Molecular MR Imaging of Renal Fibrogenesis in Mice.

BACKGROUND: In most CKDs, lysyl oxidase oxidation of collagen forms allysine side chains, which then form stable crosslinks. We hypothesized that MRI with the allysine-targeted probe Gd-oxyamine (OA) could be used to measure this process and noninvasively detect renal fibrosis. METHODS: Two mouse models were used: hereditary nephritis in Col4a3-deficient mice (Alport model) and a glomerulonephritis model, nephrotoxic nephritis (NTN). MRI measured the difference in kidney relaxation rate, ΔR1, after intravenous Gd-OA administration. Renal tissue was collected for biochemical and histological analysis. RESULTS: ΔR1 was increased in the renal cortex of NTN mice and in both the cortex and the medulla of Alport mice. Ex vivo tissue analyses showed increased collagen and Gd-OA levels in fibrotic renal tissues and a high correlation between tissue collagen and ΔR1. CONCLUSIONS: Magnetic resonance imaging using Gd-OA is potentially a valuable tool for detecting and staging renal fibrogenesis.

Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques.

HIV-infected infants are at an increased risk of progressing rapidly to AIDS in the first weeks of life. Here, we evaluated immunological and virological parameters in 25 SIV-infected infant rhesus macaques to understand the factors influencing a rapid disease outcome. Infant macaques were infected with SIVmac251 and monitored for 10 to 17 weeks post-infection. SIV-infected infants were divided into either typical (TypP) or rapid (RP) progressor groups based on levels of plasma anti-SIV antibody and viral load, with RP infants having low SIV-specific antibodies and high viral loads. Following SIV infection, 11 out of 25 infant macaques exhibited an RP phenotype. Interestingly, TypP had lower levels of total CD4 T cells, similar reductions in CD4/CD8 ratios and elevated activation of CD8 T cells, as measured by the levels of HLA-DR, compared to RP. Differences between the two groups were identified in other immune cell populations, including a failure to expand activated memory (CD21-CD27+) B cells in peripheral blood in RP infant macaques, as well as reduced levels of germinal center (GC) B cells and T follicular helper (Tfh) cells in spleens (4- and 10-weeks post-SIV). Reduced B cell proliferation in splenic germinal GCs was associated with increased SIV+ cell density and follicular type 1 interferon (IFN)-induced immune activation. Further analyses determined that at 2-weeks post SIV infection TypP infants exhibited elevated levels of the GC-inducing chemokine CXCL13 in plasma, as well as significantly lower levels of viral envelope diversity compared to RP infants. Our findings provide evidence that early viral and immunologic events following SIV infection contributes to impairment of B cells, Tfh cells and germinal center formation, ultimately impeding the development of SIV-specific antibody responses in rapidly progressing infant macaques.

Clinical and Analytic Accuracy of Simultaneously Acquired Hemoglobin Measurements: A Multi-Institution Cohort Study to Minimize Redundant Laboratory Usage.

OBJECTIVES: Frequent diagnostic blood sampling contributes to anemia among critically ill children. Reducing duplicative hemoglobin testing while maintaining clinical accuracy can improve patient care efficacy. The objective of this study was to determine the analytical and clinical accuracy of simultaneously acquired hemoglobin measurements with different methods. DESIGN: Retrospective cohort study. SETTING: Two U.S. children's hospitals. PATIENTS: Children (< 18 yr old) admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified hemoglobin results from complete blood count (CBC) panels paired with blood gas (BG) panels and point-of-care (POC) devices. We estimated analytic accuracy by comparing hemoglobin distributions, correlation coefficients, and Bland-Altman bias. We measured clinical accuracy with error grid analysis and defined mismatch zones as low, medium, or high risk-based on deviance from unity and risk of therapeutic error. We calculated pairwise agreement to a binary decision to transfuse based on a hemoglobin value. Our cohort includes 49,004 ICU admissions from 29,926 patients, resulting in 85,757 CBC-BG hemoglobin pairs. BG hemoglobin was significantly higher (mean bias, 0.43-0.58 g/dL) than CBC hemoglobin with similar Pearson correlation ( R2 ) (0.90-0.91). POC hemoglobin was also significantly higher, but of lower magnitude (mean bias, 0.14 g/dL). Error grid analysis revealed only 78 (< 0.1%) CBC-BG hemoglobin pairs in the high-risk zone. For CBC-BG hemoglobin pairs, at a BG hemoglobin cutoff of greater than 8.0 g/dL, the "number needed to miss" a CBC hemoglobin less than 7 g/dL was 275 and 474 at each institution, respectively. CONCLUSIONS: In this pragmatic two-institution cohort of greater than 29,000 patients, we show similar clinical and analytic accuracy of CBC and BG hemoglobin. Although BG hemoglobin values are higher than CBC hemoglobin values, the small magnitude is unlikely to be clinically significant. Application of these findings may reduce duplicative testing and decrease anemia among critically ill children.

