Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as “ESKAPE pathogens” on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus (S. aureus) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis, and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.
Resting and exercise fuel metabolism was assessed in three different phases of the menstrual cycle, characterized by different levels of estrogen relative to progesterone: early follicular (EF, low estrogen and progesterone), midfollicular (MF, elevated estrogen, low progesterone), and midluteal (ML, elevated estrogen and progesterone). It was hypothesized that exercise glucose utilization and whole body carbohydrate oxidation would decrease sequentially from the EF to the MF to the ML phase. Normal-weight healthy females, experiencing a regular menstrual cycle, were recruited. Subjects were moderately active but not highly trained. Testing occurred after 3 days of diet control and after an overnight fast (12-13 h). Resting (2 h) and exercise (50% maximal O 2 uptake, 90 min) measurements of whole body substrate oxidation, tracer-determined glucose flux, and substrate and hormone concentrations were made. No significant difference was observed in whole body fuel oxidation during exercise in the three phases (nonprotein respiratory exchange ratio: EF 0.84 ± 0.01, MF 0.85 ± 0.01, ML 0.85 ± 0.01) or in rates of glucose appearance or disappearance. There were, however, significantly higher glucose (P < 0.05) and insulin (P < 0.001) concentrations during the first 45 min of exercise in the ML phase vs. EF and MF phases. In conclusion, whole body substrate oxidation and glucose utilization did not vary significantly across the menstrual cycle in moderately active women, either at rest or during 90 min of moderate-intensity exercise. During the ML phase, however, this similar pattern of substrate utilization was associated with greater glucose and insulin concentrations. Both estrogen and progesterone are elevated during the ML phase of the menstrual cycle, suggesting that one or both of these sex steroids may play a role in this response.Keywords substrate oxidation; female sex steroids; glucose metabolism IN PREMENOPAUSAL WOMEN, the menstrual cycle represents a continuous state of change in terms of the female sex steroid environment. Determining how the menstrual cycle phase affects various aspects of metabolism is necessary to provide a comprehensive understanding of normal physiology in women. It is also important to establish the necessity of controlling for sex steroid hormone status when women are included in metabolic studies. This is relevant both to the resting condition and during perturbations common to everyday life, such as exercise. Copyright © 2002 the American Physiological SocietyAddress for reprint requests and other correspondence: T. J. Horton, Center for Human Nutrition, Box C225, Univ. of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262 (E-mail: Tracy.Horton@uchsc.edu).. NIH Public Access Author ManuscriptAm J Physiol Endocrinol Metab. Author manuscript; available in PMC 2011 June 27. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptData would suggest that the normal cyclical variation in estrogen and/or progesterone could affect a number of ...
The health benefits of regular recreational physical activity are well known in reducing secondary health consequences of a sedentary lifestyle in the general population. However, individuals with physical disabilities participate less frequently in recreational activity compared with those without disabilities. Although evidence on the impact of recreational physical activity on quality of life in this population is in its infancy, regular recreational and sports activity participation has shown to have a positive association with improvements in quality of life, life satisfaction, community reintegration, mood, and employment in those with disabilities. Facilitators of participating in adaptive sports include a desire to improve social support, physical fitness, health, and fun. Unfortunately, those with disabilities face numerous barriers to participate in adaptive sports including accessibility, transportation, awareness, finances, and physical and cognitive impairments. Further studies are needed to investigate facilitators and barriers to participating in adaptive sports to capitalize on the physical and psychosocial benefits of regular recreational activity. The aim of this article is to review the available literature on the effects of adaptive sports participation on quality of life.
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