Partial body fat percentage as a predictor of fragility fractures in a large cohort: a cross-sectional study.

Objectives: BMI is a component of fracture risk calculators; however, it may be too simplistic to predict fracture risk. There is emerging evidence for the role that fat plays as a predictor of fracture. Partial body fat percentage (PBF%) may be a novel way to predict both hip and non-hip fractures. The aim of this study is to evaluate PBF% as a predictor of fragility fractures. Methods: A multivariate logistic regression analysis was conducted looking at PBF% as a predicter of both non-hip and hip fractures in an observational cohort. Our results were adjusted for age, biological sex, gender, smoking status, excess alcohol consumption (>3 units/day), current steroid therapy and the T-scores in both femurs. To allow for comparison, the same model was used with BMI, height and weight as the primary predictor of fracture. A subgroup analysis was conducted stratified by fracture site. A sensitivity analysis using a negative binomial regression was conducted. Results: A total of 31 447 patients were included in our analysis [mean age 64.9 years (s.d. 12.9)]. PBF% was shown to predict all non-hip fractures after adjustment [odds ratio (OR) 22.14 (95% CI 15.08, 32.50)]. Hip fractures were not predicted by our model [OR 4.19 (95% CI 0.43, 41.46)]. Sensitivity analysis demonstrated a lack of predictive capability for hip fracture but not non-hip fractures. Conclusion: PBF% may be a suitable predictor for all non-hip fractures, independent of confounding variables. More research is needed on whether it can predict hip fractures.

Single-Molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-Related CARTPT-Expressing Smooth Muscle Cells.

BACKGROUND: Although single-cell RNA-sequencing is commonly applied to dissect the heterogeneity in human tissues, it involves the preparation of single-cell suspensions via cell dissociation, causing loss of spatial information. In this study, we employed high-resolution single-cell transcriptome imaging to reveal rare smooth muscle cell (SMC) types in human thoracic aortic aneurysm (TAA) tissue samples. METHODS: Single-molecule spatial distribution of transcripts from 140 genes was analyzed in fresh-frozen human TAA samples with region and sex-matched controls. In vitro studies and tissue staining were performed to examine human CART prepropeptide (CARTPT) regulation and function. RESULTS: We captured thousands of cells per sample including a spatially distinct CARTPT-expressing SMC subtype enriched in male TAA samples. Immunoassays confirmed human CART (cocaine- and amphetamine-regulated transcript) protein enrichment in male TAA tissue and truncated CARTPT secretion into cell culture medium. Oxidized low-density lipoprotein, a cardiovascular risk factor, induced CARTPT expression, whereas CARTPT overexpression in human aortic SMCs increased the expression of key osteochondrogenic transcription factors and reduced contractile gene expression. Recombinant human CART treatment of human SMCs further confirmed this phenotype. Alizarin red staining revealed calcium deposition in male TAA samples showing similar localization with human CART staining. CONCLUSIONS: Here, we demonstrate the feasibility of single-molecule imaging in uncovering rare SMC subtypes in the diseased human aorta, a difficult tissue to dissociate. We identified a spatially distinct CARTPT-expressing SMC subtype enriched in male human TAA samples. Our functional studies suggest that human CART promotes osteochondrogenic switch of aortic SMCs, potentially leading to medial calcification of the thoracic aorta.

Bone mineral density in patients diagnosed with giant cell arteritis taking glucocorticoids: a case-control study.

Objective: The standard treatment for GCA is high-dose glucocorticoids (GCs). It is unknown whether GCs are more detrimental to BMD at the spine or the hip. The aim of this study was to investigate the effect of GCs on BMD at the lumbar spine and hip in patients with GCA being treated with GCs. Methods: Patients who were referred for DXA at a hospital in the north-west of England between 2010 and 2019 were included. Two patient groups were identified: patients with GCA on current GC (cases) were matched 1:4 based on age and biological sex to those referred to the scanner with no indication for scanning (controls). Logistic models were fitted looking at the spine and hip BMD, unadjusted and adjusted for height and weight. Results: As would be expected, this gave an adjusted odds ratio (OR) of 0.280 (95% CI 0.071, 1.110) at the lumbar spine, OR of 0.238 (95% CI 0.033, 1.719) at the left femoral neck, OR of 0.187 (95% CI 0.037, 0.948) at the right femoral neck, OR of 0.005 (95% CI 0.001, 0.021) at the left total hip and OR of 0.003 (95% CI 0.001, 0.015) at the right total hip. Conclusion: The study has shown that patients diagnosed with GCA receiving GC treatment have a lower BMD at the right femoral neck, left total hip and right total hip compared with controls in patients of the same age and biological sex after adjusting for height and weight.

Stem cells for the treatment of glioblastoma: a 20-year perspective.

