eHealth and the hearing aid adult patient journey: a state-of-the-art review.

The number and variety of eHealth services for adults and older adults who use hearing aids (HAs) are growing rapidly. This area holds promise to increase cost-efficiency, enable better access to care, and improve patient outcomes and satisfaction. Despite the increasing interest in this field, an up-to-date picture of recent research in the area of eHealth for adults with HAs is lacking. In this state-of-the-art review we assessed the literature from the past decade about eHealth use in the HA adult patient journey. Systematic searches were conducted in CINAHL, PubMed, Scopus, and Web of Science. A total of 34 peer-reviewed empirical records were identified from the searches and from the reference lists of searched records. Records were characterized based on: eHealth platform (i.e.: offline, Internet-based, or mobile-based), service [i.e.: education and information, screening and assessment, hearing rehabilitation, or general (tele-audiology)], and phase of the patient journey (i.e.: pre-fitting, fitting, or post-fitting). The review highlighted a growing interest in the field, as revealed by an increasing trend over the search period, from 2 records in 2009-2010 up to 17 records in 2015-2016. Internet-based platforms were the most frequently used (present in more than half of the included records), with a stable trend in the period. About one-third of the records introduced services over offline platforms, whereas mobile-based platforms were used only in 6 out of 34 records, suggesting that the clinical uptake of mobile services is still limited compared to more mature offline and Internet-based platforms. Most of the eHealth services observed were related to the areas of education and information (42.5%) and hearing rehabilitation (40.4%), whereas 10.7% were related to screening and assessment, and 6.4% to general tele-audiology services. Many services covered different phases of the patient journey, especially the fitting and post-fitting phases. Overall, this review showed that the field of eHealth in the context of HA rehabilitation in adults has grown in the recent past. Research is still needed to increase the uptake and efficacy of eHealth in clinical practice, especially in terms of technology developments, technical and clinical validation, and optimization of strategies for service delivery.

Defect-Engineered Metal-Organic Frameworks as Nanocarriers for Pharmacotherapy: Insights into Intracellular Dynamics at The Single Particle Level.

Nanoscale Metal-Organic Frameworks (nanoMOFs) are widely implemented in a host of assays involving drug delivery, biosensing catalysis, and bioimaging. However, the cell pathways and cell fate remain poorly understood. Here, a new fluorescent nanoMOF integrating ATTO 655 into surface defects of colloidal UiO-66 is synthesized, allowing to track the spatiotemporal localization of Single nanoMOF in live cells. density functional theory reveals the stronger binding of ATTO 655 to the Zr6 cluster nodes compared with phosphate and Alendronate Sodium. Parallelized tracking of the spatiotemporal localization of thousands of nanoMOFs and analysis using machine learning platforms reveals whether nanoMOFs remain outside as well as their cellular internalization pathways. To quantitatively assess their colocalization with endo/lysosomal compartments, a colocalization proxy approach relying on the nanoMOF detection of particles in one channel to the signal in the corresponding endo/lysosomal compartments channel, considering signal versus local background intensity ratio and signal-to-noise ratio is developed. This strategy mitigates colocalization value inflation from high or low signal expression in endo/lysosomal compartments. The results accurately measure the nanoMOFs' colocalization from early to late endosomes and lysosomes and emphasize the importance of understanding their intracellular dynamics based on single-particle tracking for optimal and safe drug delivery.

Deep learning assisted single particle tracking for automated correlation between diffusion and function.

Sub-cellular diffusion in living systems reflects cellular processes and interactions. Recent advances in optical microscopy allow the tracking of this nanoscale diffusion of individual objects with an unprecedented level of precision. However, the agnostic and automated extraction of functional information from the diffusion of molecules and organelles within the sub-cellular environment, is labor-intensive and poses a significant challenge. Here we introduce DeepSPT, a deep learning framework to interpret the diffusional 2D or 3D temporal behavior of objects in a rapid and efficient manner, agnostically. Demonstrating its versatility, we have applied DeepSPT to automated mapping of the early events of viral infections, identifying distinct types of endosomal organelles, and clathrin-coated pits and vesicles with up to 95% accuracy and within seconds instead of weeks. The fact that DeepSPT effectively extracts biological information from diffusion alone illustrates that besides structure, motion encodes function at the molecular and subcellular level.

