Insigneo

The human fingertip can detect small tactile features with a spatial acuity roughly the width of a fingerprint ridge. However, how individual ridges deform under contact to support accurate and high-precision tactile feedback is currently unknown. The complex mechanical structure of the glabrous skin, composed of multiple layers and intricate morphology within which mechanoreceptors are embedded, makes this question challenging. Here, we used optical coherence tomography to image and track sub-surface deformations of hundreds of individual fingerprint ridges across ten participants and four individual contact events at high spatial resolution in vivo. We calculated strain patterns in both the stratum corneum and viable epidermis in response to a variety of passively applied tactile stimuli, including static indentation, stick-to-slip events, sliding of a flat surface in different directions, and interaction with small tactile features, such as edges and grooves. We found that ridges could stretch, compress, and undergo considerable shearing orthogonal to the skin surface, but there was limited horizontal shear. Therefore, it appears that the primary components of ridge deformation and, potentially, neural responses are deformations of the ridge flanks and their relative movement, rather than overall bending of the ridges themselves. We conclude that the local distribution of mechanoreceptors across the ridges might be ideally suited to extract the resulting strain gradients and that the fingertip skin may possess a higher mechanical spatial resolution than that of a single ridge.

We predicted the fracture outcomes of simulated falls from standing height using biofidelic finite element models of older adults in Singapore. We further investigated the influence of trochanteric soft tissue thickness, measured from scans and equations estimating standing trochanteric soft tissue thickness from DXA and BMI, on predicted fracture outcomes. Biofidelic finite element models were built using DXA scans from 280 older Singaporean adults enrolled in the Targeted Assessment and Recruitment of Geriatrics for Effective Fall Prevention Treatments study. Models were created using different trochanteric soft tissue thickness: measured from 3D optical scans in standing (reference), measured from whole-body DXA, estimated from whole-body DXA, and estimated from BMI. Predicted fracture outcomes from sideways falls were compared across these models. The number of predicted hip fractures was higher among Chinese participants compared to Indians (females: 2.4×, males: 2.3×) and Malays (females: 2.5×, males: 1.3×). Trochanteric soft tissue thickness was the dominant factor influencing impact force and force attenuation at the greater trochanter. The whole-body DXA model had a 26% false prediction rate compared to the reference model, while the models using estimated values from whole-body DXA and BMI had false prediction rates of 1% and 9%, respectively. Biofidelic finite element models built using image data captures population-based differences in hip fracture risk for the three main ethnic groups in Singapore. In the absence of 3D optical scans, predicting soft tissue shapes based on whole-body DXA scans, commonly available in clinical practice, yields similar fracture predictions based on simulated falls.

ABSTRACTBackgroundImpaired insight can be understood clinically as a loss of ability to appropriately recognize one's own disease status. Investigating insight in Alzheimer's disease (AD) and its relation to longitudinal changes in brain structure is important to understand the disease progression.ObjectiveTo examine how the character of insight changes with disease stage and assess whether baseline levels of impaired insight can predict rate of brain atrophy across a period of 30 months in a cohort of subjects consisting of subjective memory complaint (SMC), mild cognitive impairment (MCI), AD, and cognitively normal (CN) controls.MethodsData from 794 eligible participants were extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Insight levels were estimated by the Measurement of Everyday Cognition (ECog). Impairment was further categorized into overestimation or underestimation of ability. Brain atrophy rates were estimated by measuring change in gray matter volume within 30 months.ResultsOverestimating ability was significantly correlated with increased whole‐brain atrophy rates (p < 0.001) independent of general cognitive decline. Overestimation of ability exhibited significant correlations with increased atrophy in specific regions of the brain including the medial temporal lobe, fusiform gyrus, and hippocampus.DiscussionThe present results suggest a statistically significant correlation between overestimation of ability and increased rates of subsequent brain atrophy. This is particularly notable in regions of the brain such as the hippocampus. However, further study into the phenomenon of insight and its progression over the disease course is required before its potential clinical utility can be fully assessed.

