Per- and polyfluoroalkyl substances (PFAS), often termed "forever chemicals," are a diverse group of persistent fluorinated compounds, including the well-known perfluorooctanesulfonic acid (PFOS), which has been identified as lethal to bee larvae. However, the risk of PFAS exposure through pollen, a bee's primary food source, has not been thoroughly investigated. In controlled greenhouse experiments, Cannabis sativa L.
View Article and Find Full Text PDFBackground: Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively.
View Article and Find Full Text PDFTo eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is the antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acid side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenic (UPEC), the primary causative agent of urinary tract infections, have developed sophisticated defense systems to protect themselves from HOCl.
View Article and Find Full Text PDFThe process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived 'evolutionary history'. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract.
View Article and Find Full Text PDFUnlabelled: To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acids side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenic (UPEC), the primary causative agent of urinary tract infections (UTIs), have developed sophisticated defense systems to protect themselves from HOCl.
View Article and Find Full Text PDFThe renin angiotensin aldosterone system is a key regulator of blood pressure. Aldosterone is the final effector of this pathway, acting predominantly via mineralocorticoid receptors. Aldosterone facilitates the conservation of sodium and, with it, water and acts as a powerful stimulus for potassium excretion.
View Article and Find Full Text PDFThe glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously, we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. In this study, we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action.
View Article and Find Full Text PDFBackground: A 9-year-old boy with Berlin Heart biventricular assist device for diagnosis of dilated cardiomyopathy developed progressive reduction in left ventricular assist device(VAD) emptying and evidence of low cardiac output despite alterations to the device settings. Computed tomography revealed that the Dacron graft attaching the systemic cannula to the ascending aorta was stenosed.
Method & Result: A minimally invasive approach with novel circuit modification was used to achieve antegrade stenting of the stenosed graft.
Pesticides are frequently employed to enhance agricultural production. Neonicotinoid pesticides (including imidacloprid) are often used to control sucking insects but have been shown to impact aquatic crustaceans. Imidacloprid is highly water soluble and has been detected in estuaries where it has been applied in adjacent catchments.
View Article and Find Full Text PDFThe endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice.
View Article and Find Full Text PDFPer- and polyfluoroalkyl substances (PFASs) are frequently detected in aquatic environments. Longer chained perfluoroalkyl acids (PFAAs), in particular, have been found to bioaccumulate in a broad range of aquatic biota. PFAAs have a physiochemical similarity to naturally occurring fatty acids and could potentially disrupt metabolic processes, however, there has been limited study in this area, especially in aquatic species.
View Article and Find Full Text PDFObjective: To analyse the epidemiology of otosclerosis in a British cohort collected between 2011 and 2017.
Design: Retrospective cohort study.
Setting: Five UK ENT Departments.
Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
May 2018
The composition and integrity of the bacterial cytoplasmic membrane is critical to the survival of staphylococci in dynamic environments and it is important to investigate how the cell membrane responds to changes in the environmental conditions. The staphylococcal membrane differs from eukaryotic and many other bacterial cell membranes by having a high abundance of branch fatty acids and relatively few unsaturated fatty acids. The range of available methods for extraction and efficient analyses of staphylococcal fatty acids was initially appraised to identify the best potential procedures for appraisal.
View Article and Find Full Text PDFOtitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown.
View Article and Find Full Text PDFSweat contains amino acids and electrolytes derived from plasma and athletes can lose 1-2L of sweat per hour during exercise. Sweat may also contain contributions of amino acids as well as urea, sodium and potassium from the natural moisturizing factors (NMF) produced in the stratum corneum. In preliminary experiments, one participant was tested on three separate occasions to compare sweat composition with surface water washings from the same area of skin to assess contributions from NMF.
View Article and Find Full Text PDFStaphylococcus aureus is an opportunistic pathogen responsible for a high proportion of nosocomial infections. This study was conducted to assess the bacterial responses in the cytoplasmic composition of amino acids and ribosomal proteins under various environmental conditions designed to mimic those on the human skin or within a wound site: pH6-8, temperature 35-37°C, and additional 0-5% NaCl. It was found that each set of environmental conditions elicited substantial adjustments in cytoplasmic levels of glutamic acid, aspartic acid, proline, alanine and glycine (P< 0.
View Article and Find Full Text PDFOtosclerosis is a relatively common heterogenous condition, characterized by abnormal bone remodelling in the otic capsule leading to fixation of the stapedial footplate and an associated conductive hearing loss. Although familial linkage and candidate gene association studies have been performed in recent years, little progress has been made in identifying disease-causing genes. Here, we used whole-exome sequencing in four families exhibiting dominantly inherited otosclerosis to identify 23 candidate variants (reduced to 9 after segregation analysis) for further investigation in a secondary cohort of 84 familial cases.
View Article and Find Full Text PDFAcute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used.
View Article and Find Full Text PDFA novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells.
View Article and Find Full Text PDFWe conducted a survey to compare antimicrobial stewardship outcomes considered to be most important with those used in practice as metrics. Respondent opinion of important outcomes compared with those collected as metrics were antimicrobial use (15% vs 73%), antimicrobial cost (10% vs 73%), appropriateness of antimicrobial use (56% vs 51%), infection-related mortality rate (34% vs 7%), and antibiotic-associated length of stay (22% vs 12%). Patient outcomes are important to many practitioners but are rarely used as metrics.
View Article and Find Full Text PDFBackground: Diabetic foot infection (DFI) is a serious, difficult-to-treat infection, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower response rates in MRSA skin infections have been reported. This analysis assessed the outcome and safety of daptomycin therapy in patients with a DFI caused by MRSA.
View Article and Find Full Text PDFStaphylococcus lugdunensis has emerged as a major cause of community-acquired and nosocomial infections. This bacterium can rapidly adapt to changing environmental conditions to survive and capitalize on opportunities to colonize and infect through wound surfaces. It was proposed that S.
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