Interfacial engineering for biomolecule immobilisation in microfluidic devices.

Microfluidic devices are used for various applications in biology and medicine. From on-chip modelling of human organs for drug screening and fast and straightforward point-of-care (POC) detection of diseases to sensitive biochemical analysis, these devices can be custom-engineered using low-cost techniques. The microchannel interface is essential for these applications, as it is the interface of immobilised biomolecules that promote cell capture, attachment and proliferation, sense analytes and metabolites or provide enzymatic reaction readouts.

Mitochondrial Membrane Potential and Lactate Dehydrogenase Activity in a Model of Acute In Vitro Ischemia/Reperfusion Injury.

Experimental models of cardiac ischemia/reperfusion injury have served as useful tools in isolating the sequence of events and mechanisms involved following an infarct. The in vitro coverslip ischemia model in neonatal myocytes is key in observing acute cellular and organelle changes during ischemia and in reperfusion. Here we use neonatal mouse ventricular myocytes, and describe two experimental readouts of lactate dehydrogenase assay, for cell damage/injury and measurement of mitochondrial membrane potential.

The Impact of Frenotomy on Gastroesophageal Reflux in Pediatric Ankyloglossia: A Systematic Review.

Objective: This systematic review was conducted to assess if there are changes in gastroesophageal reflux (GER) outcomes after frenotomy in infants with ankyloglossia.

Methods: Systematic Review. CINAHL, Cochrane, EMBASE, Pubmed, and Scopus were searched from inception to May 20, 2023.

Synthesis and Structure-Activity Relationships for Glutamate Transporter Allosteric Modulators.

Excitatory amino acid transporters (EAATs) are essential CNS proteins that regulate glutamate levels. Excess glutamate release and alteration in EAAT expression are associated with several CNS disorders. Previously, we identified positive allosteric modulators (PAM) of EAAT2, the main CNS transporter, and have demonstrated their neuroprotective properties .

Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19.

Background: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19.

Methods: Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection.

Effect of Verapamil, a P-glycoprotein-1 and Cytochrome P450 3A4 Inhibitor, on Pharmacokinetics and Metabolic Stability of Ripretinib: A Drug-Drug Interaction Study in Rats.

Background And Objectives: Ripretinib was developed to target a whole range of KIT proto-oncogene mutations and platelet-derived growth factor receptor A (PDGFR-A) kinases found in certain cancers and myeloproliferative neoplasms, particularly gastrointestinal stromal tumours (GISTs). This study investigated the effect of verapamil, a potential inhibitor of P-glycoprotein-1 (P-gp1) and cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics of ripretinib in rats when administered orally together. This study also assessed the metabolic stability and in vitro cellular absorption of ripretinib in the presence of verapamil.

Mitochondrial membrane potential instability on reperfusion after ischemia does not depend on mitochondrial Ca uptake.

Physiologic Ca entry via the Mitochondrial Calcium Uniporter (MCU) participates in energetic adaption to workload but may also contribute to cell death during ischemia/reperfusion (I/R) injury. The MCU has been identified as the primary mode of Ca import into mitochondria. Several groups have tested the hypothesis that Ca import via MCU is detrimental during I/R injury using genetically-engineered mouse models, yet the results from these studies are inconclusive.

Positive Schemas, Coping, and Quality of Life in Pediatric Recurrent Abdominal Pain.

Pediatric recurrent abdominal pain is commonly associated with negative impacts on quality of life (QOL). Positive schemas (core beliefs about the self with subthemes of self-efficacy, optimism, trust, success, and worthiness) are a resilience factor that has not yet been examined within a pediatric recurrent pain context. This cross-sectional study examined (a) associations between positive schemas, pain coping, and youth QOL, and (b) exploratory analyses to investigate whether specific positive schema subthemes predicted QOL outcomes in youth with recurrent abdominal pain.

Inhibiting O-GlcNAcylation impacts p38 and Erk1/2 signaling and perturbs cardiomyocyte hypertrophy.

The dynamic cycling of O-linked GlcNAc (O-GlcNAc) on and off Ser/Thr residues of intracellular proteins, termed O-GlcNAcylation, is mediated by the conserved enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase. O-GlcNAc cycling is important in homeostatic and stress responses, and its perturbation sensitizes the heart to ischemic and other injuries. Despite considerable progress, many molecular pathways impacted by O-GlcNAcylation in the heart remain unclear.

Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma.

Individuals with hematologic malignancies are at increased risk for severe coronavirus disease 2019 (COVID-19), yet profound analyses of COVID-19 vaccine-induced immunity are scarce. Here we present an observational study with expanded methodological analysis of a longitudinal, primarily BNT162b2 mRNA-vaccinated cohort of 60 infection-naive individuals with B cell lymphomas and multiple myeloma. We show that many of these individuals, despite markedly lower anti-spike IgG titers, rapidly develop potent infection neutralization capacities against several severe acute respiratory syndrome coronavirus 2 variants of concern (VoCs).

Shielding Surfaces from Viruses and Bacteria with a Multiscale Coating.

The spread of viral and bacterial pathogens mediated by contact with surfaces is a leading cause of infection worldwide. COVID-19 and the continuous rise of deaths associated with antibiotic-resistant bacteria highlight the need to impede surface-mediated transmission. A sprayable coating with an intrinsic ability to resist the uptake of bacteria and viruses from surfaces and droplets, such as those generated by sneezing or coughing, is reported.

