Initial Studies Research Articles

Using depth sensors for a fall risk prediction system for socially vulnerable older adults with cognitive impairment

AbstractFalls and fall‐related injuries are significant public health issues for adults 65 years of age and older. Over a third of older adults (OA) fall each year and 10‐20% of falls result in serious injuries such as fractures and head trauma. Cognitive impairment is a leading risk factor for falls in OA. Over 60% of OA with MCI fall annually – two to three times the rate of those without cognitive impairment. OA living in low‐resource neighborhoods with poor housing conditions have twice the risk of falling. We have developed a technology‐based intervention called Sense4Safety that facilitates fall risk management and fall risk reduction for older adults (OA) with cognitive impairment living in low‐resource communities. Specifically, the intervention is designed to to 1) identify escalating risk for falls real‐time through in‐home passive sensor monitoring using depth sensors; 2) employ machine learning to inform individualized alerts for fall risk; and 3) link OA with a nurse tele‐coach who guides them in implementing evidence‐based individualized plans to reduce fall‐risk. The nurse coach is accessible via video‐conferencing or phone to discuss fall prevention and risk reduction strategies with the OA and their trusted other depending on the patterns identified in sensor‐detected changes in functional mobility and gait. The measurable primary outcomes include number of fall and near‐fall events, number of fall‐related hospitalizations, functional mobility, self‐reports of fear of falling and perceived independence. We have conducted an initial feasibility study of the intervention with 10 older adults in low income housing settings for a period of 3 months. The Sense4Safety intervention has the potential to become a feasible and cost‐effective approach to increase safety and quality of life for community dwelling low income OA with cognitive impairment and prevent or reduce falls. Currently, in most cases fall risk is addressed only after an adverse event has occurred or cognitive decline has progressed significantly. This intervention changes that paradigm to maximize safety and promote aging in place.

Subsequent welding of mild steel in the pipeline industry: mechanical, wear and microstructure characteristics

In this work, an attempt was made to join MS IS2062 using a combination of gas tungsten arc welding (GTAW) and shielded metal arc welding (SMAW) processes using various welding parameters to get the best weldability. An initial scanning electron microscope study was conducted to determine the microstructure of the sample. In addition to measuring and correlating microstructures and welding parameters, mechanical properties like tensile strength and microhardness are also measured. Here, friction force (FF) and specific wear rate (SWR) were carried out to analyse the tribological behaviour of the weld joint. It was found that the weld MS IS2062 by subsequent welding achieved 15% and 5% higher yield strength and 5% and 4% harder than SMAW and GTAW. Pull-off and cracks were found in the tensile fracture image, and changes in grain boundaries have been observed in the microstructural study. The contact pressure shows the greatest influence on roughness and FF; at the same time, velocity influences the SWR, as found in the experimental results. The subsequent welding process was performed with good stabilisation by balancing between the SMAW and GTAW welding, and to obtain superior properties, we must optimise our results and choose the best possible method.

Reliability of VPA Learning Over Repeat Exposures Across an Extended Interval Using Automated Remote Method

AbstractBackgroundThe current study examined the test‐retest reliability of a newly developed Learning Over Repeat Exposures (LORE) paradigm using Verbal Paired‐Associates. This LORE paradigm involves the acquisition of a set of 8 verbal paired associates over a 5‐day “burst”. In this investigation, two bursts, separated by a nine‐month interval, were compared to assess the stability of novel learning outcome measures, such as the learning slope (between day 1 and the day of max performance) and first overnight forgetting.MethodAn opportunistically recruited sample of 14 participants (out of an initial pilot study of N = 20) completed the VPA‐LORE task using the Cambridge Cognition ‘NeuroVocalix’ platform, which employs text‐to‐speech and automated speech recognition technology to remotely administer and score the task, enabling its potential use at scale. The task structure consists of an immediate recall following presentation on the first day of a burst, and a single recall attempt followed by a presentation on subsequent days. As with the pilot study, neither floor nor ceiling effects were observed, and performance was in the expected range.ResultThe observed moderate to strong correlations between the two bursts revealed good reliability for the measures examined: learning slope from day 1 to day of max score, r s = .815, first day immediate recall, r s = .736, max pairs learned, r s = .707, and day 1 forgetting r s = .702. In total, participants missed only a few visits, with six missing sessions out of a total of 140 sessions, representing 4.3% of all sessions. The retention of 14 participants from the original pilot study also highlights the feasibility and acceptability of this method.ConclusionThese results suggest that the VPA‐LORE paradigm, delivered via the NeuroVocalix platform, is a stable and reliable assessment tool even when considering extended intervals between bursts and accounting for missing data. The novel learning measures derived from the VPA‐LORE paradigm provide valuable insights into learning processes and could further enhance cognitive assessment. Future research could explore the applicability of the paradigm for clinical populations and longitudinal studies in cognitive assessment.