Web-Based Tool Designed to Encourage Supplemental Nutrition Assistance Program Use in Urban College Students: Usability Testing Study.

BACKGROUND: Food insecurity continues to be a risk for college students in the United States. It is associated with numerous problems, such as chronic health conditions, increased stress and anxiety, and a lower grade point average. After COVID-19, the Supplemental Nutrition Assistance Program (SNAP) benefits were extended to college-aged students; however, there were some barriers to participation, which persisted such as lack of perceived food insecurity risk, lack of knowledge regarding the SNAP application process, the complexity of determining eligibility, and stigma associated with needing social assistance. A technology-enhanced tool was developed to address these barriers to SNAP enrollment and encourage at-risk college students to apply for SNAP. OBJECTIVE: The purpose of this study was to test the usability and acceptability of a web-based SNAP screening tool designed for college-aged students. METHODS: College students aged 18-25 years were recruited to participate in 2 rounds of usability testing during fall 2022. Participants tested the prototype of a web-based SNAP screener tool using a standardized think-aloud method. The usability and acceptability of the tool were assessed using a semistructured interview and a 10-item validated System Usability Scale questionnaire. Audio recordings and field notes were systematically reviewed by extracting and sorting feedback as positive or negative comments. System Usability Scale questionnaire data were analyzed using the Wilcoxon signed rank test and sign test. RESULTS: A total of 12 students (mean age 21.8, SD 2.8 years; n=6, 50% undergraduate; n=11, 92% female; n=7, 58% Hispanic or Black or African American; n=9, 78% low or very low food security) participated in both rounds of user testing. Round 1 testing highlighted overall positive experiences with the tool, with most participants (10/12) stating that the website fulfills its primary objective as a support tool to encourage college students to apply for SNAP. However, issues related to user interface design, navigation, and wording of some questions in the screening tool were noted. Key changes after round 1 reflected these concerns, including improved design of response buttons and tool logo and improved clarity of screening questions. The overall system usability showed slight, but not statistically significant, improvement between round 1 and round 2 (91.25 vs 92.50; P=.10, respectively). CONCLUSIONS: Overall usability findings suggest that this web-based tool was highly usable and acceptable to urban college students and could be an effective and appealing approach as a support tool to introduce college students to the SNAP application process. The findings from this study will inform further development of the tool, which could eventually be disseminated publicly among various college campuses.

Engineering Saccharomyces cerevisiae for the de novo Production of Halogenated Tryptophan and Tryptamine Derivatives.

The indole scaffold is a recurring structure in multiple bioactive heterocycles and natural products. Substituted indoles like the amino acid tryptophan serve as a precursor for a wide range of natural products with pharmaceutical or agrochemical applications. Inspired by the versatility of these compounds, medicinal chemists have for decades exploited indole as a core structure in the drug discovery process. With the aim of tuning the properties of lead drug candidates, regioselective halogenation of the indole scaffold is a common strategy. However, chemical halogenation is generally expensive, has a poor atom economy, lacks regioselectivity, and generates hazardous waste streams. As an alternative, in this work we engineer the industrial workhorse Saccharomyces cerevisiae for the de novo production of halogenated tryptophan and tryptamine derivatives. Functional expression of bacterial tryptophan halogenases together with a partner flavin reductase and a tryptophan decarboxylase resulted in the production of halogenated tryptophan and tryptamine with chlorine or bromine. Furthermore, by combining tryptophan halogenases, production of di-halogenated molecules was also achieved. Overall, this works paves the road for the production of new-to-nature halogenated natural products in yeast.

Deep learning assisted single particle tracking for automated correlation between diffusion and function.

