Cost-benefit analysis of intervention reducing young stock mortality in Ethiopia.

Livestock provide meat, milk, draught labour, are used for breeding, and act as a store of value for smallholder farmers. High young stock mortality (YSM) has the potential to cause significant financial loss. The Young Stock Mortality Reduction Consortium collaborated on a project to deliver a package of basic health and husbandry interventions to reduce YSM for cattle and small ruminants in mixed and pastoral production systems in Ethiopia.

Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory.

Vaximap: route optimisation for housebound vaccination.

During the United Kingdom's Covid-19 vaccination campaign, general practitioners (GPs) have held responsibility for vaccinating housebound patients. This presented them with a large, complex and unfamiliar logistical challenge, namely determining the most time-efficient route to visit multiple patients at their home address. In response to a lack of existing solutions tailored specifically to vaccination, and in light of overwhelming demand, Vaximap ( https://www.

ASL-BIDS, the brain imaging data structure extension for arterial spin labeling.

Arterial spin labeling (ASL) is a non-invasive MRI technique that allows for quantitative measurement of cerebral perfusion. Incomplete or inaccurate reporting of acquisition parameters complicates quantification, analysis, and sharing of ASL data, particularly for studies across multiple sites, platforms, and ASL methods. There is a strong need for standardization of ASL data storage, including acquisition metadata.

Neuroinflammatory disease disrupts the blood-CNS barrier via crosstalk between proinflammatory and endothelial-to-mesenchymal-transition signaling.

Breakdown of the blood-central nervous system barrier (BCNSB) is a hallmark of many neuroinflammatory disorders, such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), we show that endothelial-to-mesenchymal transition (EndoMT) occurs in the CNS before the onset of clinical symptoms and plays a major role in the breakdown of BCNSB function. EndoMT can be induced by an IL-1β-stimulated signaling pathway in which activation of the small GTPase ADP ribosylation factor 6 (ARF6) leads to crosstalk with the activin receptor-like kinase (ALK)-SMAD1/5 pathway.

A Patient-Centered Approach to Research Prioritization in Prostate Cancer.

Purpose: Research priorities are often set by expert clinicians and researchers. We sought to apply an established process in patient-centered research to engage survivors and their caregivers in prioritizing research topics in prostate cancer.

Materials And Methods: A prostate cancer patient survey network, formed in partnership with Us TOO and the National Alliance of State Prostate Cancer Coalitions, engaged in a series of mixed-methods studies to prioritize comparative effectiveness research questions.

OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator.

Background: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS).

Methods: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms.

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage.

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin.

Injectable and Self-Healing Hydrogels with Double-Dynamic Bond Tunable Mechanical, Gel-Sol Transition and Drug Delivery Properties for Promoting Periodontium Regeneration in Periodontitis.

Injection of a hydrogel loaded with drugs with simultaneous anti-inflammatory and tissue regenerating properties can be an effective treatment for promoting periodontal regeneration in periodontitis. Nevertheless, the design and preparation of an injectable hydrogel with self-healing properties for tunable sustained drug release is still highly desired. In this work, polysaccharide-based hydrogels were formed by a dynamic cross-linked network of dynamic Schiff base bonds and dynamic coordination bonds.

Fibroblast Memory in Development, Homeostasis and Disease.

Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus.

Contribution of glycosaminoglycans to the structural and mechanical properties of tendons - A multiscale study.

Tendinopathy of the Achilles tendon contributes to a large range of disorders, including mechanical damage and degenerative diseases. Glycosaminoglycans (GAGs), are thought to play a role in the mechanical strength of tendons by forming cross-links between collagen molecules and allowing the transmission of forces between fibrils. This study assessed the response of GAG-depleted tendons to damage induced by fatigue loading, investigating the mechanical damage (stiffness, hysteresis and maximum load), macrostructural changes (tenocyte morphology, fiber anisotropy and waviness) assessed by confocal imaging and nanostructural changes (fibril D-periodicity length) within the same non-viable intact tendons.

A multiscale study of morphological changes in tendons following repeated cyclic loading.

The response of white New Zealand rabbit Achilles tendons to load was assessed using mechanical measures and confocal arthroscopy (CA). The progression of fatigue-loading-induced damage of the macro- (tenocyte morphology, fiber anisotropy and waviness), as well as the mechanical profile, were assessed within the same non-viable intact tendon in response to prolonged cyclic and static loading (up to four hours) at different strain levels (3%, 6% and 9%). Strain-mediated repeated loading induced a significant decline in mechanical function (p < 0.

An AFM study of the nanostructural response of New Zealand white rabbit Achilles tendons to cyclic loading.

