Dual client binding sites in the ATP-independent chaperone SurA.

The ATP-independent chaperone SurA protects unfolded outer membrane proteins (OMPs) from aggregation in the periplasm of Gram-negative bacteria, and delivers them to the β-barrel assembly machinery (BAM) for folding into the outer membrane (OM). Precisely how SurA recognises and binds its different OMP clients remains unclear. Escherichia coli SurA comprises three domains: a core and two PPIase domains (P1 and P2).

Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways.

Amyloid formation by α-synuclein (αSyn) occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Deciphering the residues that regulate αSyn amyloid fibril formation will not only provide mechanistic insight but may also reveal targets to prevent and treat disease. Previous investigations have identified several regions of αSyn to be important in the regulation of amyloid formation, including the non-amyloid-β component (NAC), P1 region (residues 36 to 42), and residues in the C-terminal domain.

Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in Cells.

The β-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in cells.

Protein-lipid charge interactions control the folding of outer membrane proteins into asymmetric membranes.

Biological membranes consist of two leaflets of phospholipid molecules that form a bilayer, each leaflet comprising a distinct lipid composition. This asymmetry is created and maintained in vivo by dedicated biochemical pathways, but difficulties in creating stable asymmetric membranes in vitro have restricted our understanding of how bilayer asymmetry modulates the folding, stability and function of membrane proteins. In this study, we used cyclodextrin-mediated lipid exchange to generate liposomes with asymmetric bilayers and characterize the stability and folding kinetics of two bacterial outer membrane proteins (OMPs), OmpA and BamA.

Litigation in thyroid surgery: a pan-specialty review of National Health Service (UK) data.

Objective: Thyroid surgery carries risks that significantly impact patients. This paper describes the landscape of thyroid surgery related litigation claims in the National Health Service from April 2015 to April 2020, to establish learning points in order to improve patient care and minimise litigation risk.

Methods: Data were requested from National Health Service Resolution and Hospital Episode Statistics.

Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells.

The β-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in E.

Getting it right first time: national survey of surgical site infection 2019.

Introduction: Surgical site infections (SSIs) are associated with increased morbidity and mortality. Deep SSI, or prosthetic joint infection (PJI), is associated with revision surgery involving longer operative times with higher infection rates, longer length of stay (LoS) and high costs in addition to the catastrophic effect on the patient. The surveillance of SSI is important for patient decision making, identification of outliers for support and maximising focussed improvement.

Gabapentin, a human therapeutic medication and an environmental substance transferring at trace levels to horses: a case report.

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine.

Hospital dentistry litigation in England: clinical negligence claims against the NHS 2015-2020.

Introduction Litigation against the NHS in England is rising. The aim of this study was to determine the incidence and characteristics of hospital dentistry clinical negligence claims in England.Methods A retrospective review was undertaken of all clinical negligence claims in England held by NHS Resolution relating to hospital dentistry between April 2015 and April 2020.

Litigation in pediatric otorhinolaryngology: Lessons in improving patient care.

Objective(s): Medico-legal claims involving children place a substantial financial burden on health services and have a profound emotional and psychological impact on clinicians. Our objective was to analyze both the common causes and cost of litigation in pediatric otorhinolaryngology.

Methods: A retrospective review of all clinical negligence claims within pediatric otolaryngology (0-17 years inclusive) in NHS (National Health Service) England held by the clinical negligence service 'NHS Resolution between' 4/2013 and 4/2020.

Synthesis and characterization of d -barbarin for use in barbarin-related research.

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d -barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D -barbarin synthesis commenced with production of d -2-oxo-2-phenylacetaldehyde oxime (d -oxime) from d -acetophenone via butylnitrite in an ethoxide/ethanol solution.

Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding.

Correct folding of outer membrane proteins (OMPs) into the outer membrane of Gram-negative bacteria depends on delivery of unfolded OMPs to the β-barrel assembly machinery (BAM). How unfolded substrates are presented to BAM remains elusive, but the major OMP chaperone SurA is proposed to play a key role. Here, we have used hydrogen deuterium exchange mass spectrometry (HDX-MS), crosslinking, in vitro folding and binding assays and computational modelling to show that the core domain of SurA and one of its two PPIase domains are key to the SurA-BAM interaction and are required for maximal catalysis of OMP folding.

