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Unraveling the complexity of biomatrices is a persisting challenge in many areas of the life sciences. The detection of soluble signaling molecules—cytokines and growth factors—within multicomponent biopolymer scaffolds is of particular interest as they control important biological processes such as the development of tissues, pathologies, and regeneration. The application of time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) for the detection of interleukin‐8 (IL‐8), a chemokine involved in inflammation and cancer, is explored within biopolymer matrices of different complexity. To establish the workflow, IL‐8 is embedded with graded mass fractions in thin biopolymer matrices consisting of heparin and/or bovine serum albumin, followed by a comprehensive ToF‐SIMS analysis of the prepared samples. Partial least square regression models are developed and successfully applied to detect IL‐8 mass fractions down to 1 ppm on the basis of the measured ToF‐SIMS spectra. The methodology is successfully applied to detect IL‐8 in Matrigel and poly(ethylene glycol)‐heparin matrices with similar sensitivity. Given the high performance of state‐of‐the‐art SIMS instruments and the increasing power of machine learning algorithms, it is envisioned that the established approach, in combination with other methods, will enable a comprehensive assessment of soluble signaling molecules in (engineered) matrix‐supported 3D cell and organoid cultures. The power of time‐of‐flight secondary ion mass spectrometry‐partial least square regression to detect interleukin‐8, a chemokine involved in inflammation and cancer, down to mass fractions of 1 ppm within biopolymer matrices, including Matrigel and glycosaminoglycan‐based hydrogels, is demonstrated. In combination with other methods, the established approach will enable the comprehensive assessment of signaling molecules in matrix‐supported 3D cell and organoid cultures.

Detonation nanodiamonds (NDs) are a novel class of carbon-based nanomaterials, and have received a great deal of attention in biomedical applications, due to their high biocompatibility, facile surface functionalization, and commercialized synthetic fabrication. We were able to transfer the NDs from large-size agglomerate suspensions to homogenous coatings. ND suspensions have been used in various techniques to coat on commercially available substrates of pure Ti and Si. Scanning electron microscopy (SEM) imaging and nanoindentation show that the densest and strongest coating of NDs was generated when using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide (EDC/NHS)-mediated coupling to macroscopic silanized surfaces. In the next step, the feasibility of DNA-mediated coupling of NDs on macroscopic surfaces is discussed using fluorescent microscopy and additional particle size distribution, as well as zeta potential measurements. This work compares different ND coating strategies and describes the straightforward technique of grafting single-stranded DNA onto carboxylated NDs via thioester bridges.

Osteoporosis is associated with increased fragility of bone and a subsequent increased risk of fracture. The diagnosis of osteoporosis is intimately linked with the imaging and quantification of bone and BMD. Scanning modalities, such as dual-energy X-ray absorptiometry or quantitative CT, have been developed and honed over the past half century to provide measures of BMD and bone microarchitecture for the purposes of clinical practice and research. Combined with fracture prediction tools such as Fracture Risk Assessment Tool (FRAX) (which use a combination of clinical risk factors for fracture to provide a measure of risk), these elements have led to a paradigm shift in the ability to diagnose osteoporosis and predict individuals who are at risk of fragility fracture. Despite these developments, a treatment gap exists between individuals who are at risk of osteoporotic fracture and those who are receiving therapy. In this Review, we summarize the epidemiology of osteoporosis, the history of scanning modalities, fracture prediction tools and future directions, including the most recent developments in prediction of fractures.This Review highlights various medical imaging techniques and fracture prediction tools that are used to diagnosis osteoporosis and discusses the potential importance of screening in at-risk populations.

Background Ageing is commonly associated with sarcopenia (SP) and osteoporosis (OP), both of which are associated with disability, impaired quality of life, and mortality. The aims of this study were to explore the relationships between SP, OP, frailty, and multimorbidity in community‐dwelling older adults participating in the Hertfordshire Cohort Study (HCS) and to determine whether coexistence of OP and SP was associated with a significantly heavier health burden. Methods At baseline, 405 participants self‐reported their comorbidities. Cut‐offs for low grip strength and appendicular lean mass index were used according to the EWSGOP2 criteria to define SP. OP was diagnosed when T‐scores of < −2.5 were present at the femoral neck or the participant reported use of the anti‐OP medications including hormone replacement therapy (HRT), raloxifene, or bisphosphonates. Frailty was defined using the standard Fried definition. Results One hundred ninety‐nine men and 206 women were included in the study. Baseline median (interquartile range) age of participants was 75.5 (73.4–77.9) years. Twenty‐six (8%) and 66 (21.4%) of the participants had SP and OP, respectively. Eighty‐three (20.5%) reported three or more comorbidities. The prevalence of pre‐frailty and frailty in the study sample was 57.5% and 8.1%, respectively. Having SP only was strongly associated with frailty [odds ratio (OR) 8.28, 95% confidence interval (CI) 1.27, 54.03; P = 0.027] while the association between having OP alone and frailty was weaker (OR 2.57, 95% CI 0.61, 10.78; P = 0.196). The likelihood of being frail was substantially higher in the presence of coexisting SP and OP (OR 26.15, 95% CI 3.13, 218.76; P = 0.003). SP alone and OP alone were both associated with having three or more comorbidities (OR 4.71, 95% CI 1.50, 14.76; P = 0.008 and OR 2.86, 95% CI 1.32, 6.22; P = 0.008, respectively) although the coexistence of SP and OP was not significantly associated with multimorbidity (OR 3.45, 95% CI 0.59, 20.26; P = 0.171). Conclusions Individuals living with frailty were often osteosarcopenic. Multimorbidity was common in individuals with either SP or OP. Early identification of SP and OP not only allows implementation of treatment strategies but also presents an opportunity to mitigate frailty risk.

Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

Here we present a description of the UKCA StratTrop chemical mechanism, which is used in the UKESM1 Earth system model for CMIP6. The StratTrop chemical mechanism is a merger of previously well-evaluated tropospheric and stratospheric mechanisms, and we provide results from a series of bespoke integrations to assess the overall performance of the model.We find that the StratTrop scheme performs well when compared to a wide array of observations. The analysis we present here focuses on key components of atmospheric composition, namely the performance of the model to simulate ozone in the stratosphere and troposphere and constituents that are important for ozone in these regions. We find that the results obtained for tropospheric ozone and its budget terms from the use of the StratTrop mechanism are sensitive to the host model; simulations with the same chemical mechanism run in an earlier version of the MetUM host model show a range of sensitivity to emissions that the current model does not fall within.Whilst the general model performance is suitable for use in the UKESM1 CMIP6 integrations, we note some shortcomings in the scheme that future targeted studies will address.

Musculoskeletal disorders are common among older people. Preventive strategies require understanding of age-related changes in strength, function and body composition, including how they interrelate. We have described, and examined associations between, 9-year changes in these parameters among 2917 Health, Aging and Body Composition Study participants (aged 70–79 years). Appendicular lean mass (ALM), whole body fat mass and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. For each characteristic annualised percentage changes were calculated; measures of conditional change (independent of baseline) were derived and their interrelationships were examined using Pearson correlations; proportion of variance at 9-year follow-up explained by baseline level was estimated; and mean trajectories in relation to age were estimated using linear mixed models. Analyses were stratified by sex. Median [lower quartile, upper quartile] annual percentage declines were grip strength (1.5 [0.0, 2.9]), gait speed (2.0 [0.6, 3.7]), ALM (0.7 [0.1, 1.4]), fat mass (0.4 [− 1.1, 1.9]) and hip BMD (0.5 [0.0, 1.1]). Declines were linear for ALM and accelerated over time for other characteristics. Most conditional change measures were positively correlated, most strongly between ALM, fat mass and hip BMD ( r  > 0.28). Proportion of variation at follow-up explained by baseline was lower for grip strength and gait speed (39–52%) than other characteristics (69–86%). Strength and function declined more rapidly, and were less correlated between baseline and follow-up, than measures of body composition. Therefore, broader intervention strategies to prevent loss of strength and function in later life are required as those targeting body composition alone may be insufficient.

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70–79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2–3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10–14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p < 0.05) with increased rates of mortality; fully-adjusted hazard ratios per SD lower gait speed and grip strength were 1.27 (95% CI 1.19, 1.36) and 1.14 (1.07, 1.21), respectively. Risk factors of hospital admission included lower levels and greater declines in gait speed and grip strength, and greater declines in hip BMD. Lower levels and greater declines in fat mass and hip BMD were associated with low trauma fracture. Lower gait speed, higher fat mass, and both lower levels and greater declines in grip strength were related to recurrent falls. Lower baseline levels and greater declines in musculoskeletal parameters were related to adverse outcomes. Interventions to maximize peak levels in earlier life and reduce rates of age-related decline may reduce the burden of disease in this age group.

The developmental patterns of subcortical brain volumes in males and females observed in previous studies have been inconsistent. To help resolve these discrepancies, we examined developmental trajectories using three independent longitudinal samples of participants in the age-span of 8–22 years (total 216 participants and 467 scans). These datasets, including Pittsburgh (PIT; University of Pittsburgh, USA), NeuroCognitive Development (NCD; University of Oslo, Norway), and Orygen Adolescent Development Study (OADS; The University of Melbourne, Australia), span three countries and were analyzed together and in parallel using mixed-effects modeling with both generalized additive models and general linear models. For all regions and across all samples, males were found to have significantly larger volumes as compared to females, and significant sex differences were seen in age trajectories over time. However, direct comparison of sample trajectories and sex differences identified within samples were not consistent. The trajectories for the amygdala, putamen, and nucleus accumbens were most consistent between the three samples. Our results suggest that even after using similar preprocessing and analytic techniques, additional factors, such as image acquisition or sample composition may contribute to some of the discrepancies in sex specific patterns in subcortical brain changes across adolescence, and highlight region-specific variations in congruency of developmental trajectories. •Sex differences were seen in age trajectories over time based on three samples.•General additive models can assess presumed sex differences in trajectory shape.•Despite identical data processing and analysis, discrepancies existed between the samples.•Amygdala, putamen, and nucleus accumbens patterns were most consistent between samples.