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  1. Abstract About 70% of people with osteogenesis imperfecta (OI) experience hearing loss. There is no cure for OI, and therapies to ameliorate hearing loss rely on conventional treatments for auditory impairments in the general population. The success rate of these treatments in the OI population with poor collagenous tissues is still unclear. Here, we conduct a systematic review and meta-analysis on the efficacy of treatments addressing hearing loss in OI. This study conforms to the reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Data sources include published articles in Medline via PubMed, Web of Science, Scopus, and Embase, from their inception to November 2020. Studies included individuals with OI undergoing a hearing loss treatment, having pre- and postoperative objective assessment of hearing function at a specified follow-up length. Our search identified 1144 articles, of which 67 were reviewed at full-text screening. A random-effects meta-analysis was conducted on the selected articles (n = 12) of people with OI that underwent stapes surgery. Success was assessed as the proportion of ears with a postoperative Air–Bone Gap (ABG) ≤ 10 dB. A systematic review was conducted on the remaining articles (n = 13) reporting on other treatments. No meta-analysis was conducted on the latter duemore »to the low number of articles on the topic and the nature of single case studies. The meta-analysis shows that stapes surgeries have a low success rate of 59.08 (95% CI 45.87 to 71.66) in the OI population. The systematic review revealed that cochlear implants, bone-anchored hearing aids, and other implantable hearing aids proved to be feasible, although challenging, in the OI population, with only 2 unsuccessful cases among the 16 reviewed single cases. This analysis of published data on OI shows poor clinical outcomes for the procedures addressing hearing loss. Further studies on hearing loss treatments for OI people are needed. Notably, the mechanisms of hearing loss in OI need to be determined to develop successful and possibly non-invasive treatment strategies.« less
    Free, publicly-accessible full text available December 1, 2023
  2. The middle ear is part of the ear in all terrestrial vertebrates. It provides an interface between two media, air and fluid. How does it work? In mammals, the middle ear is traditionally described as increasing gain due to Helmholtz’s hydraulic analogy and the lever action of the malleus-incus complex: in effect, an impedance transformer. The conical shape of the eardrum and a frequency-dependent synovial joint function for the ossicles suggest a greater complexity of function than the traditional view. Here we review acoustico-mechanical measurements of middle ear function and the development of middle ear models based on these measurements. We observe that an impedance-matching mechanism (reducing reflection) rather than an impedance transformer (providing gain) best explains experimental findings. We conclude by considering some outstanding questions about middle ear function, recognizing that we are still learning how the middle ear works.
    Free, publicly-accessible full text available October 10, 2023
  3. Free, publicly-accessible full text available October 1, 2023
  4. Background The mechanical rupture of an atheroma cap may initiate a thrombus formation, followed by an acute coronary event and death. Several morphology and tissue composition factors have been identified to play a role on the mechanical stability of an atheroma, including cap thickness, lipid core stiffness, remodeling index, and blood pressure. More recently, the presence of microcalcifications (μCalcs) in the atheroma cap has been demonstrated, but their combined effect with other vulnerability factors has not been fully investigated. Materials and methods We performed numerical simulations on 3D idealized lesions and a microCT-derived human coronary atheroma, to quantitatively analyze the atheroma cap rupture. From the predicted cap stresses, we defined a biomechanics-based vulnerability index (VI) to classify the impact of each risk factor on plaque stability, and developed a predictive model based on their synergistic effect. Results Plaques with low remodeling index and soft lipid cores exhibit higher VI and can shift the location of maximal wall stresses. The VI exponentially rises as the cap becomes thinner, while the presence of a μCalc causes an additional 2.5-fold increase in vulnerability for a spherical inclusion. The human coronary atheroma model had a stable phenotype, but it was transformed into a vulnerablemore »plaque after introducing a single spherical μCalc in its cap. Overall, cap thickness and μCalcs are the two most influential factors of mechanical rupture risk. Conclusions Our findings provide supporting evidence that high risk lesions are non-obstructive plaques with softer (lipid-rich) cores and a thin cap with μCalcs. However, stable plaques may still rupture in the presence of μCalcs.« less
    Free, publicly-accessible full text available October 6, 2023
  5. Abstract Purpose . Laboratory models of human arterial tissues are advantageous to examine the mechanical response of blood vessels in a simplified and controllable manner. In the present study, we investigated three silicone-based materials for replicating the mechanical properties of human arteries documented in the literature. Methods . We performed uniaxial tensile tests up to rupture on Sylgard184, Sylgard170 and DowsilEE-3200 under different curing conditions and obtained their True (Cauchy) stress-strain behavior and Poisson’s ratios by means of digital image correlation (DIC). For each formulation, we derived the constitutive parameters of the 3-term Ogden model and designed numerical simulations of tubular models under a radial pressure of 250 mmHg. Results . Each material exhibits evident non-linear hyperelasticity and dependence on the curing condition. Sylgard184 is the stiffest formulation, with the highest shear moduli and ultimate stresses at relative low strains ( μ 184  = 0.52–0.88 MPa, σ 184  = 15.90–16.54 MPa, ε 184  = 0.72–0.96). Conversely, Sylgard170 and DowsilEE-3200 present significantly lower shear moduli and ultimate stresses that are closer to data reported for arterial tissues ( μ 170  = 0.33–0.7 MPa σ 170  = 2.61–3.67 MPa, ε 170  = 0.69–0.81; μ dow = 0.02–0.09 MPa σ dow = 0.83–2.05 MPa, ε dow = 0.91–1.05). Undermore »radial pressure, all formulations except DowsilEE-3200 at 1:1 curing ratio undergo circumferential stresses that remain in the elastic region with values ranging from 0.1 to 0.18 MPa. Conclusion . Sylgard170 and DowsilEE-3200 appear to better reproduce the rupture behavior of vascular tissues within their typical ultimate stress and strain range. Numerical models demonstrate that all three materials achieve circumferential stresses similar to human common carotid arteries (Sommer et al 2010), making these formulations suited for cylindrical laboratory models under physiological and supraphysiological loading.« less
    Free, publicly-accessible full text available August 2, 2023