Sub-cellular diffusion in living systems reflects cellular processes and interactions. Recent advances in optical microscopy allow the tracking of this nanoscale diffusion of individual objects with an unprecedented level of precision. However, the agnostic and automated extraction of functional information from the diffusion of molecules and organelles within the sub-cellular environment, is labor-intensive and poses a significant challenge. Here we introduce DeepSPT, a deep learning framework to interpret the diffusional 2D or 3D temporal behavior of objects in a rapid and efficient manner, agnostically. Demonstrating its versatility, we have applied DeepSPT to automated mapping of the early events of viral infections, identifying distinct types of endosomal organelles, and clathrin-coated pits and vesicles with up to 95% accuracy and within seconds instead of weeks. The fact that DeepSPT effectively extracts biological information from diffusion alone indicates that besides structure, motion encodes function at the molecular and subcellular level.

The number of persons with alcohol problems in the Danish population.

AIMS: A) To qualify the existing estimates of the prevalence of heavy drinking, harmful alcohol use and alcohol dependency by applying adjustment for non-participation. B) To describe socio-demographic correlates of heavy drinkers. METHODS: Data came from the Danish Health Interview Survey 2005, which included a personal interview of 14,566 individuals (response rate 66.7 %), and of 5,552 individuals who completed a self-administered questionnaire containing the Alcohol Use Disorder Test (AUDIT) (response rate 50.9%). Heavy drinkers were defined as consuming >14/21 drinks/week (women/men). Identification of harmful alcohol users and dependent drinkers was based on the score of specific AUDIT questions (harmful alcohol use a score of ≥4 in questions 7-10, dependent drinkers ≥4 in questions 4-6). Adjustment for non-participation was performed using data from the Danish National Patient Registry. RESULTS: In the Danish population, 20% were heavy drinkers (862,876 persons 95% confidence interval (95% CI): 672,002-1,195,069), 14% had harmful alcohol use (620,301 persons 95% CI: 439,221-944,992), 3% were dependent drinkers (147,528 persons 95% CI: 118,196-188,384). Being male was associated with heavy drinking (odds ratio (OR): 1.70; 95% CI: 1.53-1.89), as was being a single male (OR: 1.27; 95% CI: 1.01-1.61) and being a smoker (men: OR: 1.96; 95% CI: 1.67-2.30 / women: OR: 2.08; 95% CI: 1.72-2.52). CONCLUSIONS: The number of heavy drinkers in the Danish population and the number of people with harmful alcohol use is considerably higher than earlier prevalence estimates. The number of dependent drinkers is similar to earlier estimates.

Mobilisation of epistaxis patients--a prospective, randomised study documenting a safe patient care regime.

OBJECTIVE: The project aimed at determining whether patients admitted to hospital for the treatment of epistaxis can be mobilised instead of the conventional regime of bed rest without increasing the risks of new bleeding episodes. BACKGROUND: A survey of nursing regimes for epistaxis patients has shown that patients were prescribed bed rest in 11 of 16 hospital departments. This prescription has been based on the assumption that bed rest reduces the risk of renewed bleeding. There is no scientific documentation of the need for bed rest demonstrating any reduced risks of new bleeding episodes. However, these patients are generally older and sustain an increased risk of further complications related to bed rest itself. DESIGN: The study was a prospective, randomised 1:1 parallel-group trial with 100 participants admitted to our department for the treatment of epistaxis. METHODS: Participants were randomly assigned to mobilisation or bed rest. Further, general demographic baseline data were registered including treatment modalities, hypertension, haemophilic disorders, anticoagulant therapy and diabetes. RESULTS: In the study group (mobilisation), 21 participants experienced new bleeding episodes against 29 maintaining haemostasis. In the control group (immobilisation), 24 participants experienced new bleeding episodes against 26. The odds ratio for bleeding when mobilised was 0·784 with a confidence interval of (0·356-1·728). Thus, there was no statistically significant evidence that mobilisation increased the risk of new bleeding episodes. CONCLUSION: There was no statistical evidence to support the practice of bed rest to reduce the risk of renewed bleeding episodes in patients with primary epistaxis. This suggested that these patients can be mobilised without any increased risk of new haemorrhage. RELEVANCE TO CLINICAL PRACTICE: Mobilisation during hospital stay can maintain patients' levels of functionality, which will prevent both complications of bed rest and loss of self-esteem.