Using the axonal protein neurofilament light to distinguish psychiatric and neurodegenerative disorders across a program of clinical research studies

Introduction:There is an urgent need for clinical blood biomarkers which can rule in/out neurological disorders early in those with psychiatric symptoms, personality or behavioural changes and/or functional decline together with cognitive symptoms. The neuronal axonal protein neurofilament light (NfL) is released from damaged neuronal axons and can be measured in in blood and cerebrospinal fluid (CSF). We have undertaken a series of studies aimed at examining the clinical utility of blood and CSF NfL in assisting with the distinction between psychiatric and neurodegenerative / neurological disorders.Methods:Since 2016 we have measured blood and CSF NfL levels across multiple psychiatric and neurological populations recruited through Neuropsychiatry, Royal Melbourne Hospital and our collaborators (national and international). We have described our findings in a series of published studies. Data from our ongoing work, in larger cohorts and diagnostic groups, will be presented. The diagnostic groups include people with psychiatric disorders (schizophrenia, bipolar disorder, depression, functional neurological disorders), neurodegenerative disorders (Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, Niemann-Pick Type C) and neurological disorders (e.g., epilepsy).Results:Our initial pilot study (n=129) found that CSF NfL was a promising biomarker in differentiating psychiatric from neurological disorders. In our larger follow up larger study (n=498) which included more diagnostic groups CSF NfL levels exhibited high accuracy (91%), sensitivity (92%), and specificity (87%) in differentiating psychiatric from neurological disorders, and distinguished behavioural variant frontotemporal dementia from frontal lobe syndrome phenocopies/mimics, with high accuracy. We have found that NfL is not elevated in people with treatment resistant schizophrenia compared to controls and is elevated in people with Niemann-Pick Type C compared to people with psychiatric disorders and controls. Further (unpublished) data has shown that these findings are replicated with plasma NfL levels across 400 further psychiatric, neurological and control participants.Conclusions:NfL is a highly promising biomarker which differentiates psychiatric from neurological disorders with high sensitivity and specificity. The translation of NfL levels into standard clinical practice could substantially improve the clinical diagnostic process in people with complex neuropsychiatric and cognitive disorders.

A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells

A long-lived latent reservoir of HIV-1-infected CD4 Tcells persists with antiretroviral therapy and prevents cure. We report that the emergence of latently infected primary CD4 Tcells requires the activity of histone deacetylase enzymes HDAC1/2 and HDAC3. Data from targeted HDAC molecules, an HDAC3-directed PROTAC, and CRISPR-Cas9 knockout experiments converge on a model where either HDAC1/2 or HDAC3 targeting can prevent latency, whereas all three enzymes must be targeted to achieve latency reversal. Furthermore, HDACi treatment targets features of memory Tcells that are linked to proviral latency and persistence. Latency prevention is associated with increased H3K9ac at the proviral LTR promoter region and decreased H3K9me3, suggesting that this epigenetic switch is a key proviral silencing mechanism that depends on HDAC activity. These findings support further mechanistic work on latency initiation and eventual clinical studies of HDAC inhibitors to interfere with latency initiation.

