Creating a learning health system to include environmental determinants of health: The GroundsWell experience.

Introduction: Policies aiming to prevent ill health and reduce health inequalities need to consider the full complexity of health systems, including environmental determinants. A learning health system that incorporates environmental factors needs healthcare, social care and non-health data linkage at individual and small-area levels. Our objective was to establish privacy-preserving household record linkage for England to ensure person-level data remain secure and private when linked with data from households or the wider environment.

Effects on mortality of shielding clinically extremely vulnerable patients in Liverpool, UK, during the COVID-19 pandemic.

Objective: This study evaluates the impact of England's COVID-19 shielding programme on mortality in the City of Liverpool in North West England.

Study Design: Shielded and non-shielded people are compared using data from linked routine health records on all people registered with a general practitioner in Liverpool from April 2020 to June 2021.

Methods: A discrete time hazard model and interactions between the shielding status and the periods of higher risk of transmission are used to explore the effects of shielding across the major phases of the COVID-19 pandemic.

A Finite Element Model of Cerebral Vascular Injury for Predicting Microbleeds Location.

Finite Element (FE) models of brain mechanics have improved our understanding of the brain response to rapid mechanical loads that produce traumatic brain injuries. However, these models have rarely incorporated vasculature, which limits their ability to predict the response of vessels to head impacts. To address this shortcoming, here we used high-resolution MRI scans to map the venous system anatomy at a submillimetre resolution.

The impact of an integrated care intervention on mortality and unplanned hospital admissions in a disadvantaged community in England: A difference-in-differences study.

Background: Many health systems are experimenting with integrated care models to improve outcomes and reduce healthcare demand. Evidence for effects on health service utilisation is variable, with few studies investigating impacts on mortality or differences by socioeconomic group.

Objective: To examine the impact of a multidisciplinary, integrated care team intervention on emergency admissions and mortality, and whether effects differed by deprivation group.

Smoothed particle hydrodynamic modelling of the cerebrospinal fluid for brain biomechanics: Accuracy and stability.

The Cerebrospinal Fluid (CSF) can undergo shear deformations under head motions. Finite Element (FE) models, which are commonly used to simulate biomechanics of the brain, including traumatic brain injury, employ solid elements to represent the CSF. However, the limited number of elements paired with shear deformations in CSF can decrease the accuracy of their predictions.

Retrospective observational study of the impact on emergency admission of telehealth at scale delivered in community care in Liverpool, UK.

Objective: To assess the effect of a real world, ongoing telehealth service on the use of secondary healthcare.

Design: A retrospective observational study with anonymous matched controls.

Setting: Primary and community healthcare.

Luminescent Gold(III) Thiolates: Supramolecular Interactions Trigger and Control Switchable Photoemissions from Bimolecular Excited States.

A new family of cyclometallated gold(III) thiolato complexes based on pyrazine-centred pincer ligands has been prepared, (C^N ^C)AuSR, where C^N ^C=2,6-bis(4-Bu C H )pyrazine dianion and R=Ph (1), C H tBu-4 (2), 2-pyridyl (3), 1-naphthyl (1-Np, 4), 2-Np (5), quinolinyl (Quin, 6), 4-methylcoumarinyl (Coum, 7) and 1-adamantyl (8). The complexes were isolated as yellow to red solids in high yields using mild synthetic conditions. The single-crystal X-ray structures revealed that the colour of the deep-red solids is associated with the formation of a particular type of short (3.

A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation.

Unlabelled: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, is implicated as a possible therapy for airway inflammation via induction of the transcription factor NF-E2-related factor 2 (NRF2). In this proof-of-concept clinical study, we show that supplementation of SFN with broccoli sprout homogenate in healthy human subjects did not induce expression of antioxidant genes or protect against neutrophilic airway inflammation in an ozone-exposure model. Therefore, dietary sulforaphane supplementation is not a promising candidate for larger scale clinical trials targeting airway inflammation.

Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.

Background: Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI.

Methods: We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures.

Duration of action of hypertonic saline on mucociliary clearance in the normal lung.

Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases.

Enzyme-substrate complexes of allosteric citrate synthase: evidence for a novel intermediate in substrate binding.

The citrate synthase (CS) of Escherichia coli is an allosteric hexameric enzyme specifically inhibited by NADH. The crystal structure of wild type (WT) E. coli CS, determined by us previously, has no substrates bound, and part of the active site is in a highly mobile region that is shifted from the position needed for catalysis.

Urea as a protein destabilizing agent in electrospray ionisation.

Urea is well known as a denaturant of proteins, but there is also evidence that millimolar amounts of urea may in fact stabilize protein complexes. Advances in mass spectrometric analysis have given us the opportunity to test the effect of urea on several noncovalent complexes in buffered solutions. We expected to see lower charge states if folded proteins were more compact (and therefore more stable), and higher charge states if the proteins were denatured.

Variation in mortality rates among long-term care facilities for residents with lower respiratory tract infection.

Objective: To identify variables contributing to interfacility differences in mortality among residents of long-term care facilities who have lower respiratory tract infection.