Characterization of resistance to a recombinant hexameric Fas-ligand (APO010) in human cancer cell lines.

Multiple myeloma remains a hard-to-treat cancer as all patients eventually progress because of drug resistance. Thus, there is a need for novel and non-cross-resistant treatment options, and we aimed to address this issue by introducing a new immuno-oncology drug (APO010) in multiple myeloma treatment. APO010 is a hexameric Fas-ligand that mimics cytotoxic T-lymphocyte signaling through the Fas-receptor to induce apoptosis. APO010 is currently in clinical trials with multiple myeloma patients. Thus, an understanding of the mechanisms contributing to resistance to APO010 will be essential for future clinical studies with APO010, and it might be possible to develop strategies to circumvent this resistance. We developed APO010-resistant variants of human multiple myeloma cell lines (LP1, MOLP-8, and KMS-12-BM) and a human Burkitt's lymphoma cell line (Raji) by exposing the cells to gradually increasing concentrations of APO010 over a period of 6-12 months. The resistant cell lines were characterized on the basis of immunocytochemistry, Fas-receptor protein expression, mRNA expression analysis, and pathway analysis. APO010-resistant cell lines exhibited a 4- to 520-fold increase in resistance to APO010 and still remained sensitive to other chemotherapeutics. Downregulation of the Fas-receptor protein expression was observed in all resistant cell lines. mRNA expression analysis of the resistant versus parental cell lines confirmed a significant alteration in FAS expression between sensitive and resistant cell lines (p = 0.03), while pathway analysis revealed alterations in mRNA signaling pathways of Fas. On the basis of the pre-clinical data obtained, it can be concluded that downregulation of Fas-receptor can mediate resistance to APO010.

Performance of children and adolescents with Asperger syndrome or high-functioning autism on advanced theory of mind tasks.

Although a number of advanced theory of mind tasks have been developed, there is a dearth of information on whether performances on different tasks are associated. The present study examined the performance of 21 children and adolescents with diagnoses of Asperger syndrome (AS) and 20 typically developing controls on three advanced theory of mind tasks: The Eyes Task, the Strange Stories, and the Stories from Everyday Life. The participants in the clinical group demonstrated lower performance than the controls on all the three tasks. The pattern of findings, however, indicates that these tasks may share different information-processing requirements in addition to tapping different mentalizing abilities.

User-Innovated eHealth Solutions for Service Delivery to Older Persons With Hearing Impairment.

PURPOSE: The successful design and innovation of eHealth solutions directly involve end users in the process to seek a better understanding of their needs. This article presents user-innovated eHealth solutions targeting older persons with hearing impairment. Our research question was: What are the key users' needs, expectations, and visions within future hearing rehabilitation service delivery? METHOD: We applied a participatory design approach to facilitate the design of future eHealth solutions via focus groups. We involved older persons with hearing impairment (n = 36), significant others (n = 10), and audiologists (n = 8) following 2 methods: (a) human-centered design for interactive systems and (b) user innovation management. Through 3 rounds of focus groups, we facilitated a process progressing from insights and visions for requirements (Phase 1), to app such as paper version wireframes (Phase 2), and to digital prototypes envisioning future eHealth solutions (Phase 3). Each focus group was video-recorded and photographed, resulting in a rich data set that was analyzed through inductive thematic analysis. RESULTS: The results are presented via (a) a storyboard envisioning future client journeys, (b) 3 key themes for future eHealth solutions, (c) 4 levels of interest and willingness to invest time and effort in digital solutions, and (d) 2 technical savviness types and their different preferences for rehabilitation strategies. CONCLUSIONS: Future eHealth solutions must offer personalized rehabilitation strategies that are appropriate for every person with hearing impairment and their level of technical savviness. Thus, a central requirement is anchoring of digital support in the clients' everyday life situations by facilitating easy access to personalized information, communication, and learning milieus. Moreover, the participants' visions for eHealth solutions call for providing both traditional analogue and digital services. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.7310729.

