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Materials currently used to repair or replace a heart valve are not durable. Their limited durability related to structural degeneration or thrombus formation is attributed to their inadequate mechanical properties and biocompatibility profiles. Our hypothesis is that a biostable material that mimics the structure, mechanical and biological properties of native tissue will improve the durability of these leaflets substitutes and in fine improve the patient outcome. Here, we report the development, optimization, and testing of a biomimetic, multilayered material (BMM), designed to replicate the native valve leaflets. Polycarbonate urethane and polycaprolactone have been processed as film, foam, and aligned fibers to replicate the leaflet's architecture and anisotropy, through solution casting, lyophilization, and electrospinning. Compared to the commercialized materials, our BMMs exhibited an anisotropic behavior and a closer mechanical performance to the aortic leaflets. The material exhibited superior biostability in an accelerated oxidization environment. It also displayed better resistance to protein adsorption and calcification in vitro and in vivo. These results will pave the way for a new class of advanced synthetic material with long-term durability for surgical valve repair or replacement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mingze Sun has patent Biomimetic polymeric composite for heart valve repair pending to The Trustees of Columbia University in the City of New York. David Kalfa has patent Biomimetic polymeric composite for heart valve repair pending to The Trustees of Columbia University in the City of New York., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Otologic surgery in guinea pig requires head immobilization for microscopic manipulation. Existing commercially available stereotaxic frames are expensive and impede access to the ear as they rely on ear bars or mouthpieces to secure the head., Method: Prototype head holders were designed using the Solidworks 2019 software and 3D-printed using Formlabs Form 2 Printers with photopolymer resin. The head holder consists of a C-shaped brace with adjustable radial inserts of 1/4-20 UNC standard screws with cone point tips providing head fixation for animals of various sizes. The C-shaped brace is attached to a rod that can be secured to a commercially available micromanipulator. The head holder design was tested during in vivo guinea pig experiments where their head motion with (n = 22) and without the head holder (n = 2) was evaluated visually through a stereotaxic microscope at 24× magnification during surgery., Results: The head holder design was easy to use and allowed for both nose cone administration of anesthesia and access to the ear for intraoperative auditory testing and manipulation. Functionally, the head holder successfully minimized head movement. Furthermore, harvested round window membranes evaluated at 72 hours following surgery showed precise perforations with the use of head holder., Conclusion: The novel 3D-printed head holder enables simultaneous access for nose cone administration of anesthesia and surgical manipulation of the ear and brain. Moreover, it provides a modular, intuitive, and economical alternative to commercial stereotaxic devices for minimizing head motion during small animal surgery., Competing Interests: Dr. Anil K. Lalwani serves on the Medical Advisory Board for Advanced Bionics and on the Surgical Advisory Board for MED-EL. For the remaining authors, no conflicts of interest were declared., (Copyright © 2021, Otology & Neurotology, Inc.)

Key Points: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts. We combined ∼4 mmHg ambient P C O 2 with the strict head-down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one-half of the subjects. We demonstrate no change in arterialized P C O 2 , cerebrovascular reactivity to CO 2 or the hypercapnic ventilatory response. Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro-ocular syndrome., Abstract: Chronically elevated carbon dioxide (CO 2 ) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head-down tilt bed rest (HDTBR) in a mild hypercapnic environment ( P C O 2 = ∼4 mmHg), we investigated arterialized P C O 2 , cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized P C O 2 was not significantly different from the pre-HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (-0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022-0.043; P < 0.001), which remained elevated by 0.021 (0.011-0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre-HDTBR levels 13 days after BR with a change of -0.001 (-0.009 to 0.007; P = 0.991). Compared to pre-HDTBR, cerebrovascular reactivity during and after HDTBR did not change. Baseline ventilation, ventilatory recruitment threshold and the slope of the ventilatory response were similar between pre-HDTBR and all other time points. Taken together, these data suggest that the mildly increased ambient P C O 2 combined with 30 days of strict 6° HDTBR did not change arterialized P C O 2 levels. Therefore, the experimental conditions were not sufficient to elicit a detectable physiological response., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Microperforations in the round window membrane have been suggested for enhancing the rate and reliability of drug delivery into the cochlea. Intratympanic injection, the most common delivery method, involves injecting therapy into the middle ear to establish a reservoir from which drug diffuses across the round window membrane into the cochlea. This process is highly variable because (i) the reservoir, if liquid, can lose contact with the membrane and (ii) diffusion across the membrane is intrinsically variable even with a stable reservoir. To address these respective sources of variability, we compared the thermoreversible hydrogel poloxamer 407 (P407) to saline as a drug carrier and studied the effect of membrane microperforations on drug diffusion rate. We used Rhodamine B as a drug proxy to measure permeance across an artificial membrane in a horizontal diffusion cell. We found that permeance of Rhodamine B from a saline reservoir was an order of magnitude higher than that from a P407 reservoir across unperforated membranes. Moreover, permeance increased with total perforation cross-sectional area regardless of number of perforations (p < 0.05 for all saline-based experiments), but the same association was not found with P407. Rather, for a P407 reservoir, only a large perforation increased permeance (p < 0.001), while multiple small perforations did not (p = 0.749). These results confirm that for drug dissolved in saline, multiple small perforations can effectively enhance diffusion. However, for drug dissolved in P407, larger perforations are necessary., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cells directly probe and respond to the physicomechanical properties of their extracellular environment, a dynamic process which has been shown to play a key role in regulating both cellular adhesive processes and differential cellular function. Recent studies indicate that stem cells show lineage-specific differentiation when cultured on substrates approximating the stiffness profiles of specific tissues. Although tissues are associated with a range of Young's modulus values for bulk rigidity, at the subcellular level, tissues are comprised of heterogeneous distributions of rigidity. Lithographic processes have been widely explored in cell biology for the generation of analytical substrates to probe cellular physicomechanical responses. In this work, it is shown for the first time that that direct-write e-beam exposure can significantly alter the rigidity of elastomeric poly(dimethylsiloxane) substrates and a new class of 2D elastomeric substrates with controlled patterned rigidity ranging from the micrometer to the nanoscale is described. The mechanoresponse of human mesenchymal stem cells to e-beam patterned substrates was subsequently probed in vitro and significant modulation of focal adhesion formation and osteochondral lineage commitment was observed as a function of both feature diameter and rigidity, establishing the groundwork for a new generation of biomimetic material interfaces., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

American colleges lose half their students in the four years after matriculation. This high attrition rate with its waste of brainpower and cost in human well-being suggests that our institutions of higher education are not very conducive to optimal development of students. Especially those who begin the race for the diploma from the lower end of the socioeconomic spectrum are disadvantaged from the start. Recently, attention has been focused across the nation on the failures of the educational process at lower levels. However, the negative consequences ofcollege failure or dropout for individuals and for society are no less than the consequences of dropout from the secondary schools.It is probable that in half or more of all the dropouts and flunkouts from American universities, psychosocial difficulties are an important factor in the failure. Preventive psychiatric measures on the campuses could reduce both educational losses and future psychiatric casualties. These preventive measures and the role of mental health professionals in colleges are elaborated.