Metabolic engineering improves transduction efficiency and downstream vector isolation by altering the lipid composition of extracellular vesicle-enclosed AAV.

Adeno-associated viruses (AAV) are promising vectors for gene therapy due to their efficacy in vivo. However, there is room for improvement to address key limitations such as the pre-existing immunity to AAV in patients, high-dose toxicity, and relatively low efficiency for some cell types. This study introduces a metabolic engineering approach, using knockout of the enzyme phosphatidylserine synthase 1 (PTDSS1) to increase the abundance of extracellular vesicle-enclosed AAV (EV-AAV) relative to free AAV in the supernatant of producer cells, simplifying downstream purification processes.

Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes.

Background: Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively.

A perfused multi-well bioreactor platform to assess tumor organoid response to a chemotherapeutic gradient.

There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC in the region near the perfusion channel versus the region far from the channel.

Go with the flow: modeling unique biological flows in engineered platforms.

Interest in recapitulating in vivo phenomena in vitro using organ-on-a-chip technology has grown rapidly and with it, attention to the types of fluid flow experienced in the body has followed suit. These platforms offer distinct advantages over in vivo models with regards to human relevance, cost, and control of inputs (e.g.

Ischaemic bowel perforation secondary to a gravid uterus in a patient with treated inflammatory bowel disease and an ileoanal pouch: a case report.

The diagnosis of visceral perforation during pregnancy is often delayed and the management complex. A 32-year-old primigravid woman in her second trimester presented with abdominal pain and a pre-existing ileoanal pouch. Initial imaging was negative but later imaging was suggestive of serious pathology.

Projection Microstereolithographic Microbial Bioprinting for Engineered Biofilms.

Microbes are critical drivers of all ecosystems and many biogeochemical processes, yet little is known about how the three-dimensional (3D) organization of these dynamic organisms contributes to their overall function. To probe how biofilm structure affects microbial activity, we developed a technique for patterning microbes in 3D geometries using projection stereolithography to bioprint microbes within hydrogel architectures. Bacteria were printed and monitored for biomass accumulation, demonstrating postprint viability of cells using this technique.

Three-dimensional bioprinting of aneurysm-bearing tissue structure for endovascular deployment of embolization coils.

Various types of embolization devices have been developed for the treatment of cerebral aneurysms. However, it is challenging to properly evaluate device performance and train medical personnel for device deployment without the aid of functionally relevant models. Currentaneurysm models suffer from a lack of key functional and morphological features of brain vasculature that limit their applicability for these purposes.

Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE) is an emerging electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short, bipolar pulses (1-10μs) in a series of 80-100 bursts (1 burst/s, 100μs on-time). Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages must be applied to generate ablations comparable in size.

Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation.

High-frequency irreversible electroporation (H-FIRE) is a technique that uses pulsed electric fields that have been shown to ablate malignant cells. In order to evaluate the clinical potential of H-FIRE to treat glioblastoma (GBM), a primary brain tumor, we have studied the effects of high-frequency waveforms on therapy-resistant glioma stem-like cell (GSC) populations. We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes.

Neural correlates of perceived physical and mental fatigability in older adults: A pilot study.

This pilot work examined associations of brain grey matter volumes (GMV) with perceived fatigability in older adults to elucidate disablement mechanisms. A subsample (n = 29; age = 77.2 ± 5.

Mental Health During Environmental Crisis and Mass Incident Disasters.

Veterinarians responding to animal health-related incidents are in the same class as first responders and should be aware of similar mental health concerns. Cultivating resiliency, identifying symptoms, and linking individuals to support systems are practical strategies to provide positive outcomes for veterinarians facing difficult experiences. This article explores veterinarians as first responders and farm stress; an overview of mental health responses to trauma; strategies and interventions for individuals, families, communities, and veterinarians; a discussion of boundaries and threshold for managing crisis; barriers and considerations for service provision; and a summary and discussion of future research and curriculum opportunities.

The Feasibility of Enhancing Susceptibility of Glioblastoma Cells to IRE Using a Calcium Adjuvant.

Irreversible electroporation (IRE) is a cellular ablation method used to treat a variety of cancers. IRE works by exposing tissues to pulsed electric fields which cause cell membrane disruption. Cells exposed to lower energies become temporarily permeable while greater energy exposure results in cell death.

The Role of Organizational Culture in Operating Room Turnaround Time.

This analysis looks at the application of a robust process improvement methodology to achieve a sustained organizational change. The implementation took place in a safety net hospital's operating suites that had a problem with relatively long, nonproductive turnover times between surgical procedures. Organizational leadership empowered stakeholders to use Lean and Six-Sigma tools to develop more efficient organizational processes.

Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier.

The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier.

Racial and Ethnic Heterogeneity in the Association Between Total Cholesterol and Pediatric Obesity.

Total cholesterol (TC) directly correlates with overweight/obesity, but it remains unclear if this association varies by race and ethnicity. We assessed the association as well as the racial/ethnic heterogeneity in this relationship. Data on 63,863 children were assessed using electronic medical records between 2010 and 2011.

A Comparison of Teaching Modalities and Fidelity of Simulation Levels in Teaching Resuscitation Scenarios.

Introduction: The purpose of our study was to examine the ability of novices to learn selected aspects of Advanced Cardiac Life Support (ACLS) in training conditions that did not incorporate simulation compared to those that contained low- and high-fidelity simulation activities. We sought to determine at what level additional educational opportunities and simulation fidelity become superfluous with respect to learning outcomes.

Methods: Totally 39 medical students and physician assistant students were randomly assigned to 4 training conditions: control (lecture only), video-based didactic instruction, low-, and high-fidelity simulation activities.

Innovative use of technologies and methods to redesign care: the problem of care transitions.

Organizations are redesigning models of care in today's rapidly changing health care environment. Using proven innovation techniques maximizes likelihood of effective change. Our safety-net hospital aims to reduce high emergency department visit, admission, and readmission rates, key components to health care cost control.