Analytical and Computational Modeling of Sustained-Release Drug Implants in the Vitreous Humor.

Sustained ocular drug delivery systems are necessary for patients needing regular drug therapy since frequent injection is painful, undesirable, and risky. One type of sustained-release systems includes pellets loaded with the drug, encapsulated in a porous shell that can be injected into the vitreous humor. There the released drug diffuses while the physiological flow of water provides the convective transport.

Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78.

Rapalogues are powerful therapeutic modalities for breast cancer; however, they suffer from low solubility and dose-limiting side effects. To overcome these challenges, we developed a long-circulating multiheaded drug carrier called 5FA, which contains rapamycin-binding domains linked with elastin-like polypeptides (ELPs). To target these "Hydra-ELPs" toward breast cancer, we here linked 5FA with four distinct peptides which are reported to engage the cell surface form of the 78 kDa glucose-regulated protein (csGRP78).

Quantifying Propagation Velocity from Engineered Cardiac Tissues with High-Speed Fluorescence Microscopy and Automated Analysis Software.

Many acquired or inherited forms of heart disease as well as drugs are known to increase the susceptibility of patients to arrhythmias. To predict arrhythmogenic events and discover new therapeutic strategies to mitigate them, approaches to efficiently quantify the velocity of propagation in engineered cardiac tissues are important research tools. In this chapter, we describe how to collect videos of propagating calcium waves in engineered cardiac tissues with a high-speed camera mounted on an inverted fluorescence microscope.

Modeling Patient-Specific Muscular Dystrophy Phenotypes and Therapeutic Responses in Reprogrammed Myotubes Engineered on Micromolded Gelatin Hydrogels.

models of patient-derived muscle allow for more efficient development of genetic medicines for the muscular dystrophies, which often present mutation-specific pathologies. One popular strategy to generate patient-specific myotubes involves reprogramming dermal fibroblasts to a muscle lineage through MyoD induction. However, creating physiologically relevant, reproducible tissues exhibiting multinucleated, aligned myotubes with organized striations is dependent on the introduction of physicochemical cues that mimic the native muscle microenvironment.

Code-free machine learning for object detection in surgical video: a benchmarking, feasibility, and cost study.

Objective: While the utilization of machine learning (ML) for data analysis typically requires significant technical expertise, novel platforms can deploy ML methods without requiring the user to have any coding experience (termed AutoML). The potential for these methods to be applied to neurosurgical video and surgical data science is unknown.

Methods: AutoML, a code-free ML (CFML) system, was used to identify surgical instruments contained within each frame of endoscopic, endonasal intraoperative video obtained from a previously validated internal carotid injury training exercise performed on a high-fidelity cadaver model.

Heterogeneous pdgfrb+ cells regulate coronary vessel development and revascularization during heart regeneration.

Endothelial cells emerge from the atrioventricular canal to form coronary blood vessels in juvenile zebrafish hearts. We find that pdgfrb is first expressed in the epicardium around the atrioventricular canal and later becomes localized mainly in the mural cells. pdgfrb mutant fish show severe defects in mural cell recruitment and coronary vessel development.

Engineering the Cellular Microenvironment of Post-infarct Myocardium on a Chip.

Myocardial infarctions are one of the most common forms of cardiac injury and death worldwide. Infarctions cause immediate necrosis in a localized region of the myocardium, which is followed by a repair process with inflammatory, proliferative, and maturation phases. This repair process culminates in the formation of scar tissue, which often leads to heart failure in the months or years after the initial injury.

Engineering skeletal muscle tissues with advanced maturity improves synapse formation with human induced pluripotent stem cell-derived motor neurons.

To develop effective cures for neuromuscular diseases, human-relevant models of neuromuscular tissues are critically needed to probe disease mechanisms on a cellular and molecular level. However, previous attempts to co-culture motor neurons and skeletal muscle have resulted in relatively immature neuromuscular junctions (NMJs). In this study, NMJs formed by human induced pluripotent stem cell (hiPSC)-derived motor neurons were improved by optimizing the maturity of the co-cultured muscle tissue.

