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Cathleen S. Colón-Emeric 《Current osteoporosis reports》2013,11(4):270-275
Osteoporosis and related fractures disproportionately impact patients with advanced age, those with the frailty phenotype, and those with multiple comorbidities. Recent studies report a changing incidence in fracture type among the oldest old throughout the world, a finding not satisfactorily explained by advances in treatment of lifestyle factors. A growing recognition of the importance of muscle and bone interaction is leading to improved understanding of the underlying biochemical pathways linking them and new therapeutic targets. New models of care for frail older populations, particularly after hip fracture, are being developed but have been challenged to identify appropriate outcomes to target. An appreciation for the relationship between age-related comorbidities, fracture risk, and competing mortality risk is essential for practitioners caring for the oldest-old population. 相似文献
24.
Janet L. Barnes-Farrell Steven M. Rumery Cathleen A. Swody 《Experimental aging research》2013,39(1):87-98
Health care workers from five nations (Brazil, Croatia, Poland, Ukraine, U.S.A.) completed the Survey of Health Care Professionals, which includes measures of on-the-job and off-the-job conditions/concerns, as well as ratings of work-related strains, self-ratings of work performance and work ability, and measures of chronological and psychological age. Consistent with previous research, workers generally reported that they felt, looked, acted, and preferred to be younger than their chronological age. In addition, feeling old relative to one's chronological age was positively associated with several indicators of job-related strain for several nations, replicating findings reported earlier in a U.S. manufacturing sample. Significant differences were observed among nations on all of the psychological age variables measured in this study. Differences among nations were also observed for levels of concern with work conditions and off-the-job conditions. Furthermore, examination of relationships of age variables with work/off-the-job stressors and work strains/outcomes revealed different patterns of relationships among the five nations participating in the study. Findings point to the need for additional attention to psychological age variables in studies of work and aging, with particular emphasis on cultural and socioeconomic conditions that may influence their interplay. 相似文献
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Medora J. Huseby Andrew C. Kruse Jeff Digre Petra L. Kohler Jillian A. Vocke Ethan E. Mann Kenneth W. Bayles Gregory A. Bohach Patrick M. Schlievert Douglas H. Ohlendorf Cathleen A. Earhart 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(32):14407-14412
Biofilms are surface-associated communities of microbes encompassed by an extracellular matrix. It is estimated that 80% of all bacterial infections involve biofilm formation, but the structure and regulation of biofilms are incompletely understood. Extracellular DNA (eDNA) is a major structural component in many biofilms of the pathogenic bacterium Staphylococcus aureus, but its role is enigmatic. Here, we demonstrate that beta toxin, a neutral sphingomyelinase and a virulence factor of S. aureus, forms covalent cross-links to itself in the presence of DNA (we refer to this as biofilm ligase activity, independent of sphingomyelinase activity) producing an insoluble nucleoprotein matrix in vitro. Furthermore, we show that beta toxin strongly stimulates biofilm formation in vivo as demonstrated by a role in causation of infectious endocarditis in a rabbit model. Together, these results suggest that beta toxin cross-linking in the presence of eDNA assists in forming the skeletal framework upon which staphylococcal biofilms are established. 相似文献
26.
Membrane‐bound stem cell factor is the major but not only driver of fibroblast‐induced murine skin mast cell differentiation
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Mandy Leist Cathleen Annett Sünder Sebastian Drube Carolin Zimmermann Astrid Geldmacher Martin Metz Marcus Maurer 《Experimental dermatology》2017,26(3):255-262
The maintenance and modulation of cutaneous mast cell (MC) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MCs. Fibroblast‐derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation. The mechanisms of fibroblast‐induced skin MC differentiation, including the role of SCF, however, remain insufficiently characterized and understood. Using cocultures of immature murine MCs and fibroblasts, we found that the adhesion of immature MCs to fibroblasts via VCAM‐1 and α4β7 integrin is very important for subsequent differentiation, which is driven by fibroblast membrane‐bound SCF and additional fibroblast‐derived membrane‐bound signals. Thus, our results show that fibroblast‐induced MC differentiation is induced by direct cell–cell contact and involves both Kit‐dependent and Kit‐independent pathways. Our findings add to the understanding of how immature mast cells mature in murine skin and encourage further analyses of the underlying mechanisms, which may result in novel targets for the modulation of skin mast cell driven diseases. 相似文献
27.
