The time course of the endplate current is determined by the rate and equilibrium constants for acetylcholine receptor (AChR) activation. We measured these constants in single-channel currents from AChRs with mutations at the neurotransmitter-binding sites, in loop C. The main findings are: (a) Almost all perturbations of loop C generate heterogeneity in the channel open probability ("modes").
View Article and Find Full Text PDFObjectives/hypothesis: To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma.
Study Design: Cohort study.
Methods: Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry who developed head and neck squamous cell carcinoma (HNSCC) were analyzed.
Background And Objectives: Respiratory illnesses are the leading cause of pediatric hospitalizations in the United States, and a major focus of efforts to improve quality of care. Understanding factors associated with poor outcomes will allow better targeting of interventions for improving care. The objective of this study was to identify patient and hospital factors associated with prolonged length of stay (LOS) or complications during pediatric hospitalizations for asthma or lower respiratory infection (LRI).
View Article and Find Full Text PDFCleanrooms have been considered microbially-reduced environments and are used to protect human health and industrial product assembly. However, recent analyses have deciphered a rather broad diversity of microbes in cleanrooms, whose origin as well as physiological status has not been fully understood. Here, we examined the input of intact microbial cells from a surrounding built environment into a spacecraft assembly cleanroom by applying a molecular viability assay based on propidium monoazide (PMA).
View Article and Find Full Text PDFBiochem Pharmacol
October 2015
The interaction of a small molecule made in one cell with a large receptor made in another is the signature event of cell signaling. Understanding the structure and energy changes associated with agonist activation is important for engineering drugs, receptors and synapses. The nicotinic acetylcholine receptor (AChR) is a ∼300kD ion channel that binds the neurotransmitter acetylcholine (ACh) and other cholinergic agonists to elicit electrical responses in the central and peripheral nervous systems.
View Article and Find Full Text PDFThis review examines handling and processing of spleen biopsies and splenectomy specimens with the aim of providing the pathologist with guidance in optimizing examination and diagnosis of splenic disorders. It also offers recommendations as to relevant reporting factors in gross examination, which may guide diagnostic workup. The role of splenic needle biopsies is discussed.
View Article and Find Full Text PDFFanconi anemia (FA) is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs). Mutations in 17 genes (FANCA-FANCS) have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2), UBE2T.
View Article and Find Full Text PDFThe uncultivated "Candidatus Altiarchaeum hamiconexum" (formerly known as SM1 Euryarchaeon) carries highly specialized nano-grappling hooks ("hami") on its cell surface. Until now little is known about the major protein forming these structured fibrous cell surface appendages, the genes involved or membrane anchoring of these filaments. These aspects were analyzed in depth in this study using environmental transcriptomics combined with imaging methods.
View Article and Find Full Text PDFObjective: To determine whether perioperative transfusion of as little as one unit of packed red blood cells in the operating room or the day after surgery is associated with measurably increased odds for perioperative ischemic stroke and myocardial infarction.
Design: Retrospective cohort study of hospital administrative data.
Setting: 346 hospitals in the United States participating in the claims based Premier Perspective database from 1 January 2009 to 31 March 2012.
Key Points: A conserved proline in M1 causes a kink between α and π helical segments. The kink is under greater tension in the resting versus active conformation. The kink and the agonist do not interact directly.
View Article and Find Full Text PDFFanconi anemia (FA) is a genetically and phenotypically heterogeneous disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer, particularly hematological malignancies and solid tumors of the head and neck. The main role of FA proteins is in the repair of DNA interstrand crosslinks (ICLs). FA results from pathogenic variants in at least sixteen distinct genes, causing genomic instability.
View Article and Find Full Text PDFSemin Diagn Pathol
January 2015
Epstein Barr virus (EBV)-related lymphoproliferative processes occur in the head and neck ranging from reactive processes such as infectious mononucleosis to high grade malignant lymphomas. EBV is a ubiquitous herpes virus that infects more than 90% of adults worldwide, and is generally transferred though saliva. Primary infection can occur throughout life.
View Article and Find Full Text PDFEndophytes have an intimate and often symbiotic interaction with their hosts. Less is known about the composition and function of endophytes in trees. In order to evaluate our hypothesis that plant genotype and origin have a strong impact on both, endophytes of leaves from 10 Olea europaea L.
View Article and Find Full Text PDFSpace agencies maintain highly controlled cleanrooms to ensure the demands of planetary protection. To study potential effects of microbiome control, we analyzed microbial communities in two particulate-controlled cleanrooms (ISO 5 and ISO 8) and two vicinal uncontrolled areas (office, changing room) by cultivation and 16S rRNA gene amplicon analysis (cloning, pyrotagsequencing, and PhyloChip G3 analysis). Maintenance procedures affected the microbiome on total abundance and microbial community structure concerning richness, diversity and relative abundance of certain taxa.
View Article and Find Full Text PDFBackground: Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common.
Purpose: To determine whether automated real-time electronic sepsis alerts can: (1) accurately identify sepsis and (2) improve process measures and outcomes.
Data Sources: We systematically searched MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from database inception through June 27, 2014.
Background: Repeat blood cultures are frequently obtained in children with persistent fever and neutropenia (FN), but their clinical impact is uncertain.
Methods: We identified children with persistent FN in the context of hematologic malignancy or hematopoietic stem cell transplantation from July 2006 to June 2012. For each episode, we reviewed blood cultures to determine the yield of true positive and false positive results.
Importance: Medicare currently penalizes hospitals for high readmission rates for seniors but does not account for common age-related syndromes, such as functional impairment.
Objective: To assess the effects of functional impairment on Medicare hospital readmissions given the high prevalence of functional impairments in community-dwelling seniors.
Design, Setting, And Participants: We created a nationally representative cohort of 7854 community-dwelling seniors in the Health and Retirement Study, with 22,289 Medicare hospitalizations from January 1, 2000, through December 31, 2010.
Context: Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymphoma and many related large B-cell lymphomas and aggressive B-cell lymphomas.
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