Therapeutic potential and impact of nanoengineered patient-derived mesenchymal stem cells in a murine resection and recurrence model of human glioblastoma.

Confounding results of engineered mesenchymal stem cells (MSCs) used as cellular vehicles has plagued technologies whereby success or failure of novel approaches may be dismissed or inaccurately ascribed solely to the biotechnology platform rather than suitability of the human donor. Polymeric materials were screened for non-viral engineering of MSCs from multiple human donors to deliver bone morphogenic protein-4 (BMP4), a protein previously investigated in clinical trials for glioblastoma (GBM) to combat a subpopulation of highly invasive and tumorigenic clones. A "smart technology" that target the migratory and stem-like nature of GBM will require: (1) a cellular vehicle (MSC) which can scavenge and target residual cells left behind after surgical debulking and deliver; (2) anti-glioma cargo (BMP4).

A framework for three-dimensional statistical shape modeling of the proximal femur in Legg-Calvé-Perthes disease.

Purpose: The pathomorphology of Legg-Calvé-Perthes disease (LCPD) is a key contributor to poor long-term outcomes such as hip pain, femoroacetabular impingement, and early-onset osteoarthritis. Plain radiographs, commonly used for research and in the clinic, cannot accurately represent the full extent of LCPD deformity. The purpose of this study was to develop and evaluate a methodological framework for three-dimensional (3D) statistical shape modeling (SSM) of the proximal femur in LCPD.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces.

Short-term dietary changes are reflected in the cerebral content of adult ring-billed gulls.

Omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) are produced primarily in aquatic ecosystems and are considered essential nutrients for predators given their structural role in vertebrates' cerebral tissues. Alarmingly, with urbanization, many aquatic animals now rely on anthropogenic foods lacking n3-LCPUFAs. In this study undertaken in Newfoundland (Canada), we tested whether recent or longer term diet explains the cerebral fatty acid composition of ring-billed gulls (), a seabird that now thrives in cities.

Suprachoroidal gene transfer with nonviral nanoparticles in large animal eyes.

Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human-sized minipig eye that suprachoroidal injection of 50 μl of NPs containing 19.2 μg of GFP expression plasmid caused GFP expression in photoreceptors and RPE throughout the entire eye with no toxicity.

Small tube-nosed seabirds fledge on the full moon and throughout the lunar cycle.

Many seabirds are attracted to anthropogenic light, and the risk is greater for recent fledglings. Moon phase predicts the probability of stranding (fewer birds strand on the full moon), but it remains uncertain whether moon phase is associated with when young seabirds fledge. Fledging behaviour of nocturnal, burrowing seabirds can be difficult to monitor using traditional methods but can provide insight into environmental factors that influence the risk of stranding.

Digital financial services for health in support of universal health coverage: qualitative programmatic case studies from Kenya and Rwanda.

Background: This document describes two qualitative programmatic case studies documenting experiences implementing digital financial services (DFS) for health with a focus on expanding access to universal health coverage (UHC). The CBHI 3MS system in Rwanda and the i-PUSH and Medical Credit Fund programs in Kenya were selected because they represent innovative use of digital financing technologies to support UHC programs at scale.

Methods: These studies were conducted from April-August 2021 as part of a broader digital financial services landscape assessment that used a mixed methods process evaluation to answer three questions: 1) what was the experience implementing the program, 2) how was it perceived to influence health systems performance, and 3) what was the client/beneficiary experience? Qualitative interviews involved a range of engaged stakeholders, including implementers, developers, and clients/users from the examined programs in both countries.

Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses.

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due its self-adjuvating and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles have been successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window would benefit from further improvement.

T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

Objective: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip.

Research Question: is T1Gd lower in areas of cartilage overlying BMLs in the hip?

Design: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds.

Fire intensity impacts on physiological performance and mortality in Pinus monticola and Pseudotsuga menziesii saplings: a dose-response analysis.

Fire is a major cause of tree injury and mortality worldwide, yet our current understanding of fire effects is largely based on ocular estimates of stem charring and foliage discoloration, which are error prone and provide little information on underlying tree function. Accurate quantification of physiological performance is a research and forest management need, given that declining performance could help identify mechanisms of-and serve as an early warning sign for-mortality. Many previous efforts have been hampered by the inability to quantify the heat flux that a tree experiences during a fire, given its highly variable nature in space and time.