Engineered RecA Constructs Reveal the Minimal SOS Activation Complex.

The SOS response is a bacterial DNA damage response pathway that has been heavily implicated in bacteria's ability to evolve resistance to antibiotics. Activation of the SOS response is dependent on the interaction between two bacterial proteins, RecA and LexA. RecA acts as a DNA damage sensor by forming lengthy oligomeric filaments (RecA*) along single-stranded DNA (ssDNA) in an ATP-dependent manner. RecA* can then bind to LexA, the repressor of SOS response genes, triggering LexA degradation and leading to induction of the SOS response. Formation of the RecA*-LexA complex therefore serves as the key "SOS activation signal." Given the challenges associated with studying a complex involving multiple macromolecular interactions, the essential constituents of RecA* that allow LexA cleavage are not well defined. Here, we leverage head-to-tail linked and end-capped RecA constructs as tools to define the minimal RecA* filament that can engage LexA. In contrast to previously postulated models, we found that as few as three linked RecA units are capable of ssDNA binding, LexA binding, and LexA cleavage. We further demonstrate that RecA oligomerization alone is insufficient for LexA cleavage, with an obligate requirement for ATP and ssDNA binding to form a competent SOS activation signal with the linked constructs. Our minimal system for RecA* highlights the limitations of prior models for the SOS activation signal and offers a novel tool that can inform efforts to slow acquired antibiotic resistance by targeting the SOS response.

Discovering antiviral restriction factors and pathways using genetic screens.

Viral infections activate the powerful interferon (IFN) response that induces the expression of several hundred IFN stimulated genes (ISGs). The principal role of this extensive response is to create an unfavourable environment for virus replication and to limit spread; however, untangling the biological consequences of this large response is complicated. In addition to a seemingly high degree of redundancy, several ISGs are usually required in combination to limit infection as individual ISGs often have low to moderate antiviral activity. Furthermore, what ISG or combination of ISGs are antiviral for a given virus is usually not known. For these reasons, and since the function(s) of many ISGs remains unexplored, genome-wide approaches are well placed to investigate what aspects of this response result in an appropriate, virus-specific phenotype. This review discusses the advances screening approaches have provided for the study of host defence mechanisms, including clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9), ISG expression libraries and RNA interference (RNAi) technologies.

"It was just for us": qualitative evaluation of an exercise intervention for African-American couples.

BACKGROUND: Promoting long-term exercise adherence should be a key focus for health and fitness professionals working to reduce obesity and cardiometabolic health disparities, and all-cause mortality in inactive African-American (AA) adults. Data have suggested that romantic partners can improve long-term exercise adherence and that this dyadic approach should be examined in exercise interventions. Therefore, the purpose of this study was to conduct a qualitative evaluation of a pilot exercise intervention conducted in older AA couples. METHODS: Two semi-structured focus groups were utilized to compare participants' perceptions of and experiences during the pilot intervention across two randomly assigned treatment conditions (exercising together with partner [ET; n = 8] versus exercising separately [ES: n = 6]). Participants (mean age: 64.7 ± 6.8 years) of a previous 12-week pilot exercise intervention (walking ≥3 days/week, 30 min/day plus supervised resistance training 2 days/week) were interviewed. Verbatim transcripts were coded using an open coding approach. RESULTS: Three key themes (intervention value/benefits, intervention difficulties, and suggested improvements) emerged. Although all couples identified health and relationship benefits of the intervention, some differences surfaced within themes across the two intervention groups. CONCLUSIONS: Overall, these qualitative data suggest that couples had a positive experience while participating in the pilot study. In addition, key learning points to improve the intervention were identified including a more gradual transition to independent exercise, more flexibility training, and the incorporation of tangential education. These data will help investigators continue to develop the intervention, which is ultimately designed to promote long-term exercise adherence to reduce cardiometabolic health disparities in the AA community.