An Analysis of a National Administrative Dataset Demonstrating No Evidence of Increase in Elective Primary Total Hip Arthroplasty Dislocation Rates When Postoperative Hip Precautions are Not Used.

Background: The purpose of this study is to determine whether there is a higher dislocation rate when postoperative hip precautions are not used for primary total hip arthroplasty (THA).

Methods: A survey was conducted of the hip precautions used by orthopaedic departments in England performing elective primary THA. From the responses to the survey an interrupted time series analysis was performed using the hospital admissions data from the Hospital Episode Statistics (HES) database during the period April 1, 2011 to December 31, 2019 and subsequent dislocations of these prostheses up to June 30, 2020.

Detergent-Free Functionalization of Hybrid Vesicles with Membrane Proteins Using SMALPs.

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis, and synthetic biology. However, functionalization of HVs with membrane proteins remains laborious and expensive, creating a significant current challenge in the field. Here, using a new approach of extraction with styrene-maleic acid (SMA), we show that a membrane protein (cytochrome ) directly transfers into HVs with an efficiency of 73.

Sporadic worldwide "clusters" of feed driven Zilpaterol identifications in racing horses: a review and analysis.

Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer.

Background: Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival.

Lessons from rhinology and facial plastic surgery clinical negligence claims in England 2013-2018.

Objective: This study reviewed all rhinology clinical negligence claims in the National Health Service in England between 2013 and 2018.

Method: All clinical negligence claims held by National Health Service Resolution relating to rhinology in England between 1 April 2013 and 1 April 2018 were reviewed.

Results: There were 171 rhinology related claims with a total estimated potential cost of £13.

Pregnancy outcome in women with transfused beta-thalassemia in France.

Because of chronic anemia, hypogonadotropic hypogonadism, and iron chelation, pregnancy in homozygous and heterozygous compound beta-thalassemia patients stays a challenge. Pregnancies of transfused beta-thalassemia women registered in the French National Registry, conducted between 1995 and 2015, are described. These pregnancies were compared with pregnancies in healthy women and to data previously published in the literature.

The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding.

The folding of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria is catalysed by the β-barrel assembly machinery (BAM). How lateral opening in the β-barrel of the major subunit BamA assists in OMP folding, and the contribution of membrane disruption to BAM catalysis remain unresolved. Here, we use an anti-BamA monoclonal antibody fragment (Fab1) and two disulphide-crosslinked BAM variants (lid-locked (LL), and POTRA-5-locked (P5L)) to dissect these roles.

Litigation in breast surgery: unique insights from the English National Health Service experience.

Background: The increase in medical negligence claims against the National Health Service (NHS) over the past decade has had a detrimental impact on limited financial and human resources that could otherwise be available for direct clinical care. The aim of this study was to review litigation claims in breast surgery as part of the national Getting It Right First Time quality improvement initiative, with the aim of identifying opportunities to improve clinical practice and patient safety.

Methods: All general and plastic surgical claims notified to NHS Resolution between April 2012 and April 2018 were reviewed.

Variability in COVID-19 in-hospital mortality rates between national health service trusts and regions in England: A national observational study for the Getting It Right First Time Programme.

Background: A key first step in optimising COVID-19 patient outcomes during future case-surges is to learn from the experience within individual hospitals during the early stages of the pandemic. The aim of this study was to investigate the extent of variation in COVID-19 outcomes between National Health Service (NHS) hospital trusts and regions in England using data from March-July 2020.

Methods: This was a retrospective observational study using the Hospital Episode Statistics administrative dataset.

What can be learned from litigation in otology? A review of clinical negligence claims in England 2013-2018.

Background: Litigation in the National Health Service continues to rise with a 9.4 per cent increase in clinical negligence claims from the period 2018 and 2019 to the period 2019 and 2020. The cost of these claims now accounts for 1.