Apolipoprotein E epsilon 4 in an autopsy series of various dementing disorders.

Apolipoprotein E (APOE) allele epsilon 4 is a risk factor for Alzheimer's disease (AD) and has also been associated with impaired recovery from brain injury. Previous studies on APOE epsilon 4 in dementing disorders other than AD have been rather conflicting, in particular concerning frontotemporal dementia (FTD) and vascular dementia (VD). In the present study we determined APOE genotype in an autopsy series of demented subjects and non-demented controls from the Netherlands Brain Bank. We attempted to create as clear-cut diagnostic groups as possible and paid close attention to AD-type histopathological changes in all cases. In comparison with the APOE epsilon 4 allele frequency in controls (0.12; n=163 subjects), the APOE epsilon 4 allele frequency was significantly increased in AD (0.42; n=320, p<0.0001), as well as in AD with Lewy bodies (0.43; n=41, p<0.0001) and in demented subjects with no other neuropathological findings than AD-histopathology insufficient for a diagnosis of AD (0.29; n=41, p<0.001). However, the APOE epsilon 4 allele frequency was not significantly increased in FTD (0.18; n=49), VD (0.10; n=20) or in Lewy body disease without concomitant AD changes (0.13; n=12). As concerns dementing disorders, our results suggest that APOE epsilon 4 is selectively associated with the presence of AD-type histopathology.

Data warehouse for assessing animal health, welfare, risk management and -communication.

The objective of this paper is to give an overview of existing databases in Denmark and describe some of the most important of these in relation to establishment of the Danish Veterinary and Food Administrations' veterinary data warehouse. The purpose of the data warehouse and possible use of the data are described. Finally, sharing of data and validity of data is discussed. There are databases in other countries describing animal husbandry and veterinary antimicrobial consumption, but Denmark will be the first country relating all data concerning animal husbandry, -health and -welfare in Danish production animals to each other in a data warehouse. Moreover, creating access to these data for researchers and authorities will hopefully result in easier and more substantial risk based control, risk management and risk communication by the authorities and access to data for researchers for epidemiological studies in animal health and welfare.

Loneliness and social support in adolescent boys with autism spectrum disorders.

Loneliness and perceived social support were examined in 39 adolescent boys with autism spectrum disorders (ASD) by means of a self-labeling loneliness measure, the UCLA Loneliness Scale (third version), and the Social Support Scale for Children. Twenty-one percent of the boys with ASD described themselves as often or always feeling lonely. Compared with 199 boys from regular schools in a national probability study, ASD was strongly associated with often or always feeling lonely (OR: 7.08, p < .0005), as well as with a higher degree of loneliness (F(1,229) = 11.1, p < .005). Perceived social support from classmates, parents, and a close friend correlated negatively with loneliness in ASD. The study, therefore, indicates a high occurrence of loneliness among adolescent boys with ASD and points at perceived social support as an important protective factor.

A click chemistry approach to pleuromutilin conjugates with nucleosides or acyclic nucleoside derivatives and their binding to the bacterial ribosome.

Pleuromutilin and its derivatives are antibacterial drugs that inhibit protein synthesis in bacteria by binding to ribosomes. To promote rational design of pleuromutilin based drugs, 19 pleuromutilin conjugates with different nucleoside fragments as side chain extensions were synthesized by a click chemistry protocol. Binding was assessed by chemical footprinting of nucleotide U2506 in 23S rRNA, and all conjugates bind to varying degree reflecting their binding affinity to the peptidyl transferase center. The side chain extensions also show various protections at position U2585. Docking studies of the conjugates with the highest affinities support the conclusion that despite the various conjugations, the pleuomutilin skeleton binds in the same binding pocket. The conjugated triazole moiety is well accommodated, and the nucleobases are placed in different pockets in the 50S ribosomal subunit. The derivative showing the highest affinity and a significantly better binding than pleuromutilin itself contains an adenine-9-ylpropylene triazole conjugate to pleuromutilin C-22.

