidney disease using NORA application.

INTRODUCTION: Diabetic Kidney Disease (DKD) is the most common cause of end-stage chronic kidney disease (CKD), conditioning these patients to a worse renal prognosis and higher cardiovascular mortality and/or requirement for renal replacement therapy. The use of novel information and communication technologies (ICTs) focused on the field of health, may facilitates a better quality of life and disease control in these patients. Our objective is to evaluate the effect of monitoring DKD patients using NORA-app. MATERIAL AND METHODS: Prospective feasibility/validation study of NORA-app in patients with DKD stage G3bA3 or higher, followed in outpatient clinics of a tertiary care hospital. NORA-app is an application for smartphones designed to control risk factors, share educational medical information, communicate via chat with health professionals, increase treatment compliance (Morisky-Green), and collect patient reported outcomes such as anxiety and depression using HADs scale. Clinical-laboratory variables were collected at 3 months and compared to control patients who declined using NORA-app. RESULTS: From 01/01/2021 to 03/03/2022 the use of NORA-app was offered to 118 patients, 82 accepted and 36 declined (controls). After a mean follow-up period of 6,04 months and at the time of data extraction 71 (86.6%) NORA-app patients remain active users, 2 have completed the follow-up at one year and 9 are inactive (3 due to death and 6 due to non-locatable). There were no differences in baseline characteristics including Creatinine [2.1 (1.6-2.4) vs. 1.9 (1.5-2.5)] mg/dL and alb/creat [962 (475-1784) vs. 1036 (560-2183)] mg/gr between Nora and control patients respectively. The therapeutic compliance rate in the NORA-app group was 77%, improving at 90 days to 91%. Patients in the NORA-group showed significantly lower levels of alb/creat than controls (768(411-1971) mg/g Vs 2039 (974-3214) p = 0.047) at 90-day follow-up. CONCLUSIONS: In patients with DKD the use of NORA-app was maintained in the long-term, leading to high levels of treatment compliance, and achieving a better disease control. Our study suggests that the generalized use of ICTs may help in the personalized monitoring of these patients to delay the progression of kidney disease.

Efficacy of an Artificial Intelligence App (Aysa) in Dermatological Diagnosis: Cross-Sectional Analysis.

BACKGROUND: Dermatology is an ideal specialty for artificial intelligence (AI)-driven image recognition to improve diagnostic accuracy and patient care. Lack of dermatologists in many parts of the world and the high frequency of cutaneous disorders and malignancies highlight the increasing need for AI-aided diagnosis. Although AI-based applications for the identification of dermatological conditions are widely available, research assessing their reliability and accuracy is lacking. OBJECTIVE: The aim of this study was to analyze the efficacy of the Aysa AI app as a preliminary diagnostic tool for various dermatological conditions in a semiurban town in India. METHODS: This observational cross-sectional study included patients over the age of 2 years who visited the dermatology clinic. Images of lesions from individuals with various skin disorders were uploaded to the app after obtaining informed consent. The app was used to make a patient profile, identify lesion morphology, plot the location on a human model, and answer questions regarding duration and symptoms. The app presented eight differential diagnoses, which were compared with the clinical diagnosis. The model's performance was evaluated using sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1-score. Comparison of categorical variables was performed with the χ2 test and statistical significance was considered at P<.05. RESULTS: A total of 700 patients were part of the study. A wide variety of skin conditions were grouped into 12 categories. The AI model had a mean top-1 sensitivity of 71% (95% CI 61.5%-74.3%), top-3 sensitivity of 86.1% (95% CI 83.4%-88.6%), and all-8 sensitivity of 95.1% (95% CI 93.3%-96.6%). The top-1 sensitivities for diagnosis of skin infestations, disorders of keratinization, other inflammatory conditions, and bacterial infections were 85.7%, 85.7%, 82.7%, and 81.8%, respectively. In the case of photodermatoses and malignant tumors, the top-1 sensitivities were 33.3% and 10%, respectively. Each category had a strong correlation between the clinical diagnosis and the probable diagnoses (P<.001). CONCLUSIONS: The Aysa app showed promising results in identifying most dermatoses.

