Remote monitoring of patients with rheumatoid arthritis: a mixed methods evaluation across six hospitals in London, UK.

OBJECTIVES: This study evaluated the scale-up of a remote monitoring (RM) service, capturing monthly Rheumatoid Arthritis Impact of Disease scores and patient-generated text messages, for patients with rheumatoid arthritis (RA; in remission or with low disease activity) attending routine outpatient clinics across six hospitals. We explored patients and staff experiences and implementation outcomes. METHODS: A pragmatic, mixed methods approach was used, with active patient involvement throughout. We undertook a rapid review, analysed service-level data, and conducted a patient survey and patient and staff interviews, informed by the Capability, Opportunity, Motivation, Behaviour (COM-B) and Exploration, Preparation, Implementation, Sustainment (EPIS) theoretical frameworks. RESULTS: The review included 37 articles, covering themes of patient and clinician acceptability, engagement, feasibility and clinical impact. Service-level data (n = 202) showed high levels of patient engagement with the service. The patient survey (n = 155) showed patients felt the service was easy to use, had confidence in it and felt it improved access to care. Patient interview (n = 22) findings mirrored those of the survey. Motivating factors included increased responsiveness and ease of contact with clinical teams. Views from staff interviews (n = 16) were more mixed. Some implementation barriers were specific to roll-out sites. Prioritisation of staff needs was emphasised. CONCLUSION: Patients were positive about the service and engagement was high. Staff views and engagement were more mixed. Results suggest that equal levels of patient and staff engagement are required for sustainability. These findings further our understanding of the implementation challenges to scaling RM interventions for patients with RA in routine care settings.

Longitudinal analysis of cortisol changes during pubertal development in indigenous Qom girls.

Pubertal research has primarily focused on hypothalamic-pituitary-gonadal axis (HPG) regulation of puberty, though the hypothalamic-pituitary-adrenal axis (HPA) is increasingly considered critical. Heightened HPA function proxied by increasing cortisol levels may play a role in accelerated pubertal timing. However, the extent to which cortisol varies across ages and its relation to pubertal changes in linear growth are less well substantiated. We explored relationships between age, linear growth, adiposity, C-peptide (proxy for insulin), and cortisol across puberty, and we tested whether higher cortisol levels are associated with earlier ages at menarche and peak height velocity. We utilize longitudinal data (n = 777 urine samples) from Qom females ages 7-14 (n = 46) and test our pre-registered analysis using Bayesian longitudinal mixed effects models and joint modeling techniques. We find limited evidence supporting the overarching hypothesis that HPA upregulation is associated with pubertal maturation or timing. We find some evidence that HPA upregulation, as proxied by cortisol, may be more clearly related to differences in relative linear growth at early-mid puberty, as measured by height-for-age z-scores. Transdisciplinary perspectives on puberty, including the assumption that stressors acting via cortisol accelerate pubertal development, are discussed.

Magnetic resonance metrics for identification of cuprizone-induced demyelination in the mouse model of neurodegeneration: a review.

Neurodegenerative disorders, including Multiple Sclerosis (MS), are heterogenous disorders which affect the myelin sheath of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) provides a non-invasive method for studying, diagnosing, and monitoring disease progression. As an emerging research area, many studies have attempted to connect MR metrics to underlying pathophysiological presentations of heterogenous neurodegeneration. Most commonly, small animal models are used, including Experimental Autoimmune Encephalomyelitis (EAE), Theiler's Murine Encephalomyelitis (TMEV), and toxin models including cuprizone (CPZ), lysolecithin, and ethidium bromide (EtBr). A contrast and comparison of these models is presented, with focus on the cuprizone model, followed by a review of literature studying neurodegeneration using MRI and the cuprizone model. Conventional MRI methods including T1 Weighted (T1W) and T2 Weighted (T2W) Imaging are mentioned. Quantitative MRI methods which are sensitive to diffusion, magnetization transfer, susceptibility, relaxation, and chemical composition are discussed in relation to studying the CPZ model. Overall, additional studies are needed to improve both the sensitivity and specificity of MRI metrics for underlying pathophysiology of neurodegeneration and the relationships in attempts to clear the clinico-radiological paradox. We therefore propose a multiparametric approach for the investigation of MR metrics for underlying pathophysiology.

