Absence of \u3ci\u3eStreptococcus pneumoniae \u3c/i\u3e Capsule Increases Bacterial Binding, Perisstence, and Inflammation In Corneal Infection

The role of the pneumococcal polysaccharide capsule is largely unclear for Streptococcus pneumoniae keratitis, an ocular inflammatory disease that develops as a result of bacterial infection of the cornea. In this study, capsule-deficient strains were compared to isogenic parent strains in their ability to adhere to human corneal epithelial cells. One isogenic pair was further used in topical ocular infection of mice to assess the contribution of the capsule to keratitis. The results showed that non-encapsulated pneumococci were significantly more adherent to cells, persisted in significantly higher numbers on mouse corneas in vivo, and caused significant increases in murine ocular IL9, IL10, IL12-p70, MIG, and MIP-1-gamma compared to encapsulated S. pneumoniae. These findings indicate that the bacterial capsule impedes virulence and the absence of capsule impacts inflammation following corneal infection

Factors influencing high school coaches’ adoption of injury prevention programs

OBJECTIVES: Despite documented efficacy of injury prevention programs (IPPs) to reduce sport-related lower extremity injury risk, there is evidence of a lack of widespread IPP adoption by high school coaches. This study identified factors related to non-adoption of IPPs by assessing coaches’ knowledge, attitudes, and behaviors related to prevention programs and comparing attitudes between adopter and non-adopter coaches. DESIGN: Cross-sectional METHODS: Head soccer and basketball coaches (n=141) from 15 Oregon high schools were invited to complete a web-based survey assessing their IPP-related knowledge, attitudes, and behaviors. RESULTS: Of the 66 coach respondents, 52% reported being aware of IPPs; 21% reported using an IPP with their team; and 9% reported having their student-athletes perform the IPP exactly as designed. No apparent differences in the attitudes towards the importance of injury prevention or the effectiveness of IPPs were identified between coaches that did and did not adopt an IPP. Perceptions that efficacious IPPs do not offer a relative advantage over coaches’ existing practices, do not align with coaches’ needs (compatibility), and are difficult to implement in their setting (complexity) emerged as key factors underlying coaches’ decisions not to adopt a program. Of those that did report adopting an IPP, just 43% (6/14) reported implementing the program as designed. CONCLUSIONS: Improving preventative practices of high school coaches requires more than improved dissemination to increase coach awareness. To improve the rate of IPP adoption and implementation fidelity, coach education should directly address issues related to relative advantage, compatibility, and complexity.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The article is published in the Journal of Science and Medicine in Sport and available at: https://doi.org/10.1016/j.jsams.2015.03.00

Lower Extremity Energy Absorption and Biomechanics During Landing, Part II: Frontal-Plane Energy Analyses and Interplanar Relationships

Greater sagittal-plane energy absorption (EA) during the initial impact phase (INI) of landing is consistent with sagittal-plane biomechanics that likely increase anterior cruciate ligament (ACL) loading, but it does not appear to influence frontal-plane biomechanics. We do not know whether frontal-plane INI EA is related to high-risk frontal-plane biomechanics

Lower Extremity Energy Absorption and Biomechanics During Landing, Part I: Sagittal-Plane Energy Absorption Analyses

Eccentric muscle actions of the lower extremity absorb kinetic energy during landing. Greater total sagittal-plane energy absorption (EA) during the initial impact phase (INI) of landing has been associated with landing biomechanics considered high risk for anterior cruciate ligament (ACL) injury. We do not know whether groups with different INI EA magnitudes exhibit meaningful differences in ACL-related landing biomechanics and whether INI EA might be useful to identify ACL injury-risk potential