Using Monte Carlo Simulation to Forecast the Scientific Utility of Psychological App Studies: A Tutorial.

Mobile applications offer a wide range of opportunities for psychological data collection, such as increased ecological validity and greater acceptance by participants compared to traditional laboratory studies. However, app-based psychological data also pose data-analytic challenges because of the complexities introduced by missingness and interdependence of observations. Consequently, researchers must weigh the advantages and disadvantages of app-based data collection to decide on the scientific utility of their proposed app study. For instance, some studies might only be worthwhile if they provide adequate statistical power. However, the complexity of app data forestalls the use of simple analytic formulas to estimate properties such as power. In this paper, we demonstrate how Monte Carlo simulations can be used to investigate the impact of app usage behavior on the utility of app-based psychological data. We introduce a set of questions to guide simulation implementation and showcase how we answered them for the simulation in the context of the guessing game app Who Knows (Rau et al., 2023). Finally, we give a brief overview of the simulation results and the conclusions we have drawn from them for real-world data generation. Our results can serve as an example of how to use a simulation approach for planning real-world app-based data collection.

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.

An Artificial Intelligence-Based App for Self-Management of Low Back and Neck Pain in Specialist Care: Process Evaluation From a Randomized Clinical Trial.

BACKGROUND: Self-management is endorsed in clinical practice guidelines for the care of musculoskeletal pain. In a randomized clinical trial, we tested the effectiveness of an artificial intelligence-based self-management app (selfBACK) as an adjunct to usual care for patients with low back and neck pain referred to specialist care. OBJECTIVE: This study is a process evaluation aiming to explore patients' engagement and experiences with the selfBACK app and specialist health care practitioners' views on adopting digital self-management tools in their clinical practice. METHODS: App usage analytics in the first 12 weeks were used to explore patients' engagement with the SELFBACK app. Among the 99 patients allocated to the SELFBACK interventions, a purposive sample of 11 patients (aged 27-75 years, 8 female) was selected for semistructured individual interviews based on app usage. Two focus group interviews were conducted with specialist health care practitioners (n=9). Interviews were analyzed using thematic analysis. RESULTS: Nearly one-third of patients never accessed the app, and one-third were low users. Three themes were identified from interviews with patients and health care practitioners: (1) overall impression of the app, where patients discussed the interface and content of the app, reported on usability issues, and described their app usage; (2) perceived value of the app, where patients and health care practitioners described the primary value of the app and its potential to supplement usual care; and (3) suggestions for future use, where patients and health care practitioners addressed aspects they believed would determine acceptance. CONCLUSIONS: Although the app's uptake was relatively low, both patients and health care practitioners had a positive opinion about adopting an app-based self-management intervention for low back and neck pain as an add-on to usual care. Both described that the app could reassure patients by providing trustworthy information, thus empowering them to take actions on their own. Factors influencing app acceptance and engagement, such as content relevance, tailoring, trust, and usability properties, were identified. TRIAL REGISTRATION: ClinicalTrials.gov NCT04463043; https://clinicaltrials.gov/study/NCT04463043.

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.

Hypothalamic and hippocampal transcriptome changes in AppNL-G-F mice as a function of metabolic and inflammatory dysfunction.

The progression of Alzheimer's disease (AD) has a silent phase that predates characteristic cognitive decline and eventually leads to active cognitive deficits. Metabolism, diet, and obesity have been correlated to the development of AD but is poorly understood. The hypothalamus is a brain region that exerts homeostatic control on food intake and metabolism and has been noted to be impacted during the active phase of Alzheimer's disease. This study, in using an amyloid overexpression AppNL-G-F mouse model under normal metabolic conditions, examines blood markers in young and old male AppNL-G-F mice (n = 5) that corresponds to the silent and active phases of AD, and bulk gene expression changes in the hypothalamus and the hippocampus. The results show a large panel of inflammatory mediators, leptin, and other proteins that may be involved in weakening the blood brain barrier, to be increased in the young AppNL-G-F mice but not in the old AppNL-G-F mice. There were also several differentially expressed genes in both the hypothalamus and the hippocampus in the young AppNL-G-F mice prior to amyloid plaque formation and cognitive decline that persisted in the old AppNL-G-F mice, including GABRa2 receptor, Wdfy1, and several pseudogenes with unknown function. These results suggests that a larger panel of inflammatory mediators may be used as blood markers to detect silent AD, and that a change in leptin and gene expression in the hypothalamus exist prior to cognitive effects, suggesting a coupling of metabolism with amyloid plaque induced cognitive decline.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aß generation.