Regional glymphatic abnormality in behavioral variant frontotemporal dementia

AbstractBackgroundThe pattern of glymphatic inflow overlaps with the geographic pattern of behavioral variant frontotemporal dementia (bvFTD). The glymphatic function has not yet been explored in bvFTD. The spatial correlation between regional glymphatic function and bvFTD remain unknown.MethodA total of 60 patients with bvFTD and 61 age‐ and sex‐matched healthy controls (HCs) were selected from two independent cohorts (discovery dataset from Xuanwu Hospital and replication dataset from the Frontotemporal Lobar Degeneration Neuroimaging Initiative study). All participant underwent neuropsychological assessment. Glymphatic measures evaluated from multimodal neuroimaging data, including choroid plexus volume, diffusion along perivascular space (DTI‐ALPS) index, and coupling between blood‐oxygen‐level‐dependent signals and cerebrospinal fluid signals (BOLD‐CSF coupling), were compared between the two groups. To evaluate glymphatic regional function, DTI‐ALPS and BOLD‐CSF coupling were further divided into anterior, middle, and posterior parts. BvFTD‐related metabolic pattern was identified using spatial covariance analysis based on [l8F]‐FDG‐PET.ResultPatients with bvFTD showed higher choroid plexus volume (P < 0.001); middle DTI‐ALPS (P < 0.001); and weaker anterior BOLD‐CSF coupling (P < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI‐ALPS was negatively associated with the expression of the bvFTD‐related metabolic pattern (r = ‐0.51, P = 0.029) and positively related with regional standardized uptake value ratios of [l8F]‐FDG‐PET in bvFTD‐related brain regions (r = 0.44–0.60, P range: 0.008–0.039). Worse glymphatic function is associated with more severe global cognition decline, disease severity, and neuropsychiatric symptoms. In addition, anterior DTI‐ALPS was higher than posterior DTI‐ALPS (P < 0.001), whereas anterior BOLD‐CSF coupling was lower than posterior BOLD‐CSF coupling (P < 0.001).ConclusionOur findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD.

Surgery for Obstructive Azoospermia

Microsurgical technique in male infertility has progressed significantly since the introduction of intracytoplasmic sperm infection (ICSI) 30 years ago. The searching of sperm available for ICSI becomes the main tasks for reproductive andrologists. At the initial study for patients with azoospermia, it is crucial to differentiate obstructive causes from non-obstructive categories. Testis biopsy is still a gold standard testing method to confirm obstructive azoospermia (OA). For patients with OA, the choice spectrum of treatment is broad. Basically, sperm can be retrieved from anywhere upstream the blocking spot along the male reproductive tract. However, it is not always that infertile couples consider ICSI as their treatment of choice. The choice of treatment should be prioritized according to patients’ concerns. The concerns include age of female partner, the patency of oviducts, the presence of infection in the seminal plasma, DNA fragmentation index of sperm, failure of prior use of downstream sperm for in vitro fertilization (IVF) or ICSI, religious limitation, economical affordability, number of babies expected and techniques available from the surgeons. For techniques view, the surgeons should be equipped with capabilities of techniques for sperm retrieval from the testis (testicular sperm extraction, abbreviated TESE) and epididymis (percutaneous epididymal sperm extraction abb. PESA; or microscopic epididymal sperm aspiration abb. MESA). Besides, techniques of microsurgical anastomosis of vas (vasectomy reversal or vaso-vasostomy) and epididymal tubule (vaso-epididymostomy) after scrotal exploration are also required. Other special conditions of obstructive azoospermia are also included, such as congenital absence of vas deferens (CBAVD) or causes for dry ejaculation (including diabetes neuropathy, or post retroperitoneal surgery), or obstruction of ejaculatory ducts. Herein, I would like to share the experiences on treatment of various types of obstructive azoospermia, via scrotal exploration and the techniques of epididymovasostomy. Besides, different techniques of sperm retrieval like MESA and TESE are also demonstrated.

Subtle cognitive difficulties increase risk of neurodegeneration, incident mild cognitive impairment, and dementia in older women.

