Late-onset aortic regurgitation after device closure of atrial septal defect.

A 10-year-old girl underwent successful device closure of a 15-mm atrial septal defect with a short and thick retroaortic rim using a 16-mm atrial septal occluder from the conventional approach under transesophageal echocardiographic guidance. There were no periprocedural complications. The aortic valve was noted to be trileaflet and competent.

Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells.

Our understanding of the transitions of human embryonic stem cells (hESCs) between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of hESCs as they transition from primed to naïve pluripotency which includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for formation of the actin ring, to establish uniform cell mechanics within naïve colonies, to promote nuclear translocation of the Hippo pathway effectors YAP and TAZ, and for effective transition to naïve pluripotency.

Smoking enhances proliferation, inflammatory markers, and immunoglobulins in peripheral blood mononuclear cells from Graves' patients.

Graves' disease (GD) and Graves' ophthalmopathy (GO) are complex autoimmune diseases. This study delved into the impact of cigarette smoke extract (CSE), simvastatin, and/or diclofenac on peripheral blood mononuclear cells (PBMCs). Specifically, we explored alterations in IL-1B, IL-6, PTGS2 expression, B- and T-lymphocyte proliferation, and Immunoglobulin G (IgG) production.

Effect of Peri-operative Blood Transfusion on Neurological Outcome Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study.

Background: Anemia is a common complication of aneurysmal subarachnoid hemorrhage and is associated with unfavorable outcomes. Whether the physiological benefits of transfusion for anemia surpass the risk of blood transfusion remains to be determined.

Objectives: The primary outcome was to evaluate the impact of peri-operative blood transfusion on the long-term neurological outcome, assessed by Glasgow Outcome Scale Extended at 3 months.

Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.

Notch receptors control tissue morphogenic processes that involve coordinated changes in cell architecture and gene expression, but how a single receptor can produce these diverse biological outputs is unclear. Here, we employ a 3D model of a human ductal epithelium to reveal tissue morphogenic defects result from loss of Notch1, but not Notch1 transcriptional signaling. Instead, defects in duct morphogenesis are driven by dysregulated epithelial cell architecture and mitogenic signaling which result from the loss of a transcription-independent, Notch1 cortical signaling mechanism that ultimately functions to stabilize adherens junctions and cortical actin.

'Chip'-ing away at morphogenesis - application of organ-on-chip technologies to study tissue morphogenesis.

Emergent cell behaviors that drive tissue morphogenesis are the integrated product of instructions from gene regulatory networks, mechanics and signals from the local tissue microenvironment. How these discrete inputs intersect to coordinate diverse morphogenic events is a critical area of interest. Organ-on-chip technology has revolutionized the ability to construct and manipulate miniaturized human tissues with organotypic three-dimensional architectures in vitro.

MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas.

Hormone secretion from pancreatic islets is essential for glucose homeostasis, and loss or dysfunction of islet cells is a hallmark of type 2 diabetes. Maf transcription factors are crucial for establishing and maintaining adult endocrine cell function. However, during pancreas development, MafB is not only expressed in insulin- and glucagon-producing cells, but also in Neurog3+ endocrine progenitor cells, suggesting additional functions in cell differentiation and islet formation.

Notch1 cortical signaling regulates epithelial architecture and cell-cell adhesion.

Notch receptors control tissue morphogenic processes that involve coordinated changes in cell architecture and gene expression, but how a single receptor can produce these diverse biological outputs is unclear. Here we employ a 3D organotypic model of a ductal epithelium to reveal tissue morphogenic defects result from loss of Notch1, but not Notch1 transcriptional signaling. Instead, defects in duct morphogenesis are driven by dysregulated epithelial cell architecture and mitogenic signaling which result from loss of a transcription-independent Notch1 cortical signaling mechanism that ultimately functions to stabilize adherens junctions and cortical actin.

Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy.

Objectives: Our previous published studies have focused on safety and effectiveness of using therapeutic ultrasound (TUS) for treatment of type 2 diabetes mellitus (T2DM) in preclinical models. Here we present a set of simulation studies to explore potential ultrasound application schemes that would be feasible in a clinical setting.

Methods: Using the multiphysics modeling tool OnScale, we created two-dimensional (2D) models of the human abdomen from CT images captured from one normal weight adolescent patient, and one obese adolescent patient.

MAFA and MAFB regulate exocytosis-related genes in human β-cells.

Aims: Reduced expression of exocytotic genes is associated with functional defects in insulin exocytosis contributing to impaired insulin secretion and type 2 diabetes (T2D) development. MAFA and MAFB transcription factors regulate β-cell physiology, and their gene expression is reduced in T2D β cells. We investigate if loss of MAFA and MAFB in human β cells contributes to T2D progression by regulating genes required for insulin exocytosis.

The MafA-target gene PPP1R1A regulates GLP1R-mediated amplification of glucose-stimulated insulin secretion in β-cells.

The amplification of glucose-stimulated insulin secretion (GSIS) through incretin signaling is critical for maintaining physiological glucose levels. Incretins, like glucagon-like peptide 1 (GLP1), are a target of type 2 diabetes drugs aiming to enhance insulin secretion. Here we show that the protein phosphatase 1 inhibitor protein 1A (PPP1R1A), is expressed in β-cells and that its expression is reduced in dysfunctional β-cells lacking MafA and upon acute MafA knock down.

Effect of Therapeutic Ultrasound on the Release of Insulin, Glucagon, and Alpha-Amylase from Ex Vivo Pancreatic Models.

