Decreasing Nurses' Anxiety About Pediatric End-of-Life Care With Simulation.

Background: Caring for pediatric patients at the end of life (EOL) can lead to anxiety and burnout for critical care nurses. New graduate nurses (NGNs) often report receiving inadequate education related to EOL care and then enter the workforce with limited clinical experience in caring for patients at EOL. A quality improvement project at a pediatric academic hospital sought to determine whether a simulation-based educational program for NGNs working in critical care could reduce anxiety about EOL care.

Quality Decision-Making Practices in Pharmaceutical Companies and Regulatory Authorities: Current and Proposed Approaches to Its Documentation.

Background: Pharmaceutical companies and regulatory agencies endeavor to relate their decision making with outcomes to improve future decision making and to ensure that gained knowledge is fed back into a learning system. Nevertheless, such a correlation can only be achieved by documenting the expected outcome of a decision at the time it is made, enabling comparison of the expected outcome with the actual result.

Methods: Participants at an international workshop discussed how the documentation of decisions could be evolved as companies and agencies look to improve their knowledge base.

The Confluence of Accelerated Regulatory and Health Technology Assessment Access Pathways.

There is a growing interest in aligning accelerated regulatory pathways with flexible access and reimbursement pathways to expedite the equitable availability of high-quality, safe, and effective medicines that provide a value-based approach to meeting society's most important healthcare needs. The Centre for Innovation in Regulatory Science (CIRS) identified key issues regarding the confluence of regulatory and health technology assessment processes from discussions and presentations given by international regulators, health technology assessment bodies, payers, patient representatives, and multinational pharmaceutical company representatives on this topic at CIRS workshops held in 2014 and 2017 that focused on the commonalties and differences across these pathways. Recent publications have also been highlighted.

Mitochondrial reticulum for cellular energy distribution in muscle.

Intracellular energy distribution has attracted much interest and has been proposed to occur in skeletal muscle via metabolite-facilitated diffusion; however, genetic evidence suggests that facilitated diffusion is not critical for normal function. We hypothesized that mitochondrial structure minimizes metabolite diffusion distances in skeletal muscle. Here we demonstrate a mitochondrial reticulum providing a conductive pathway for energy distribution, in the form of the proton-motive force, throughout the mouse skeletal muscle cell.

Phosphatidylserine vesicles enable efficient en bloc transmission of enteroviruses.

A central paradigm within virology is that each viral particle largely behaves as an independent infectious unit. Here, we demonstrate that clusters of enteroviral particles are packaged within phosphatidylserine (PS) lipid-enriched vesicles that are non-lytically released from cells and provide greater infection efficiency than free single viral particles. We show that vesicular PS lipids are co-factors to the relevant enterovirus receptors in mediating subsequent infectivity and transmission, in particular to primary human macrophages.

Study of the development of the mouse thoracic aorta three-dimensional macromolecular structure using two-photon microscopy.

Using the intrinsic optical properties of collagen and elastin, two-photon microscopy was applied to evaluate the three-dimensional (3D) macromolecular structural development of the mouse thoracic aorta from birth to 60 days old. Baseline development was established in the Scavenger Receptor Class B Type I-Deficient, Hypomorphic Apolipoprotein ER61 (SR-BI KO/ApoeR61(h/h)) mouse in preparation for modeling atherosclerosis. Precise dissection enabled direct observation of the artery wall in situ.

Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor.

Endothelial secretion of von Willebrand factor (VWF) from intracellular organelles known as Weibel-Palade bodies (WPBs) is required for platelet adhesion to the injured vessel wall. Here we demonstrate that WPBs are often found near or within autophagosomes and that endothelial autophagosomes contain abundant VWF protein. Pharmacological inhibitors of autophagy or knockdown of the essential autophagy genes Atg5 or Atg7 inhibits the in vitro secretion of VWF.

Restricted mitochondrial protein acetylation initiates mitochondrial autophagy.

Because nutrient-sensing nuclear and cytosolic acetylation mediates cellular autophagy, we investigated whether mitochondrial acetylation modulates mitochondrial autophagy (mitophagy). Knockdown of GCN5L1, a component of the mitochondrial acetyltransferase machinery, diminished mitochondrial protein acetylation and augmented mitochondrial enrichment of autophagy mediators. This program was disrupted by SIRT3 knockdown.

Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of β-oxidation of fatty acids and blocks cell division in the amastigote stage.

Recently, we described the existence of the ubiquitin fold modifier 1 (Ufm1) and its conjugation pathway in Leishmania donovani. We demonstrated the conjugation of Ufm1 to proteins such as mitochondrial trifunctional protein (MTP) that catalyses β-oxidation of fatty acids in L. donovani.

High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.

Background: Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients.

Coronary artery wall imaging in mice using osmium tetroxide and micro-computed tomography (micro-CT).

The high spatial resolution of micro-computed tomography (micro-CT) is ideal for 3D imaging of coronary arteries in intact mouse heart specimens. Previously, micro-CT of mouse heart specimens utilized intravascular contrast agents that hardened within the vessel lumen and allowed a vascular cast to be made. However, for mouse coronary artery disease models, it is highly desirable to image coronary artery walls and highlight plaques.

Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins.

Aims: Nitric oxide (NO) and protein S-nitrosylation (SNO) play important roles in ischemic preconditioning (IPC)-induced cardioprotection. Mitochondria are key regulators of preconditioning, and most proteins showing an increase in SNO with IPC are mitochondrial. The aim of this study was to address how IPC transduces NO/SNO signaling to mitochondria in the heart.

Innovations in performance assessment: a criterion based performance assessment for advanced practice nurses using a synergistic theoretical nursing framework.