AbstractBackgroundIdentifying individuals with preclinical Alzheimer’s disease and related disorders (ADRD) is important for prevention and eventual treatment. Here we aimed to integrate overall test performance with episodic memory process scores in a cohort of older women to identify those with subtle cognitive difficulties (SCD; e.g., individuals with the earliest declines in cognitive ability preceding a diagnosis of mild cognitive impairment (MCI) or dementia) and determine subsequent risk of MCI, dementia, and neuroimaging indices of neurodegeneration.MethodParticipants included 2,186 community‐dwelling older women without MCI or dementia (Mage = 73.4±3.8 years) who completed a comprehensive neuropsychological assessment as part of the Women’s Health Initiative Study of Cognitive Aging (WHISCA: 1999‐2000). Women were assessed annually for MCI and dementia until 2021, and 1,024 women underwent structural magnetic resonance imaging (sMRI) of the brain in 2005‐6. Women were classified as cognitively normal (CN), early SCD (e‐SCD; two episodic memory process scores 1 SD below normative means or one process score and one performance score 1 SD below normative means), or late SCD (l‐SCD; two overall performance scores 1 SD below normative means) at WHISCA baseline using validated criteria from the Alzheimer’s Disease Neuroimaging Cohort (Thomas et al., 2018 Journal of Alzheimer’s Disease). We used Cox proportional hazards to examine associations between SCD status and risk of developing MCI/dementia. Linear regressions were used to examine associations between SCD status and MRI indices of AD‐related neurodegeneration, global cerebrovascular damage, and brain volumes of structures that make up the medial temporal lobe. All associations were adjusted for sociodemographic, lifestyle, and clinical characteristics.ResultWomen with e‐SCD and l‐SCD were 1.58 (p<0.001) and 3.01 (p<0.001) times as likely to develop MCI/dementia compared to CN women, respectively (Figure 1). Women with l‐SCD (β = 0.20; p<0.001) had more AD‐related neurodegeneration compared to CN women (Table 1). Women with e‐SCD had marginally significantly greater AD‐related neurodegeneration (β = 0.14; p = 0.073) and had smaller volumes in the entorhinal cortex (β = ‐0.22; p = 0.009) compared to CN women.ConclusionOur study demonstrates the usefulness of the SCD criteria for the early identification of cognitively normal women who are at increased risk of MCI, dementia, and neurodegeneration.

Vegetative response of shallot (Allium cepa Aggregatum group) bulbs on vernalization and gibberellin treatment in different environments

This research is an initial study of the effects of vernalization and Gibberellins in two different environments. The research was conducted in a split-split plot design with three factors and three times repetition. The main plot was the environment (environment 1, environment 2), the split plot was vernalization temperature (3±2 and 9±2°C), and split-split plot was Gibberellin concentration (0, 50, 100, 150 ppm). The result showed that the vernalizations and Gibberellin have significantly affected plant height (p<0.01). The environment significantly affected plant height, number of tillers, and number of leaves. There was an interaction between Gibberellin and environment treatment on plant height and an interaction between vernalization, Gibberellin, and environment on the number of leaves. The environment with temperature: 29±2.18°C, RH: 45±9.14%, light intensity: 9272±7669 μmol m-2 S-1 showed plant height and the number of tillers higher than other environments, contrary to the number of leaves. According to the principal component analysis, this environment is more suitable for all vernalization and Gibberellin treatments than other environments. The results of this study indicate that the environment more influences vegetative growth than the other two treatments.

Co‐designing a research study with people affected by dementia: the conceptualisation and development of the ActivDem study

AbstractBackgroundMaintaining physical activity(PA) following dementia diagnosis may decelerate decline to disability and dependency. It is unclear which socio‐ecological factors influence PA participation in people with dementia(PwD) and therefore may be effective interventional components for promotion of PA. To address this research gap, the ActivDem study was designed(see Table 1 for initial research aims). To ensure ActivDem met the needs of PwD, we aimed to co‐design the research aims, methodology and grant application with public patient involvement contributors.MethodA call for contributors (i.e. people with cognitive impairment/dementia carers, current and former/dementia care professionals) was advertised via dementia research networks, dementia care facilities (e.g. daycares, memory cafés), charities (e.g. Alzheimer’s Society Research Network Volunteers) and social media. Interested contributors were invited to participate in either participatory workshops held on Zoom or a one‐to‐one phone call. Contributors were asked four broad questions(Table 2). Initial study aims and methods were discussed with contributors. Aims and methods were refined based on contributors’ feedback and themes raised during the discussion. Ten contributors reviewed the grant application to ensure aims, methodology and public patient involvement/engagement plans met the priorities of people affected by dementia.ResultThirty contributors participated in workshops/phonecalls. Contributors described experiences of PA decline in PwD post‐diagnosis; common themes expressed included loss of independence and confidence, increased feeling of burden, greater fall risk, frailty, and worse mental health. They identified potential facilitators/barriers for maintaining PA following dementia diagnosis(Table 2). They highlighted the role carers play in facilitating PA by supporting and motivating PwD to stay active and advocated for inclusion of carer‐focused investigations. Contributors felt that PA research for PwD should be prioritised and findings linked in to information/support services for carers. The study’s aims and methods were adapted to include an exploration of carers’ psychosocial wellbeing and care management strategies(Table 1). Scales relating to proposed facilitators/barriers of PA were identified, approved by contributors and implemented in the methods.ConclusionThis work supported the conceptualisation and development of the ActivDem study. Ten contributors formed the ActivDem Public Patient Advisory Group, advising and supporting study management, data collection and interpretation, and dissemination of results.

