Many people with neurological disorders are at high risk of osteoporosis and fragility fractures. Such fractures are a leading cause of disability and premature mortality. There are various underlying mechanisms, including reduced bone mineral density from biomechanical factors (eg, reduced muscle strength), inflammation and/or medications such as glucocorticoids, together with an increased risk of falls. Neurologists are well placed to initiate measures to protect bone health. In this review, we address the epidemiological associations between bone health, fracture risk and different neurological disorders and elucidate the potential underlying mechanisms. We set out overarching principles for managing bone health in the context of neurological disorders, together with guidance for specific diseases.

Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity. 22 participants were included in a prospective observational study. Maximum Elongation Index (EI) in ektacytometry served as the readout for erythrocyte deformability. Inflammatory status was assessed using C-reactive protein (CRP) and self-reported symptoms associated with inflammatory activation (Sickness Questionnaire Scores, SicknessQ). In a univariate linear regression, both CRP and SicknessQ scores significantly predicted EI (CRP: F(1,20) = 7.751, p < 0.05 (0.011), R = 0.279; SicknessQ: F(1,18) = 4.831, p < 0.05 (0.041), R = 0.212). Sensitivity analyses with multivariable linear regression correcting for age showed concordant findings. Results suggest a linear relationship between erythrocyte deformability and biochemical and clinical markers of systemic inflammation. Replication of findings in a larger study, and mechanisms and clinical consequences need further in investigation.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify the blood-brain barrier (BBB) permeability-surface area product. Serial measurements can indicate changes in BBB health, of interest to the study of normal physiology, neurological disease, and the effect of therapeutics. We performed a scan-rescan study to inform both sample size calculation for future studies and an appropriate reference change value for patient care. The final dataset included 28 healthy individuals (mean age 53.0 years, 82% female) scanned twice with mean interval 9.9 weeks. DCE-MRI was performed at 3T using a 3D gradient echo sequence with whole brain coverage, T1 mapping using variable flip angles, and a 16-min dynamic sequence with a 3.2-s time resolution. Segmentation of white and grey matter (WM/GM) was performed using a 3D magnetization-prepared gradient echo image. The influx constant K was calculated using the Patlak method. The primary outcome was the within-subject coefficient of variation (CV) of K in both WM and GM. K values followed biological expectations in relation to known GM/WM differences in cerebral blood volume (CBV) and consequently vascular surface area. Subject-derived arterial input functions showed marked within-subject variability which were significantly reduced by using a venous input function (CV of area under the curve 46 vs. 12%, p < 0.001). Use of the venous input function significantly improved the CV of K in both WM (30 vs. 59%, p < 0.001) and GM (21 vs. 53%, p < 0.001). Further improvement was obtained using motion correction, scaling the venous input function by the artery, and using the median rather than the mean of individual voxel data. The final method gave CV of 27% and 17% in WM and GM, respectively. No further improvement was obtained by replacing the subject-derived input function by one standard population input function. CV of K was shown to be highly sensitive to dynamic sequence duration, with shorter measurement periods giving marked deterioration especially in WM. In conclusion, measurement variability of 3D brain DCE-MRI is sensitive to analysis method and a large precision improvement is obtained using a venous input function.

There is growing evidence that inflammation impairs erythrocyte structure and function. We assessed the impact of mild systemic inflammation on erythrocyte fragility in three different settings. In order to investigate causation, erythrocyte osmotic fragility was measured in mice challenged with a live attenuated bacterial strain to induce low-grade systemic inflammation; a significant increase in erythrocyte osmotic fragility was observed. To gather evidence that systemic inflammation is associated with erythrocyte fragility in humans, two observational studies were conducted. First, using a retrospective study design, the relationship between reticulocyte-based surrogate markers of haemolysis and high-sensitivity C-reactive protein was investigated in 9292 healthy participants of the UK Biobank project. Secondly, we prospectively assessed the relationship between systemic inflammation (measured by the urinary neopterin/creatinine ratio) and erythrocyte osmotic fragility in a mixed population (n = 54) of healthy volunteers and individuals with long-term medical conditions. Both human studies were in keeping with a relationship between inflammation and erythrocyte fragility. Taken together, we conclude that mild systemic inflammation increases erythrocyte fragility and may contribute to haemolysis. Further research is needed to assess the molecular underpinnings of this pathway and the clinical implications in inflammatory conditions.

Detecting multiple sclerosis (MS) relapses remains challenging due to symptom variability and confounding factors, such as flare-ups and infections. Methylprednisolone (MP) is used for severe relapses, decreasing the number of contrast-enhancing lesions on MRI. The influx constant (K) derived from dynamic contrast-enhanced MRI (DCE-MRI), a marker of blood-brain barrier (BBB) permeability, has shown promise as a predictor of disease activity in relapsing-remitting MS (RRMS).

