Examining the uptake of predictive BRCA testing in the UK; findings and implications.

Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors of testing and time-to-receipt of testing.

Viral Etiology, Clinical Features and Antibiotic Use in Children <5 Years of Age in the Gambia Presenting With Influenza-like Illness.

Background: Knowledge regarding the prevalence, clinical features and etiology of pediatric influenza-like illness (ILI) remains limited in African settings. Furthermore, it is likely that many children presenting with ILI receive antibiotics unnecessarily. More data are required to develop antimicrobial stewardship practice and guide effective vaccine strategies.

Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells.

By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combinatorial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling.

Atropine Penalization Versus Occlusion Therapies for Unilateral Amblyopia after the Critical Period of Visual Development: A Systematic Review.

Introduction: Amblyopia therapy appears to be most effective in children under the age of 7 years, but results from randomized control trials (RCTs) have shown that occlusion therapy and/or atropine penalization therapy may improve visual acuity in an older age group. Which of these two therapies is the most effective with fewer adverse effects in an older age group has not yet been agreed upon.

Methods: We systematically searched the literature for RCTs that compared atropine penalization therapy and occlusion therapy in terms of their visual acuity outcomes and adverse events and performed a meta-analysis on the visual acuity data obtained.

BβArg448Lys polymorphism is associated with altered fibrin clot structure and fibrinolysis in type 2 diabetes.

Both type 2 diabetes (T2DM) and Bβ448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BβArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BβArg448Lys on fibrin network characteristics in T2DM.

Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota.

Genome-scale metabolic models derived from human gut metagenomic data can be used as a framework to elucidate how microbial communities modulate human metabolism and health. We present AGORA (assembly of gut organisms through reconstruction and analysis), a resource of genome-scale metabolic reconstructions semi-automatically generated for 773 human gut bacteria. Using this resource, we identified a defined growth medium for Bacteroides caccae ATCC 34185.

A microfluidics-based in vitro model of the gastrointestinal human-microbe interface.

Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface.

The human gut microbiome in health: establishment and resilience of microbiota over a lifetime.

With technological advances in culture-independent molecular methods, we are uncovering a new facet of our natural history by accounting for the vast diversity of microbial life which colonizes the human body. The human microbiome contributes functional genes and metabolites which affect human physiology and are, therefore, considered an important factor for maintaining health. Much has been described in the past decade based primarily on 16S rRNA gene amplicon sequencing regarding the diversity, structure, stability and dynamics of human microbiota in their various body habitats, most notably within the gastrointestinal tract (GIT).

Molecular effects of autoimmune-risk promoter polymorphisms on expression, exon choice, and translational efficiency of interferon regulatory factor 5.

The rs2004640 single nucleotide polymorphism and the CGGGG copy-number variant (rs77571059) are promoter polymorphisms within interferon regulatory factor 5 (IRF5). They have been implicated as susceptibility factors for several autoimmune diseases. IRF5 uses alternative promoter splicing, where any of 4 first exons begin the mRNA.

Inhibition of endothelial cell Ca²⁺ entry and transient receptor potential channels by Sigma-1 receptor ligands.

Background And Purpose: The Sigma-1 receptor (Sig1R) impacts on calcium ion signalling and has a plethora of ligands. This study investigated Sig1R and its ligands in relation to endogenous calcium events of endothelial cells and transient receptor potential (TRP) channels.

Experimental Approach: Intracellular calcium and patch clamp measurements were made from human saphenous vein endothelial cells and HEK 293 cells expressing exogenous human TRPC5, TRPM2 or TRPM3.

Hypoglycaemic syncope in children secondary to beta-blockers.

It has been reported that young children taking beta-blockers may be at risk of hypoglycaemia when fasting. However, hypoglycaemia is not listed as a side effect of beta-blockers in the British National Formulary for Children. We present five patients (out of approximately 570 patients at our institution who were prescribed regular beta-blockers over the same time period) who had severe hypoglycaemic episodes whilst taking beta-blockers for prevention of arrhythmia.

In vivo studies of polyacrylate nanoparticle emulsions for topical and systemic applications.

We have recently reported on a new nanomedicine containing antibiotic-conjugated polyacrylate nanoparticles, which has shown activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and no cytotoxicity toward human dermal cells. The water-based nanoparticle emulsion is capable of solubilizing lipophilic antibiotics for systemic administration, and the nanoparticle drug delivery vehicle has shown protective properties for antibiotics from hydrolytic cleavage by bacterial penicillinases, thus rejuvenating the drug's activity against resistant microbes such as MRSA. Here we report the first in vivo study of this penicillin-conjugated nanoparticle emulsion in determining toxicological responses initiated upon systemic and topical application in a murine model.

