Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

The effect of heel-to-toe drop of running shoes on patellofemoral joint stress during running

BackgroundTraditional running shoes with heel-to-toe drops is thought to be a contributor to increased patellofemoral joint stress, which is proposed as a mechanism of patellofemoral pain.Research questionIs there an increase in patellofemoral joint stress when running in shoes with drops compared to running in shoes without a drop?MethodsLower limbs kinematics and ground reaction force were collected from eighteen healthy runners during over-ground running in shoes with 15 mm, 10 mm, 5 mm drops, and without a drop. Patellofemoral joint force and stress were calculated from the kinematic and kinetic data using a biomechanical model of the patellofemoral joint.ResultsThe peak patellofemoral joint stress was increased by more than 15% when running in shoes with 15 mm and 10 mm drops compared to running in shoes without a drop (p = 0.003, p = 0.001). The knee flexion angle was significantly increased when running in shoes with 15 mm, 10 mm and 5 mm drops (p = 0.014, p = 0.003, p = 0.002), the knee extension moment (p = 0.009, p = 0.002) and patellofemoral joint force (p = 0.003, p = 0.001) were increased when running in shoes with 15 mm and 10 mm drops, compared to running in shoes without a drop.SignificanceCompared to running in shoes without a drop, running in shoes with drops > 5 mm increase the peak patellofemoral joint stress significantly, which is mainly due to the increased knee extension moment.     

Neutrophils and neutrophil extracellular trap components: Emerging biomarkers and therapeutic targets for age-related eye diseases

Age-related eye diseases, including dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy, represent a major global health issue based on their increasing prevalence and disabling action. Unraveling the molecular mechanisms underlying these diseases will provide novel opportunities to reduce the burden of age-related eye diseases and improve eye health, contributing to sustainable development goals achievement. The impairment of neutrophil extracellular traps formation/degradation processes seems to be one of these mechanisms. These traps formed by a meshwork of DNA and neutrophil cytosolic granule proteins may exacerbate the inflammatory response promoting chronic inflammation, a pivotal cause of age-related diseases. In this review, we describe current findings that suggest the role of neutrophils and their traps in the pathogenesis of the above-mentioned age-related eye diseases. Furthermore, we discuss why these cells and their constituents could be biomarkers and therapeutic targets for dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy. We also examine the therapeutic potential of some neutrophil function modulators and provide several recommendations for future research in age-related eye diseases.