Sticking together: independent evolution of biofilm formation in different species of staphylococci has occurred multiple times via different pathways.

Background: Staphylococci cause a wide range of infections, including implant-associated infections which are difficult to treat due to the presence of biofilms. Whilst some proteins involved in biofilm formation are known, the differences in biofilm production between staphylococcal species remains understudied. Currently biofilm formation by Staphylococcus aureus is better understood than other members of the genus as more research has focused on this species.

The Changing Landscape for Human Absorption, Metabolism, and Excretion: Practical Experiences From a Data Analysis of 500 Studies.

Coincidental with the intensified regulatory and industry focus on the design and conduct of human absorption, metabolism, and excretion (hAME) studies in the past 12 months, we have recently completed our 500th cohort involving radiolabeled test item administration to humans. Here, we build upon a recent industry white paper in this journal and share some of our own experiences as a Contract Research Organization based upon collaborations with numerous pharma companies and their differing approaches to design and timing, to add further context to the discussion regarding hAME studies and the pivotal role that drug metabolism and pharmacokinetics plays. In this article, we explore how both changing relationships within the industry and shifting regulatory guidelines are impacting strategies, and compare EU and US pre-study approval requirements, before evaluating the trends from over 500 studies conducted at our global facilities conducted over more than 30 years.

Disseminated Peritoneal Tuberculosis Initially Misdiagnosed as Nephrogenic Ascites.

A middle-aged immigrant male from a region with endemic tuberculosis who had a history of end-stage kidney disease presented to the emergency room for routine hemodialysis and abdominal swelling. He was admitted to the medicine service for suggested daily dialysis to improve his volume overload, which was attributed to nephrogenic ascites. He was found to have several findings concerning for systemic illness, including fevers, night sweats, hypercalcemia, lymphadenopathy, omental thickening, ascitic fluid with a serum ascites albumin gradient of less than 1.

Evaluation of right ventricular strain in two separate cohorts with precapillary pulmonary hypertension.

Evaluation for right ventricular (RV) dysfunction is an important part of risk assessment in care of patients with pulmonary hypertension (PH) as it is associated with morbidity and mortality. Echocardiography provides a widely available and acceptable method to assess RV function. RV global longitudinal strain (RVGLS), a measure of longitudinal shortening of RV deep muscle fibers obtained by two-dimensional echocardiography, was previously shown to predict short-term mortality in patients with PH.

Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups.

Background: Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported.

Objective: To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present.

Design, Setting, And Participants: Microbiome profiles were interrogated in sample collections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204).

Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package.

Pharmacokinetics and ADME Characterization of Intravenous and Oral [C]-Linerixibat in Healthy Male Volunteers.

Linerixibat, an oral small-molecule ileal bile acid transporter inhibitor under development for cholestatic pruritus in primary biliary cholangitis, was designed for minimal absorption from the intestine (site of pharmacological action). This study characterized the pharmacokinetics, absorption, metabolism, and excretion of [C]-linerixibat in humans after an intravenous microtracer concomitant with unlabeled oral tablets and [C]-linerixibat oral solution. Linerixibat exhibited absorption-limited flip-flop kinetics: longer oral versus intravenous half-life (6-7 hours vs.

Laboratory Stock Variants of the Archetype Silver Resistance Plasmid pMG101 Demonstrate Plasmid Fusion, Loss of Transmissibility, and Transposition of Tn// Into the Host Chromosome.

Typhimurium carrying the multidrug resistance (MDR) plasmid pMG101 was isolated from three burns patients in Boston United States in 1973. pMG101 was transferrable into other spp. and hosts and carried what was a novel and unusual combination of AMR genes and silver resistance.

Genome-Scale Metabolic Model Driven Design of a Defined Medium for M1cam.

, the most frequent cause of food-borne bacterial gastroenteritis, is a fastidious organism when grown in the laboratory. Oxygen is required for growth, despite the presence of the metabolic mechanism for anaerobic respiration. Amino acid auxotrophies are variably reported and energy metabolism can occur through several electron donor/acceptor combinations.

Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease.

Enteroaggregative E. coli (EAEC) are a major cause of diarrhoea worldwide. Due to their heterogeneity and carriage in healthy individuals, identification of diagnostic virulence markers for pathogenic strains has been difficult.

An Innovative Approach to Characterize Clinical ADME and Pharmacokinetics of the Inhaled Drug Nemiralisib Using an Intravenous Microtracer Combined with an Inhaled Dose and an Oral Radiolabel Dose in Healthy Male Subjects.

An innovative open-label, crossover clinical study was used to investigate the excretion balance, pharmacokinetics, and metabolism of nemiralisib-an inhaled phosphoinositide 3-kinase delta inhibitor being developed for respiratory diseases. Six healthy men received a single intravenous microtracer of 10 g [C]nemiralisib with a concomitant inhaled nonradiolabeled 1000 g dose followed by an oral 800 g dose of [C]nemiralisib 14 days later. Complementary methods including accelerator mass spectrometry allowed characterization of a range of parameters including oral absorption (F), proportion of nemiralisib escaping gut wall metabolism (F), hepatic extraction (E), fraction of dose absorbed from inhaled dose (F), and renal clearance.