Transient Immune Activation in BCG-Vaccinated Infant Rhesus Macaques Is Not Sufficient to Influence Oral Simian Immunodeficiency Virus Infection.

BCG vaccination has been demonstrated to increase levels of activated CD4+ T cells, thus potentially influencing mother-to-child transmission of human immunodeficiency virus (HIV). To assess the risk of BCG vaccination in HIV infection, we randomly assigned newborn rhesus macaques to receive BCG vaccine or remain unvaccinated and then undergo oral simian immunodeficiency virus (SIV) challenges 3 weeks later. We observed elevated levels of activated peripheral CD4+ T cells (ie, HLA-DR+CD38+CCR5+ CD4+ T cells) by week 3 after vaccination. BCG was also associated with an altered immune gene expression profile, as well as with monocyte activation in both peripheral blood and the draining axillary lymph node, indicating significant BCG vaccine-induced immune activation. Despite these effects, BCG vaccination did not increase the rate of SIV oral transmission or disease progression. Our findings therefore identify patterns of T-cell and monocyte activation that occur after BCG vaccination but do not support the hypothesis that BCG vaccination is a risk factor for postnatal HIV transmission or increased pathogenesis in infants.

Do behavior and emotions improve after pediatric epilepsy surgery? A systematic review.

OBJECTIVE: The objective was to systematically review studies that have focused on behavioral and emotional functioning before (baseline) and after (follow-up) pediatric epilepsy surgery. METHODS: The systematic review was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched from inception. Findings are described with respect to (1) changes in behavior and emotions between baseline and follow-up, (2) factors associated with changes in behavior and emotions, and (3) impact of study quality on findings. RESULTS: Fifteen studies met inclusion criteria. The majority of studies employed parent report screening checklists. In these studies, scores were reported to have significantly improved at follow-up on at least one domain in seven studies and not to have changed significantly in two studies. In no studies was a deterioration in behavior noted. In studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical diagnoses, no significant change was noted in the numbers of children diagnosed at baseline and at follow-up. In total, 21 children lost diagnoses, whereas 16 children developed new diagnoses. A better seizure outcome was associated with improvements in behavioral-emotional functioning at follow-up in three of the four studies where it was considered. In terms of study quality, none of the studies was rated as strong (ie, had no weak ratings on a quality assessment tool). SIGNIFICANCE: There is some evidence of improvement in emotional and behavioral functioning after epilepsy surgery. However, this is confined to scores on parent-reported screening measures of emotional and behavioral symptoms and not clinical diagnoses. Future research should focus on including responses from multiple respondents (child, parent, teacher) when using screening instruments, but also diagnostic interviews. There is a need for long-term follow-up (beyond 2 years) with sufficiently large sample sizes including data from nonsurgery controls to understand factors associated with changes in functioning postsurgery.

Experiences and needs of parents of young children with active epilepsy: A population-based study.

The aim of the study was to gain a comprehensive understanding of the experiences and needs of parents of young children with epilepsy from a total population sample. The parents (mothers (n = 38), fathers (n = 9)) of 40/53 (75% of total population) young children (1-7 years; 23 males, 17 females) with 'active' epilepsy (had a seizure in the last year or taking Anti-epileptic drugs (AEDs)) were interviewed either in person or over the telephone using a semistructured interview schedule. The families were resident in the south of the UK. The interviews were audio-recorded, transcribed, and coded using thematic analysis. Thematic analysis revealed six main themes: diagnostic journey, parental perception of epilepsy management, awareness and impact of associated neurobehavioral difficulties, inconsistent availability of therapeutic and educational supports, impact on family functioning, and need for parental support. Parents reported often having difficulty accessing a professional knowledgeable about epilepsy. While parents were generally satisfied with the initial information they received about seizures and their management, they reported that the association between epilepsy and neurobehavioral issues was often not broached. These developmental/behavioral difficulties often had a bigger impact on child wellbeing and family functioning, but provision of therapeutic and educational supports for the difficulties was often very patchy. Parents noted that early onset epilepsy and associated neurobehavioral difficulties often have a very significant impact on family functioning including increased restrictions on family activities and increased financial burden. Parents would like informational and emotional support to extend beyond the time of epilepsy diagnosis. There is a clear need for comprehensive childhood epilepsy services to include provision for identification and management of child neurobehavioral needs and a focus on family-centered care.

