Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice.

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes.

Endothelial force sensing signals to parenchymal cells to regulate bile and plasma lipids.

How cardiovascular activity interacts with lipid homeostasis is incompletely understood. We postulated a role for blood flow acting at endothelium in lipid regulatory organs. Transcriptome analysis was performed on livers from mice engineered for deletion of the flow-sensing PIEZO1 channel in endothelium.

Are Mass Shootings in the U.S. Increasing? Understanding How Differing Definitions of Politically Charged Events Impact People's Perceptions of Expected Trends in Visualizations.

Visualizations of mass shooting incidents in the United States appearing in the media can influence people's beliefs and attitudes. However, different data sources each use their own definition of mass shootings, resulting in varying counts and trends of these incidents across the sources. To investigate the effects of these varying definitions on public perceptions, we conducted a crowdsourced study using data from four sources-Mother Jones, Mass Shooter Database, Everytown for Gun Safety, and The Washington Post.

OMEF biochip for evaluating red blood cell deformability using dielectrophoresis as a diagnostic tool for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a prevalent and debilitating disease with numerous health risks, including cardiovascular diseases, kidney dysfunction, and nerve damage. One important aspect of T2DM is its association with the abnormal morphology of red blood cells (RBCs), which leads to increased blood viscosity and impaired blood flow. Therefore, evaluating the mechanical properties of RBCs is crucial for understanding the role of T2DM in cellular deformability.

Studying Adipose Endothelial Cell/Adipocyte Cross-Talk in Human Subcutaneous Adipose Tissue.

Microvascular endothelial cells (MVECs) have many critical roles, including control of vascular tone, regulation of thrombosis, and angiogenesis. Significant heterogeneity in endothelial cell (EC) genotype and phenotype depends on their vascular bed and host disease state. The ability to isolate MVECs from tissue-specific vascular beds and individual patient groups offers the opportunity to directly compare MVEC function in different disease states.

Postbiotic butyrate: role and its effects for being a potential drug and biomarker to pancreatic cancer.

Postbiotics are produced by microbes and have recently gained importance in the field of oncology due to their beneficial effects to the host, effectiveness against cancer cells, and their ability to suppress inflammation. In particular, butyrate dominates over all other postbiotics both in quantity and anticancer properties. Pancreatic cancer (PC), being one of the most malignant and lethal cancers, reported a decreased 5-year survival rate in less than 10% of the patients.

Spike- and nucleocapsid-based gold colloid assay toward the development of an adhesive bandage for rapid SARS-CoV-2 immune response detection and screening.

Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are important biomarkers used for the diagnosis and screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in both symptomatic and asymptomatic individuals. These antibodies are highly specific to the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus. This paper outlines the development steps of a novel hybrid (vertical-lateral-vertical) flow assay in the form of a finger-stick point-of-care device, similar to an adhesive bandage, designed for the timely detection and screening of IgM and IgG immune responses to SARS-CoV-2 infections.

The impact of road safety strategy and policy on admissions to a national rehabilitation hospital; a 5-year retrospective review and reflection on trauma data.

Background: Globally, road traffic collisions (RTCs) are a common cause of death and disability. Although many countries, including Ireland, have road safety and trauma strategies, the impact on rehabilitation services is unclear. This study explores how admissions with RTC related injuries to a rehabilitation facility has changed over 5 years and how they contrast to major trauma audit (MTA) serious injury data from the same timeframe.

Machine learning-enabled high-entropy alloy discovery.

High-entropy alloys are solid solutions of multiple principal elements that are capable of reaching composition and property regimes inaccessible for dilute materials. Discovering those with valuable properties, however, too often relies on serendipity, because thermodynamic alloy design rules alone often fail in high-dimensional composition spaces. We propose an active learning strategy to accelerate the design of high-entropy Invar alloys in a practically infinite compositional space based on very sparse data.

Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity.

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD.

Elevated ATP, cytokines and potential microglial inflammation distinguish exfoliation glaucoma from exfoliation syndrome.

Glaucoma is the second leading cause of blindness. Exfoliation syndrome (XFN) is a risk factor for exfoliation glaucoma (XFG) which is a secondary open angle glaucoma. XFG is difficult to manage with a worse prognosis.

Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity.

Piezo1 forms mechanically activated nonselective cation channels that contribute to endothelial response to fluid flow. Here we reveal an important role in the control of capillary density. Conditional endothelial cell-specific deletion of Piezo1 in adult mice depressed physical performance.

Pharmacology of TRPC Channels and Its Potential in Cardiovascular and Metabolic Medicine.

