Changes in cardiac-driven perivascular fluid movement around the MCA in a pharmacological model of acute hypertension detected with non-invasive MRI.

Perivascular spaces mediate a complex interaction between cerebrospinal fluid and brain tissue that may be an important pathway for solute waste clearance. Their structural or functional derangement may contribute to the development of age-related neurogenerative conditions. Here, we employed a non-invasive low b-value diffusion-weighted ECG-gated MRI method to capture perivascular fluid movement around the middle cerebral artery of the anaesthetised rat brain. Using this method, we show that such MRI estimates of perivascular fluid movement directionality are highly sensitive to the cardiac cycle. We then show that these measures of fluid movement directionality are decreased in the angiotensin-II pharmacological model of acute hypertension, with an associated dampening of vessel pulsatility. This translational MRI method may, therefore, be useful to monitor derangement of perivascular fluid movement associated with cardiovascular pathologies, such as hypertension, in order to further our understanding of perivascular function in neurology.

APOLLO: A genome-scale metabolic reconstruction resource of 247,092 diverse human microbes spanning multiple continents, age groups, and body sites.

Computational modelling of microbiome metabolism has proved instrumental to catalyse our understanding of diet-host-microbiome-disease interactions through the interrogation of mechanistic, strain- and molecule-resolved metabolic models. We present APOLLO, a resource of 247,092 human microbial genome-scale metabolic reconstructions spanning 19 phyla and accounting for microbial genomes from 34 countries, all age groups, and five body sites. We explored the metabolic potential of the reconstructed strains and developed a machine learning classifier able to predict with high accuracy the taxonomic strain assignments. We also built 14,451 sample-specific microbial community models, which could be stratified by body site, age, and disease states. Finally, we predicted faecal metabolites enriched or depleted in gut microbiomes of people with Crohn's disease, Parkinson disease, and undernourished children. APOLLO is compatible with the human whole-body models, and thus, provide unprecedented opportunities for systems-level modelling of personalised host-microbiome co-metabolism. APOLLO will be freely available under https://www.vmh.life/.

A Case for Unifying Accelerometry-Derived Movement Behaviors and Tests of Exercise Capacity for the Assessment of Relative Physical Activity Intensity.

Albert Einstein taught us that "everything is relative." People's experience of physical activity (PA) is no different, with "relativism" particularly pertinent to the perception of intensity. Markers of absolute and relative intensities of PA have different but complimentary utilities, with absolute intensity considered best for PA guideline adherence and relative intensity for personalized exercise prescription. Under the paradigm of exercise and PA as medicine, our Technical Note proposes a method of synchronizing accelerometry with the incremental shuttle walking test to facilitate description of the intensity of the free-living PA profile in absolute and relative terms. Our approach is able to generate and distinguish "can do" or "cannot do" (based on exercise capacity) and "does do" or "does not do" (based on relative intensity PA) classifications in a chronic respiratory disease population, facilitating the selection of potential appropriate individually tailored interventions. By synchronizing direct assessments of exercise capacity and PA, clearer insights into the intensity of PA performed during everyday life can be gleaned. We believe the next steps are as follows: (1) to determine the feasibility and effectiveness of using relative and absolute intensities in combination to personalize the approach, (2) to determine its sensitivity to change following interventions (eg, exercise-based rehabilitation), and (3) to explore the use of this approach in healthier populations and in other long-term conditions.

Public Use of the "Your COVID Recovery" Website Designed to Help Individuals Manage Their COVID-19 Recovery: Observational Study.

BACKGROUND: At the start of the COVID-19 pandemic, unprecedented pressure was placed on health care services globally. An opportunity to alleviate this pressure was to introduce a digital health platform that provided COVID-19-related advice and helped individuals understand and manage their COVID-19 symptoms. Therefore, in July 2020, the Your COVID Recovery website was launched by the National Health Service of England with the aim of creating a practical tool that provides advice and support to individuals recovering from COVID-19. The website includes information on many of the key COVID-19 symptoms. To date, public use of the Your COVID Recovery website and user behavior remain unknown. However, this information is likely to afford insight into the impact of the website and most commonly experienced COVID-19 symptoms. OBJECTIVE: This study aimed to evaluate public use of the Your COVID Recovery website, a digital health platform that provides support to individuals recovering from COVID-19, and determine user behavior during its first year of operation. METHODS: Google Analytics software that was integrated into the Your COVID Recovery website was used to assess website use and user behavior between July 31, 2020, and July 31, 2021. Variables that were tracked included the number of users, user country of residence, traffic source, number of page views, number of session views, and mean session duration. User data were compared to COVID-19 case data downloaded from the UK government's website. RESULTS: During the study period, 2,062,394 users accessed the Your COVID Recovery website. The majority of users were located in the United Kingdom (1,265,061/2,062,394, 61.30%) and accessed the website via a search engine (1,443,057/2,062,394, 69.97%). The number of daily website users (n=15,298) peaked on January 18, 2021, during the second wave of COVID-19 in the United Kingdom. The most frequently visited pages after the home page were for the following COVID-19 symptoms: Cough (n=550,190, 12.17%), Fatigue (n=432,421, 9.56%), Musculoskeletal pain (n=406,859, 9.00%), Taste and smell (n=270,599, 5.98%), and Breathlessness (n=203,136, 4.49%). The average session duration was 1 minute 13 seconds. CONCLUSIONS: A large cohort of individuals actively sought help with their COVID-19 recovery from the website, championing the potential of this tool to target an unmet health care need. User behavior demonstrated that individuals were primarily seeking advice on how to relieve and manage COVID-19 symptoms, especially symptoms of cough, fatigue, and musculoskeletal pain. COVID-19 rehabilitation programs should use the results of this study to ensure that the program content meets the needs of the post-COVID-19 population.