Physiological and behavioral characteristics of SuperAgers from everyday activities: An NIH U19 SuperAging Research Initiative study protocol

AbstractBackgroundStudying factors contributing to exceptional memory performances beyond the 8th decade, can be a valuable model for understanding dementia risk, prevention, and underlying mechanisms. Age‐associated changes in biological and physiological complexity, or system responsivity, form the foundation of the loss of complexity hypothesis in aging (Lipsitz &amp; Goldberger, JAMA, 1992). Project 1 under the multisite NIH U19 SuperAging Research Initiative uses state‐of‐the‐art wearable technology, and data from real‐world contexts, to test the supposition that SuperAgers have preserved physiologic and behavioral complexity relative to their Controls in the domains of physical activity, autonomic responsiveness, sleep, and social engagement.MethodSuperAgers are enrolling from five U.S. and Canadian sites of the SuperAging Research Initiative. SuperAgers refer to individuals aged 80 and older who have memory capacity considered average for those 2‐3 decades younger. In a fully remote data collection protocol, participants wear a multi‐sensor array comprised of 1 skin‐mounted trunk sensor (with ECG) and 2 wearable limb sensors, continuously over a 14‐day period with scheduled rest breaks every 3‐4 days. Participants complete a baseline orientation visit, and three brief check‐in visits with the study team over video conference. Using custom algorithms, developed by our research team, we will examine time‐varying changes in indices of physiologic and behavioral complexity, across multiple body systems, using both volume‐based and established multi‐scale entropy approaches to quantify differences between SuperAgers and their typically aging Controls. We plan to analyze sensor derived complexity metrics in relation to self‐reports of life‐space mobility.ResultWe will overview our remote data collection protocol and semi‐automated analytics pipeline. Barriers and facilitators to remote data collection will be discussed Preliminary data (N = ∼ 40) will be presented, with select case study examples. We will provide preliminary sensor adherence and user‐feedback from the cohort, comprised of a diverse sample of SuperAgers and Controls.ConclusionThis is the first study to test the loss of complexity hypothesis across multiple physiological and behavioral domains simultaneously and in exceptional cognitive aging. Using sensitive tools to capture dynamic and complex behaviors, we will characterize SuperAgers in a way not afforded by point‐in‐time assessments that dominate the current literature.

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer.

The association between cigarette smoking and the increased risk of many cancers is well established. Conversely, epidemiological studies of smokeless tobacco demonstrate decreased risk, or no elevated risk, of certain cancers versus smoking. However, it is unclear what role, if any, nicotine plays in these associations. The objective of this systematic review was to synthesize the available evidence from preclinical studies that examined the potential association between nicotine and the initiation and/or progression of cancer. MEDLINE, Embase, PsychInfo, and Cochrane Database of Systematic Reviews were searched for articles published from inception until February 13, 2022. Studies were eligible for inclusion if they evaluated animal cancer or tumor models, compared nicotine and non-nicotine groups, and evaluated measures of cancer initiation or progression. Among 1,137 identified articles, 61 were included in qualitative synthesis. Twelve studies reported data on tumor initiation, and 54 studies reported data on tumor progression. The majority of the tumor initiation studies did not identify an association between nicotine exposure and an increased risk of spontaneous tumor initiation. Results of tumor progression studies were inconsistent and varied across the reported measures, cancer type being evaluated, and animal cancer model used. Overall, the quality of reporting was poor, with many studies not demonstrating a high level of internal and/or external validity. In conclusion, although animal models have provided invaluable data for human health risk assessments of chemical exposures, the heterogeneity across the studies included in this systematic review make the interpretation and generalizability of the results difficult.