SIL1, an endoplasmic reticulum (ER)-resident protein, is reported to play a protective role in Alzheimer's disease (AD). However, the effect of SIL1 on amyloid precursor protein (APP) processing remains unclear. In this study, the role of SIL1 in APP processing was explored both in vitro and in vivo. In the in vitro experiment, SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695. In the in vivo experiment, AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates. Western blotting (WB), immunohistochemistry, RNA sequencing (RNA-seq), and behavioral experiments were performed to evaluate the relevant parameters. Results indicated that SIL1 expression decreased in APP23/PS45 mice. Overexpression of SIL1 significantly decreased the protein levels of APP, presenilin-1 (PS1), and C-terminal fragments (CTFs) of APP in vivo and in vitro. Conversely, knockdown of SIL1 increased the protein levels of APP, ß-site APP cleavage enzyme 1 (BACE1), PS1, and CTFs, as well as APP mRNA expression in 2EB2 cells. Furthermore, SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice. Importantly, Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice. These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

An app promoting weight gain prevention via healthy behaviours amongst young women with a family history of breast cancer: Acceptability and usability assessment.

BACKGROUND: Breast cancer is the most frequent female malignancy in the UK. Around 20% of cases are linked to weight gain, excess weight and health behaviours. We designed a weight gain prevention, health behaviour intervention for young women at increased risk. METHODS: The study comprised a single arm observational study over 2 months testing acceptability and usability of the intervention: online group welcome event, app and private Facebook group. Females aged 18-35 years at moderate or high risk of breast cancer (>17% lifetime risk) were recruited via invite letters and social media posts. The app included behaviour change techniques and education content. Online questionnaires were completed at baseline, as well as at 1 and 2 months. We also assessed feasibility of study procedures. RESULTS: Both recruitment methods were successful. Thirty-five women were recruited, 26% via social media posts. Median age was 33 (interquartile range = 28.2-34.5) years, the majority (94.1%) were of White ethnicity. Thirty-four participants were included in the analyses, of which 94% downloaded the app. Median self-monitoring logs per participant during the study period was 10.0 (interquartile range = 4.8-28.8). App quality mean (SD) score was 3.7 (0.6) at 1 and 2 months (scale: 1-5). Eighty-nine per cent rated the app at average or above at 1 month and 75.0% at 2 months. Nineteen women (55.9%) joined the Facebook group and there were 61 comments and 83 reactions and votes from participants during the study period. CONCLUSIONS: This first iteration of the app and intervention was well received and is suitable to progress to the next stage of refining and further testing.

A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease.

BACKGROUND: Amyloid beta protein (Aß) is a treatment target in Alzheimer's Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aß. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aß metabolism using Stable Isotope Labeling Kinetic (SILK) analysis. METHODS: Double-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) confirmed by low CSF Aß42/40 were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21-23 days, then underwent CSF catheter placement, intravenous infusion of 13C6-leucine, and CSF sampling for 36 h. Safety and tolerability were assessed through participant reports, EKG and laboratory tests. CSF SILK analysis measured Aß40, 38 and 42 with immunoprecipitation-mass spectrometry. Baseline and day 21 CSF APP, Aß and other biomarkers were measured with immunoassays. The Mini-Mental State Exam and ADAS-cog12 were given at baseline and day 21. RESULTS: From June 2017 to December 2021, 19 participants were enrolled, randomized within dose cohorts (5 active: 3 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aß40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs. placebo groups. CONCLUSIONS: Posiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects. TRIAL REGISTRATION: NCT02925650 on clinicaltrials.gov (registered on 10-24-2016).