The nanostructural response of New Zealand white rabbit Achilles tendons to a fatigue damage model was assessed quantitatively and qualitatively using the endpoint of dose assessments of each tendon from our previous study. The change in mechanical properties was assessed concurrently with nanostructural change in the same non-viable intact tendon. Atomic force microscopy was used to study the elongation of D-periodicities, and the changes were compared both within the same fibril bundle and between fibril bundles.

The influence of glycosaminoglycan proteoglycan side chains on tensile force transmission and the nanostructural properties of Achilles tendons.

This study investigates the nanostructural mechanisms that lie behind load transmission in tendons and the role of glycosaminoglycans (GAGs) in the transmission of force in the tendon extracellular matrix. The GAGs in white New Zealand rabbit Achilles tendons were enzymatically depleted, and the tendons subjected to cyclic loading at 6% strain for up to 2 hr. A nanoscale morphometric assessment of fibril deformation under strain was linked with the decline in the tendon macroscale mechanical properties.

Deletion of Reduces Eosinophilic Inflammation and Interleukin-5 Expression in a Murine Model of Rhinitis.

Background: ARF nucleotide-binding site opener (ARNO) is a guanine nucleotide-exchange factor for ADP-ribosylation factor proteins. ARF nucleotide-binding site opener also binds MyD88, and small-molecule inhibition of ARNO reduces inflammation in animal models of inflammatory arthritis and acute inflammation. However, whether genetic deletion of in mice reduces pathologic inflammation has not yet been reported.

Engineering the Human Fc Region Enables Direct Cell Killing by Cancer Glycan-Targeting Antibodies without the Need for Immune Effector Cells or Complement.

Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to noncovalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization.

Toblerone: Surface-Based Partial Volume Estimation.

Partial volume effects (PVE) present a source of confound for the analysis of functional imaging data. Correction for PVE requires estimates of the partial volumes (PVs) present in an image. These estimates are conventionally obtained via volumetric segmentation, but such an approach may not be accurate for complex structures such as the cortex.

A review of methods to measure tendon dimensions.

Tendons are soft tissues of the musculoskeletal system that are designed to facilitate joint movement. Tendons exhibit a wide range of mechanical properties matched to their functions and, as a result, have been of interest to researchers for many decades. Dimensions are an important aspect of tendon properties.

Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-β-cyclodextrin and Hyperbranched Polyglycerol Derivative.

Introducing genes into drug-delivery system for a combined therapy has become a promising strategy for cancer treatment. However, improving the in vivo therapy effect resulted from the high delivery efficiency, low toxicity, and good stability in the blood remains a challenge. For this purpose, the supramolecular inclusion was considered to construct a high-efficiency drug and gene co-delivery system in this work.

Redox-responsive chemosensitive polyspermine delivers ursolic acid targeting to human breast tumor cells: The depletion of intracellular GSH contents arouses chemosensitizing effects.

Antitumor efficacy of ursolic acid (UA) is seriously limited due to its low hydrophilicity and needy bioavailability. To overcome these obstacles, chemosensitive polyspermine (CPSP) conjugated with UA and folic acid (FA) as a novel targeted prodrug was designed and successfully synthesized in this investigation. This prodrug not only showed high aqueous solubility, GSH-triggered degradation and good biocompatibility, but also exhibited better inhibition effect on the tumor cells proliferation in comparison with free UA.

Synthesis of Janus Au nanorods/polydivinylbenzene hybrid nanoparticles for chemo-photothermal therapy.

Chemo-photothermal therapy has attracted tremendous attention due to its synergistic effect in killing cancer cells, making it one of the most efficient therapies. Although most of the applied core-shell hybrid nanoparticles (NPs) can perform such a function, the lowering of their thermal efficiency through polymer coating and limited drug loading capacity severely limit their performance. Janus NPs with exposed metal and a polymer/silica matrix show improved chemo- and photothermal-efficiency, but have a complicated synthesis, and their loading capacity for hydrophobic drugs still needs to be optimized.

Reduction-Responsive Codelivery System Based on a Metal-Organic Framework for Eliciting Potent Cellular Immune Response.

Utilizing nanoparticles to deliver subunit vaccines can be viewed as a promising strategy for enhancing the immune response, especially with regard to cellular immunity to fight against infectious viruses and malignant cancer. Nevertheless, its applications are still far from practicality because of some limitations such as high cost, non-biocompatibility, non-biodegradability, and the inefficient stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal-organic framework (MOF) MIL-101-Fe-NH nanoparticles as carriers to fabricate an innovative reduction-responsive antigen delivery system for cotransporting the antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide.

Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.

Hydrogels with shape memory behavior and internal structure have wide applications in fields ranging from tissue engineering and medical instruments to drug delivery; however, creating the hydrogels has proven to be extremely challenging. This study presents a three-dimensional (3D) printing technology to fabricate the shape memory hydrogels with internal structure (SMHs) by combining sodium alginate (alginate) and pluronic F127 diacrylate macromer (F127DA). SMHs were constituted by a dual network structure.