Global development and adaptive behaviour in children with early-onset epilepsy: a population-based case-control study.

AIM: There are limited population-based data on global development and adaptive behaviour in children with early-onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early-onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties. METHOD: The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community-based study involving children (1-7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally-matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices. RESULTS: Forty-eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy-one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non-white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without. INTERPRETATION: Children with early-onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions. WHAT THIS PAPER ADDS: Children with early-onset epilepsy are at significant risk of intellectual disability. Developmental impairment is associated with use of polytherapy but not with any seizure parameters. Developmental profiles in young children with epilepsy differ from other conditions.

Knowledge of and attitudes towards epilepsy among teachers: A systematic review.

The objective of this study was to systematically review research that has focused on knowledge of and attitudes towards epilepsy among teachers. Embase, PubMed, PsycINFO, Google Scholar, and Cochrane library databases from 2000 to 2017 were searched. Cross-sectional and interventional studies were included and analyzed for quality. Thematic analysis was used to identify common themes in the results. Fifty-four eligible studies (17,256 total participants in 27 different countries) were identified in the search period including seven studies that focused on assessing attitudes and knowledge before and after an educational intervention. It was not possible to systematically analyze levels of knowledge and nature of attitudes because of the wide variety of mostly bespoke study specific instruments used. Few studies employed valid and reliable instruments. Thematic analysis revealed three main themes in the results: 1.) deficits in knowledge and negative attitudes were pervasive across all studies; 2.) teachers often had a negative attitude towards participation of children with epilepsy in physical activities/sport; and 3.) teachers often expressed limited knowledge of seizure management/emergency procedures. There was a lower level of knowledge and more negative attitudes among teachers towards epilepsy compared with other conditions. All studies focusing on interventions showed that at least some aspects of knowledge and attitudes improved as a result of teacher participation in an educational intervention, but study quality was universally rated as low. A higher level of education and experience of teaching a child with epilepsy was significantly associated with greater knowledge in a number of studies. Additionally, having experience of teaching a child with epilepsy and greater assessed knowledge of epilepsy were associated with more positive attitudes. The wide range of methods used makes it difficult to generalize regarding level of attitudes and knowledge among teachers towards epilepsy. Nevertheless, all studies indicate that there are some deficits in knowledge of and negative attitudes towards epilepsy among teachers. It would appear that knowledge and attitudes can be improved by educational interventions. Future research should focus on developing psychometrically sound assessment instruments that can be used globally and on identifying the most effective ways of delivering efficacious educational initiatives employing robust study designs.

Parenting stress and perceived stigma in mothers of young children with epilepsy: A case-control study.

The aim was to provide data on parenting stress and perceived stigma in mothers (n = 47) of young children with epilepsy, and to compare findings with those of mothers (n = 48) of developmental, age- and gender-matched children with nonepilepsy-related neurodisability (neurological and/or neurodevelopmental concerns). The mothers of young children (1-7 years) with epilepsy and mothers of children with neurodisability in a defined geographical area of the UK, completed the Parenting Stress Index-4th Edition (PSI-4) and a measure of perceived stigma. Factors associated with parenting stress and stigma were analyzed using linear regression. Thirty-eight percent of mothers of children with epilepsy scored in the at-risk range (>85th percentile) on the Total Stress score of the PSI-4 (Neurodisability 21%) (p = 0.06). Significantly more mothers of children with epilepsy scored in the at-risk range on the Parent-Child Dysfunctional Interaction subscale than mothers of children with neurodisability (Epilepsy 45% vs. Neurodisability 21%; p = 0.01), but not on the Parental Distress subscale (Epilepsy 32% vs. Neurodisability 23%; p = 0.33) or Difficult Child (Epilepsy 57% vs. Neurodisability 46%; p = 0.26) subscales. There was no statistically significant difference in perceived stigma between mothers in both groups (p = 0.51). Factors significantly associated with increased parenting stress in the group with epilepsy were child behavior difficulties (p < 0.001) and maternal sleep difficulties (p = 0.02). Lower child developmental level was the only factor independently associated with increased stigma in the group with epilepsy (p = 0.08). Mothers of young children with epilepsy report high levels of parenting stress and higher levels of difficulties with parent-child interaction compared with that of mothers of children with nonepilepsy-related neurodisability. Parenting stress and stigma in epilepsy were not associated with epilepsy factors. Efforts at reducing parenting stress and stigma should focus on interventions targeting child development and maternal sleep.