Insights Into Bone Marrow Niche Stability: An Adhesion and Metabolism Route.

The bone marrow microenvironment provides critical cues for hematopoietic stem cell (HSC) self-renewal and differentiation and contributes to their malignant conversion. The microenvironment comprises a complex mixture of multiple cell types, soluble factors, and extracellular matrix in specialized regions termed 'niches.' Positioning of the various cellular players within these niches depends on their repertoire of adhesion molecules and chemotactic signaling, involving integrins and chemokine receptors and the corresponding intracellular players such as kinases and GTPases.

An Unexpected Finding of Hepatosplenomegaly in a Pediatric Patient.

Gaucher disease (GD) is a rare autosomal recessive metabolic disorder. It is characterized by a deficiency of lysosomal glucocerebrosidase, which results in the accumulation of glycosphingolipid substrates, primarily glucosylceramide, in the phagocyte system. In GD Type 1, the liver, spleen, and bone marrow are typically affected.

Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice.

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show that cyclic GMP-selective phosphodiesterase 9A inhibition (PDE9-I) in both male and ovariectomized female mice suppresses preestablished severe diet-induced obesity/CMS with or without superimposed mild cardiac pressure load. PDE9-I reduces total body, inguinal, hepatic, and myocardial fat; stimulates mitochondrial activity in brown and white fat; and improves CMS, without significantly altering activity or food intake.

MitoWave: Spatiotemporal analysis of mitochondrial membrane potential fluctuations during I/R.

Mitochondria exhibit unstable inner membrane potentials (ΔΨ) when subjected to stress, such as during ischemia/reperfusion (I/R). Understanding the mechanism of ΔΨ instability involves characterizing and quantifying this phenomenon in an unbiased and reproducible manner. Here, we describe a simple analytical workflow called "MitoWave" that combines wavelet transform methods and image segmentation to unravel dynamic ΔΨ changes in the cardiac mitochondrial network during I/R.

Health-related quality of life in youth with abdominal pain: An examination of optimism and pain self-efficacy.

Objectives: Abdominal pain adversely impacts children with functional gastrointestinal disorders (FGIDs) or organic gastrointestinal disorders (OGIDs); findings are inconsistent regarding diagnosis and health-related quality of life (HRQoL). This study utilizes a positive psychology framework to understand the experience of youth with abdominal pain (i.e.

Mitochondrial Ca in heart failure: Not enough or too much?

Ca serves as a ubiquitous second messenger mediating a variety of cellular processes including electrical excitation, contraction, gene expression, secretion, cell death and others. The identification of the molecular components of the mitochondrial Ca influx and efflux pathways has created a resurgent interest in the regulation of mitochondrial Ca balance and its physiological and pathophysiological roles. While the pace of discovery has quickened with the availability of new cellular and animal models, many fundamental questions remain to be answered regarding the regulation and functional impact of mitochondrial Ca in health and disease.

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial.

Background: Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain.

Methods: We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg).

Nuclear-mitochondrial communication involving miR-181c plays an important role in cardiac dysfunction during obesity.

Aims: In cardiomyocytes, there is microRNA (miR) in the mitochondria that originates from the nuclear genome and matures in the cytoplasm before translocating into the mitochondria. Overexpression of one such miR, miR-181c, can lead to heart failure by stimulating reactive oxygen species (ROS) production and increasing mitochondrial calcium level ([Ca]). Mitochondrial calcium uptake 1 protein (MICU1), a regulatory protein in the mitochondrial calcium uniporter complex, plays an important role in regulating [Ca].

Microwave-assisted synthesis, biological evaluation and molecular docking studies of new coumarin-based 1,2,3-triazoles.

Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, eco-friendly protocol a copper(i)-catalyzed click reaction between various substituted arylazides and terminal alkynes. The synthetic route was easy to access and gave excellent yields under microwave irradiation conditions compared to the conventional heating route. The structures of all the compounds were characterized by IR, H NMR, C NMR spectroscopy and mass spectrometry.

Global knockout of ROMK potassium channel worsens cardiac ischemia-reperfusion injury but cardiomyocyte-specific knockout does not: Implications for the identity of mitoKATP.

The renal-outer-medullary‑potassium (ROMK) channel, mutated in Bartter's syndrome, regulates ion exchange in kidney, but its extra-renal functions remain unknown. Additionally, ROMK was postulated to be the pore-forming subunit of the mitochondrial ATP-sensitive K channel (mitoK), a mediator of cardioprotection. Using global and cardiomyocyte-specific knockout mice (ROMK-GKO and ROMK-CKO respectively), we characterize the effects of ROMK knockout on mitochondrial ion handling, the response to pharmacological K channel modulators, and ischemia/reperfusion (I/R) injury.

Bioinspired surface modification of orthopedic implants for bone tissue engineering.

Biomedical implants have been widely used in various orthopedic treatments, including total hip arthroplasty, joint arthrodesis, fracture fixation, non-union, dental repair, etc. The modern research and development of orthopedic implants have gradually shifted from traditional mechanical support to a bioactive graft in order to endow them with better osteoinduction and osteoconduction. Inspired by structural and mechanical properties of natural bone, this review provides a panorama of current biological surface modifications for facilitating the interaction between medical implants and bone tissue and gives a future outlook for fabricating the next-generation multifunctional and smart implants by systematically biomimicking the physiological processes involved in formation and functioning of bones.