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BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS−based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Motoneurons are one of the highest energy demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultra-structure, transport and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression are not fully understood yet. Here we utilize hiPCS derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in Fused in Sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons is accompanied by an overall upregulation of mitochondrial components and significant increase in metabolic rates that corresponds to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of disease motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms.

Previous methods used to infer axon diameter distributions using magnetic resonance imaging (MRI) primarily use single diffusion encoding sequences such as pulsed gradient spin echo (PGSE) and are thus sensitive to axons of diameters >5 μm. We applied oscillating gradient spin echo (OGSE) sequences to study human axons in the 1–2 μm range in the corpus callosum, which include the majority of axons constituting cortical connections. The ActiveAx model was applied to calculate the fitted mean effective diameter for axons (AxD) and was compared with values found using histology. Axon diameters from histological data were calculated using three different datasets; true diameters (minimum diameter), a combination of minimum and maximum diameters, and diameters measured across a consistent diffusion direction. The AxD estimates from MRI were 1.8 ± 0.1 μm to 2.34 ± 0.04 μm with an average of 2.0 ± 0.2 μm for the ActiveAx model. The histology AxD values were 1.43 ± 0.02 μm when using the true minimum axon diameters, 5.52 ± 0.02 μm when using the combination of minimum and maximum axon diameters, and 2.20 ± 0.02 μm when collecting measurements across a consistent diffusion direction. This experiment demonstrates the first known usage of OGSE to calculate axon diameters in the human corpus callosum on a 1–2 μm scale. The importance for the model to account for axonal orientation dispersion is indicated by histological results which more closely match the MRI model results depending on the direction of axon diameter measurements. These initial steps using this non-invasive imaging method can be applied to future methodology to develop in vivo axon diameter measurements in human brain tissue.

Background/Aims The Bath Ankylosing Spondylitis Metrology Index (BASMI) is used in the monitoring of those living with axial spondyloarthritis (axSpA); it is the recommended and validated measure of movement in this patient group. As a physical outcome measure its use has been challenging during the COVID-19 pandemic. The aim of this project is to assess the current application of the BASMI in axSpA services across the UK. Methods A survey was devised to explore when the BASMI is used, by whom and the reasons for its use. The AStretch committee reviewed and re-drafted the questions. The survey was shared across multiple platforms and email professional distribution lists, and was open 2nd-12th October 2021. Results 74 UK healthcare professionals completed the survey. It is mostly physiotherapists who undertake the BASMI (69%); some other clinicians also measure: nurses (10%), medics (9%), physiotherapy support workers (10%), healthcare support workers (2%). Confidence in performing the BASMI averaged at 3.5/5. The majority of respondents record the BASMI in the electronic record (73%); app-based solutions are developing (7%) and paper-only recording diminishing (20%). When asked about frequency, most respondents (73%) recorded “it depends”, implying that the BASMI is used on an individual patient basis. Table 1 presents data with regards to why the BASMI is undertaken, scored by participant ranking, and free text responses about reasons for use. Conclusion A large sample size was recruited for this survey, implying a good level of interest in better understanding the current application of the BASMI. It is evident clinicians use the BASMI on newly-diagnosed patients as a priority in their assessment and shared-decision making. Other aspects such as addressing poor movement and adherence to exercise are ranked highly. The reported reasons for BASMI use are varied, and its application not standardised across UK rheumatology teams. This might reflect the diverse trajectory of axSpA and the importance of seeing patients as individuals. How and why we undertake physical outcome measures is crucial for consideration as we currently consider remote versus face-to-face consult pathways for our axSpA cohort. There is enough evidence here to recommend ongoing, regular application of the BASMI in a traditional face-to-face setting. Disclosure K. Weight: None. W.J. Gregory: Honoraria; W.G. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer Novartis and UCB. H. Chambers: None. E. Clarke: Honoraria; E. C. has received speaker fees from Novartis UK. M. Daly: None. A. Davie: None. J.C. Elkins: None. S. Gaikwad: None. H. Harrison: None. C. Longton: Shareholder/stock ownership; C.L. is a shareholder in Astra Zeneca. Honoraria; C.L. has received speaker fees from Novartis. M. Martin: Honoraria; M.M. has received speaker, conference registration and advisory board fees from Abbvie, Novartis (not since 2018). Grants/research support; M.M. received grant monies from the National Axial Spondyloarthritis Society in 2017. M. Motion: None. S. Voules: None. M. McDonald: None. C. Jeffries: Honoraria; C.J. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer, Novartis and UBC.

Background Modern treat-to-target approaches to rheumatoid arthritis (RA) involve frequent monitoring of disease activity with the goal of disease remission or a low disease activity. The Rheumatoid Arthritis Impact of Disease (RAID) is a multidimensional, validated patient-reported outcome measure that covers seven domains, which has been found to discriminate between active and non-active disease. Applying smartphone apps to monitoring of RA is described as an innovation which has been implemented in the UK and USA. The proposed study will evaluate the feasibility of scaled implementation of a remote monitoring service based on RAID for eligible patients with RA at three NHS organisations (trusts) in south east London, UK. Methods Pragmatic formative service evaluation study informed by implementation theory and incorporating the perspectives of RA service users throughout. The study will follow a multi-method approach. Rapid evidence review will be carried out to identify implementation approaches used in similar services. Quantitative data will be collected from a cross-sectional sample of service users through a web-based questionnaire assessing patient satisfaction, as well as service-level data routinely collected by trusts and from the remote monitoring system and documentation produced in developing and implementing the remote monitoring service. Qualitative data will be collected from approximately 30 clinical and non-clinical staff and 20-30 patients purposively sampled to conduct semi-structured interviews to explore their perspectives on remote monitoring in RA. The evaluation will be supported by established implementation frameworks, including EPIS (Exploration, Preparation, Implementation and Sustainment) and COM-B (Capability-Opportunity-Motivation-Behaviour), which will be used to guide data generation and to inform the framework analysis of qualitative data. Discussion This pragmatic study will enhance the understanding of implementation process and outcomes and will explore the potential to scale up the remote monitoring system in RA. A larger scale hybrid study can be designed based on the dataset the current study will produce to offer definitive clinical and implementation evaluation.