Computed tomography enables 3D anatomic imaging at a high spatial resolution, but requires delivery of an x-ray contrast agent to distinguish tissues with similar or low x-ray attenuation. Gold ...nanoparticles (AuNPs) have gained recent attention as an x-ray contrast agent due to exhibiting a high x-ray attenuation, nontoxicity and facile synthesis and surface functionalization for colloidal stability and targeted delivery. Potential diagnostic applications include blood pool imaging, passive targeting and active targeting, where actively targeted AuNPs could enable molecular imaging by computed tomography. This article summarizes the current state of knowledge for AuNP x-ray contrast agents within a paradigm of key structure-property-function relationships in order to provide guidance for the design of AuNP contrast agents to meet the necessary functional requirements in a particular application. Functional requirements include delivery to the site of interest (e.g., blood, tumors or microcalcifications), nontoxicity during delivery and clearance, targeting or localization at the site of interest and contrast enhancement for the site of interest compared with surrounding tissues. Design is achieved by strategically controlling structural characteristics (composition, mass concentration, size, shape and surface functionalization) for optimized properties and functional performance. Examples from the literature are used to highlight current design trade-offs that exist between the different functional requirements.
Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, ...highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking. The complexity of the biological underpinnings of depression coupled with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to disentangle exercise's effects on depression. Notwithstanding our limited understanding of these effects, clinical evidence uniformly argues for the use of exercise to treat depression. Regrettably, exercise remains underutilized despite being an accessible, low-cost alternative/adjunctive intervention that can simultaneously reduce depression and improve overall health. To address the gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until the science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care.
Stroke is a leading cause of long-term disability in the US, yet a feasible assessment measure with predictive value for components of the International Classification of Functioning, Disability, and ...Health (ICF) Core Set for Stroke is lacking. The purpose of the present study was to explore the predictive value of potential assessment measures on factors within each ICF component in stroke survivors.
Demographic, anthropometric, blood-based biomarker, physical functioning, and Global Physical Activity Questionnaire data were collected on stroke survivors in the 2011-2018 NHANES cycles. Potential predictors (handgrip strength relative to weight, age, sex, race, education level, marital status, poverty ratio, stroke chronicity) of physical function, activities of daily living (ADLs), participation in social activities, metabolic syndrome, and meeting physical activity recommendations were evaluated using weighted linear and ordinal logistic regression.
Relative handgrip strength was a significant predictor of physical function, difficulty participating in ADLs and social activities, and odds of meeting physical activity recommendations. As relative handgrip strength increased, these factors improved among stroke survivors.
To decrease disability rates and optimize function among stroke survivors, the use of assessment measures like relative handgrip strength that may predict multiple ICF components is warranted.
There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a ...promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.
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Abstract Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently ...available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (μCT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated. In the current study we tested the ability of μCT to estimate six BMDD parameters: mean, heterogeneity (assessed by the full-width-at-half-maximum (FWHM) and the coefficient of variation (CoV)), the upper and lower 5% cutoffs of the frequency distribution, and peak mineralization) in rat sized femoral cortical bone samples. We used backscatter scanning electron microscopy (bSEM) as the standard. Aluminum and hydroxyapatite phantoms were used to identify optimal scanner settings (70 kVp, and 57 μA, with a 1500 ms integration time). When using hydroxyapatite samples that spanned a broad range of mineralization levels, high correlations were found between μCT and bSEM for all BMDD parameters (R2 ≥ 0.92, p < 0.010). When using cortical bone samples from rats and various species machined to mimic rat cortical bone geometry, significant correlations between μCT and bSEM were found for mean mineralization (R2 = 0.65, p < 0.001), peak mineralization (R2 = 0.61, p < 0.001) the lower 5% cutoff (R2 = 0.62, p < 0.001) and the upper 5% cutoff (R2 = 0.33, p = 0.021), but not for heterogeneity, measured by FWHM (R2 = 0.05, p = 0.412) and CoV (R2 = 0.04, p = 0.469). Thus, while mean mineralization and most parameters used to characterize the BMDD can be assessed with μCT in rat sized cortical bone samples, caution should be used when reporting the heterogeneity.
Background
Containment of the coronavirus disease 2019 (COVID‐19) pandemic requires the public to change behavior under social distancing mandates. Social media are important information ...dissemination platforms that can augment traditional channels communicating public health recommendations. The objective of the study was to assess the effectiveness of COVID‐19 public health messaging on Twitter when delivered by emergency physicians and containing personal narratives.
Methods
On April 30, 2020, we randomly assigned 2,007 U.S. adults to an online survey using a 2 × 2 factorial design. Participants rated one of four simulated Twitter posts varied by messenger type (emergency physician vs. federal official) and content (personal narrative vs. impersonal guidance). The main outcomes were perceived message effectiveness (35‐point scale), perceived attitude effectiveness (PAE; 15‐point scale), likelihood of sharing Tweets (7‐point scale), and writing a letter to their governor to continue COVID‐19 restrictions (write letter or none).