Knockdown of microglial iron import gene, DMT1, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer's disease.

Background: Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer's disease (AD). In vitro, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo. These studies determined the effects of microglial-specific knockdown of Slc11a2 on AD-related cognitive decline and microglial transcriptional phenotype. Methods: In vitro experiments and RT-qPCR were used to assess a role for DMT1 in amyloid-ß-associated inflammation. To determine the effects of microglial Slc11a2 knockdown on AD-related phenotypes in vivo, triple-transgenic Cx3cr1 Cre - ERT2 ;Slc11a2 flfl;APP/PS1 + or - mice were generated and administered corn oil or tamoxifen to induce knockdown at 5-6 months of age. Both sexes underwent behavioral analyses to assess cognition and memory (12-15 months of age). Hippocampal CD11b + microglia were magnetically isolated from female mice (15-17 months) and bulk RNA-sequencing analysis was conducted. Results: DMT1 inhibition in vitro robustly decreased Aß-induced inflammatory gene expression and cellular iron levels in conditions of excess iron. In vivo, Slc11a2 KD APP/PS1 female, but not male, mice displayed a significant worsening of memory function in Morris water maze and a fear conditioning assay, along with significant hyperactivity compared to control WT and APP/PS1 mice. Hippocampal microglia from Slc11a2 KD APP/PS1 females displayed significant increases in Enpp2, Ttr, and the iron-export gene, Slc40a1, compared to control APP/PS1 cells. Slc11a2 KD cells from APP/PS1 females also exhibited decreased expression of markers associated with disease-associated microglia (DAMs), such as Apoe, Ctsb, Csf1, and Hif1α. Conclusions: This work suggests a sex-specific role for microglial iron import gene Slc11a2 in propagating behavioral and cognitive phenotypes in the APP/PS1 model of AD. These data also highlight an association between loss of a DAM-like phenotype in microglia and cognitive deficits in Slc11a2 KD APP/PS1 female mice. Overall, this work illuminates an iron-related pathway in microglia that may serve a protective role during disease and offers insight into mechanisms behind disease-related sex differences.

Increasing the Survival of a Neuronal Model of Alzheimer's Disease Using Docosahexaenoic Acid, Restoring Endolysosomal Functioning by Modifying the Interactions between the Membrane Proteins C99 and Rab5.

Docosahexaenoic acid (DHA, C22:6 ω3) may be involved in various neuroprotective mechanisms that could prevent Alzheimer's disease (AD). Its influence has still been little explored regarding the dysfunction of the endolysosomal pathway, known as an early key event in the physiopathological continuum triggering AD. This dysfunction could result from the accumulation of degradation products of the precursor protein of AD, in particular the C99 fragment, capable of interacting with endosomal proteins and thus contributing to altering this pathway from the early stages of AD. This study aims to evaluate whether neuroprotection mediated by DHA can also preserve the endolysosomal function. AD-typical endolysosomal abnormalities were recorded in differentiated human SH-SY5Y neuroblastoma cells expressing the Swedish form of human amyloid precursor protein. This altered phenotype included endosome enlargement, the reduced secretion of exosomes, and a higher level of apoptosis, which confirmed the relevance of the cellular model chosen for studying the associated deleterious mechanisms. Second, neuroprotection mediated by DHA was associated with a reduced interaction of C99 with the Rab5 GTPase, lower endosome size, restored exosome production, and reduced neuronal apoptosis. Our data reveal that DHA may influence protein localization and interactions in the neuronal membrane environment, thereby correcting the dysfunction of endocytosis and vesicular trafficking associated with AD.

Mutational Landscape of Alzheimer's Disease and Frontotemporal Dementia: Regional Variances in Northern, Central, and Southern Italy.

Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP, PSEN1, PSEN2, MAPT, GRN, and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1, 11 MAPT, 9 PSEN2, and 4 APP. Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.

Perceived impact of a smartphone application: Knowledge, awareness, attitudes, and intention to change an abnormal neck posture among smartphone-addicted undergraduates.