Symptoms of depression, anxiety, and stress in parents of young children with epilepsy: A case controlled population-based study.

The objective was to provide population-based data on depression, anxiety, and stress in parents of young children with epilepsy and to compare findings with those of parents of developmental-, age-, and gender-matched children with nonepilepsy-related neurodisability (neurological and/or neurodevelopmental concerns). The parents (mothers and fathers) of 47 (89% ascertainment) young children (1-7years) with epilepsy in a defined geographical area of the UK completed the Depression Anxiety Stress Scales - Short Form (DASS-21), a screening measure for depression, anxiety, and stress. The responses of parents of children with epilepsy were compared with parents of developmental-, age-, and gender-matched children with nonepilepsy-related neurodisability (n=48). Factors associated with parental symptoms were analyzed using regression. In the group with epilepsy, 47 mothers and 39 fathers completed the DASS-21. Seventy-two percent of mothers scored in the at-risk range on at least one DASS-21 subscale (Fathers 49%). Mothers of children with epilepsy were significantly more likely to score in the at risk range than fathers on depression (55% vs. 33%), anxiety (47% vs. 26%), and stress (55% vs. 31%) subscales (all p<0.05). Mothers of children with epilepsy were also significantly more likely to score in the at-risk range than mothers of children with neurodisability on measures of depression (p=0.005) and stress (p=0.03). There was not a significant difference between fathers in both groups on any measures. In the group with epilepsy, increased child emotional-behavioral difficulties were associated with increased DASS-21 scores on multivariable analysis (p=0.04). Mothers of young children with epilepsy are at high risk for mental health difficulties, and all should be screened for such difficulties. There is a need to explore what parent and/or child focused interventions might be useful to reduce the mental health difficulties reported by mothers of young children with epilepsy.

Molecular Magnetic Resonance Imaging of Lung Fibrogenesis with an Oxyamine-Based Probe.

Fibrogenesis is the active production of extracellular matrix in response to tissue injury. In many chronic diseases persistent fibrogenesis results in the accumulation of scar tissue, which can lead to organ failure and death. However, no non-invasive technique exists to assess this key biological process. All tissue fibrogenesis results in the formation of allysine, which enables collagen cross-linking and leads to tissue stiffening and scar formation. We report herein a novel allysine-binding gadolinium chelate (GdOA), that can non-invasively detect and quantify the extent of fibrogenesis using magnetic resonance imaging (MRI). We demonstrate that GdOA signal enhancement correlates with the extent of the disease and is sensitive to a therapeutic response.

A Janus Chelator Enables Biochemically Responsive MRI Contrast with Exceptional Dynamic Range.

We introduce a new biochemically responsive Mn-based MRI contrast agent that provides a 9-fold change in relaxivity via switching between the Mn3+ and Mn2+ oxidation states. Interchange between oxidation states is promoted by a "Janus" ligand that isomerizes between binding modes that favor Mn3+ or Mn2+. It is the only ligand that supports stable complexes of Mn3+ and Mn2+ in biological milieu. Rapid interconversion between oxidation states is mediated by peroxidase activity (oxidation) and l-cysteine (reduction). This Janus system provides a new paradigm for the design of biochemically responsive MRI contrast agents.

Parental anxiety in childhood epilepsy: A systematic review.