Results
The physician/personal (PP) message had the strongest effect and significantly improved all main messaging outcomes except for letter writing. Unadjusted mean differences between PP and federal/impersonal (FI) were as follows: perceived messaging effectiveness (3.2 95% CI = 2.4 to 4.0), PAE (1.3 95% CI = 0.8 to 1.7), and likelihood of sharing (0.4 95% CI = 0.15 to 0.7). For letter writing, PP made no significant impact compared to FI (odds ratio = 1.14 95% CI = 0.89 to 1.46).
Conclusions
Emergency physicians sharing personal narratives on Twitter are perceived to be more effective at communicating COVID‐19 health recommendations compared to federal officials sharing impersonal guidance.
X-linked hypophosphatemia (XLH) is caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX). Loss of functional PHEX ...results in elevated fibroblast growth factor 23 (FGF23), impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily by osteocytes, suppresses bone formation by antagonizing canonical Wnt-signaling and is reported to be elevated in XLH patients. Our previous study reported that a monoclonal antibody to sclerostin (Scl-Ab) decreases FGF23 and increases phosphate and bone mass in growing Hyp mice (XLH murine model). In the current study, we investigated the efficacy of Scl-Ab in treating XLH pathophysiology in adult Hyp mice that are past the period of rapid skeletal growth (12 and 20-weeks old). We hypothesized that Scl-Ab would not only increase bone formation, bone strength and bone mass, but would also normalize phosphate regulating hormones, FGF23, parathyroid hormone (PTH), and vitamin 1,25(OH)2D. Scl-Ab treatment increased cortical area, trabecular bone volume fraction, trabecular bone formation rate, and the bending moment in both sexes of both age groups. Scl-Ab treatment suppressed circulating levels of intact FGF23 and c-term FGF23 in treated male and female wild-type and Hyp mice of both age groups and improved both vitamin 1,25(OH)2D and PTH. Scl-Ab treated Hyp mice also showed evidence of increased renal expression of the sodium-phosphate co-transporter, NPT2a, specifically in the female Hyp mice. Our study suggests that Scl-Ab treatment can improve several skeletal and metabolic pathologies associated with XLH, further establishes the role of sclerostin in the regulation of FGF23 and provides evidence that Scl-Ab can improve phosphate regulation by targeting the bone-renal axis.
•Sclerostin antibody decreases fibroblast growth factor-23, increases vitamin 1,25(OH)2D, and decreases parathyroid hormone in adult Hyp mice.•Sclerostin antibody treatment increases bone mass, bone formation rate, and bone strength in adult Hyp mice.•Sclerostin antibody treatment increases NPT2a protein expression, particularly in female Hyp mice.
Although complex in nature, the pathophysiology of depression involves reduced or impaired neuroplastic capabilities. Restoring or enhancing neuroplasticity may serve as a treatment target for ...developing therapies for depression. Aerobic exercise (AEx) has antidepressant benefits and may enhance neuroplasticity in depression although the latter has yet to be substantiated. Therefore, we sought to examine the acute effect of AEx on neuroplasticity in depression.
Sixteen individuals with (DEP; 13 female; age = 28.5 ± 7.3; Montgomery-Äsberg Depression Rating Scale MADRS = 21.3 ± 5.2) and without depression (HC; 13 female; age 27.2 ± 7.5; MADRS = 0.8 ± 1.2) completed three experimental visits consisting of 15 min of low intensity AEx (LO) at 35% heart rate reserve (HRR), high intensity AEx (HI) at 70% HRR, or sitting (CON). Following AEx, excitatory paired associative stimulation (PAS25ms) was employed to probe neuroplasticity. Motor evoked potentials (MEP) were assessed via transcranial magnetic stimulation before and after PAS25ms to indicate acute changes in neuroplasticity.
PAS25ms primed with HI AEx led to significant increases in MEP amplitude compared to LO and CON. HI AEx elicited enhanced PAS25ms-induced neuroplasticity for up to 1-h post-PAS. There were no significant between-group differences.
HI AEx enhances PAS measured neuroplasticity in individuals with and without depression. HI AEx may have a potent influence on the brain and serve as an effective primer, or adjunct, to therapies that seek to harness neuroplasticity.
•Fifteen minutes of high intensity aerobic exercise enhanced neuroplasticity.•A window of enhanced neuroplasticity may persist for at least 1-h post-exercise.•Exercise-enhanced neuroplasticity was not inhibited by depression.•Aerobic exercise may be used to prime the brain for other therapeutic strategies.
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