The contractile response of the heart can be altered by disease-related protein modifications to numerous contractile proteins. By utilizing an IAANS labeled fluorescent troponin C, , we examined the effects of ten disease-related troponin modifications on the Ca2+ binding properties of the troponin complex and the reconstituted thin filament. The selected modifications are associated with a broad range of cardiac diseases: three subtypes of familial cardiomyopathies (dilated, hypertrophic and restrictive) and ischemia-reperfusion injury. Consistent with previous studies, the majority of the protein modifications had no effect on the Ca2+ binding properties of the isolated troponin complex. However, when incorporated into the thin filament, dilated cardiomyopathy mutations desensitized (up to 3.3-fold), while hypertrophic and restrictive cardiomyopathy mutations, and ischemia-induced truncation of troponin I, sensitized the thin filament to Ca2+ (up to 6.3-fold). Kinetically, the dilated cardiomyopathy mutations increased the rate of Ca2+ dissociation from the thin filament (up to 2.5-fold), while the hypertrophic and restrictive cardiomyopathy mutations, and the ischemia-induced truncation of troponin I decreased the rate (up to 2-fold). The protein modifications also increased (up to 5.4-fold) or decreased (up to 2.5-fold) the apparent rate of Ca2+ association to the thin filament. Thus, the disease-related protein modifications alter Ca2+ binding by influencing both the association and dissociation rates of thin filament Ca2+ exchange. These alterations in Ca2+ exchange kinetics influenced the response of the thin filament to artificial Ca2+ transients generated in a stopped-flow apparatus. Troponin C may act as a hub, sensing physiological and pathological stimuli to modulate the Ca2+-binding properties of the thin filament and influence the contractile performance of the heart.

This study evaluated the effects of exercise on cardiac troponin I (cTnI) concentrations in healthy, adult horses. Fifteen fit, healthy horses determined to have a normal cardiovascular system completed a standardized exercise test on a high-speed treadmill. Heparinized blood was collected for plasma cTnI concentrations before maximal exercise, and 1, 3, 6, 9, 12 and 24 h post-exercise. The cTnI concentrations were measured with a commercial system (Stratus CS, Dade Behring, Inc.). Results were analysed by a multivariate ANOVA, where indicated post hoc analysis was done by Tukey-Kramer HSD and significance was placed at p , 0.05.All horses had elevations in cTnI concentrations after maximal exercise. Values for cTnI trended higher at 3 h (0.066^0.011 ng ml 21 ) and 6 h (0.062^0.011 ng ml 21 ) post-exercise compared with pre-exercise (0.039^0.007 ng ml 21 ), although this did not reach statistical significance. Mean cTnI concentrations were within our normal reference range at all time points, although four individuals were above our normal range after exercise.These data show that short-term, high-intensity exercise induces a small rise in plasma cTnI in normal horses. This should be kept in mind when evaluating cTnI concentrations in horses that have recently completed intense exercise. In addition, these data suggest that 3-6 h after intense exercise may be the optimal time for measurement of cTnI concentrations in horses with suspected exercise-induced myocardial damage.

Yellow nail syndrome is a rare disease of unclear etiology. We describe a patient who develops yellow nail syndrome, with primary nail and sinus manifestations, shortly after amalgam dental implants. A study of the patient's nail shedding showed elevated nail titanium levels. The patient had her dental implants removed and had complete resolution of her sinus symptoms with no change in her nail findings. Since the patient's nail findings did not resolve we do not believe titanium exposure is a cause of her yellow nail syndrome but perhaps a possible relationship exists between titanium exposure and yellow nail syndrome that requires further studies.

BackgroundThe impact of cardiac troponin (cTn) testing on the downstream use of cardiovascular services is not well understood. We conducted this large-scale single centre cohort study to investigate the patterns of testing that result from the use of cTn.MethodsWe conducted this investigation using data collected between 1 January 2013 and 18 December 2015 from an academically affiliated tertiary care centre. Data from all hospitalised patients evaluated with cTn (Roche Elecsys cTn-T) assay were collected from our integrated data repository and divided into two cohorts: all cTn assays negative (<0.03 µg/L) versus at least one elevated (≥0.03 µg/L). The main outcomes were the frequency of use cardiovascular services and mortality.ResultsAmong 26 663 subjects, 18.6% had at least one elevated cTn assay; acute myocardial infarction was diagnosed in 3.9% overall. More men received cardiac catheterisation and cardiology consultation (OR 1.29, 95% CI 1.20 to 1.39 and OR 1.45, 95% CI 1.31 to 1.61) while African-American patients were less likely to have either catheterisation (OR 0.85, 95% CI 0.77 to 0.93) or consultation (OR 0.72, 95% CI 0.63 to 0.82) performed. Mortality was associated with detectable cTn (HR 2.05, P<0.0001).ConclusionsAmong hospitalised patients evaluated with cTn, we observed patterns of underuse and overuse of cardiovascular services. These patterns may have further relevance when high-sensitivity cTn assays are available in the USA. Sex and race-based disparities in cardiovascular services persist.

BackgroundDespite efforts by professional societies to reduce low value care, many reports indicate that unnecessary tests, such as nuclear myocardial perfusion imaging (MPI), are commonly used in contemporary practice. The degree to which lack of awareness and professional liability concerns drive these behaviors warrants further study. We sought to investigate patient and provider perceptions about MPI in asymptomatic patients, the Choosing Wisely (CW) campaign, and professional liability concerns.MethodsWe administered an anonymous, paper-based survey with both discrete and open-response queries to subjects in multiple outpatient settings at our facilities. The survey was completed by 456 respondents including 342 patients and 114 physicians and advanced practice providers between May and August 2014. Our outcome was to compare patient and provider perceptions about MPI in asymptomatic patients and related factors.ResultsPatients were more likely than providers to report that MPI was justified for asymptomatic patients (e.g. asymptomatic with family history of heart disease 75% versus 9.2%, p < 0.0001). In free responses to the question “What would be an inappropriate reason for MPI?” many responses echoed the goals of CW (for example, “If you don’t have symptoms”, “If the test is too risky”, “For screening or in asymptomatic patients”). A minority of providers were aware of CW while even fewer patients were aware (37.2% versus 2.7%, p < 0.0001). Over one third of providers (38.9%) admitted to ordering MPI out of concern for professional liability including 48.3% of VA affiliated providers.ConclusionsWhile some patients and providers are aware of the low value of MPI in patients without symptoms, others are enthusiastic to use it for a variety of scenarios. Concerns about professional liability likely contribute, even in the VA setting. Awareness of the Choosing Wisely campaign is low in both groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-017-2510-y) contains supplementary material, which is available to authorized users.