Bone marrow cellularity is routinely estimated from a small number of two-dimensional histology sections, making assessment sensitive to section representativeness, processing artefacts and observer interpretation. Three-dimensional (3D) x-ray histology (XRH), using x-ray computed microtomography (µCT), enables non-destructive whole-block imaging of trephine biopsies. This study evaluated whether XRH combined with Gaussian peak modelling could provide a pragmatic whole-block volumetric bone marrow cellularity (VBMC) estimate from formalin-fixed paraffin-embedded (FFPE) trephine biopsy blocks.Six routinely processed FFPE bone marrow trephine blocks were imaged using µCT-based XRH at ∼15 µm spatial resolution. VBMC was defined as the red-marrow (RM) fraction of the marrow soft-tissue compartment, RM/(RM + intra-biopsy wax), with wax serving as the volumetric proxy for adipocyte/yellow marrow space. Whole-volume greyscale histograms were modelled using a three-peak Gaussian approach representing intra-biopsy wax, RM and demineralised trabecular matrix. Peak-height and area-under-the-curve metrics were compared with whole-volume 3D segmentation and clinical two-dimensional (2D) cellularity estimates.Gaussian peak modelling successfully approximated the segmented tissue-phase distributions. The peak-height-derived VBMC metric showed the closest agreement with whole-volume 3D segmentation, with an average absolute percentage difference of 9.3%, compared with 18.6% for clinical expert 2D cellularity estimates. The area-under-the-curve metric followed similar trends but consistently overestimated VBMC. Clinical 2D cellularity broadly followed whole-biopsy trends but showed one discordant case not explained by slice-position sampling alone. XRH also enabled unrestricted virtual reslicing and visualisation of sectioning-associated artefacts prior to further microtomy.Pre-sectioning XRH combined with Gaussian peak modelling provides a rapid, segmentation-free route to volumetric cellularity estimation from intact clinical FFPE trephine blocks. The approach supports objective whole-biopsy assessment while remaining compatible with routine histopathology workflows, reflecting the expected limitations of section-based visual estimation despite its role as the current clinical standard. In the near term, it could provide a non-disruptive adjunct to conventional 2D cellularity reporting, pending larger validation studies.

Incident microhemorrhages and superficial siderosis are hemorrhagic magnetic resonance imaging (MRI) abnormalities relevant to amyloid-related imaging abnormalities with hemosiderin deposition (ARIA-H) risk stratification, but evidence exploring their short-term dynamic predictors remains limited.

A position paper released by the European Association of Nuclear Medicine emphasised the need for multidisciplinary engagement to establish dosimetry-based personalised treatment in Radionuclide therapy (RNT). The uncertainty analysis results often ignored in routine clinical practice should be incorporated into the dose calculations to improve the efficacy and accuracy of treatment. In this study, patients with haematological malignancies undergoing radioimmunotherapy were evaluated. Our study aimed to calculate the uncertainties associated with each parameter of the single time point (STP) dosimetry chain and compare the with multiple time points (MTP) in the bone marrow and liver results.

BackgroundDementia diagnosis is challenging and often delayed. Brain imaging techniques such as single-photon emission computed tomography (SPECT) imaging can help identify subtle changes in brain perfusion. Artificial intelligence methods may support results interpretation for early diagnosis.ObjectiveTo develop and validate multivariate models for the early diagnosis of Alzheimer's disease (AD), using brain perfusion SPECT imaging and interpretable artificial intelligence methods in a real-world clinical setting.MethodsTwo logistic regression models were developed using a training dataset of 420 SPECT scans and tested on an independent clinical dataset of 443 scans. Model 1 was designed to identify abnormal perfusion patterns, while Model 2 identified perfusion changes associated with AD. Input features were extracted from anatomical volumes of interest, with feature selection performed using the Minimum Redundancy Maximum Relevance (MRMR) algorithm.ResultsThe models demonstrated good classification performance using real-world clinical data. Model 1 achieved an area under receiver operator characteristic (AUROC) Curve of 0.89 (Sensitivity 76%, Specificity 87%) in identifying abnormal brain perfusion. Model 2 achieved an AUROC of 0.86 (Sensitivity 87%, Specificity 72%) in identifying AD.ConclusionsMultivariate logistic regression models trained on real-world clinical data show promise as clinical decision support tools for the diagnosis of AD from brain perfusion SPECT imaging. The models use features from clinically relevant brain regions, which enhances interpretability. Future research should focus on expanding model applicability to other dementia types and on prospective evaluation of their utility in improving diagnostic accuracy, consistency, and care pathways in diverse clinical environments.

