Determination of Initial Rates of Lipopolysaccharide Transport.

Nonvesicular lipid trafficking pathways are an important process in every domain of life. The mechanisms of these processes are poorly understood in part due to the difficulty in kinetic characterization. One important class of glycolipids, lipopolysaccharides (LPS), are the primary lipidic component of the outer membrane of Gram-negative bacteria.

Navigating Identity: The Intersection of Social and Biological Identity from the World War II Battle of Tarawa.

The 1943 Battle of Tarawa resulted in the loss of approximately 1,000 US service members on or around Betio Island, Tarawa Atoll, Republic of Kiribati. Nearly half these casualties were accounted for after the battle. The Defense POW/MIA Accounting Agency (DPAA) has worked to identify the remaining ∼510 unaccounted-for service members and has successfully identified ∼160 service members to date.

Trotter and Gleser's (1958) equations outperform Trotter and Gleser's (1952) equations in stature estimation of the US White males.

Unlabelled: Trotter and Gleser presented two sets of stature estimation equations for the US White males in their 1952 and 1958 studies. Following Trotter's suggestion favouring the 1952 equations simply due to the smaller standard errors, the 1958 equations have been seldom used and have gone without additional systematic validation tests. This study aims to assess the performance of the Trotter and Gleser 1952, Trotter and Gleser 1958, and FORDISC equations for the White males in a quantitative and systematic way, particularly when applied to the WWII and Korean War casualties.

Suppressor Mutations in LptF Bypass Essentiality of LptC by Forming a Six-Protein Transenvelope Bridge That Efficiently Transports Lipopolysaccharide.

Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) of many Gram-negative bacteria, providing a barrier against the entry of toxic molecules. In Escherichia coli, LPS is exported to the cell surface by seven essential proteins (LptA-G) that form a transenvelope complex. At the inner membrane, the ATP-binding cassette (ABC) transporter LptBFG associates with LptC to power LPS extraction from the membrane and transfer to the periplasmic LptA protein, which is in complex with the OM translocon LptDE.

The structure of COPI vesicles and regulation of vesicle turnover.

COPI-coated vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi to the endoplasmic reticulum. The COPI coat exists as a stable heptameric complex in the cytosol termed coatomer and is recruited en bloc to the membrane for vesicle formation. Recruitment of COPI onto membranes is mediated by the Arf family of small GTPases, which, in their GTP-bound state, bind both membrane and coatomer.

Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Background & Aims: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint.

Methods: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH.

Structural basis of unidirectional export of lipopolysaccharide to the cell surface.

Gram-negative bacteria are surrounded by an inner cytoplasmic membrane and by an outer membrane, which serves as a protective barrier to limit entry of many antibiotics. The distinctive properties of the outer membrane are due to the presence of lipopolysaccharide. This large glycolipid, which contains numerous sugars, is made in the cytoplasm; a complex of proteins forms a membrane-to-membrane bridge that mediates transport of lipopolysaccharide from the inner membrane to the cell surface.

A cysteine-based molecular code informs collagen C-propeptide assembly.

Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen's C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization.

XBP1s activation can globally remodel N-glycan structure distribution patterns.

Classically, the unfolded protein response (UPR) safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated spliced X-box binding protein 1 (XBP1s)-mediated response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s activation for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease.

Outer Membrane Translocon Communicates with Inner Membrane ATPase To Stop Lipopolysaccharide Transport.

The survival of Gram-negative bacteria depends on assembly of the asymmetric outer membrane, which creates a barrier that prevents entry of toxic molecules including antibiotics. The outer leaflet of the outer membrane is composed of lipopolysaccharide, which is made at the inner membrane and pushed across a protein bridge that spans the inner and outer membranes. We have developed a fluorescent assay to follow lipopolysaccharide (LPS) transport across a bridge linking proteoliposomes that mimic the inner and outer membranes.

A cluster of residues in the lipopolysaccharide exporter that selects substrate variants for transport to the outer membrane.

Most Gram-negative bacteria assemble lipopolysaccharides (LPS) on their surface to form a permeability barrier against many antimicrobials. LPS is synthesized at the inner membrane and then transported to the outer leaflet of the outer membrane. Although the overall LPS structure is conserved, LPS molecules can differ in composition at the species and strain level.

Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge.

Gram-negative bacteria have an outer membrane that serves as a barrier to noxious agents in the environment. This protective function is dependent on lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must be transported to the cell surface.

Mapping and Exploring the Collagen-I Proteostasis Network.

Collagen-I is the most abundant protein in the human body, yet our understanding of how the endoplasmic reticulum regulates collagen-I proteostasis (folding, quality control, and secretion) remains immature. Of particular importance, interactomic studies to map the collagen-I proteostasis network have never been performed. Such studies would provide insight into mechanisms of collagen-I folding and misfolding in cells, an area that is particularly important owing to the prominence of the collagen misfolding-related diseases.

XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans.

The molecular architecture of the mature N-glycome is dynamic, with consequences for both normal and pathologic processes. Elucidating cellular mechanisms that modulate the N-linked glycome is, therefore, crucial. The unfolded protein response (UPR) is classically responsible for maintaining proteostasis in the secretory pathway by defining levels of chaperones and quality control proteins.