The aim was to systematically review studies that have focused on symptoms of anxiety reported by parents of children (0-18 years) with epilepsy. PubMed was used to identify relevant studies. Selected studies were reviewed with respect to prevalence of above threshold scores and comparisons with controls on standardized measures of anxiety. Studies are also reported with respect to factors associated with parental anxiety, impact on child outcomes, and comparisons with studies that have included equivalent measures of symptoms of depression. Fifteen studies that met inclusion criteria were identified. None of the studies were population based. The percentage of parents scoring above cutoffs on standardized measures of anxiety was 9-58%. In comparison with parents of healthy controls, parents of children with epilepsy had higher mean scores in two of three studies where this was measured. Possible correlates of parental anxiety in childhood epilepsy that were considered varied widely across studies. Factors such as seizure frequency and use of antiepileptic drugs (AEDs) have been associated with parental anxiety in some but not all studies. With respect to child outcome, increased parental anxiety has been associated with lower quality of life and lower scores on adaptive behavior domains. Symptoms of anxiety are common among parents of children with epilepsy. There is a need for more systematic, representative studies to identify the prevalence of clinically significant anxiety and track the course of symptoms. Such studies will help to identify more clearly factors associated with parental anxiety and impact of symptoms on child and parent outcomes. Intervention studies are needed to evaluate approaches that target a reduction in symptoms and the potential impact on parental and child functioning. Furthermore, there is a need to evaluate the impact of antiepileptic therapies and interventions that focus on child neurobehavioral comorbidities on parental anxiety.

Investigating the links between objective social media use, attentional control, and psychological distress.

Social media use (SMU) has been associated with negative mental health outcomes and has been implicated in inhibitory attentional control deficits. However, findings have been inconsistent, in part due to methodological limitations in past studies (e.g., over-reliance on self-report SMU and attentional control measures). Therefore, the aim of the present study was to examine the associations between SMU, psychological distress (including depression, anxiety, and stress), and inhibitory attentional control, using objective measures of SMU and inhibitory attentional control. Participants (N = 425) completed the DASS-21 and an antisaccade task, and SMU data was accessed via mobile phones, as minutes/week spent using TikTok, Instagram, Snapchat, Facebook, and Twitter/X. Bivariate correlations were examined, and a moderation analysis was conducted to determine whether attentional control moderated the association between SMU and psychological distress. Our findings revealed that SMU was positively associated with attentional control and anxiety, while TikTok use was positively associated with attentional control, and Facebook use with psychological distress. However, the observed associations were very small, suggesting that the links between SMU and both psychological distress and attentional control may be over-stated, particularly in studies that have utilised self-report SMU measures. No moderating effect of attentional control on the relationship between SMU and psychological distress was observed. These findings highlight the importance of utilising objective SMU and cognitive measures when examining the links between SMU, mental health, and cognitive processes (like attentional control), and to corroborate findings based on associations with self-report SMU indicators.

Validity and Reliability of a Telehealth Physical Fitness and Functional Assessment Battery for Ambulatory Youth With and Without Mobility Disabilities: Observational Measurement Study.

BACKGROUND: Youth (age 15-24 years) with and without disability are not adequately represented enough in exercise research due to a lack of time and transportation. These barriers can be overcome by including accessible web-based assessments that eliminate the need for on-site visitations. There is no simple, low-cost, and psychometrically sound compilation of measures for physical fitness and function that can be applied to youth with and without mobility disabilities. OBJECTIVE: The first purpose was to determine the statistical level of agreement of 4 web-modified clinical assessments with how they are typically conducted in person at a laboratory (convergent validity). The second purpose was to determine the level of agreement between a novice and an expert rater (interrater reliability). The third purpose was to explore the feasibility of implementing the assessments via 2 metrics: safety and duration. METHODS: The study enrolled 19 ambulatory youth: 9 (47%) with cerebral palsy with various mobility disabilities from a children's hospital and 10 (53%) without disabilities from a university student population. Participants performed a battery of tests via videoconferencing and in person. The test condition (teleassessment and in person) order was randomized. The battery consisted of the hand grip strength test with a dynamometer, the five times sit-to-stand test (FTST), the timed up-and-go (TUG) test, and the 6-minute walk test (6MWT) either around a standard circular track (in person) or around a smaller home-modified track (teleassessment version, home-modified 6-minute walk test [HM6MWT]). Statistical analyses included descriptive data, intraclass correlation coefficients (ICCs), and Bland-Altman plots. RESULTS: The mean time to complete the in-person assessment was 16.9 (SD 4.8) minutes and the teleassessment was 21.1 (SD 5.9) minutes. No falls, injuries, or adverse events occurred. Excellent convergent validity was shown for telemeasured hand grip strength (right ICC=0.96, left ICC=0.98, P<.001) and the TUG test (ICC=0.92, P=.01). The FTST demonstrated good agreement (ICC=0.95, 95% CI 0.79-0.98; P=.01). The HM6MWT demonstrated poor absolute agreement with the 6MWT. However, further exploratory analysis revealed a strong positive correlation between the tests (r=0.83, P<.001). The interrater reliability was excellent for all tests (all ICCs>0.9, P<.05). CONCLUSIONS: This study suggests that videoconference assessments are convenient and useful measures of fitness and function among youth with and without disabilities. This paper presents operationalized teleassessment procedures that can be replicated by health professionals to produce valid and reliable measurements. This study is a first step toward developing teleassessments that can bypass the need for on-site data collection visitations for this age group. Further research is needed to identify psychometrically sound teleassessment procedures, particularly for measures of cardiorespiratory endurance or walking ability.