Current adjuvant strategies to combat antimicrobial resistance such as β-lactamase inhibitors and efflux pump blockers prevent antibiotic degradation or export. We introduce a fundamentally different approach: exploiting bacterial nutrient sensing to drive antibiotic influx and overwhelm resistance. Fosfomycin is transported into bacterial cytoplasm via the glucose-6-phosphate (G6P) channel UhpT, which is activated by G6P. We demonstrate that fluorinated glucose-6-phosphate analogues showed superior activation of UhpT, leading to higher fosfomycin influx. In Escherichia coli, 3-fluoro-D-glucopyranosyl-6-phosphate showed 128-fold potentiation of fosfomycin, reversed fosA-mediated fosfomycin resistance, and displayed profound suppression of resistance evolution. In Staphylococcus aureus, 4-fluoro-D-glucopyranosyl-6-phosphate achieved 32-fold potentiation and broke fosB-mediated resistance. Furthermore, co-administration of these analogues improved Galleria mellonella survival (75-80%) versus fosfomycin monotherapy (30-40%). We demonstrate this high potentiation effect is combination of metabolic stability, persistent extracellular presence and favorable binding to the sensor protein. This influx-targeting strategy establishes a new paradigm to revive legacy antibiotics against multidrug-resistant pathogens.

Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65-75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch's ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.

ALL_EARS@UoS is a patient and public involvement and engagement (PPIE) group for people with lived experience of hearing loss. The purpose of the group is to share experiences of hearing loss and hearing healthcare, inform research and improve services for patients at University of Southampton Auditory Implant Service. A year after inception, we wanted to critically reflect on the value and challenges of the group. Four members of ALL_EARS@UoS were recruited to an evaluation steering group. This paper reports the evaluation of the group using the UK Standards for Public Involvement.

A small but persistent proportion of individuals do not gain the expected benefit from cochlear implants(CI). A step-change in the understanding of factors affecting outcomes could come through data science. This study evaluates clinical data capture to assess the quality and utility of CI user's health records for data science, by assessing the recording of otitis media. Otitis media was selected as it is associated with the development of sensorineural hearing loss and may affect cochlear implant outcomes.

To test the hypothesis that pulsing of intracranial pressure has an association with cognition, we measured cognitive score and pulsing of the tympanic membrane in 290 healthy subjects. This hypothesis was formed on the assumptions that large intracranial pressure pulses impair cognitive performance and tympanic membrane pulses reflect intracranial pressure pulses.290 healthy subjects, aged 20–80 years, completed the Montreal Cognitive Assessment Test. Spontaneous tympanic membrane displacement during a heart cycle was measured from both ears in the sitting and supine position. We applied multiple linear regression, correcting for age, heart rate, and height, to test for an association between cognitive score and spontaneous tympanic membrane displacement. Significance was set at P < 0.0125 (Bonferroni correction.)

A significant association was seen in the left supine position (p = 0.0076.) The association was not significant in the right ear supine (p = 0.28) or in either ear while sitting. Sub-domains of the cognitive assessment revealed that executive function, language and memory have been primarily responsible for this association.

In conclusion, we have found that spontaneous pulses of the tympanic membrane are associated with cognitive performance and believe this reflects an association between cognitive performance and intracranial pressure pulses.

Incident microhemorrhages and superficial siderosis are hemorrhagic magnetic resonance imaging (MRI) abnormalities relevant to amyloid-related imaging abnormalities with hemosiderin deposition (ARIA-H) risk stratification, but evidence exploring their short-term dynamic predictors remains limited.

Despite national efforts to improve research inclusion, people from underserved communities remain underrepresented in dementia trials. Barriers occur at the point of initial engagement and also within the participation pathway itself, as the structure and burden of early screening procedures can discourage continuation. ACCESS D (Advancing Community Collaboration and Engagement Strategies in Dementia) aims to address these challenges by testing a community-based model that combines co-produced engagement events, low-burden research participation, and real-time support from the South Central Ambulance Service (SCAS), a trusted, community-visible National Health Service (NHS) healthcare workforce serving the counties of Hampshire, Oxfordshire, Buckinghamshire and Berkshire in Southern England, UK.

To examine stakeholder experiences of remote neurology outpatient care and to co-produce an evidence-based framework to support safe, equitable and sustainable service delivery.

Dementias, including those caused by Alzheimer's Disease (AD), are a leading global cause of death, necessitating improvements in early detection and development of more effective disease-modifying therapies. Well-validated pen-and-paper measures serve as the primary method used for cognitive assessment in research and clinical trials in AD. However, these suffer from rater error, infrequent "snapshot" bias, and have limited sensitivity to early-stage pathology, which presents challenges for measuring efficacy in prevention trials. Recent technological advances offer the potential to measure subtle cognitive changes and account for day-to-day variability through real-world data collection. The Cumulus Neuroscience NeuLogiq® platform ("the platform"), is comprised of a wireless electroencephalography (EEG) headset, tablet-based cognitive tasks based on well-established paradigms which were designed to be user-friendly based on patient panel inputs, third party integrations (mood, speech and sleep assessments) and cloud-based analytics. This platform has demonstrated utility in healthy populations and may enable objective, frequent, and patient-centered disease tracking in AD and other CNS disorders.