Estimating the COVID-19 Prevalence in Spain With Indirect Reporting via Open Surveys.

During the initial phases of the COVID-19 pandemic, accurate tracking has proven unfeasible. Initial estimation methods pointed toward case numbers that were much higher than officially reported. In the CoronaSurveys project, we have been addressing this issue using open online surveys with indirect reporting.

In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor.

In order to measure the effective diffusion coefficient of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the "contour method" and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result.

Tools, techniques, and future opportunities for characterizing the mechanobiology of uterine myometrium.

The myometrium is the smooth muscle layer of the uterus that generates the contractions that drive processes such as menstruation and childbirth. Aberrant contractions of the myometrium can result in preterm birth, insufficient progression of labor, or other difficulties that can lead to maternal or fetal complications or even death. To investigate the underlying mechanisms of these conditions, the most common model systems have conventionally been animal models and human tissue strips, which have limitations mostly related to relevance and scalability, respectively.

Contact photolithography-free integration of patterned and semi-transparent indium tin oxide stimulation electrodes into polydimethylsiloxane-based heart-on-a-chip devices for streamlining physiological recordings.

Controlled electrical stimulation is essential for evaluating the physiology of cardiac tissues engineered in heart-on-a-chip devices. However, existing stimulation techniques, such as external platinum electrodes or opaque microelectrode arrays patterned on glass substrates, have limited throughput, reproducibility, or compatibility with other desirable features of heart-on-a-chip systems, such as the use of tunable culture substrates, imaging accessibility, or enclosure in a microfluidic device. In this study, indium tin oxide (ITO), a conductive, semi-transparent, and biocompatible material, was deposited onto glass and polydimethylsiloxane (PDMS)-coated coverslips as parallel or point stimulation electrodes using laser-cut tape masks.

Engineering Shape-Controlled Microtissues on Compliant Hydrogels with Tunable Rigidity and Extracellular Matrix Ligands.

In vitro models that recapitulate key aspects of native tissue architecture and the physical microenvironment are emerging systems for modeling development and disease. For example, the myocardium consists of layers of aligned and coupled cardiac myocytes that are interspersed with supporting cells and embedded in a compliant extracellular matrix (ECM). These cell-cell and cell-matrix interactions are known to be important regulators of tissue physiology and pathophysiology.

Brain biomarkers and neuropsychological outcomes of pediatric posterior fossa brain tumor survivors treated with surgical resection with or without adjuvant chemotherapy.

Purpose: Children with brain tumors experience cognitive late effects, often related to cranial radiation. We sought to determine differential effects of surgery and chemotherapy on brain structure and neuropsychological outcomes in children who did not receive cranial radiation therapy (CRT).

Methods: Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery, 11 treated with surgery and chemotherapy) underwent neuroimaging and neuropsychological assessment a mean of 4.

Mitochondrial architecture in cardiac myocytes depends on cell shape and matrix rigidity.

Contraction of cardiac myocytes depends on energy generated by the mitochondria. During cardiac development and disease, the structure and function of the mitochondrial network in cardiac myocytes is known to remodel in concert with many other factors, including changes in nutrient availability, hemodynamic load, extracellular matrix (ECM) rigidity, cell shape, and maturation of other intracellular structures. However, the independent role of each of these factors on mitochondrial network architecture is poorly understood.

Neuromuscular disease modeling on a chip.

Organs-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development.

Optical Clearing of Skeletal Muscle Bundles Engineered in 3-D Printed Templates.

Many techniques for engineering and interrogating three-dimensional (3-D) muscle bundles from animal- or patient-derived myoblasts have recently been developed to overcome the limitations of existing in vitro and in vivo model systems. However, many approaches for engineering 3-D muscle bundles rely on specialized and time-consuming techniques, such as photolithography for fabrication and cryosectioning for histology. Cryosectioning also limits visualization to a single plane instead of the entire 3-D structure.