Covid-19 infection and arterial hypertension: the relationship between the two entities

Background: The aim of the study was to breakdown the relationship and its nature between the two pathological entities arterial hypertension (AHT) and SARS-CoV-2 infection. The analysis of existing literature on both topics has been conducted. Sources including journals, books, existing publications and online platforms like Google Academic, PubMed, HINARI were used as search engines. Additionally, guidelines and circulars from European Society of Cardiology, American Heart Association and other respective bodies were also referred to. Data from large meta-analyses and clinical studies were included to bring out the relationship study. Pathophysiological breakdown of the two entities, contradicting proposals regarding treatment, new treatment modalities and de novo onset of AHT in post-Covid infection were included to delineate the relationship between the two pathological entities. Conclusions: Findings emphasize that the role of arterial hypertension in SARS-CoV-2 infection is mediated through its effect on the regulation of Renin Angiotensin Aldosteron System (RAAS), inflammation and immune responses. De-novo arterial hypertension was also reported in post SARS-CoV-2 infection patients. Though some initial studies hypothesized that RAAS inhibitors may add to clinical adversities, most studies afterward disproved the same and in fact revealed a protective role of the same. Angiotensin Converting Enzyme 2 (ACE2) is proposed as a treatment option in SARS-CoV-2 infection.

OP142 Progression Analysis Versus Traditional Methods To Quantify Slowing Of Disease Progression In Alzheimer’s Disease

IntroductionNew statistical methodology, known as progression models for repeated measures (PMRM), can estimate the slowing of progression (percentage slowing or time delay) of Alzheimer’s disease from trial data on disease-modifying therapies. We compared the PMRM methodology with mixed models for repeated measures (MMRM) and Cox time-to-event analysis on simulated trial data with respect to their power and interpretability of estimates.MethodsTwo novel models were included: PMRM (estimating slowing of progression and allowing different rates across visits) and proportional-slowing PMRM. Clinical Dementia Rating (CDR) Sum of Boxes score and progression to dementia as assessed by CDR global score were the primary outcomes for MMRM/PMRM and the Cox model, respectively. Subject-level placebo arm trajectories were jointly simulated based on estimated CDR mean trajectories and joint temporal correlation structure of 538 amyloid-positive patients with mild cognitive impairment who met typical disease-modifying trial inclusion criteria from the Alzheimer’s Disease Neuroimaging Initiative study. Active arm trajectories were simulated to show an average 20 percent slowing of disease progression, compared with placebo, at each visit. We conducted 1,000 simulations across multiple scenarios, varying the number of patients per arm (200 to 700) and clinical trial duration (18 to 36 months).ResultsThe power of PMRM models was greater than that of MMRM, and much greater than that of the Cox model whose power never exceeded 45 percent. PMRM models accurately estimated the underlying treatment effect (median 20% slowed progression, which translated to a delay in progression of 5 and 7 months at trial durations of 24 and 36 months, respectively), unlike quantifications of the MMRM (median estimated 25% reduction in decline), and the Cox model (median estimated hazard ratio of 0.9).ConclusionsFor disease-modifying therapies, PMRM estimates may have a more intuitive clinical interpretation in terms of delayed progression than MMRM or Cox models and enable a description of the amount of time spent in less severe disease stages. Among all the methods studied, PMRM offered the best combination of interpretability and power.

