Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.
View Article and Find Full Text PDFThis study examines the in vitro effects of a soluble protein hydrolysate (SPH) derived from Atlantic salmon (Salmo salar) on incretin receptor activity and pancreatic islet cell protection to explore the mechanisms underlying SPH's observed benefits on weight loss and metabolic health in overweight individuals. SPH demonstrated a dose-dependent enhancement of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor activity, with significant increases of 2.4-fold ( < 0.
View Article and Find Full Text PDFBackground: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.
Objectives: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.
This research paper aimed to demonstrate that mammary secretions provided by sheep farmers across Scotland from cases of clinical mastitis are free from environmental contamination, as well as to provide information on the major bacterial causes of disease and levels of antimicrobial resistance. Mastitis represents one of most significant diseases of small ruminant production worldwide. and coagulase-negative Staphylococcal species are common pathogens isolated from cases of sheep mastitis.
View Article and Find Full Text PDFBackground: Alterations in upper respiratory microbiomes have been implicated in shaping host health trajectories, including by limiting mucosal pathogen colonization. However, limited comparative studies of respiratory microbiome development and functioning across age groups have been performed. Herein, we perform shotgun metagenomic sequencing paired with pathogen inhibition assays to elucidate differences in nasal and oral microbiome composition and intermicrobial interactions across healthy 24-month-old infant (n = 229) and adult (n = 100) populations.
View Article and Find Full Text PDFThe oral microbiome has been understudied as a reservoir for clinical pathogens, including drug-resistant strains. Understanding how alterations in microbiome functioning render this site vulnerable to colonization is essential, as multidrug-resistant organisms (MDRO) carriage is a major risk factor for developing serious infections. To advance our knowledge of oral MDRO carriage and protection against pathogen colonization conferred by native microbiota, we examined microbiomes from individuals colonized by MDROs (n=33) and non-colonized age-matched controls (n=30).
View Article and Find Full Text PDFFungus-farming ants cultivate multiple lineages of fungi for food, but, because fungal cultivar relationships are largely unresolved, the history of fungus-ant coevolution remains poorly known. We designed probes targeting >2000 gene regions to generate a dated evolutionary tree for 475 fungi and combined it with a similarly generated tree for 276 ants. We found that fungus-ant agriculture originated ~66 million years ago when the end-of-Cretaceous asteroid impact temporarily interrupted photosynthesis, causing global mass extinctions but favoring the proliferation of fungi.
View Article and Find Full Text PDFObjectives: To review and evaluate available literature on spectral computed tomography (SCT) bone mineral density (BMD) measurement in adult thoracolumbar vertebrae of unenhanced images compared to quantitative computed tomography (QCT), to understand its current clinical utility.
Key Findings: Keyword searches in four databases identified four cross-sectional studies which acquired an SCT BMD measurement in thoracolumbar vertebrae and compared this respectively to QCT, which were then critically appraised using the AXIS tool for cross-sectional studies. 862 vertebrae were measured between T10-S1 in 368 patients.
Cytokines, chemokines, and interferons are released in response to viral infection with the ultimate aim of viral clearance. However, in SARS-CoV-2 infection, there is an imbalanced immune response, with raised cytokine levels but only a limited interferon response with inefficient viral clearance. Furthermore, the inflammatory response can be exaggerated, which risks both acute and chronic sequelae.
View Article and Find Full Text PDFUnlabelled: Multidrug-resistant is one of the most clinically important pathogens in the world, with infections leading to high rates of morbidity and mortality in both humans and animals. The ability of to form biofilms protects cells from antibiotics and promotes the transfer of antibiotic resistance genes; therefore, new strategies aimed at inhibiting biofilm growth are urgently needed. Probiotic species, including are gaining interest as potential therapies against for their ability to reduce colonization and virulence.
View Article and Find Full Text PDFThis manuscript examines the principle of "Do No Harm" in DoD Global Health Engagement (GHE) efforts. It highlights the potential positive and negative consequences of health investments and explores how unintentional harm is addressed in a global health context. The manuscript also discusses the involvement of the U.
View Article and Find Full Text PDFMetabolic disorders are increasingly prevalent conditions that manifest pathophysiologically along a continuum. Among reported metabolic risk factors, elevated fasting serum glucose (FSG) levels have shown the most substantial increase in risk exposure. Ultimately leading to insulin resistance (IR), this condition is associated with notable deteriorations in the prognostic outlook for major diseases, including neurodegenerative diseases, cancer risk, and mortality related to cardiovascular disease.
View Article and Find Full Text PDFHuman papillomavirus (HPV)-associated multiphenotypic sinonasal carcinoma is a rare and recently described epithelial neoplasm exhibiting myoepithelial differentiation and morphological overlap with salivary gland neoplasms, especially adenoid cystic carcinoma; it is commonly associated with HPV, especially type 33. It has mainly been reported in the nasal cavity and paranasal sinuses with a single case reported in the breast. Herein, we report the first vulval example in a 47-year-old patient who presented with a large craggy mass in the region of the Bartholin gland.
View Article and Find Full Text PDFBackground: Alterations in upper respiratory microbiomes have been implicated in shaping host health trajectories, including by limiting mucosal pathogen colonization. However, limited comparative studies of respiratory microbiome development and functioning across age groups have been performed. Herein, we perform shotgun metagenomic sequencing paired with pathogen inhibition assays to elucidate differences in nasal and oral microbiome composition and functioning across healthy 24-month-old infant (n=229) and adult (n=100) populations.
View Article and Find Full Text PDFIn the absence of suitable indicators of adolescent socioeconomic status, the Family Affluence Scale (FAS) was first developed in Scotland 25 years ago. Since then, it has been adapted for use in the Health Behaviour in School-Aged Children (HBSC) Study to research inequalities in adolescent health in Europe and North America. FAS has also been used as an indicator of adolescent socioeconomic status in research studies outside of HBSC, worldwide.
View Article and Find Full Text PDFDisturbance events can impact ecological community dynamics. Understanding how communities respond to disturbances and how those responses can vary is a challenge in microbial ecology. In this study, we grew a previously enriched specialized microbial community on either cellulose or glucose as a sole carbon source and subjected them to one of five different disturbance regimes of varying frequencies ranging from low to high.
View Article and Find Full Text PDFAneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon.
View Article and Find Full Text PDFObjectives: The fluoroscopy environment poses a potential occupational radiation exposure risk to theatre personnel. Risks can be mitigated with effective application of radiation protection knowledge and methods. This review aimed to determine the link between orthopaedic surgeon's knowledge and the use of appropriate safety methods when using fluoroscopy.
View Article and Find Full Text PDFIntroduction Dental professionals have an ethical and legal obligation to diagnose and manage medical emergencies which may occur in primary dental care.Aims and objectives To investigate the prevalence of medical emergencies in UK primary dental care and explore the medical emergency training needs of UK primary dental care professionals.Design and setting Cross-sectional survey, targeting dentists, dental hygienists and dental therapists across the UK working within primary dental care.
View Article and Find Full Text PDFBackground: HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort.
View Article and Find Full Text PDFRecent research highlights the key role of iron dyshomeostasis in the pathogenesis of prostate cancer (PCa). PCa cells are heavily dependent on bioavailable iron, which frequently results in the reprogramming of iron uptake and storage pathways. Although advanced-stage PCa is currently incurable, bioactive peptides capable of modulating key iron-regulatory genes may constitute a means of exploiting a metabolic adaptation necessary for tumor growth.
View Article and Find Full Text PDF