Jacob E. Resch Cathleen N. Brown Stephen N. Macciocchi C. Munro Cullum Damond Blueitt Michael S. Ferrara 《Journal of Athletic Training》2015,50(12):1292-1298
ContextSymptom presentation and recovery after sport concussion (SC) are variable. Empirically based models documenting typical symptom duration would assist health care providers in managing return to play after SC.ObjectiveTo develop a prediction model for SC symptom duration.DesignCross-sectional study.SettingTwo National Collegiate Athletic Association Division I university laboratories.Intervention(s)Participants completed the Revised Head Injury Scale (HIS-r), Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), and Sensory Organization Test within 24 hours of SC diagnosis.ResultsThe final formula consisted of the HIS-r''s self-reported neck pain, drowsiness, tingling, and nervousness duration and ImPACT total symptom severity (R = 0.62, R2 = 39%, R2adj = 34.2%, P < .001). Approximately 29% (R2cv = 29%) of the variance associated with total days symptomatic after SC was explained by our preliminary formula when cross-validated. The current formula correctly identified 76% of participants who recovered within 10 days of injury.ConclusionsOur results suggest that self-reported duration of 4 symptoms during the initial 24 hours after injury along with total symptom severity as measured by ImPACT accounted for a considerable amount of variance associated with days symptomatic after SC in collegiate athletes. Until the formula is cross-validated in a college-aged sample, caution is warranted in using it clinically.Key Words: traumatic brain injuries, prediction, prolonged recovery, symptom severity, symptom duration
Key Points
- A formula to predict symptom resolution after sport concussion primarily consisting of initial symptom duration and severity correctly identified 76% of National Collegiate Athletic Association Division I collegiate athletes who recovered within 10 days.
- Before it can be used clinically, the formula must be cross-validated on larger samples.
28.
Thorsten Derlin Sebastian Schmuck Cathleen Juhl Steffi Teichert Johanna Zörgiebel Hans-Jürgen Wester Sophie M. Schneefeld Almut C. A. Walte James T. Thackeray Tobias L. Ross Frank M. Bengel 《Molecular imaging and biology》2018,20(4):650-658
Purpose
[68Ga]Trishydroxypyridinone (THP)–prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [68Ga]THP-PSMA.Procedures
[68Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [68Ga]PSMA I&T.Results
Physiologic uptake of [68Ga]THP-PSMA was significantly lower in salivary glands (P?<?0.0001), liver (P?<?0.0001), spleen (P?<?0.0001), and kidneys (P?<?0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T.Conclusion
[68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [68Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.29.
Cathleen S. Colón-Emeric Carl F. Pieper Courtney H. Van Houtven Janet M. Grubber Kenneth W. Lyles Joanne Lafleur Robert A. Adler 《Mayo Clinic proceedings. Mayo Clinic》2018,93(12):1749-1759
Objective
To determine the association between dual-energy x-ray absorptiometry (DXA) testing for osteoporosis and subsequent fractures in US male veterans without a previous fracture.Patients and Methods
This is a propensity score–matched observational study using Centers for Medicare and Medicaid Services and Veterans Affairs (VA) data from January 1, 2000, through December 31, 2010, with a mean follow-up time of 4.7 years (range, 0-10 years). Men receiving VA primary care aged 65 to 99 years without a previous fracture (N=2,539,812) were included. Men undergoing DXA testing were propensity score matched with untested controls in a 1:3 ratio, indicating the probability of DXA testing within the next year. Time to first clinical fracture was the primary outcome. Comorbidities, demographic characteristics, medications, DXA results, and osteoporosis treatment were defined using administrative data and natural language processing. A landmark analysis contingent on surviving to 12 months after screening was completed, accounting for competing risk of mortality.Results
During follow-up of 153,311 men tested by DXA and 390,158 controls, 56,083 (10.3%) had sustained a fracture and 111,774 (20.6%) died. Overall, DXA testing was not associated with a decrease in fractures; conclusions are limited by unmeasured confounders and low medication initiation and adherence in those meeting treatment thresholds (12% of follow-up time). In contrast, DXA testing in prespecified subgroups was associated with a lower risk of fracture in comparison to the overall population who underwent DXA testing: androgen deprivation therapy (hazard ratio [HR], 0.77; 95% CI, 0.66-0.89), glucocorticoids (HR, 0.77; 95% CI, 0.72-0.84), age 80 years and older (HR, 0.85; 0.81-0.90), 1 or more VA guideline risk factors (HR, 0.91; 95% CI, 0.87-0.95), and high Fracture Risk Assessment Tool using body mass index score (HR, 0.90; 95% CI, 0.86-0.95).Conclusion
Current VA DXA testing practices are ineffective overall; interventions to improve treatment adherence are needed. Targeted DXA testing in higher-risk men was associated with a lower fracture risk. 相似文献30.