Design: Multicenter, prospective, 1-year observational study.

Setting: Twenty-one long-term care facilities in 4 geographic areas of Canada.

Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis.

This pilot study was undertaken to characterise the pharmacokinetics, pharmacodynamics and potential clinical efficacy of levofloxacin 750 mg once daily for 5 days for treatment of women with acute uncomplicated pyelonephritis. Four women diagnosed with acute pyelonephritis were enrolled. Following pre-therapy specimen collection, an initial oral dose of 750 mg levofloxacin was administered.

Use of diagnostic tests for presumed lower respiratory tract infection in long-term care facilities.

Objectives: To describe the current use of diagnostic tests for management of presumed lower respiratory tract infection in selected long-term care facilities (LTCFs) in Canada and to correlate test use with facility and resident characteristics.

Design: Prospective, 12-month multicenter cohort study.

Setting: A convenience sample of 21 LTCFs in Canada.

Method for estimating the isotopic distributions of metabolically labeled proteins by MALDI-TOFMS: application to NMR samples.

We have developed an efficient method of estimating metabolic incorporation of heavy isotopes into proteins, including those where a single amino acid carries the label. The protein is digested with trypsin, and the resulting peptide mixture is examined directly by MALDI-TOF mass spectrometry. Peptides are chosen for analysis if they contain one or more labeled atoms and also exhibit clearly separated mass spectra.

Proteomic identification of AP2 gamma as a rat placental lactogen II trophoblast cell-specific enhancer binding protein.

The factors that regulate the developmental expression of the rodent prolactin gene family in placenta remain poorly defined. We previously identified an enhancer element in the 5' flanking region of one family member, rat placental lactogen II (rPLII), which could target reporter gene expression to the placenta in transgenic mice; this enhancer functioned in the Rcho rat trophoblast cell line but not in the rat pituitary GC cell line. In further experiments to identify the factors that bind this element, we have selectively enriched for DNA binding proteins in nuclear extract from Rcho cells using magnetic beads coupled to a 43-bp enhancer oligonucleotide.

Characterization of a large subunit catalase truncated by proteolytic cleavage.

The large subunit catalase HPII from Escherichia coli can be truncated by proteolysis to a structure similar to small subunit catalases. Mass spectrometry analysis indicates that there is some heterogeneity in the precise cleavage sites, but approximately 74 N-terminal residues, 189 C-terminal residues, and a 9-11-residue internal fragment, including residues 298-308, are removed. Crystal structure refinement at 2.

Multiple equilibria of the Escherichia coli chaperonin GroES revealed by mass spectrometry.

Nanospray time-of-flight mass spectrometry has been used to study the assembly of the heptamer of the Escherichia coli cochaperonin protein GroES, a system previously described as a monomer-heptamer equilibrium. In addition to the monomers and heptamers, we have found measurable amounts of dimers and hexamers, the presence of which suggests the following mechanism for heptamer assembly: 2 Monomers <--> Dimer; 3 Dimers <--> Hexamer; Hexamer + Monomer <--> Heptamer. Equilibrium constants for each of these steps, and an overall constant for the Monomer <--> Heptamer equilibrium, have been estimated from the data.

Catalase-peroxidases (KatG) exhibit NADH oxidase activity.

Catalase-peroxidases (KatG) produced by Burkholderia pseudomallei, Escherichia coli, and Mycobacterium tuberculosis catalyze the oxidation of NADH to form NAD+ and either H2O2 or superoxide radical depending on pH. The NADH oxidase reaction requires molecular oxygen, does not require hydrogen peroxide, is not inhibited by superoxide dismutase or catalase, and has a pH optimum of 8.75, clearly differentiating it from the peroxidase and catalase reactions with pH optima of 5.

Defining regulatory regions in the rat prolactin gene family locus using a large P1 genomic clone.

Members of the large rat prolactin gene family located on chromosome 17 are expressed in one or more placental trophoblast cell types and maternal decidua at specific times during pregnancy. Studies to identify the factors involved in these highly specific developmental expression patterns, using limited amounts of 5'-flanking DNA, have met with only partial success. Here we report the isolation and characterization of an 80-kb rat genomic clone, P1 12830, containing linked rat placental lactogen II, rat prolactin-like protein-I, and rat prolactin-like protein-B genes with substantial amounts of 5'- and 3'-flanking DNA as well as a rat placental lactogen II-related pseudogene, the first to be described in this gene family.

Characterization of the catalase-peroxidase KatG from Burkholderia pseudomallei by mass spectrometry.

The electron density maps of the catalase-peroxidase from Burkholderia pseudomallei (BpKatG) presented two unusual covalent modifications. A covalent structure linked the active site Trp111 with Tyr238 and Tyr238 with Met264, and the heme was modified, likely by a perhydroxy group added to the vinyl group on ring I. Mass spectrometry analysis of tryptic digests of BpKatG revealed a cluster of ions at m/z 6585, consistent with the fusion of three peptides through Trp111, Tyr238, and Met264, and a cluster at m/z approximately 4525, consistent with the fusion of two peptides linked through Trp111 and Tyr238.