Liquid formulations of platelet-rich fibrin (Liquid-PRF) have been shown to promote oral soft tissue healing for some clinical applications, however, the efficacy of liquid-PRF as a standalone treatment remains uncertain. The aim of the present study was to investigate the effects of liquid-PRF on oral cells in vitro using two-dimensional cell culture and three-dimensional tissue-engineered oral mucosa models. Media was conditioned with liquid-PRF prepared from blood samples and applied to oral fibroblasts, keratinocytes and tissue-engineered oral mucosa models. Metabolic activity, migration, proliferation and epithelial morphology were assessed. Liquid-PRF was shown to be biocompatible, with no cytotoxic effects observed on oral mucosa cells or 3D oral mucosa models. Cytokine analysis confirmed the presence of key growth factors, including PDGF-BB, TGF-β1, and EGF. Liquid-PRF increased oral fibroblast proliferation and promoted keratinocyte migration in 2D cultures. In tissue-engineered oral mucosa models, liquid-PRF showed no significant improvement in metabolic activity, epithelium thickness, morphology or proliferative capacity. The results suggest that growth factors in liquid-PRF were able to stimulate the proliferation and migration of oral mucosa cells in 2D culture, however these effects could not be demonstrated in 3D oral mucosa models. Factors secreted from liquid PRF were able to support the growth of cells and the development and maintenance of a healthy epithelium. Despite improvements in keratinocyte migration and fibroblast proliferation the results from 3D models indicate that factors secreted from liquid-PRF alone may not be sufficient to stimulate oral soft tissue repair.

ABSTRACT Atherosclerosis progresses from fatty streaks to complex plaques, with rupture leading to life-threatening complications. Endothelial-to-mesenchymal transition (EndMT) is associated with advanced atherosclerotic plaques, but its role in plaque progression remains unclear. To investigate this, we analyzed the role of TWIST1, a key EndMT-driving transcription factor, in plaque development. Using single-cell RNA sequencing of atherosclerotic plaques from hypercholesterolemic mice with inducible deletion of Twist1 from endothelial cells ( Twist1 ECKO ApoE -/- ) we demonstrate that Twist1 regulates endothelial cell heterogeneity by promoting cell states expressing EndMT markers. Cell tracking confirmed that Twist1 induces EndMT in advanced plaques. Mechanistically, we found that TWIST1 contributes to EndMT by promoting endothelial migration and proliferation through the transcriptional coactivator PELP1. Additionally, TWIST1 induces AEBP1 transcription, which upregulates COL4A1 to drive endothelial proliferation. Analyses of murine brachiocephalic plaques show that endothelial Twist1 promotes plaque growth, collagen deposition, and ACTA2-positive cell accumulation, hallmarks of plaque stability, while reducing necrosis and macrophage infiltration, features of plaque instability. Moreover, TWIST1 expression was associated with asymptomatic human carotid atherosclerosis and predicts favourable clinical outcomes. These findings challenge the prevailing view that EndMT destabilizes plaques, by suggesting that TWIST1-driven EndMT can promote plaque stability, offering new insights into atherosclerosis pathophysiology and therapeutic potential.

We examined the role of subtypes of adenosine receptors in bladder dysfunction and changes in the adenosine receptor expression in the bladder using male rats with partial bladder outlet obstruction (BOO). In Sprague-Dawley rats (male 8-weeks old), BOO was produced by a partial ligation of the urethra along a metal rod of a 1.2 mm outer diameter. Control rats underwent sham operation. Awake cystometrograms (CMG) were first recorded during saline instillation, and then an adenosine A1 receptor agonist (CCPA, 4.1 μM), an adenosine A2A antagonist (ZM241385, 15 μM), or inosine (1 mM) were applied intravesically in sham and BOO rats. In addition, mRNA levels of adenosine receptor subtypes in the bladder wall were measured using RT-PCR. Histological studies of bladder specimen were also performed. Weights of BOO bladders were significantly (p < 0.0001) larger compared with sham bladders. In CMG, a number of non-voiding contractions (NVCs), bladder contraction amplitudes during voiding, bladder capacity, and post-void residual (PVR) were significantly (p < 0.001) increased compared with sham rats. Voiding efficiency (VE) was significantly (p < 0.001) reduced in BOO versus sham rats. Intravesical application of CCPA or inosine did not induce statistically significant effects on CMG parameters in BOO rats. Yet, ZM241385 induced a significant (p = 0.040) reduction in NVCs of BOO rats. mRNA levels of adenosine A2A and A3 receptors were significantly (p < 0.0001 and p = 0.0145, respectively) upregulated in the BOO bladder mucosa, whereas adenosine A2B receptors showed a significant (p < 0.0001) reduction in the BOO bladder mucosa compared with sham bladders. Histologically, we found the thickened detrusor muscle layer in BOO versus sham rats. The male rat model of BOO seems to be suitable for exploring urethral obstruction-related bladder dysfunction at the compensated phase. In addition, the adenosine A2A receptor subtype would be a potential target for the treatment of male BOO patients with bladder overactivity. A clinical trial registration is not required as this study reported the basic research data using animal models.