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Despite the number of technologies used, the diagnosis of perioperative myocardial infarction is still a challenge. Studies conducted in surgical series have demonstrated that cardiac troponins (cTns) have both a superior diagnostic sensitivity and specificity, compared with other traditional techniques, and an independent power to predict short- and long-term prognosis. Nevertheless, some points need to be clarified. They include the usefulness of cTns in patients with end-stage renal failure; the standardization of the cTns cut-off for the diagnosis of myocardial injury; the timing of postoperative blood samplings; the cost-effectiveness of a screening in asymptomatic patients; and the possible therapeutic strategies. [ABSTRACT FROM AUTHOR]

Comments on the diagnostic and prognostic role of cardiac troponins (Ctns), a biological marker of myocardial injury. Relationship between the prognostic power of Ctns elevation and its high specificity and sensitivity as a marker of myocardial injury; Need to prove whether postoperative cTns elevation may predict cardiovascular events.

Describes the case of a 65-year-old female patient presenting with umbilical metastasis from ovarian carcinoma. Presence of an asymptomatic, brown nodule on her umbilicus; Combination chemotherapy; Disease background.

An abstract of the study "Sildenafil improves alveolar gas diffusion and exercise ventilation efficiency in heart failure patients," by C. Fiorentini et al. is presented.

Aims: Flow-mediated brachial artery vasodilatation is an index of endothelial function. Published literature describes only supine data and no study has been performed during vertical displacement. This subject deserves investigation for two main reasons: humans spend the larger part of their life in the upright position; this position has significant effects on neural vascular regulation. Methods: In 21 healthy men (25 ± 2 years) the flow-dependent brachial artery vasodilating response to distal circulatory arrest was assessed by Doppler ultrasound imaging, while supine and during 20° and 60° head-up tilting (HUT). In 11 of these subjects the vasodilating response to nitroglycerine was also explored. Results: Absolute and percentage increments in brachial calibre during hyperaemia after deflation of the occluding cuff became increasingly greater at 20° (+0.44 mm) and 60° (+0.92 mm) HUT (P < 0.01), compared with the horizontal position (+0.27 mm), and the arterial dilatation for an increase in flow (0.98 ± 0.08 and 1.68 ± 0.06 mm mL-1 min-1 x 1000, respectively) was larger (P < 0.01) than occurred while supine (0.41 ± 0.05 mm mL-1 min-1 x 1000). Nitroglycerine-mediated vasodilatation at 60° HUT was similar to that in the supine position. Conclusion: The orthostatic stimulus is associated with an increase of the flow-mediated brachial artery vasodilatation, which is proportional to the degree of displacement. The mechanism of this effect does not consist of changes in nitric oxide sensitivity. [ABSTRACT FROM AUTHOR]

The bacterial product CNF1, through its action on the Rho GTPases, is emerging as a modulator of crucial signalling pathways involved in selected neurological diseases characterized by mitochondrial dysfunctions. Mitochondrial impairment has been hypothesized to have a key role in paramount mechanisms underlying Rett syndrome (RTT), a severe neurologic rare disorder. CNF1 has been already reported to have beneficial effects in mouse models of RTT. Using human RTT fibroblasts from four patients carrying different mutations, as a reliable disease-in-a-dish model, we explored the cellular and molecular mechanisms, which can underlie the CNF1-induced amelioration of RTT deficits. We found that CNF1 treatment modulates the Rho GTPases activity of RTT fibroblasts and induces a considerable re-organization of the actin cytoskeleton, mainly in stress fibres. Mitochondria of RTT fibroblasts show a hyperfused morphology and CNF1 decreases the mitochondrial mass leaving substantially unaltered the mitochondrial dynamic. From a functional perspective, CNF1 induces mitochondrial membrane potential depolarization and activation of AKT in RTT fibroblasts. Given that mitochondrial quality control is altered in RTT, our results are suggestive of a reactivation of the damaged mitochondria removal via mitophagy restoration. These effects can be at the basis of the beneficial effects of CNF1 in RTT., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The Cytotoxic Necrotizing Factor 1 (CNF1) is a bacterial toxin secreted by certain Escherichia coli strains causing severe pathologies, making it a protein of pivotal interest in toxicology. In parallel, the CNF1 capability to influence important neuronal processes, like neuronal arborization, astrocytic support, and efficient ATP production, has been efficiently used in the treatment of neurological diseases, making it a promising candidate for therapy. Nonetheless, there are still some unsolved issues about the CNF1 mechanism of action and structuration probably caused by the difficulty to achieve sufficient amounts of the full-length protein for further studies. Here, we propose an efficient strategy for the production and purification of this toxin as a his-tagged recombinant protein from E. coli extracts (CNF1-H8). CNF1-H8 was expressed at the low temperature of 15°C to diminish its characteristic degradation. Then, its purification was achieved using an immobilized metal affinity chromatography (IMAC) and a size exclusion chromatography so as to collect up to 8 mg of protein per liter of culture in a highly pure form. Routine dynamic light scattering (DLS) experiments showed that the recombinant protein preparations were homogeneous and preserved this state for a long time. Furthermore, CNF1-H8 functionality was confirmed by testing its activity on purified RhoA and on HEp-2 cultured cells. Finally, a first structural characterization of the full-length toxin in terms of secondary structure and thermal stability was performed by circular dichroism (CD). These studies demonstrate that our system can be used to produce high quantities of pure recombinant protein for a detailed structural analysis. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:150-159, 2018., (© 2017 American Institute of Chemical Engineers.)