[Access to health care for migrants]. / Adgang til sundhedsydelser for migranter.

Migrants include a broad category of individuals moving from one place to another, either forced or voluntarily. Ethnicity and migration are interacting concepts which may act as determinants for migrants' health and access to health care. This access to health care may be measured by studying utilisation patterns or clinical outcomes like morbidity and mortality. Migrants' access to health care may be affected by several factors relating to formal and informal barriers. Informal barriers include economic and legal restrictions. Formal barriers include language and psychological and sociocultural factors.

[Proton magnetic resonance spectroscopy in the evaluation of cognitive disturbances]. / Protonmagnetisk resonans-spektroskopi til vurdering af kognitive forstyrrelser.

Magnetic resonance spectroscopy can detect metabolic changes in the brain, including changes in N-acetyl aspartate, a metabolite generally believed to be a marker of neuronal integrity. The correlations between metabolic changes and cognitive status in normal subjects and in a range of neurological and psychiatric disorders are reviewed. Magnetic resonance spectroscopy seems to be a way to monitor the efficacy of existing and new treatments to prevent the development of cognitive deficits in a number of diseases.

The Strange Stories test--a replication study of children and adolescents with Asperger syndrome.

The aim of the present study was to assess the ability of 21 children and adolescents with Asperger syndrome (AS) of normal intelligence to infer mental states in a story context using Happe's Strange Stories test. The participants in the AS group were compared with an age-matched control group (N=20) of normally developing children and adolescents on a test of social understanding. The test material comprised social communication such as Pretence, Joke, Lie, White Lie, Figure of Speech, Misunderstanding, Persuasion, Irony, Double Bluff and Contrary Emotions, Appearance/Reality and Forgetting. As compared to the controls, the participants in the AS group performed less well on these tasks, and answered fewer correct mental state inferences, but performed well on a physical state control task. This study supports the main finding of earlier studies, showing that even individuals with AS of normal intelligence have problems in using mental state terms context-appropriately when tested on the Strange Stories test.

A new 'advanced' test of theory of mind: evidence from children and adolescents with Asperger syndrome.

BACKGROUND: The aim of the present study was to assess the ability of children and adolescents with Asperger syndrome (AS) (N = 21) to infer physical versus mental states on a new 'advanced' test of theory-of-mind - Stories from Everyday Life. The participants in the AS group were of normal intelligence and were compared with an age-matched control group (N = 20) of normally developing children and adolescents. METHOD: The test materials comprised 26 short stories or 13 pairs of different types of stories. This contextually complex theory-of-mind battery aimed to record the participants' ability to make inferences about physical as well as mental states. The first part of each story described a physical or mechanical event, and a test question then tested the participants' ability to make an inference about a physical state. The last part of the stories contained two questions, testing the ability to infer a mental state from the story context, e.g., understanding social communication such as a lie, white lie, figure of speech, misunderstanding, double bluff, irony, persuasion, contrary emotions, forgetting, jealousy, intentions, empathy and social blunders. The participants' reaction time and number of prompt questions were also recorded. RESULTS: The participants in the AS group showed significantly more problems attributing mental state inferences relative to the control group. They performed considerably better on tasks involving a physical state, but still did less well than the controls. They had a tendency to interpret behaviour and utterances literally, without regard to context, and to choose a physical explanation when a mental state answer was more appropriate. They also needed significantly more prompt questions and used significantly more time than the controls to solve the tasks, especially those involving mental state inference. CONCLUSIONS: This study supports earlier findings that individuals with AS/HFA have difficulties attributing mental states in context, but seem to have significantly fewer difficulties inferring physical states. The fact that the clinical group also used significant longer reaction time and needed significantly more prompt questions to solve the tasks relative to the control group may also be related to their problems in understanding mental states. However, the possibility remains that these difficulties could represent a separate factor - or a distinct 'cognitive style'- suggesting that at least some individuals with AS may be generally slow in solving cognitive tasks.