Design of a double acting pneumatic cartilage loading device for magnetic resonance imaging.

Studies of osteoarthritis initiation and progression that measure strain in cartilage require physiological loading levels. Many studies use magnetic resonance (MR) imaging, which necessitates a MR-compatible loading device. In this study, the design and validation of a new device, the cartilage compressive actuator (CCA), is presented.

Application of statistical shape modeling to the human hip joint: a scoping review.

Objective: The objective of this scoping review was to identify all examples of the application of statistical shape models to the human hip joint, with a focus on applications, population, methodology, and validation.

Introduction: Clinical radiographs are the most common imaging tool for management of hip conditions, but it is unclear whether radiographs can adequately diagnose or predict outcomes of 3D deformity. Statistical shape modeling, a method of describing the variation of a population of shapes using a small number of variables, has been identified as a useful tool to associate 2D images with 3D anatomy.

Poly(Beta-Amino Ester)s as High-Yield Transfection Reagents for Recombinant Protein Production.

Purpose: Transient transfection is an essential tool for recombinant protein production, as it allows rapid screening for expression without stable integration of genetic material into a target cell genome. Poly(ethylenimine) (PEI) is the current gold standard for transient gene transfer, but transfection efficiency and the resulting protein yield are limited by the polymer's toxicity. This study investigated the use of a class of cationic polymers, poly(beta-amino ester)s (PBAEs), as reagents for transient transfection in comparison to linear 25 kDa PEI, a commonly used transfection reagent.

Neotropical Birds Respond Innately to Unfamiliar Acoustic Signals.

AbstractMany animals respond to heterospecific signals that indicate the presence of food or predators. Although the benefits of responding are clear, the behavioral and cognitive mechanisms underlying responses are not. Whether responses are learned, innate, or an epiphenomenon created by following other species as they respond to signals remains unknown because most studies have involved respondents that are sympatric with their heterospecific signalers and that have therefore had opportunities to learn their signals.

Foraging on anthropogenic food predicts problem-solving skills in a seabird.

Species and populations with greater cognitive performance are more successful at adapting to changing habitats. Accordingly, urban species and populations often outperform their rural counterparts on problem-solving tests. Paradoxically, urban foraging also might be detrimental to the development and integrity of animals' brains because anthropogenic foods often lack essential nutrients such as the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are important for cognitive performance in mammals and possibly birds.

Muscle activity with 0.5 T upright MRI-DESS to measure T in biceps and triceps.

The purpose of this study was to determine if muscle activity of the biceps followed by isometric flexion changes T measured in the biceps. It is hypothesized that an increase in T will be observed in the biceps but not in the triceps after flexion exercise. Ten healthy volunteers were imaged with a one-channel neck coil while seated in a 0.

Rescue left bundle branch area pacing in coronary venous lead failure or nonresponse to biventricular pacing: Results from International LBBAP Collaborative Study Group.

Background: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) is effective in patients with heart failure, left bundle branch block (LBBB), and reduced left ventricular function. Left bundle branch area pacing (LBBAP) has been reported as an alternative option for CRT.

Objective: The purpose of this study was to assess the feasibility and outcomes of LBBAP in patients who failed conventional BVP because of coronary venous (CV) lead complications or who were nonresponders to BVP.

High-throughput and high-content bioassay enables tuning of polyester nanoparticles for cellular uptake, endosomal escape, and systemic in vivo delivery of mRNA.

Nanoparticle-based mRNA therapeutics hold great promise, but cellular internalization and endosomal escape remain key barriers for cytosolic delivery. We developed a dual nanoparticle uptake and endosomal disruption assay using high-throughput and high-content image-based screening. Using a genetically encoded Galectin 8 fluorescent fusion protein sensor, endosomal disruption could be detected via sensor clustering on damaged endosomal membranes.

Waterbird solves the string-pull test.

String-pulling is among the most widespread cognitive tasks used to test problem-solving skills in mammals and birds. The task requires animals to comprehend that pulling on a non-valuable string moves an otherwise inaccessible food reward to within their reach. Although at least 90 avian species have been administered the string-pull test, all but five of them were perching birds (passeriformes) or parrots (psittaciformes).