Objectives: Our previously published studies showed the potential of therapeutic ultrasound (US) as a novel non-pharmacological alternative for the treatment of secretory deficiencies in type 2 diabetes. Despite showing enhanced insulin release from beta cells, these studies did not explore the potential effects of US treatment on other cells in the islets of Langerhans such as glucagon-secreting alpha cells or acinar cells of the exocrine pancreas.

Methods: We applied US parameters found capable of safely stimulating insulin secretion from pancreatic beta cells (f = 800 kHz, I  = 0.

Insulin/Glucose-Responsive Cells Derived from Induced Pluripotent Stem Cells: Disease Modeling and Treatment of Diabetes.

Type 2 diabetes, characterized by dysfunction of pancreatic β-cells and insulin resistance in peripheral organs, accounts for more than 90% of all diabetes. Despite current developments of new drugs and strategies to prevent/treat diabetes, there is no ideal therapy targeting all aspects of the disease. Restoration, however, of insulin-producing β-cells, as well as insulin-responsive cells, would be a logical strategy for the treatment of diabetes.

Therapeutic Ultrasound-Induced Insulin Release in Vivo.

The tolerability and efficacy of low-frequency, low-intensity therapeutic ultrasound-induced insulin release was investigated in a pre-clinical in vivo murine model. The treatment groups received a single 5-min continuous sonication at 1 MHz and 1.0 W/cm.

Loss of MafA and MafB expression promotes islet inflammation.

Maf transcription factors are critical regulators of beta-cell function. We have previously shown that reduced MafA expression in human and mouse islets is associated with a pro-inflammatory gene signature. Here, we investigate if the loss of Maf transcription factors induced autoimmune processes in the pancreas.

The calcium channel subunit gamma-4 is regulated by MafA and necessary for pancreatic beta-cell specification.

Voltage-gated Ca (Ca) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, and the accessory ones, including subunit gamma that remains unexplored. Here, we demonstrate that Ca gamma subunit 4 (Caγ4) is downregulated in islets from human donors with diabetes, diabetic Goto-Kakizaki (GK) rats, as well as under conditions of gluco-/lipotoxic stress.

Identification and characterization of potent and selective aquaporin-3 and aquaporin-7 inhibitors.

The aquaglyceroporins are a subfamily of aquaporins that conduct both water and glycerol. Aquaporin-3 (AQP3) has an important physiological function in renal water reabsorption, and AQP3-mediated hydrogen peroxide (HO) permeability can enhance cytokine signaling in several cell types. The related aquaglyceroporin AQP7 is required for dendritic cell chemokine responses and antigen uptake.

MafA Expression Preserves Immune Homeostasis in Human and Mouse Islets.

Type 1 (T1D) and type 2 (T2D) diabetes are triggered by a combination of environmental and/or genetic factors. Maf transcription factors regulate pancreatic beta (β)-cell function, and have also been implicated in the regulation of immunomodulatory cytokines like interferon-β (IFNβ1). In this study, we assessed and co-expression with pro-inflammatory cytokine signaling genes in RNA-seq data from human pancreatic islets.

Ultrasound-Induced Insulin Release as a Potential Novel Treatmentfor Type 2 Diabetes Mellitus.

Therapeutic ultrasound presents a potential novel treatment for type 2 diabetes mellitus that utilizes the non-invasive application of ultrasound energy to treat secretory defects in the earlier stages of the disease. Our previous studies have shown that ultrasound is capable of stimulating insulin release from pancreatic beta cells, safely and effectively. This study aims to both examine the calcium-dependent mechanisms of ultrasound-mediated insulin release from pancreatic beta cells using three complementary modalities - carbon fiber amperometry, ELISA studies, and Ca2+ fluorescence imaging - and to study the translational potential of therapeutic ultrasound using transgenic hyperglycemic mice for safety and efficacy studies.

Epidural Analgesia during Labor: Attitudes among Expectant Mothers and Their Care Providers.

Introduction: Varying levels of knowledge and attitudes among parturients and physicians toward epidural analgesia result in its low utilization. We aimed to assess the knowledge, attitude, and practice of parturients, obstetricians, and anesthesiologists regarding epidural labor analgesia.

Methodology: We surveyed obstetricians, anesthesiologists, and parturients availing care and later delivered at our hospital from July 1, 2017, to December 31, 2017.

Calcium-dependent ultrasound stimulation of secretory events from pancreatic beta cells.

Background: Our previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes. The purpose of this study was to explore the temporal dynamics and Ca-dependency of ultrasound-stimulated secretory events from dopamine-loaded pancreatic beta cells in an in vitro setup.

Methods: Carbon fiber amperometry was used to detect secretion from INS-1832/13 beta cells in real time.

Therapeutic Modulation of Calcium Dynamics using Ultrasound and Other Energy-based Techniques.

Ultrasound, along with other types of energy-based methods, has been widely investigated for use in various therapeutic applications because of its ability to stimulate specific biological processes. Many of these processes are mediated by calcium (Ca2+) signaling, thus making modulation of Ca2+ dynamics an evident therapeutic target for energy-based techniques. Various diseases have been associated with abnormal Ca2+ signaling and could therefore benefit from therapeutic approaches trying to regulate the transport of Ca2+ across cell membranes.

Retinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling.

Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation.

Efficacy of Magnesium Sulphate as an Adjunct to Ropivacaine in Local Infiltration for Postoperative Pain Following Lower Segment Caesarean Section.

Introduction: Intravenous and peri-articular magnesium has been shown to reduce perioperative analgesic consumption. With this background, subcutaneous infiltration was hypothesized to potentiate the subcutaneous infiltration of local anaesthetic agent.

Aim: To comparatively evaluate the efficacy of magnesium sulphate as an adjunct to ropivacaine in local infiltration for postoperative pain following lower segment cesarean section.