Studies on the antifungal properties of N-thiolated beta-lactams.

N-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including Staphylococcus aureus and Bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. We now have found that these lactams also possess antifungal activity against Candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. The mode of action and structure-activity trends of these lactams as antifungals parallel that previously seen in our antibacterial studies.

Unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis.

This study describes the antibacterial properties of synthetically produced mixed aryl-alkyl disulfide compounds as a means to control the growth of Staphylococcus aureus and Bacillus anthracis. Some of these compounds exerted strong in vitro bioactivity. Our results indicate that among the 12 different aryl substituents examined, nitrophenyl derivatives provide the strongest antibiotic activities.

Phaeochromocytoma in children.

Phaeochromocytoma is a rare clinical entity in children. Contrary to traditional teaching, which suggested that 10% of phaeochromocytomas are "familial", a germline mutation has been identified in up to 59% (27/48) of apparently sporadic phaeochromocytomas presenting at 18 years or younger and in 70% of those presenting before 10 years of age. The inherited predisposition may be attributable to a germline mutation in the Von Hippel-Lindau gene, the genes encoding the subunits B and D of succinate dehydrogenase, the RET proto-oncogene predisposing to multiple endocrine neoplasia type 2, or the neurofibromatosis type 1 gene.

Methods for purifying and detoxifying sodium dodecyl sulfate-stabilized polyacrylate nanoparticles.

Recent research in our laboratory has centered on studies of polyacrylate and polyacrylamide nanoparticle emulsions for use in antibiotic delivery. Our goal is to develop these nanoparticle emulsions for treatment of life-threatening bacterial infections such as those caused by methicillin-resistant Staphylococcus aureus. For this intended application it is necessary to ensure that the biological activity of the emulsion is due only to the drug attached to the polymeric chain and not to any extraneous components.

Muir-Torre Syndrome: expanding the genotype and phenotype--a further family with a MSH6 mutation.

Muir-Torre Syndrome (MTS) is a phenotypic variant of HNPCC traditionally associated with mutations in the mismatch repair genes MLH1 and MSH2. We draw attention to recent reports of MTS found in association with a constitutional MSH6 mutation and describe a further MTS family with a MSH6 mutation, in whom a preponderance of extra-colonic tumours was found.

Penicillin-bound polyacrylate nanoparticles: restoring the activity of beta-lactam antibiotics against MRSA.

This report describes the preparation of antibacterially active emulsified polyacrylate nanoparticles in which a penicillin antibiotic is covalently conjugated onto the polymeric framework. These nanoparticles were prepared in water by emulsion polymerization of an acrylated penicillin analogue pre-dissolved in a 7:3 (w:w) mixture of butyl acrylate and styrene in the presence of sodium dodecyl sulfate (surfactant) and potassium persulfate (radical initiator). Dynamic light scattering analysis and atomic force microscopy images show that the emulsions contain nanoparticles of approximately 40 nm in diameter.

Antibiotic-conjugated polyacrylate nanoparticles: new opportunities for development of anti-MRSA agents.

This report describes the preparation of polyacrylate nanoparticles in which an N-thiolated beta-lactam antibiotic is covalently conjugated onto the polymer framework. These nanoparticles are formed in water by emulsion polymerization of an acrylated antibiotic pre-dissolved in a liquid acrylate monomer (or mixture of co-monomers) in the presence of sodium dodecyl sulfate as a surfactant and potassium persulfate as a radical initiator. Dynamic light scattering analysis and electron microscopy images of these emulsions show that the nanoparticles are approximately 40 nm in diameter.

Description of a new syndrome: auricular abnormalities and cleft lip in two sibs, in association with cleft palate and unusual opthalmological findings.

We describe the association of auricular abnormalities and cleft lip with or without cleft palate in two siblings. One sibling has postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus of 23 weeks gestation with severe cleft lip, cleft palate and external ear abnormalities.

Effect of food on the pharmacokinetics of multiple-dose oral voriconazole.

Aims: Voriconazole is a new triazole antifungal agent with activity against a range of clinically important and emerging pathogens. This study determined the effect of food on the pharmacokinetics of voriconazole in healthy volunteers.

Methods: This was an open, randomized, two-way crossover, multiple-dose study in male volunteers.

Voriconazole, a novel wide-spectrum triazole: oral pharmacokinetics and safety.

Aims: Voriconazole is a potent new triazole with broad-spectrum antifungal activity against clinically significant and emerging pathogens. The present study evaluated the safety, toleration, and pharmacokinetics of oral voriconazole after single and multiple dosing.

Methods: Sixty-four healthy subjects were randomized to receive treatment and 56 completed the study.