The influences of sex and posture on joint energetics during drop landings

Previous observations suggest that females utilize a more erect initial landing posture than males with sex differences in landing posture possibly related to sex-specific energy absorption (EA) strategies. However, sex-specific EA strategies have only been observed when accompanied by sex differences in initial landing posture. This study: 1) investigated the potential existence of sex-specific EA strategies, and 2) determined the influences of sex and initial landing posture on the biomechanical determinants of EA. The landing biomechanics of eighty subjects were recorded during drop landings in Preferred, Flexed, and Erect conditions. No sex differences in joint EA were identified after controlling for initial landing posture. Males and females exhibited greater ankle EA during Erect vs. Flexed landings with this increase driven by 12% greater ankle velocity, but no change in ankle extensor moment. No differences in hip and knee EA were observed between conditions. However, to achieve similar knee EA, subjects used 7% greater mean knee extensor moment but 9% less knee angular velocity during Flexed landings. The results suggest that sex-specific EA strategies do not exist, and that the magnitude of knee joint EA can be maintained by modulating the relative contributions of joint moment and angular velocity to EA.Keywords: Energy absorption, Kinetics, Kinematics, Landing biomechanic

Mathematical model of the dynamics of psychotherapy

The success of psychotherapy depends on the nature of the therapeutic relationship between a therapist and a client. We use dynamical systems theory to model the dynamics of the emotional interaction between a therapist and client. We determine how the therapeutic endpoint and the dynamics of getting there depend on the parameters of the model. Previously Gottman et al. used a very similar approach (physical-sciences paradigm) for modeling and making predictions about husband–wife relationships. Given that this novel approach shed light on the dyadic interaction between couples, we have applied it to the study of the relationship between therapist and client. The results of our computations provide a new perspective on the therapeutic relationship and a number of useful insights. Our goal is to create a model that is capable of making solid predictions about the dynamics of psychotherapy with the ultimate intention of using it to better train therapists

The Effects of Terrain and Navigation on Human Extravehicular Activity Walkback Performance on the Moon

Results of the EVA Walkback Test showed that 6 male astronauts were able to ambulate 10 km on a level treadmill while wearing a prototype EVA suit in simulated lunar gravity. However, the effects of lunar terrain, topography, and real-time navigation on ambulation performance are unknown. Primary objective: To characterize the effect of lunar-like terrain and navigation on VO2 and distance traveled during an unsuited 10 km (straight-line distance) ambulatory return in earth gravity

Substituted Aminoacetamides as Novel Leads for Malaria Treatment

Herein we describe the optimization of a phenotypic hit against Plasmodium falciparum based on an aminoacetamide scaffold. This led to N-(3-chloro-4-fluorophenyl)-2-methyl-2-{[4-methyl-3-(morpholinosulfonyl)phenyl]amino}propanamide (compound 28) with low-nanomolar activity against the intraerythrocytic stages of the malaria parasite, and which was found to be inactive in a mammalian cell counter-screen up to 25 μm. Inhibition of gametes in the dual gamete activation assay suggests that this family of compounds may also have transmission blocking capabilities. Whilst we were unable to optimize the aqueous solubility and microsomal stability to a point at which the aminoacetamides would be suitable for in vivo pharmacokinetic and efficacy studies, compound 28 displayed excellent antimalarial potency and selectivity; it could therefore serve as a suitable chemical tool for drug target identification

Discovery of a quinoline-4-carboxamide derivative with a novel mechanism of action, multistage antimalarial activity, and potent in vivo efficacy

The antiplasmodial activity, DMPK properties, and efficacy of a series of quinoline-4-carboxamides are described. This series was identified from a phenotypic screen against the blood stage of Plasmodium falciparum (3D7) and displayed moderate potency but with suboptimal physicochemical properties and poor microsomal stability. The screening hit (1, EC50 = 120 nM) was optimized to lead molecules with low nanomolar in vitro potency. Improvement of the pharmacokinetic profile led to several compounds showing excellent oral efficacy in the P. berghei malaria mouse model with ED90 values below 1 mg/kg when dosed orally for 4 days. The favorable potency, selectivity, DMPK properties, and efficacy coupled with a novel mechanism of action, inhibition of translation elongation factor 2 (PfEF2), led to progression of 2 (DDD107498) to preclinical development