Transient receptor potential canonical (TRPC) proteins assemble to form homo- or heterotetrameric, nonselective cation channels permeable to K, Na, and Ca. TRPC channels are thought to act as complex integrators of physical and chemical environmental stimuli. Although the understanding of essential physiological roles of TRPC channels is incomplete, their implication in various pathological mechanisms and conditions of the nervous system, kidneys, and cardiovascular system in combination with the lack of major adverse effects of TRPC knockout or TRPC channel inhibition is driving the search of TRPC channel modulators as potential therapeutics.

Pericyte Insulin Receptors Modulate Retinal Vascular Remodeling and Endothelial Angiopoietin Signaling.

Pericytes regulate vascular development, stability, and quiescence; their dysfunction contributes to diabetic retinopathy. To explore the role of insulin receptors in pericyte biology, we created pericyte insulin receptor knockout mice (PIRKO) by crossing PDGFRβ-Cre mice with insulin receptor (Insr) floxed mice. Their neonatal retinal vasculature exhibited perivenous hypervascularity with venular dilatation, plus increased angiogenic sprouting in superficial and deep layers.

Novel Paracrine Action of Endothelium Enhances Glucose Uptake in Muscle and Fat.

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An evaluation of the process of informed consent: views from research participants and staff.

Background: The process of informed consent for enrolment to a clinical research study can be complex for both participants and research staff. Challenges include respecting the potential participant's autonomy and information needs while simultaneously providing adequate information to enable an informed decision. Qualitative research with small sample sizes has added to our understanding of these challenges.

The Unmet Rehabilitation Needs in an Inclusion Health Integrated Care Programme for Homeless Adults in Dublin, Ireland.

Background: People who become homeless have higher morbidity and mortality, use a disproportionate amount of healthcare resources, and generate a large volume of potentially preventable healthcare and other costs compared to more privileged individuals. Although access to rehabilitation is a human right under article 26 of the United Nations Convention on the Rights of Persons with Disabilities, the rehabilitation needs of individuals with homelessness have not been explored, and this project's purpose was to establish a baseline of need for this cohort.

Methods: A prospective audit of case discussions at an inclusion health service over a 2-month period in 2018.

Noncontact Multiphysics Probe for Spatiotemporal Resolved Single-Cell Manipulation and Analyses.

Heterogeneity and spatial arrangement of individual cells within tissues are critical to the identity of the host multicellular organism. While current single-cell techniques are capable of resolving heterogeneity, they mostly rely on extracting target cells from their physiological environment and hence lose the spatiotemporal resolution required for understanding cellular networks. Here, a multifunctional noncontact scanning probe that can precisely perform multiple manipulation procedures on living single-cells, while within their physiological tissue environment, is demonstrated.

Preparing accessible and understandable clinical research participant information leaflets and consent forms: a set of guidelines from an expert consensus conference.

Background: In line with Good Clinical Practice and the Declaration of Helsinki, it is the investigator's responsibility to ensure that research participants are sufficiently informed, to enable the provision of informed consent. The Participant Information Leaflet/Informed Consent Form is key to facilitating this communication process. Although studies have indicated that clinical research Participant Information Leaflets/Informed Consent Forms are not optimal in terms of accessibility, there is little or no specific guidance available.

Elevated dimethylarginine, ATP, cytokines, metabolic remodeling involving tryptophan metabolism and potential microglial inflammation characterize primary open angle glaucoma.

Glaucoma of which primary open angle glaucoma (POAG) constitutes 75%, is the second leading cause of blindness. Elevated intra ocular pressure and Nitric oxide synthase (NOS) dysfunction are hallmarks of POAG. We analyzed clinical data, cytokine profile, ATP level, metabolomics and GEO datasets to identify features unique to POAG.

Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity.

Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are critical for coupling nutritional status and cellular growth; IGF-1R is expressed in multiple cell types including EC.

Kv1.3 voltage-gated potassium channels link cellular respiration to proliferation through a non-conducting mechanism.

Cellular energy metabolism is fundamental for all biological functions. Cellular proliferation requires extensive metabolic reprogramming and has a high energy demand. The Kv1.

A Method to Efficiently Cryopreserve Mammalian Cells on Paper Platforms.

This protocol describes a simple method to cryopreserve mammalian cells within filter papers as an alternative to conventional slow-freezing approach. The method involves treating paper fibers with fibronectin, using low concentrations of the cryoprotectant dimethyl sulfoxide (DMSO), and slow freezing cells to -80 °C at a 1 °C min rate. In our method, the biocompatibility, large surface area, 3D porosity and fiber flexibility of the paper, in combination with the fibronectin treatment, yield recovery of cells comparable to conventional approaches, with no additional fine-tuning to freezing and thawing procedures.