Glioblastoma, the deadliest form of primary brain tumor, remains a disease without cure. Treatment resistance is in large part attributed to limitations in the delivery and distribution of therapeutic agents. Over the last 20 years, numerous preclinical studies have demonstrated the feasibility and efficacy of stem cells as antiglioma agents, leading to the development of trials to test these therapies in the clinic. In this review we present and analyze these studies, discuss mechanisms underlying their beneficial effect and highlight experimental progress, limitations and the emergence of promising new therapeutic avenues. We hope to increase awareness of the advantages brought by stem cells for the treatment of glioblastoma and inspire further studies that will lead to accelerated implementation of effective therapies.

Lay abstract Glioblastoma is the deadliest and most common form of brain tumor, for which there is no cure. It is very difficult to deliver medicine to the tumor cells, because they spread out widely into the normal brain, and local blood vessels represent a barrier that most medicines cannot cross. It was shown, in many studies over the last 20 years, that stem cells are attracted toward the tumor and that they can deliver many kinds of therapeutic agents directly to brain cancer cells and shrink the tumor. In this review we analyze these studies and present new discoveries that can be used to make stem cell therapies for glioblastoma more effective to prolong the life of patients with brain tumors.

Dual-Task Processing With Identical Stimulus and Response Sets: Assessing the Importance of Task Representation in Dual-Task Interference.

Limitations in our ability to produce two responses at the same time - that is, dual-task interference - are typically measured by comparing performance when two stimuli are presented and two responses are made in close temporal proximity to when a single stimulus is presented and a single response is made. While straightforward, this approach leaves open multiple possible sources for observed differences. For example, on dual-task trials, it is typically necessary to identify two stimuli nearly simultaneously, whereas on typical single-task trials, only one stimulus is presented at a time. These processes are different from selecting and producing two distinct responses and complicate the interpretation of dual- and single-task performance differences. Ideally, performance when two tasks are executed should be compared to conditions in which only a single task is executed, while holding constant all other stimuli, response, and control processing. We introduce an alternative dual-task procedure designed to approach this ideal. It holds stimulus processing constant while manipulating the number of "tasks." Participants produced unimanual or bimanual responses to pairs of stimuli. For one set of stimuli (two-task set), the mappings were organized so an image of a face and a building were mapped to particular responses (including no response) on the left or right hands. For the other set of stimuli (one-task set), the stimuli indicated the same set of responses, but there was not a one-to-one mapping between the individual stimuli and responses. Instead, each stimulus pair had to be considered together to determine the appropriate unimanual or bimanual response. While the stimulus pairs were highly similar and the responses identical across the two conditions, performance was strikingly different. For the two-task set condition, bimanual responses were made more slowly than unimanual responses, reflecting typical dual-task interference, whereas for the one-task set, unimanual responses were made more slowly than bimanual. These findings indicate that dual-task costs occur, at least in part, because of the interfering effects of task representation rather than simply the additional stimulus, response, or other processing typically required on dual-task trials.

Fitness, Sleep-Disordered Breathing, Symptoms of Depression, and Cognition in Inactive Overweight Children: Mediation Models.

OBJECTIVES: We used mediation models to examine the mechanisms underlying the relationships among physical fitness, sleep-disordered breathing (SDB), symptoms of depression, and cognitive functioning. METHODS: We conducted a cross-sectional secondary analysis of the cohorts involved in the 2003-2006 project PLAY (a trial of the effects of aerobic exercise on health and cognition) and the 2008-2011 SMART study (a trial of the effects of exercise on cognition). A total of 397 inactive overweight children aged 7-11 received a fitness test, standardized cognitive test (Cognitive Assessment System, yielding Planning, Attention, Simultaneous, Successive, and Full Scale scores), and depression questionnaire. Parents completed a Pediatric Sleep Questionnaire. We used bootstrapped mediation analyses to test whether SDB mediated the relationship between fitness and depression and whether SDB and depression mediated the relationship between fitness and cognition. RESULTS: Fitness was negatively associated with depression ( B = -0.041; 95% CI, -0.06 to -0.02) and SDB ( B = -0.005; 95% CI, -0.01 to -0.001). SDB was positively associated with depression ( B = 0.99; 95% CI, 0.32 to 1.67) after controlling for fitness. The relationship between fitness and depression was mediated by SDB (indirect effect = -0.005; 95% CI, -0.01 to -0.0004). The relationship between fitness and the attention component of cognition was independently mediated by SDB (indirect effect = 0.058; 95% CI, 0.004 to 0.13) and depression (indirect effect = -0.071; 95% CI, -0.01 to -0.17). CONCLUSIONS: SDB mediates the relationship between fitness and depression, and SDB and depression separately mediate the relationship between fitness and the attention component of cognition.