Antibiotic killing of drug-induced bacteriostatic cells.

Background: There is a long-standing belief that bacteriostatic drugs are inherently antagonistic to the action of bactericidal antibiotics. This belief is primarily due to the fact that the action of most bactericidal antibiotics requires the target bacteria to be growing. Since bacteriostatic drugs stop the growth of treated bacteria, these drugs would necessarily work against one another.

The evolution of heteroresistance via small colony variants in Escherichia coli following long term exposure to bacteriostatic antibiotics.

Traditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics of Escherichia coli after exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days.

The dynamics of Staphylococcal infection and their treatment with antibiotics and bacteriophage in the model system.

Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents.

A bacteriophage-based validation of a personal protective equipment doffing procedure to be used with high-consequence pathogens.

Objective: To determine if the high-level personal protective equipment used in the treatment of high-consequence infectious diseases is effective at stopping the spread of pathogens to healthcare personnel (HCP) while doffing.

Background: Personal protective equipment (PPE) is fundamental to the safety of HCPs. HCPs treating patients with high-consequence infectious diseases use several layers of PPE, forming complex protective ensembles.

The Tradeoffs Between Persistence and Mutation Rates at Sub-Inhibitory Antibiotic Concentrations in .

The rational design of the antibiotic treatment of bacterial infections employs these drugs to reach concentrations that exceed the minimum needed to prevent the replication of the target bacteria. However, within a treated patient, spatial and physiological heterogeneity promotes antibiotic gradients such that the concentration of antibiotics at specific sites is below the minimum needed to inhibit bacterial growth. Here, we investigate the effects of sub-inhibitory antibiotic concentrations on three parameters central to bacterial infection and the success of antibiotic treatment, using experiments with and mathematical-computer simulation models.

Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance.

Antibiotics are considered one of the most important contributions to clinical medicine in the last century. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One form of resistance, heteroresistance, is particularly problematic; pathogens appear sensitive to a drug by common susceptibility tests.

Connecting pathogen transmission and healthcare worker cognition: a cognitive task analysis of infection prevention and control practices during simulated patient care.

Background: Relatively little is known about the cognitive processes of healthcare workers that mediate between performance-shaping factors (eg, workload, time pressure) and adherence to infection prevention and control (IPC) practices. We taxonomised the cognitive work involved in IPC practices and assessed its role in how pathogens spread.

Methods: Forty-two registered nurses performed patient care tasks in a standardised high-fidelity simulation.

Enteric Populations of are Likely to be Resistant to Phages Due to O Antigen Expression.

There is a surfeit of bioinformatic data showing that bacteriophages abound in the enteric microbiomes of humans. What is the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how are these phages maintained over time? To address these questions, we performed experiments with and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota and develop and analyze the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our models predict and experiments confirm that due to production of the O antigen, in the enteric microbiome are likely to be resistant to infection with co-occurring phages.

Bacterial cGAS senses a viral RNA to initiate immunity.

Cyclic oligonucleotide-based antiphage signalling systems (CBASS) protect prokaryotes from viral (phage) attack through the production of cyclic oligonucleotides, which activate effector proteins that trigger the death of the infected host. How bacterial cyclases recognize phage infection is not known. Here we show that staphylococcal phages produce a structured RNA transcribed from the terminase subunit genes, termed CBASS-activating bacteriophage RNA (cabRNA), which binds to a positively charged surface of the CdnE03 cyclase and promotes the synthesis of the cyclic dinucleotide cGAMP to activate the CBASS immune response.

The Evolution of Heteroresistance via Small Colony Variants in Following Long Term Exposure to Bacteriostatic Antibiotics.

Traditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics of after exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days.

What's the Matter with MICs: Bacterial Nutrition, Limiting Resources, and Antibiotic Pharmacodynamics.

The MIC of an antibiotic required to prevent replication is used both as a measure of the susceptibility/resistance of bacteria to that drug and as the single pharmacodynamic parameter for the rational design of antibiotic treatment regimes. MICs are experimentally estimated under conditions optimal for the action of the antibiotic. However, bacteria rarely grow in these optimal conditions.

The book of Lambda does not tell us that naturally occurring lysogens of are likely to be resistant as well as immune.

The most significant difference between bacteriophages functionally and ecologically is whether they are purely lytic (virulent) or temperate. Virulent phages can only be transmitted horizontally by infection, most commonly with the death of their hosts. Temperate phages can also be transmitted horizontally, but upon infection of susceptible bacteria, their genomes can be incorporated into that of their host's as a prophage and be transmitted vertically in the course of cell division by their lysogenic hosts.