Predictors of pain relief following spinal cord stimulation in chronic back and leg pain and failed back surgery syndrome: a systematic review and meta-regression analysis.

We sought to assess the extent to which pain relief in chronic back and leg pain (CBLP) following spinal cord stimulation (SCS) is influenced by patient-related factors, including pain location, and technology factors. A number of electronic databases were searched with citation searching of included papers and recent systematic reviews. All study designs were included.

The impact of early postoperative pain on health-related quality of life.

Objectives: To examine how the severity of postoperative pain affects patient's health-related quality of life (HRQoL) at 1 week following surgery and to compare two generic validated HRQoL instruments.

Methods: Patients undergoing general or orthopaedic surgery at the Royal London Hospital were randomly sampled. The following patient outcome data were collected EQ-5D (EuroQoL) pre-operatively and the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) at 24 hours postoperation; and EQ-5D, Short-Form-12 (SF-12) and APS-POQ-R at 7 days postoperation.

The economic impact of failed back surgery syndrome.

Failed back surgery syndrome (FBSS) is a generalised disorder that is characterised by chronic pain in the lower back and/or legs that persists or recurs following anatomically successful spinal surgery. This paper aims to (1) assess the burden of failed back surgery in terms of its epidemiology, impact on health outcomes and costs and (2) summarise the evidence base for the cost-effectiveness of interventions for the management of FBSS. A narrative review based on a search of MEDLINE (PubMed) up to August 2012 was undertaken.

Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review.

Purpose: Given the high burden of epilepsy on both health-related quality of life (HRQoL) and costs, identification of factors that are predictive of either reduced HRQoL or increased expenditure is central to the better future targeting and optimization of existing and emerging interventions and management strategies for epilepsy.

Methods: Searches of Medline, Embase, and Cochrane Library (up to July 2010) to identify studies examining the association between demographic, psychosocial, and condition-related factors and HRQoL, resource utilization or costs in adults with epilepsy. For each study, predictor factor associations were summarized on the basis of statistical significance and direction; the results were then combined across studies.

Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial).

Background: Chronic back and leg pain conditions result in patients' loss of function, reduced quality of life and increased costs to the society.

Aims: To assess health-related quality of life (HRQoL) and cost implications of spinal cord stimulation plus non-surgical conventional medical management (SCS group) versus non-surgical conventional medical management alone (CMM group) in the management of neuropathic pain in patients with failed back surgery syndrome.

Methods: A total of 100 patients were randomised to either the SCS or CMM group.

Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis.

This systematic review updates the understanding of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Detailed searches of a number of electronic databases were performed from March to April 2006. Citation searches of included studies were undertaken and no language restrictions were applied.

Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a comparative systematic review of efficacy and safety.

Study Design: Systematic review and meta-regression.

Objectives: To compare the efficacy and safety of balloon kyphoplasty and vertebroplasty for the treatment of vertebral compression fractures, and to examine the prognostic factors that predict outcome.

Summary Of Background Data: A previous systematic review of vertebroplasty by Levine et al in 2000 identified seven case series studies and no controlled studies.

Resident physician mentoring program in ophthalmology: the Tennessee experience.

Objective: To establish a mentoring program to provide resident physicians in ophthalmology with career guidance in practice management and to identify new and creative ways to involve future eye physicians in the legislative and political process.

Methods: A multicenter prospective study was conducted of the mentorship experiences of 24 (88.9%) of 27 resident physicians in Tennessee during the 2000-2001 academic year.

Spinal cord stimulation for failed back surgery syndrome: a decision-analytic model and cost-effectiveness analysis.

Objectives: The aim of this study was to develop a decision-analytic model to assess the cost-effectiveness of spinal cord stimulation (SCS), relative to nonsurgical conventional medical management (CMM), for patients with failed back surgery syndrome (FBSS).

Methods: A decision tree and Markov model were developed to synthesize evidence on both health-care costs and outcomes for patients with FBSS. Outcome data of SCS and CMM were sourced from 2-year follow-up data of two randomized controlled trials (RCTs).

Critical appraisal skills training for health care professionals: a randomized controlled trial [ISRCTN46272378].

Introduction: Critical appraisal skills are believed to play a central role in an evidence-based approach to health practice. The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aimed at health care professionals.

Methods: This prospective controlled trial randomized 145 self-selected general practitioners, hospital physicians, professions allied to medicine, and healthcare managers/administrators from the South West of England to a half-day critical appraisal skills training workshop (based on the model of problem-based small group learning) or waiting list control.

The cost effectiveness of spinal cord stimulation in the treatment of pain: a systematic review of the literature.

In this systematic review, we identified and evaluated studies of the cost effectiveness of spinal cord stimulation (SCS) for the treatment of chronic pain. Published reports were identified from a systematic search of a number of general medical electronic databases (Medline, CINAHL, and EMBASE), and specialist economic databases (NHS Centre for Reviews and Dissemination Economic Evaluation Database, and Health Economics Evaluation Database). Reference lists of retrieved reports were also searched, and contact was made with experts in the field.