Modelling white matter microstructure using diffusion OGSE MRI: Model and analysis choices.

Alterations in white matter (WM) microstructure of the central nervous system have been shown to be pathophysiological presentations of various neurodegenerative disorders. Current methods for measuring such WM features require ex vivo tissue samples analyzed using electron microscopy. Magnetic Resonance Imaging (MRI) diffusion-weighted pulse sequences provide a non-invasive tool for estimating such microstructural features in vivo. The current project investigated the use of two methods of analysis, including the ROI-based (Region of Interest, RBA) and voxel-based analysis (VBA), as well as four mathematical models of WM microstructure, including the ActiveAx Frequency-Independent Extra-Axonal Diffusion (AAI), ActiveAx Frequency-Dependent Extra-Axonal Diffusion (AAD), AxCaliber Frequency-Independent Extra-Axonal Diffusion (ACI), and AxCaliber Frequency-Dependent Extra-Axonal Diffusion (ACD) models. A total of three image data sets were analyzed, including two mice samples imaged at 7 T and 15.2 T. Both the AAI and AAD models provide a single value for each of the fit parameters, including axon diameter AxD¯, packing fraction fin, intra-cellular and Din and extra-cellular Dex diffusion coefficients, as well as the frequency dependence of Dex, ßex for the AAD model. The ACI and ACD models provide this, in addition to a distribution of axon diameters for a chosen ROI. VBA extends this, providing a parameter value for each voxel within the selected ROI, at the cost of increased computational load and analysis time. Overall, RBA-ACD and VBA-AAD were found to be optimal for parameter fitting to physically relevant values in a reasonable time frame. A full comparison of each combination of RBA and VBA with AAI, AAD, ACI, and ACD is provided to give the reader sufficient information to make an informed decision of which model is best for their own experiments.

Variation in maternal lactation practices associated with changes in diurnal maternal inflammation.

While the importance of human milk in shaping infant immune function is well established, the impact of at-the-nipple (ATN) breastfeeding on maternal immune status has been understudied. Since lactation evolved to support infant survival and boost maternal fitness, we predict that ATN breastfeeding will confer benefits on maternal immune function. We measure the absolute and relative frequency of different infant feeding methods (ATN breastfeeding, pumping, donated milk, other supplementation) used by postpartum women in Seattle, WA (USA). We implement Bayesian modeling to estimate the effects of ATN breastfeeding on diurnal change in secretion rate of "pro-inflammatory" salivary cytokines and C-reactive protein (CRP). Our results show that most mothers in our sample used a variety of infant feeding methods, with pumping as the most common alternative to ATN breastfeeding. We find that ATN breastfeeding is associated with non-linear effects on diurnal IL-8 and CRP. Furthermore, we find that women who report zero versus ubiquitous ATN breastfeeding exhibit opposing diurnal patterns in CRP secretion rate. This study provides evidence that variation in maternal lactation practices corresponds to differences in maternal immune responses, highlighting how measuring lactation as a continuous variable can further enhance understanding of postpartum maternal physiology.

Prevalence and duration of SARS-CoV-2 fecal shedding in breastfeeding dyads following maternal COVID-19 diagnosis.

Background: There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology. Objective: We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis. Methods: This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA. Results: Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding (P=0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater, P≤0.04) of fecal shedding in infants of mothers with COVID-19.

Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice.

Serotonin reuptake inhibitor antidepressants such as fluoxetine are widely used to treat mood disorders. The mechanisms of action include an increase in extracellular level of serotonin, neurogenesis, and growth of vessels in the brain. We investigated whether fluoxetine could have broader peripheral regenerative properties. Following prolonged administration of fluoxetine in male mice, we showed that fluoxetine increases the number of muscle stem cells and muscle angiogenesis, associated with positive changes in skeletal muscle function. Fluoxetine also improved skeletal muscle regeneration after single and multiples injuries with an increased muscle stem cells pool and vessel density associated with reduced fibrotic lesions and inflammation. Mice devoid of peripheral serotonin treated with fluoxetine did not exhibit beneficial effects during muscle regeneration. Specifically, pharmacological, and genetic inactivation of the 5-HT1B subtype serotonin receptor also abolished the enhanced regenerative process induced by fluoxetine. We highlight here a regenerative property of serotonin on skeletal muscle.