OP112 Evaluation Of A Self-Administered Smart Phone-Based Application As A Wellness Measure In A Clinical Trial Of Zanubrutinib

IntroductionAssessments self-administered via smart phone-based apps can gather patient wellness data; however, data regarding app utilization in clinical trials are limited. This study evaluated engagement with a self-administered wellness app as a supplemental tool to assess quality-of-life (QoL) in study BGB-3111-215 (NCT04116437), which included patients with B-cell malignancies treated daily with oral zanubrutinib.MethodsThis exploratory analysis evaluated the feasibility of using a voluntary device-based, self-administered activity and QoL questionnaire app (Medable, California, USA) in clinical trial patients. Feasibility was measured by rates of consent, utilization, and compliance. Consent was assessed by the percentage of patients who agreed to use the app. Utilization was assessed by the percentage of patients who engaged with the app. Compliance was assessed by actual versus scheduled engagements. The app also included passive activity tracking and a six-minute walk test.ResultsAs of 1 September 2022, 78 patients had enrolled in the study (median age 71 years) and 20 had consented to participate (26% consent rate). Eleven patients (median age 65 years) engaged with the app at least once (14% utilization rate; n=11 for the questionnaire; n=7 for the walk test). Engagement occurred a median two times (range 1 to 17) for the questionnaire and a median seven times (range 1 to 15) for the walk test. Four patients engaged with the questionnaire and six patients engaged in the walk test beyond week 12. Passive activity was collected for eight patients beyond week 12. Among patients who engaged with the QoL questionnaire and walk test, compliance rates were 18 and 21 percent, respectively.ConclusionsThis initial study showed that a subset of patients was willing to participate in the self-administered QoL questionnaire and activity tracker. Further comparison of app results and clinical trial findings are ongoing to explore factors affecting utilization and compliance rates.

Development and characterization of apple pomace and finger millet-based pasta enriched with encapsulated micronutrient

This research work focused on the incorporation of spray dried encapsulated ascorbic acid and iron gluconate powder in modified pasta. The production of the spray dried powder was composed of maltodextrin (MD 2.2–2.8 %), hydroxypropyl methylcellulose (HPMC 0.2–0.8 %) as wall materials in varying percentages, and core material consisting of iron gluconate IG (1.5 %). Among the different formulations, IGP1 yielded better iron content (44.2 ± 0.35 mg/g), hygroscopicity (21.64 ± 0.18 %), and a fewer amount of surface iron content (1.59 ± 0.22 %). IGP1 was selected for the further addition of the ascorbic acid in a ratio of AA: Fe (6:1) by weight percentage followed by the spray drying with the same parameters. The encapsulated spray dried ascorbic acid iron gluconate powder (AAIGP) was produced and incorporated in the apple pomace finger millet-based pasta at 0.25, 0.50, and 0.75 %. The pasta was selected based on the initial study conducted for the preparation of the most suitable pasta formulation (P1) that includes finger millet (10 %), apple pomace powder (4 %), HPMC (2 %), and durum semolina (84 %). The P1 fortified with AAIGP at 0.5 % addition level retained the iron content (23.74 ± 0.08 mg/100 g) and ascorbic acid content (87.51±0.11 mg/100 g) after cooking loss as suggested by the recommended dietary allowances (RDA), especially for the adolescent age-group.

Associations between normal cognitive aging and neurodegeneration

AbstractBackgroundMultiple cognitive domains, including learning, memory and psychomotor speed, show significant reductions with age. These changes are thought to reflect normal cognitive aging. However, since cerebrospinal fluid (CSF) neurodegenerative biomarkers, such as total‐tau (t‐tau) and Neurofilament light chain (NfL), also show age‐related increases in normal aging, we aimed to investigate whether age‐associated cognitive decline may be mediated by age‐associated neurodegenerative changes.MethodWe included 114 cognitively healthy participants aged 40‐80 years from The Norwegian Dementia Disease Initiation Study. All had normal concentrations of CSF Aβ42/40 ratio. Cognitively healthy was defined as demographically adjusted T‐scores ≥35 on standardized cognitive tests. We fitted mediation models using structural equation modelling (SEM), with either CSF NfL or t‐tau as a mediator between age and CERAD learning, CERAD recall, TMT‐A and TMT‐B. All variables were standardized prior to analyses; in addition, both t‐tau and NfL were log transformed due to skewness.ResultsSee table 1 for demographic and clinical characteristics. Whilst neither NfL nor t‐tau showed statistically significant mediation of age‐related cognitive decline, our results nevertheless suggest a partial mediation of NfL on age‐related cognitive decline. Here, relationships between age and CERAD learning, CERAD Recall, and TMT‐A performance were weakened whereas higher NfL was associated with worse performance, in particular for delayed memory recall. This was not observed for t‐tau in any models. See figure 1‐2.ConclusionAge‐related decline in verbal learning, memory and psychomotor speed may be partially attributable to NfL‐associated neurodegenerative changes in cognitively healthy adults. As NfL reflects axonal degeneration, these results may reflect white matter neurodegeneration in aging.