Background: Conventional analysis of exercise electrocardiogram (EX-ECG) has limited accuracy. This study aims to evaluate the potential impact of improving EX-ECG accuracy on costs of diagnosis and number of misdiagnoses of coronary artery disease (CAD)., Methods: A decision-tree model was simulated including sequential application of diagnostic procedures for suspected CAD. The model was structured in two main branches (presence or absence of CAD). A probabilistic sensitivity analysis was then performed for several combinations of improvement in test sensitivity and specificity., Results: A clear trend in cost reduction was observed at improving EX-ECG specificity (about 8-8.5 million dollars, corresponding to a 5.6-7.6% reduction according to the prevalence level). Wrong diagnoses counted for 9-13% of test. Improvements in test parameters lead to reductions in wrong diagnoses, especially when increasing specificity (8.8-12.5%)., Conclusions: A proper improvement in EX-ECG sensitivity and specificity would have a relevant impact on the costs of CAD management, while reducing the number of misdiagnoses.

Anemia is frequent in chronic heart failure (HF). To calculate what change in peak oxygen uptake ( VO(2)) should be expected in the event of changes in hemoglobin concentration, we studied the correlation between peak VO(2) and hemoglobin concentration in a large HF population. We carried out retrospective analysis of all cardiopulmonary exercise tests (CPET) performed in our HF Clinic between June 2001 and March 2009 in HF patients who had a resting hemoglobin concentration measurement taken within 7 days of the CPET. We collected 967 CPETs, 704 tests were considered maximal and analyzed. We identified 181 patients (26%) as anemic. Peak VO(2) was lower (P < 0.001) in anemic patients (971 +/- 23 ml/min) compared with nonanemic (1243 +/- 18 ml/min). The slope of the VO(2) vs. hemoglobin ratio was 109 ml/min/g/dl at peak exercise. This correlation remained significant also when several confounding variables were analyzed by multivariate analysis. As an average, each gram of hemoglobin accounts, at peak exercise, for 109 ml/min change in VO(2) which is equivalent to 0.97 ml/min/kg. Therefore, in HF patients anemia treatment should increase VO(2) by 109 ml/min for each g/dl of hemoglobin increase., (2010 Wiley-Liss, Inc.)

Objective: To compare different prediction models for assessing outcome of patients undergoing non-invasive risk stratification of suspected or known coronary artery disease., Methods: Six statistical classifiers and data mining models were applied to the prospective data bank of two different institutions. Of these, one represented the training (n = 2777) and the other one the test (n = 2679) set, each set consisting of usual clinical and stress echo information of patients followed-up for the combined endpoint of all-cause mortality and non-fatal acute coronary syndromes. The following models were used: Logistic regression, Generalized Additive Model, Projection Pursuit Regression, Linear Discriminant Analysis, Quadratic Discriminant Analysis and Artificial Neural Networks. Models were selected using the Akaike Information Criterion and compared in terms of accuracy and Negative Predictive Value, overall Misclassification Rate and ROC Area Under Curve., Results: During a median follow-up of 31 months, 573 events occurred: 271 in the training and 302 in the test set respectively. All models selected the same subset of covariates as significantly associated with the outcome. The comparison of model performance showed that: (1) Quadratic Discriminant Analysis and Artificial Neural Networks provided a worse prediction of outcome than models more closely bonded to the hypothesis of linearity of the covariates effect; (2) overall predictive capability of the best performing models was excellent (>90% and >85% for training and test set respectively); and (3) there was a substantial lack of agreement among model indications in the individual patient., Conclusions: The selection of variables and predictive models are not independent processes and may affect the performance of risk scoring systems or algorithms designed to transfer general prognostic rules into clinical practice. Thus, caution must be used in translating model prediction into strict clinical indications.