Injuries in Adults 65 Years of Age and Older Prescribed Muscle Relaxants.

OBJECTIVE: The Beers criteria list skeletal muscle relaxants (SMR) as inappropriate for individuals 65 years of age and older because of anticholinergic effects, sedation, and risk of falls/fractures. Patients 65 years of age and older presenting to U.S. primary care clinics for injury, prescribed an SMR, are at risk for these events. SMR prescribing patterns in older adults with injury have not been well studied at the population level. Using nationally representative data, the prevalence of older adults prescribed an SMR presenting to U.S. primary care clinics with injury was examined. DESIGN: A cross-sectional study analyzing 2012 National Ambulatory Medical Care Survey (NAMCS) data using bivariate and multivariate techniques. NAMCS, a nationally representative database of the U.S. population, collects data from primary care office visits and uses a multi-stage sampling strategy. SETTING: Primary care offices throughout the United States. PATIENTS, PARTICIPANTS: Adults 65 years of age and older, presenting to rural primary care clinics with injury. MAIN OUTCOME MEASURE(S): Prescription for SMR. RESULTS: Multivariate analysis yielded that the study population presenting to rural clinics for injury had 28% greater odds, non-Caucasian adults had 11% greater odds, and those who had been seen at least twice in the past 12 months had 34% greater odds of being prescribed an SMR. Logistic regression analysis also yielded that females 65 to 74 years of age had greater odds of having a prescription for an SMR. CONCLUSION: The results of this study identified disparities among adults 65 years of age and older presenting to U.S. rural primary care clinics with injury and prescribed an SMR. Adults 65 years of age and older, Collaborative.

Disparate proteome responses of pathogenic and nonpathogenic aspergilli to human serum measured by activity-based protein profiling (ABPP).

Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. There is high genomic synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. We applied activity-based protein profiling to compare unique or overexpressed activity-based probe-reactive proteins of all three fungi over time in minimal media growth and in response to human serum. We found 360 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culture in serum. Though the fungi are highly orthologous, A. fumigatus has a significantly greater number of ABP-reactive proteins across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Activity-based protein profiling identified a number of processes that were induced by human serum in A. fumigatus relative to N. fischeri and A. clavatus. These included actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher activity-based probe-protein reaction over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely pathogenic aspergilli. These unique activity-based probe-protein responses to culture condition may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice.

High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD, or if mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar, or elevated, relative to standard diet (SD) mice; thereby, IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, ß-oxidation, and respiratory chain function at levels similar to or higher than SD mice.