A methodology for using Lambda phages as a proxy for pathogen transmission in hospitals.

Background: One major concern in hospitalized patients is acquiring infections from pathogens borne on surfaces, patients, and healthcare workers (HCWs). Fundamental to controlling healthcare-associated infections is identifying the sources of pathogens, monitoring the processes responsible for their transmission, and evaluating the efficacy of the procedures employed for restricting their transmission.

Aim: To present a method using the bacteriophage Lambda (λ) to achieve these ends.

Adolescent Depression and Anxiety Treatment in Rural Schools: A Systematic Review.

Depression and anxiety are the most common mental illnesses in adolescents. Rural schools are well-positioned to narrow the access gap confronting rural adolescents experiencing depression and anxiety; however, there is a paucity of research on the treatment of depression and anxiety in rural high schools. This critical review summarized the state of the field on rural school-based interventions to reduce adolescent depression and anxiety.

Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of infections.

In response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYO, for combination phage and antibiotic treatment of infections. This K-like phage has a broad host range; all 83 tested clinical isolates of S.

Plasma-based circulating MicroRNA biomarkers for Parkinson's disease.

Background: The current "gold-standard" for Parkinson's disease (PD) diagnosis is based primarily on subjective clinical rating scales related with motor features. Molecular biomarkers that are objective and quantifiable remain attractive as clinical tools to detect PD prior to its motor onsets.

Objective: Here, we aimed to identify, develop, and validate plasma-based circulating microRNA (miRNAs) as biomarkers for PD.

Association of tubal factor infertility with elevated antibodies to Chlamydia trachomatis caseinolytic protease P.

Objective: The objective of the study was to assess antibodies against Chlamydia trachomatis heat shock proteins (HSP) in patients with tubal factor infertility (TFI), infertility controls (IFC), and fertile controls (FC). HSPs assist organisms in surviving caustic environments such as heat.

Study Design: Twenty-one TFI, 15 IFC, and 29 FC patients were enrolled after laparoscopic tubal assessment.

Increased SPARC accumulation during corneal repair.

Keratocytes can become fibroblasts and myofibroblasts during corneal injury and wound healing. We used the in vitro bovine keratocyte repair model system, which involves culturing collagenase-isolated keratocytes in serum-free media and then adding serum or serum plus TGF-beta to the culture media to induce the fibroblast and myofibroblast phenotypes, respectively, to evaluate the synthesis of secreted products by the cells. Serum and serum plus TGF-beta rapidly induced the fibroblast morphology and alpha smooth muscle actin, a marker of myofibroblasts.

Partial restoration of the keratocyte phenotype to bovine keratocytes made fibroblastic by serum.

Purpose: To determine whether keratocytes made fibroblastic in vitro by addition of fetal bovine serum to the medium regain the keratocyte phenotype after culture in serum-free medium.

Methods: Collagenase-isolated keratocytes from bovine corneas were plated in DMEM/F-12 containing 1% horse plasma, to allow cell attachment, and then cultured until day 4 in either DMEM/F-12 alone, to retain the keratocyte phenotype, or in DMEM containing 10% fetal bovine serum, to cause the keratocytes to become fibroblastic. Medium for the fibroblastic cells was replaced on day 4 with serum-free medium, and cells were cultured until day 12.

Production of prostaglandin D synthase as a keratan sulfate proteoglycan by cultured bovine keratocytes.

Purpose: To characterize the major proteoglycans produced and secreted by collagenase-isolated bovine keratocytes in culture.

Methods: Freshly isolated keratocytes from mature bovine corneas were cultured in serum-free Dulbecco's modified Eagle's medium/ F12. Secreted proteoglycans were radiolabeled with protein labeling mix ((35)S-Express; Dupont NEN Life Science Products, Boston, MA) and digested with chondroitinase ABC, keratanase, and endo-beta-galactosidase to remove glycosaminoglycan chains, and core proteins were analyzed by autoradiography and Western blot analysis.

Expression of the keratan sulfate proteoglycans lumican, keratocan and osteoglycin/mimecan during chick corneal development.

The corneal proteoglycans belong to the Leu-rich proteoglycan (LRP) gene family and contain chondroitin/dermatan (CS/DS) or keratan sulfate (KS) chains. These proteoglycans play a critical role in generating and maintaining a transparent matrix within the corneal stroma. Decorin which has CS/DS chains and lumican which has KS chains, were first to be identified in the cornea.