Acid-active proteases to optimize dietary protein digestibility: a step towards sustainable nutrition.

Introduction: Historically, prioritizing abundant food production often resulted in overlooking nutrient quality and bioavailability, however, environmental concerns have now propelled sustainable nutrition and health efficacy to the forefront of global attention. In fact, increasing demand for protein is the major challenge facing the food system in the 21st century with an estimation that 70% more food is needed by 2050. This shift has spurred interest in plant-based proteins for their sustainability and health benefits, but most alternative sources of protein are poorly digestible. There are two approaches to solve digestibility: improve the digestibility of food proteins or improve the digestive capacity of consumers. Enhancing nutrient digestibility and bioavailability across diverse protein sources is crucial, with proteases presenting a promising avenue. Research, inspired by the proteases of human breast milk, has demonstrated that exogenous microbial proteases can activate within the human digestive tract and substantially increase the digestion of targeted proteins that are otherwise difficult to fully digest. Methods: Here, we introduce the use of an acid-active family of bacterial proteases (S53) to improve the digestibility and nutritional quality of a variety of protein sources, evaluated using the INFOGEST 2.0 protocol. Results: Results from in vitro digestibility indicate that the most effective protease in the S53 family substantially improves the digestibility of an array of animal and plant-derived proteins-soy, pea, chickpea, rice, casein, and whey. On average, this protease elevated protein digestibility by 115% during the gastric phase and by 15% in the intestinal phase, based on the degree of hydrolysis. Discussion: The widespread adoption of these proteases has the potential to enhance nutritional value and contribute to food security and sustainability. This approach would complement ongoing efforts to improve proteins in the food supply, increase the quality of more sustainable protein sources and aid in the nourishment of patients with clinically compromised, fragile intestines and individuals like older adults and high-performance athletes who have elevated protein needs.

Introduction of a section for recording dementia improves data capture on the ambulance electronic patient record: evidence from a regional quality improvement project.

Introduction: Dementia is a common co-morbidity in older people who require urgent or emergency ambulance attendance and influences clinical decisions and care pathways. Following an initial audit of dementia data and consultation with staff, a specific section (tab) to record dementia was introduced on an ambulance service electronic patient record (ePR). This includes a dementia diagnosis button and a free-text section. We aimed to assess whether and how this improved recording. Methods: To re-audit the proportion of ambulance ePRs where dementia is recorded for patients aged ≥65 years, and to describe the frequency of recording in patients aged <65; to analyse discrepancies in the place of recording dementia on the ePR by comparing data from the new dementia tab and other sections of the ePR. Results: We included 112,193 ePRs of patients aged ≥65 with ambulance attendance from a six-month period. The proportion with dementia recorded in patients aged ≥65 was 16.5%, increasing to 19.9% in patients aged ≥75, as compared to 13.5% (≥65) and 16.5% (≥75) in our previous audit. In this audit, of the 16.5% (n = 18,515) of records with dementia recorded, 69.9% (n = 12,939) used the dementia button and 25.4% (n = 4704) recorded text in the dementia tab. Dementia was recorded in ePR free-text fields (but not the dementia tab) in 29.7% of records. Eighteen other free-text fields were used in addition to, or instead of, the dementia tab, including the patient's social history, previous medical history and mental health. Dementia was present on the ePR of 0.4% (n = 461) of patients aged <65. Conclusions: An ePR dementia tab enabled ambulance clinicians to standardise the location of recording dementia and may have facilitated increased recording. We would recommend other ambulance trusts capture this information in a specific section to improve information sharing and to inform care planning for this patient group.