Objectives: This study explored the perceived impact of a smartphone app on awareness, knowledge, attitudes, help-seeking, behavior change, and intention to change an abnormal posture of the neck while using smartphones among undergraduates addicted to smartphone use. Patients and methods: This descriptive survey involved smartphone-addicted undergraduates recruited between February 2022 and July 2022. The self-administered questionnaires used for gathering the data were a smartphone addiction survey and a mobile app rating scale on app-specific query assessing changes in awareness, knowledge, attitude, intention to change, health-seeking, and behavior change. Results: The questionnaire was completed by 316 participants (218 females, 98 males; mean: 20.7±2.6 years; range, 16 to 35 years). One hundred forty-two (44.9%) of the respondents strongly agreed that the app improved awareness, while 143 (45.3%) strongly agreed that the app improved knowledge about the significance of addressing abnormal posture of the neck while using smartphones. One hundred thirty-two (41.8%) were of the opinion that the app could change participant attitudes, and 135 (42.7%) agreed that the app could increase intentions toward improving abnormal posture of the neck. One hundred eighteen (37.3%) participants agreed that the app could promote help-seeking for abnormal posture of the neck. Respondents' age had a negative weak correlation with intention to treat (r=-0.191, p=0.001) and help-seeking (r=-0.199, p=0.0001). Conclusion: Most of the respondents in this study agreed that the CerviTech app could increase awareness, knowledge, attitude, intention to change, help-seeking, and behavior change of abnormal posture of the neck while using smartphones, with significant impact according to the age of the respondents regarding the intention to change and help-seeking behavior.

Effect of mobile app-based oral hygiene instructions on clinical parameters, oral bacterial diversity, and composition of subgingival microbiota in periodontitis patients.

Introduction: Oral hygiene instruction (OHI) is essential during periodontitis treatment. Various OHI approaches have been explored, including mobile apps. Objective: To evaluate the mobile app-based OHI's effect on periodontitis management by analyzing clinical parameters and subgingival microbiota. Methods: Forty-four periodontitis patients were randomly assigned into two groups. The test group (n = 22) received scaling and root planing (SRP), OHI, and mobile app-based OHI, whereas the control group (n = 22) received SRP and OHI. Full mouth plaque score (FMPS), bleeding on probing (BOP) and probing pocket depth at the sampling sites (site-PPD) were assessed at baseline, one- and three-month visits. The 16S rRNA next-generation sequencing (NGS) was used to analyze subgingival plaque samples. Results: Significant reduction in FMPS, BOP, and site-PPD at one- and three-month visits compared to baseline (p < 0.001) with no significant differences across groups (p > 0.05). In test groups, intra-group analysis showed better improvement in BOP and site-PPD (p < 0.05) than control. The diversity and composition of subgingival microbiota did not differ between groups or timepoints (p > 0.05). Conclusions: Mobile app-based OHI showed no superior effects on improving clinical parameters and subgingival microbiota compared to conventional OHI. Further investigation into its long-term impact on periodontitis treatment is needed.

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.

Automatized detection of uniparental disomies in a large cohort.

Uniparental disomy (UPD) is the inheritance of both homologues of a chromosome from only one parent. The detection of UPDs in sequencing data is not well established and a common gap in genetic diagnostics. We applied our in-house UPD detection pipeline to evaluate a cohort of 9212 samples, including multigene panels as well as exome sequencing data in a single, duo or trio constellation. We used the results to inform the design of our publicly available web app altAFplotter. UPDs categorized as heterodisomy, whole chromosome or segmental isodisomy were identified and validated with microsatellites, multiplex ligation-dependent probe amplification as well as Sanger sequencing. We detected 14 previously undiagnosed UPDs including nine isodisomies, four segmental isodisomies as well as one heterodisomy on chromosome 22. We characterized eight findings as potentially causative through homozygous pathogenic variants or imprinting disorders. Overall, our study demonstrates the utility of our UPD detection pipeline with our web app, altAFplotter, to reliably identify UPDs. This not only increases the diagnostic yield of cases with growth and metabolic disturbances, as well as developmental delay, but also enhances the understanding of UPDs that may be relevant for recurrence risks and genetic counseling.