Purpose: Health care organizations that employ advanced practice nurses are challenged to evaluate practice at this advanced level. Current evaluation methods tend to inter-mingle basic nursing competencies with competencies found in medical practice and organizational objectives that are typically derived from human resources departments. This article describes the development of a criterion-based job performance assessment for advanced nursing practice using a framework rooted in a nursing theory.

The impact of adenotonsillectomy on asthma in children.

Objective: To investigate the impact of adenotonsillectomy on asthma in the pediatric population.

Study Design: Retrospective chart review.

Methods: All children who underwent adenotonsillectomy at our institution from 2002-2007 were identified from a medical records database.

Establishing a training program for residents in robotic surgery.

Objectives/hypothesis: To develop a program for teaching robotic skills to residents. To assess the development of proficiency in basic robotic surgical skills in a resident cohort.

Study Design: Prospective educational project using a commercially available surgical robot.

Autophagic dysfunction in mucolipidosis type IV patients.

Mutations in Mucolipin 1 (MCOLN1) have been linked to mucolipidosis type IV (MLIV), a lysosomal storage disease characterized by several neurological and ophthalmological abnormalities. It has been proposed that MCOLN1 might regulate transport of membrane components in the late endosomal-lysosomal pathway; however, the mechanisms by which defects of MCOLN1 function result in mental and psychomotor retardation remain largely unknown. In this study, we show constitutive activation of autophagy in fibroblasts obtained from MLIV patients.

Krp1 (Sarcosin) promotes lateral fusion of myofibril assembly intermediates in cultured mouse cardiomyocytes.

Krp1, also called sarcosin, is a cardiac and skeletal muscle kelch repeat protein hypothesized to promote the assembly of myofibrils, the contractile organelles of striated muscles, through interaction with N-RAP and actin. To elucidate its role, endogenous Krp1 was studied in primary embryonic mouse cardiomyocytes. While immunofluorescence showed punctate Krp1 distribution throughout the cell, detergent extraction revealed a significant pool of Krp1 associated with cytoskeletal elements.

Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder associated with ciliary defects and situs inversus totalis, the complete mirror image reversal of internal organ situs (positioning). A variable incidence of heterotaxy, or irregular organ situs, also has been reported in PCD patients, but it is not known whether this is elicited by the PCD-causing genetic lesion. We studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene commonly mutated in PCD.

Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay.

Antigen detection is a useful adjunct for the diagnosis of histoplasmosis. The purpose of this study was to evaluate antigen detection in bronchoalveolar lavage (BAL) fluid using an improved second-generation Histoplasma antigen assay. Antigen was detected in 16 of 19 (84%) cases of histoplasmosis and 5 of 6 (83.

Adaptation of a nematode parasite to living within the mammalian epithelium.

Trichuris muris is a large metazoan pathogen that has been proposed to live intracellularly within living host intestinal epithelial cells. We sought to determine how Trichuris bores its way through the mucosal epithelium and to elucidate the parasite strategies for taking advantage of this intracellular niche. Since the apical surface of the mucosal epithelium is stabilized by the actin cytoskeleton and cell junctions, it remains intact over the worm following its entry into cells.

Actin filament bundles in Drosophila wing hairs: hairs and bristles use different strategies for assembly.

Actin filament bundles can shape cellular extensions into dramatically different forms. We examined cytoskeleton formation during wing hair morphogenesis using both confocal and electron microscopy. Hairs elongate with linear kinetics (approximately 1 microm/h) over the course of approximately 18 h.

The role actin filaments play in providing the characteristic curved form of Drosophila bristles.

Drosophila bristles display a precise orientation and curvature. An asymmetric extension of the socket cell overlies the newly emerging bristle rudiment to provide direction for bristle elongation, a process thought to be orchestrated by the nerve dendrite lying between these cells. Scanning electron microscopic analysis of individual bristles showed that curvature is planar and far greater near the bristle base.

Microvilli appear to represent the first step in actin bundle formation in Drosophila bristles.

During bristle development the emerging bristle shaft, socket cell, and the apical surface of thoracic epithelial cells form tiny protuberances or pimples that contain electron-dense material located on the cytoplasmic surface of the pimple tip. In a few cases short actin filaments extend from this material into the cortical cytoplasm. When cultured in the presence of jasplakinolide, an agent that prevents filament disassembly, pimples elongate to form microvilli containing a core of crosslinked filaments.

Actin filament turnover regulated by cross-linking accounts for the size, shape, location, and number of actin bundles in Drosophila bristles.

Drosophila bristle cells are shaped during growth by longitudinal bundles of cross-linked actin filaments attached to the plasma membrane. We used confocal and electron microscopy to examine actin bundle structure and found that during bristle elongation, snarls of uncross-linked actin filaments and small internal bundles also form in the shaft cytoplasm only to disappear within 4 min. Thus, formation and later removal of actin filaments are prominent features of growing bristles.

Long continuous actin bundles in Drosophila bristles are constructed by overlapping short filaments.

The actin bundles essential for Drosophila bristle elongation are hundreds of microns long and composed of cross-linked unipolar filaments. These long bundles are built from much shorter modules that graft together. Using both confocal and electron microscopy, we demonstrate that newly synthesized modules are short (1-2 microm in length); modules elongate to approximately 3 microm by growing over the surface of longitudinally adjacent modules to form a graft; the grafted regions are initially secured by the forked protein cross-bridge and later by the fascin cross-bridge; actin bundles are smoothed by filament addition and appear continuous and without swellings; and in the absence of grafting, dramatic alterations in cell shape occur that substitutes cell width expansion for elongation.