Engineering Zn/Fe Mixed Metal Oxides with Tunable Structural and Magnetic Properties for Magnetic Particle Imaging.

Engineering magnetic nanoparticles with tunable structural properties and magnetism is critical to develop desirable magnetic particle imaging (MPI) tracers for biomedical applications. Here we present a new superparamagnetic metal oxide nanoparticle with a controllable chemical composition and magnetism for imaging tumor xenografts in living mice. Superparamagnetic Zn/Fe mixed metal oxide (ZnFe-MMO) nanoparticles are fabricated via a facile one-pot co-precipitation method in water followed by thermal decomposition with tunable Zn/Fe ratios and at various calcination temperatures.

PLP1-Targeting Antisense Oligonucleotides Improve FOXG1 Syndrome Mice.

FOXG1 syndrome is a rare neurodevelopmental disorder of the telencephalon, for which there is no cure. Underlying heterozygous pathogenic variants in the () gene with resulting impaired or loss of FOXG1 function lead to severe neurological impairments. Here, we report a patient with a de novo pathogenic single nucleotide deletion c.

Improving vaccine equity by increasing vaccine thermostability.

The development, manufacture, and deployment of new vaccine technologies to combat SARS-CoV-2 enabled an unparalleled rapid response to the emerging health threat. However, the unequal global distribution of these vaccines highlighted a major gap in existing thermotolerance profiles and cold chain infrastructure that needs to be addressed to maximize their global health impact.

Effect of antibody-mediated connective tissue growth factor neutralization on lung edema in ventilator-induced lung injury in rats.

Background: Acute respiratory distress syndrome (ARDS) is characterized by alveolar edema that can progress to septal fibrosis. Mechanical ventilation can augment lung injury, termed ventilator-induced lung injury (VILI). Connective tissue growth factor (CTGF), a mediator of fibrosis, is increased in ARDS patients.

Feasibility of a Novel Geriatric Rehabilitation Program for People With COPD-induced Malnutrition and Muscle Wasting: A Qualitative Study.

Patients with COPD-induced malnutrition and muscle wasting are often frail. Consequently, traditional rehabilitation may be even counterproductive due to energy costs and there is a need for specialized rehabilitation programs, which are lacking for these patients. We developed such a program, which includes resistance training, following Nonlinear Periodized Exercise principles and physical energy management, in combination with a restriction of physical activities.

Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Pre-, and Postbiotics: A Multi-Country Multi-Center Prospective Randomized Controlled Study in Infants with Regurgitation.

This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e.

Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis.

Aims: Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma.

Methods And Results: Plaque MPO activity was assessed in rabbits ( = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis.

FDA-approved disulfiram as a novel treatment for aggressive leukemia.

Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach. Our previous evaluation of FDA-approved drugs for their antileukemic activity identified disulfiram, used for the treatment of alcoholism, as a candidate hit compound.

Biocompatibility and proteomic profiling of DMSA-coated iron nanocubes in a human glioblastoma cell line.

Superparamagnetic iron core iron oxide shell nanocubes have previously shown superior performance in magnetic resonance imaging T2 contrast enhancement compared with spherical nanoparticles. Iron core iron oxide shell nanocubes were synthesized, stabilized with dimercaptosuccinic acid (DMSA-NC) and physicochemically characterized. MRI contrast enhancement and biocompatibility were assessed .

The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model.

Septic shock is characterized by endothelial dysfunction, leading to tissue edema and organ failure. Heparan sulfate (HS) is essential for vascular barrier integrity, possibly via albumin as a carrier. We hypothesized that supplementing fluid resuscitation with HS would improve endothelial barrier function, thereby reducing organ edema and injury in a rat pneumosepsis model.

Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer's Disease.

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer's disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (A) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD.

The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model.

Background: Endothelial injury and permeability are a hallmark of sepsis. Initial resuscitation of septic patients with crystalloids is associated with aggravation of endothelial permeability, which may be related either to low protein content or to volume. We investigated whether initial resuscitation with different types of plasma or albumin decreases endothelial dysfunction and organ injury in a pneumosepsis rat model compared to the same volume of crystalloids.

Understanding COVID-19 vaccine hesitancy in health care professionals in Central and West Asia: lessons for future emergency mass vaccination campaigns.

A Quick Assessment of Vaccine Hesitancy approach was developed to collect population insights on vaccination hesitancy for low resource environments. Insights into COVID-19 vaccine hesitancy were collected through online webinars with heads of healthcare departments and anonymized online surveys of healthcare managers (HCM) and primary healthcare workers (HCW) in four countries in Central and West Asia (Armenia, Georgia, Tajikistan, and Kyrgyzstan) between 28 February 2022 and 29 March 2022. From the responses to the survey some key themes identified that underpinned in vaccine hesitancy across the region were perceived understanding of vaccine efficacy, conflict with individual religious beliefs, concerns for side effects, and the relatively rapid development of the vaccine and that improving communications strategies to address these concerns would be critical in combatting vaccine hesitancy through any future public health emergencies.