Promoting chronic disease management in persons with complex social needs: A qualitative descriptive study.

While there are both ethical and practical imperatives to address health inequity issues related to chronic disease management for persons with social complexity, existing programs often do not appropriately address the needs of these individuals. This leads to low levels of participation in programs, suboptimal chronic disease management, and higher health-care utilization. The aims of this project were to describe the challenges related to availability, accessibility, and acceptability faced by socially complex patients with Chronic Obstructive Pulmonary Disease (COPD) who were eligible, but declined enrollment in a traditional Chronic Disease Management Program (CDMP).

Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the Genomes of Marine Sponge Derived Streptomyces spp. Isolates.

The genus produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs) such as polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) which are modular and can be highly repetitive. Due to the repeats, these gene clusters can be difficult to resolve using short read next generation datasets and are often quite poorly predicted using standard approaches.

Identification of bacterial pathogens and antimicrobial resistance directly from clinical urines by nanopore-based metagenomic sequencing.

Objectives: The introduction of metagenomic sequencing to diagnostic microbiology has been hampered by slowness, cost and complexity. We explored whether MinION nanopore sequencing could accelerate diagnosis and resistance profiling, using complicated urinary tract infections as an exemplar.

Methods: Bacterial DNA was enriched from clinical urines (n = 10) and from healthy urines 'spiked' with multiresistant Escherichia coli (n = 5), then sequenced by MinION.

The mucin-degradation strategy of Ruminococcus gnavus: The importance of intramolecular trans-sialidases.

We previously identified and characterized an intramolecular trans-sialidase (IT-sialidase) in the gut symbiont Ruminococcus gnavus ATCC 29149, which is associated to the ability of the strain to grow on mucins. In this work we have obtained and analyzed the draft genome sequence of another R. gnavus mucin-degrader, ATCC 35913, isolated from a healthy individual.

The pan-genome of Lactobacillus reuteri strains originating from the pig gastrointestinal tract.

Background: Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L.

Bacterial antimicrobial metal ion resistance.

Metals such as mercury, arsenic, copper and silver have been used in various forms as antimicrobials for thousands of years with until recently, little understanding of their mode of action. The discovery of antibiotics and new organic antimicrobial compounds during the twentieth century saw a general decline in the clinical use of antimicrobial metal compounds, with the exception of the rediscovery of the use of silver for burns treatments and niche uses for other metal compounds. Antibiotics and new antimicrobials were regarded as being safer for the patient and more effective than the metal-based compounds they supplanted.

Correlates of symptoms of depression and anxiety among clinic patients in western Jamaica.

Objectives: There is a paucity of studies on psychosocial disorders in clinic populations in Jamaica. Therefore, we sought to determine the prevalence and correlates of symptoms of depression and anxiety in a clinic population in western Jamaica.

Methods: A total of 338 participants from four outpatient clinics of : A total of 338 participants from four outpatient clinics of the Western Regional Health Authority (WRHA) were screened for symptoms of depression and anxiety using questions from the Beck Depression Inventory-II and the Beck Anxiety Inventory.

Draft Genome Sequence of a Novel Lactobacillus salivarius Strain Isolated from Piglet.

Lactobacillus salivarius is part of the vertebrate indigenous microbiota of the gastrointestinal tract, oral cavity, and milk. The properties associated with some L. salivarius strains have led to their use as probiotics.

Complete Genome Sequence of the Campylobacter coli Clinical Isolate 15-537360.

Campylobacter coli strain 15-537360 was originally isolated in 2001 from a 42-year-old patient with gastroenteritis. Here, we report its complete genome sequence, which comprises a 1.7-Mbp chromosome and a 29-kbp conjugative cryptic plasmid.

Draft genomes of 12 host-adapted and environmental isolates of Pseudomonas aeruginosa and their positions in the core genome phylogeny.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen particularly associated with the inherited disease cystic fibrosis (CF). Pseudomonas aeruginosa is well known to have a large and adaptable genome that enables it to colonise a wide range of ecological niches. Here, we have used a comparative genomics approach to identify changes that occur during infection of the CF lung.

Genomic and physiological variability within Group II (non-proteolytic) Clostridium botulinum.

Background: Clostridium botulinum is a group of four physiologically and phylogenetically distinct bacteria that produce botulinum neurotoxin. While studies have characterised variability between strains of Group I (proteolytic) C. botulinum, the genetic and physiological variability and relationships between strains within Group II (non-proteolytic) C.

Crowdsourcing genomic analyses of ash and ash dieback - power to the people.

Ash dieback is a devastating fungal disease of ash trees that has swept across Europe and recently reached the UK. This emergent pathogen has received little study in the past and its effect threatens to overwhelm the ash population. In response to this we have produced some initial genomics datasets and taken the unusual step of releasing them to the scientific community for analysis without first performing our own.