Influence of the lung microbiome on antibiotic susceptibility of cystic fibrosis pathogens

The lungs of patients with cystic fibrosis (CF) are colonised by a microbial community comprised of pathogenic species, such as Pseudomonas aeruginosa and Staphylococcus aureus, and microorganisms that are typically not associated with worse clinical outcomes (considered as commensals). Antibiotics directed at CF pathogens are often not effective and a discrepancy is observed between activity of these agents in vitro and in the patient. This review describes how interspecies interactions within the lung microbiome might influence the outcome of antibiotic treatment targeted at common CF pathogens. Protective mechanisms by members of the microbiome such as antibiotic degradation (indirect pathogenicity), alterations of the cell wall, production of matrix components decreasing antibiotic penetration, and changes in metabolism are discussed. Interspecies interactions that increase bacterial susceptibility are also addressed. Furthermore, we discuss how experimental conditions, such as culture media, oxygen levels, incorporation of host-pathogen interactions, and microbial community composition may influence the outcome of microbial interaction studies related to antibiotic activity. Hereby, the importance to create in vitro conditions reflective of the CF lung microenvironment is highlighted. Understanding the role of the CF lung microbiome in antibiotic efficacy may help find novel therapeutic and diagnostic approaches to better tackle chronic lung infections in this patient population

Antibody Conjugation and Formulation

In an era where ultra-high antibody concentrations, high viscosities, low volumes, auto-injectors, and long storage requirements are already complex problems with the current unconjugated monoclonal antibodies on the market the formulation demands for antibody-drug conjugates (ADCs) are significant. Antibodies have historically been administered at relatively low concentrations through intravenous (IV) infusion due to their large size and the inability to formulate for oral delivery. Due to the high demands associated with IV infusion and the development of novel antibody targets and unique antibody conjugates more accessible routes of administration such as intramuscular (IM), and subcutaneous (SC) are being explored. This review will summarize various site-specific and non-site-specific antibody conjugation techniques in the context of antibody-drug conjugates (ADCs) and the demands of formulation for high concentration clinical implementation

Cooperation among strangers: an experiment with indefinite interaction

We study the emergence of norms of cooperation in experimental economies populated by strangers interacting indefinitely and lacking formal enforcement institutions. In all treatments the efficient outcome is sustainable as an equilibrium. We address the following questions: can these economies achieve full efficiency? Which institutions for monitoring and enforcement promote cooperation? Finally, what classes of strategies are employed to achieve high efficiency? We find that, first, cooperation can be sustained even in anonymous settings; second, some type of monitoring and punishment institutions significantly promote cooperation; and, third, subjects dislike indiscriminate strategies and prefer selective strategies.experiments, repeated games, cooperation, equilibrium selection, prisoners’ dilemma, random matching

Perspective—Challenges in Developing Wearable Electrochemical Sensors for Longitudinal Health Monitoring

Wearable electrochemical sensors have the potential to overcome the problem of infrequent clinical visits that leads to transient events of potential diagnostic importance being unduly overlooked. The promise of real-time, personalized health care has driven multidisciplinary work on fabricating various forms of wearable sensors. Although remarkable advances in device form factor and integrated circuit design have been achieved, notable hurdles, such as shelf life, reuseability, flex and sweat resistance, and longitudinal performance, remain unaddressed. This perspective seeks to summarize major advances in current wearable electrochemical sensors and to highlight the most pressing challenges that will benefit from collective research endeavors

The role of urate and xanthine oxidase in vascular oxidative stress:Future directions

Vascular oxidative stress has been shown to be a potent factor in the pathophysiology of endothelial dysfunction. Despite current optimal evidence-based therapy, mortality from various cardiovascular disorders remains high. The search for newer, novel ways of attenuating endothelial dysfunction has yielded several new and exciting possibilities, one of which is the manipulation of urate levels using xanthine oxidase inhibitors. Agents such as allopurinol have shown marked improvements in vascular endothelial function in various cohorts at risk of cardiovascular events. Most of the evidence so far comes from smaller mechanistic studies. The few large randomized controlled trials have failed to show any significant mortality benefit using these agents. This article highlights the potential avenues of further research such as dose-response, and the potential for these agents to regress left ventricular hypertrophy. The role of newer agents such as febuxostat and oxypurinol are discussed as well as potential reasons why some of the current newer agents have failed to live up to the promising early-phase data. It is crucial that these remaining questions surrounding urate, xanthine oxidase and the role of various agents that affect this important oxidative stress-generating system are answered, and therefore these promising agents should not be discarded prematurely