Vaccine research and development capacity in Central and West Asia: A path toward sustainable vaccine R&D programs.

The ability to support a comprehensive vaccine research and development (R&D) portfolio from a health security perspective has taken on enhanced significance over the past 3 years whereby countries that had existing vaccine R&D infrastructure (G7, Russia and China) have been at the forefront of global efforts to combat COVID-19. Few countries outside of these key players have the infrastructure necessary to develop national vaccine programs, though this is beginning to change with investment across many low- and middle-income countries. These same opportunities exist for countries in Central and West Asia, and in this perspective, we highlight the existing infrastructure and expertise across seven countries (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan) and propose opportunities for enhanced collaboration along with a bold proposal for establishing a new-build, regional vaccine translational research institute to facilitate the development of a robust, regional vaccine R&D environment to combat existing and future health challenges.

Site-Specific Antibody Assembly on Nanoparticles via a Versatile Coating Method for Improved Cell Targeting.

Antibody-nanoparticle conjugates are promising candidates for precision medicine. However, developing a controllable method for conjugating antibodies to nanoparticles without compromising the antibody activity represents a critical challenge. Here, a facile and generalizable film-coating method is presented using zeolitic imidazole framework-8 (ZIF-8) to immobilize antibodies on various nanoparticles in a favorable orientation for enhanced cell targeting.

The combined use of DTI and MR elastography for monitoring microstructural changes in the developing brain of a neurodevelopmental disorder model: Poly (I:C)-induced maternal immune-activated rats.

Early neuropathology mechanisms in neurodevelopmental disorders are partially understood because routine anatomical magnetic resonance imaging (MRI) cannot detect subtle brain microstructural changes in vivo during postnatal development. Therefore, we investigated the potential value of magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) in a rat model of neurodevelopmental disorder induced by maternal immune activation. We studied 12 offspring of mothers injected with polyriboinosinic-polyribocytidylic acid (poly (I:C), 4 mg/kg) on gestational day 15, plus 8 controls.

Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice.

The leukodystrophy Canavan disease is a fatal white matter disorder caused by loss-of-function mutations of the aspartoacylase-encoding gene. There are no effective treatments available and experimental gene therapy trials have failed to provide sufficient amelioration from Canavan disease symptoms. Preclinical studies suggest that Canavan disease-like pathology can be addressed by either gene replacement therapy or by lowering the expression of the N-acetyl-L-aspartate synthesizing enzyme NAT8L.

Aged versus fresh autologous platelet transfusion in a two-hit healthy volunteer model of transfusion-related acute lung injury.

Background: Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two-hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion.

The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression.

Rearrangements of the () gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome. Driven by the unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that the novel anti-cancer agent, curaxin CBL0137, induces decondensation of chromatin in cancer cells, delays leukemia progression and potentiates standard of care chemotherapies in preclinical KMT2A-rearranged leukemia models. Based on the promising potential of histone deacetylase (HDAC) inhibitors as targeted anti-cancer agents for KMT2A-rearranged leukemia and the fact that HDAC inhibitors also decondense chromatin an alternate mechanism, we investigated whether CBL0137 could potentiate the efficacy of the HDAC inhibitor panobinostat in KMT2A-rearranged leukemia models.

Suppression of the ABCA1 Cholesterol Transporter Impairs the Growth and Migration of Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy with over 80% of cases already disseminated at diagnosis and facing a dismal five-year survival rate of 35%. EOC cells often spread to the greater omentum where they take-up cholesterol. Excessive amounts of cholesterol can be cytocidal, suggesting that cholesterol efflux through transporters may be important to maintain homeostasis, and this may explain the observation that high expression of the ATP-binding cassette A1 (ABCA1) cholesterol transporter has been associated with poor outcome in EOC patients.

Magnetic resonance imaging and diffusion tensor imaging reconstruction of connectomes in a macropod, the quokka (Setonix brachyurus).

The diversity of the diprotodontids provides an excellent opportunity to study how a basic marsupial cortical plan has been modified for the needs of the mammals living in different habitats. Very little is known about the connections of the cerebral cortex with the deep brain structures (basal ganglia and thalamus) in this evolutionarily significant group of mammals. In this study, we performed mapping of brain regions and connections in a diprotodontid marsupial from data obtained from an excised brain scanned in high-field (9.

Developmental delay and late onset HBSL pathology in hypomorphic Dars1 mice.

The leukodystrophy Hypomyelination with Brainstem and Spinal cord involvement and Leg spasticity (HBSL) is caused by recessive mutations of the DARS1 gene, which encodes the cytoplasmic aspartyl-tRNA synthetase. HBSL is a spectrum disorder with disease onset usually during early childhood and no available treatment options. Patients display regression of previously acquired motor milestones, spasticity, ataxia, seizures, nystagmus, and intellectual disabilities.

Systematic Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged Leukemia.

Patients whose leukemias harbor a rearrangement of the (/) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics. The aim of this study was to identify novel candidate compounds that selectively target -rearranged (KMT2A-r) leukemia cells.