Adsorbent effectiveness of α-cellulose/humatic acid with epichlorohydrin cross-linking agent on methyl orange dye

Adsorption of methyl orange (MO) using epichlorohydrin cross-linked humic acid/cellulose composite has been carried out. This study aims to synthesize epichlorohydrin cross-linked humic acid/cellulose composites, determine the optimum pH, contact time, and initial concentration and study MO desorption. The adsorbent production begins with the isolation of cellulose from empty palm oil bunches (EFB) obtained from North Sumatra and the isolation of humic acid from peat soil obtained from Rawa Pening. Then humic acid was cross-linked to cellulose in an alkaline solution (NaOH), then epichlorohydrin was added as a cross-linking agent while heating at 600C for 2 hours. Epichlorohydrin cross-linked humic acid/cellulose adsorbents (AH/Cell-ECH) were further characterized using FTIR, XRD and SEM spectroscopy. MO solutions before and after adsorption were analyzed using UV-Vis spectrophotometry. MO desorption studies used HCl pH 4, 0.1 and 1.0 M NaCl and 40% and 60% ethanol. FTIR characterization showed that the AH/Sel-ECH adsorbents had active groups, including –OH, -C=O, and –COOH. Characterization using XRD showed diffraction peaks in the 2θ region around 11.41, 20.25, 22.55, and 42.66o, indicating the presence of galactose, xylose, glucose and polysaccharide phases. The SEM-EDX results showed that the surface of the adsorbent had non-uniform pore sizes, and the surface morphology tended to be clean and free of debris. It indicated the presence of C, O, and N elements in AH/ECH-cells and S, N elements after MO adsorption. The optimum interaction of AH/Sel-ECH with MO occurred at pH 2 with 150 mg/L MO, and a contact time of 120 minutes was obtained. MO adsorption by AH/ECH-cells followed a pseudo-second-order kinetics model and the Freundlich isotherm with an MO adsorption capacity of 9.84 x 10-5 mmol/g, respectively. Desorption studies showed that 60% ethanol was the most effective solution for desorption of MO.

Development of STEM-Integrated Static Fluid E-Modules to Improve Students' Creative Thinking and Science Process Skills

The 21st century learninghould apply the skills of grade 21 students which include the 4C skills, namely creative thinking, critical thinking, communication, and collaboration. This skill is needed in solving a problem. The learning outcomes show the low ability of students to think creatively and scientifically. The STEM integrated e-module is the solution to this problem. The purpose of this study was to determine the initial studies, the validity and practicality of using STEM integrated e-modules. This research method uses research and development research using the Hannafin and Peck development model. Research instruments include needs analysis instruments, validation questionnaires and practicality. The data analysis technique used is descriptive statistics. Based on the data that has been analyzed there are three research results. First, the results of the needs analysis obtained an average value of 69.4 in the good category. Second, product validation results obtained an average value of 84.1 with a very good category. Third, the product practicality results obtained an average value of 93 in the very good category. The implication of the results of this study is that teachers must construct students' skills through e-modules. The meaning of the results of this study is that the STEM integrated e-module is valid and practical for use in learning.

Flexural rigidity of pressurized model notochords in regular packing patterns

The biomechanics of embryonic notochords are studied using an elastic membrane model. An initial study varying internal pressure and stiffness ratio determines tension and geometric ratios as a function of internal pressure, membrane stiffness ratio, and cell packing pattern. A subsequent three-point bending study determines flexural rigidity as a function of internal pressure, configuration, and orientation. Flexural rigidity is found to be independent of membrane stiffness ratio. Controlling for number and volume of cells and their internal pressure, the eccentric staircase pattern of cell packing has more than double the flexural rigidity of the radially symmetric bamboo pattern. Moreover, the eccentric staircase pattern is found to be more than twice as stiff in lateral bending than in dorsoventral bending. This suggests a mechanical advantage to the eccentric WT staircase pattern of the embryonic notochord, over patterns with round cross-section.