Mitochondrial division inhibitor 1 (mdivi-1) increases oxidative capacity and contractile stress generated by engineered skeletal muscle.

In skeletal muscle fibers, mitochondria are densely packed adjacent to myofibrils because adenosine triphosphate (ATP) is needed to fuel sarcomere shortening. However, despite this close physical and biochemical relationship, the effects of mitochondrial dynamics on skeletal muscle contractility are poorly understood. In this study, we analyzed the effects of Mitochondrial Division Inhibitor 1 (mdivi-1), an inhibitor of mitochondrial fission, on the structure and function of both mitochondria and myofibrils in skeletal muscle tissues engineered on micromolded gelatin hydrogels.

MEASUREMENT OF THE HYDRAULIC CONDUCTIVITY OF THE VITREOUS HUMOR.

The hydraulic conductivity of the vitreous humor has been measured for the bovine eye. The experiment was carried out by placing it within upright cylindrical chamber, open at both ends, and letting its liquid content drain out of the bottom opening by gravity, through a 20m nylon mesh filter. Additional negative pressure was provided at the exit by a hanging drainage tube.

Regulation of calcium dynamics and propagation velocity by tissue microstructure in engineered strands of cardiac tissue.

Disruptions to cardiac tissue microstructure are common in diseased or injured myocardium and are known substrates for arrhythmias. However, we have a relatively coarse understanding of the relationships between myocardial tissue microstructure, propagation velocity and calcium cycling, due largely to the limitations of conventional experimental tools. To address this, we used microcontact printing to engineer strands of cardiac tissue with eight different widths, quantified several structural and functional parameters and established correlation coefficients.

Extended culture and imaging of normal and regenerating adult zebrafish hearts in a fluidic device.

Myocardial infarction and heart failure are leading causes of death worldwide, in large part because adult human myocardium has extremely limited regeneration capacity. Zebrafish are a powerful model for identifying new strategies for human cardiac repair because their hearts regenerate after relatively severe injuries. Zebrafish are also relatively scalable and compatible with many genetic tools.

Matrix-guided control of mitochondrial function in cardiac myocytes.

In ventricular myocardium, extracellular matrix (ECM) remodeling is a hallmark of physiological and pathological growth, coincident with metabolic rewiring of cardiac myocytes. However, the direct impact of the biochemical and mechanical properties of the ECM on the metabolic function of cardiac myocytes is mostly unknown. Furthermore, understanding the impact of distinct biomaterials on cardiac myocyte metabolism is critical for engineering physiologically-relevant models of healthy and diseased myocardium.

Effects of air pollution on mitochondrial function, mitochondrial DNA methylation, and mitochondrial peptide expression.

Mitochondrial DNA is sensitive to damage by exogenous reactive oxygen sources, including traffic-related air pollution (TRAP). Given the important role for mitochondria in human disease, we hypothesized that prenatal air pollution exposure may be associated with mitochondrial dysfunction and that mitochondrial-derived peptides (MDPs) might protect against these effects. In in vitro studies, 24-hour exposure to nanoparticulate matter (nPM) increased oxidation of mtDNA, decreased mitochondrial consumption rate (OCR), and decreased mtDNAcn in SH-SY5Y cells.

"I DIDN'T TELL YOU SOONER BECAUSE I DIDN'T KNOW HOW TO HANDLE IT MYSELF." DEVELOPING A VIRTUAL REALITY PROGRAM TO SUPPORT HIV-STATUS DISCLOSURE DECISIONS.

HIV status disclosure is associated with increased sorcial support and protective behaviors against HIV transmission. Yet disclosure poses significant challenges in the face of persistent societal stigma. Few interventions focus on decision-making self-efficacy, and communication skills to support disclosing HIV status to an intimate partner.