Early experiences of the Your COVID Recovery® digital programme for individuals with long COVID.

OBJECTIVES: To describe the early data from the Your COVID Recovery® digital programme and to explore the data collected from two embedded outcome measures. DESIGN: Observational. SETTING: Primary and secondary care (England-Online). PARTICIPANTS: 110 individuals completed the programme (68.1% female, 88.1% White British, age: 46.3 (10.8) years, weight: 86.5 (21.1) kg, height: 169.3 (10.0) cm). 47.2% of patients reported comorbidities. INTERVENTION: Following an assessment by a healthcare professional, individuals with long COVID were offered access to the Your COVID Recovery® digital programme. The programme comprises of four stages for the participants to progress through. Participants are encouraged to record severity of their symptoms and amount of activity they are doing on a symptom and an activity tracker. Resources and interactive material on managing symptoms of long COVID are available throughout each stage. PRIMARY OUTCOME MEASURES: Questionnaire (EuroQ0l 5-Dimension 5-Level (EQ-5D-5L) and the chronic obstructive pulmonary disease assessment test (CAT)) data were extracted from the site from 11 March 2021 until 9 November 2021. RESULTS: Participants were on the programme for 8.6 (4.3) weeks. There was a statistically significant increase in EQ-5D-5L visual analogue scale (VAS) score (pre=48.8 (19.5); post=59.9 (22.1); p<0.01). The EQ-5D-5L Index Value preintervention to postintervention did improve but not significantly (pre=0.5 (0.3); post=0.6 (0.3); p=0.09). CAT total score improved significantly preintervention to postintervention (pre=19.8 (7.2); post=15.6 (7.6); p<0.01). All CAT item scores significantly improved preintervention to postintervention (p<0.005), except the phlegm item score (p=0.168). DISCUSSION: This early data describes the impact of the Your COVID Recovery® digital programme on the first cohort of patients to complete the digital recovery programme. The outcome data are promising and should encourage uptake.

Increased blood-brain barrier permeability to water in the aging brain detected using noninvasive multi-TE ASL MRI.

PURPOSE: A fundamental goal in the drive to understand and find better treatments for dementia is the identification of the factors that render the aging brain vulnerable to neurodegenerative disease. Recent evidence indicates the integrity of the blood-brain barrier (BBB) to be an important component of functional failure underlying age-related cognitive decline. Practical and sensitive measurement is necessary, therefore, to support diagnostic and therapeutic strategies targeted at maintaining BBB integrity in aging patients. Here, we investigated changes in BBB permeability to endogenous blood water in the aging brain. METHODS: A multiple-echo-time arterial spin-labeling MRI technique, implemented on a 9.4T Bruker imaging system, was applied to 7- and 27-month-old mice to measure changes in water permeability across the BBB with aging. RESULTS: We observed that BBB water permeability was 32% faster in aged mice. This occurred along with a 2.1-fold increase in mRNA expression of aquaporin-4 water channels and a 7.1-fold decrease in mRNA expression of α-syntrophin protein, which anchors aquaporin-4 to the BBB. CONCLUSION: Age-related changes to water permeability across the BBB can be captured using noninvasive noncontrast MRI techniques.

Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI.

The glymphatics system describes a CSF-mediated clearance pathway for the removal of potentially harmful molecules, such as amyloid beta, from the brain. As such, its components may represent new therapeutic targets to alleviate aberrant protein accumulation that defines the most prevalent neurodegenerative conditions. Currently, however, the absence of any non-invasive measurement technique prohibits detailed understanding of glymphatic function in the human brain and in turn, it's role in pathology. Here, we present the first non-invasive technique for the assessment of glymphatic inflow by using an ultra-long echo time, low b-value, multi-direction diffusion weighted MRI sequence to assess perivascular fluid movement (which represents a critical component of the glymphatic pathway) in the rat brain. This novel, quantitative and non-invasive approach may represent a valuable biomarker of CSF-mediated brain clearance, working towards the clinical need for reliable and early diagnostic indicators of neurodegenerative conditions such as Alzheimer's disease.