A spectrum-driven damage Identification technique : application and validation through the numerical simulation of the Z24 Bridge

The present paper focuses on a damage identification method based on the use of the second order spectral properties of the nodal response processes. The explicit dependence on the frequency content of the outputs power spectral densities makes them suitable for damage detection and localization. The well-known case study of the Z24 Bridge in Switzerland is chosen to apply and further investigate this technique with the aim of validating its reliability. Numerical simulations of the dynamic response of the structure subjected to different types of excitation are carried out to assess the variability of the spectrum-driven method with respect to both type and position of the excitation sources. The simulated data obtained from random vibrations, impulse, ramp and shaking forces, allowed to build the power spectrum matrix from which the main eigenparameters of reference and damage scenarios are extracted. Afterwards, complex eigenvectors and real eigenvalues are properly weighed and combined and a damage index based on the difference between spectral modes is computed to pinpoint the damage. Finally, a group of vibration-based damage identification methods are selected from the literature to compare the results obtained and to evaluate the performance of the spectral index.

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

OBJECTIVE: To assess the effect of food restriction (FR) on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR). METHODS: Isolated papillary muscle preparations of the left ventricle (LV) of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY) rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet) for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1) reduction in the body weight and LV weight of SHR and WKY rats; 2) increase in the time to peak shortening and the time to peak developed tension (DT) in the hypertrophied myocardium of the SHR; 3) diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Invasive hemodynamic monitoring in the postoperative period of cardiac surgery

OBJETIVE: To assess the hemodynamic profile of cardiac surgery patients with circulatory instability in the early postoperative period (POP). METHODS: Over a two-year period, 306 patients underwent cardiac surgery. Thirty had hemodynamic instability in the early POP and were monitored with the Swan-Ganz catheter. The following parameters were evaluated: cardiac index (CI), systemic and pulmonary vascular resistance, pulmonary shunt, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), oxygen delivery and consumption, use of vasoactive drugs and of circulatory support. RESULTS: Twenty patients had low cardiac index (CI), and 10 had normal or high CI. Systemic vascular resistance was decreased in 11 patients. There was no correlation between oxygen delivery (DO2) and consumption (VO2), p=0.42, and no correlation between CVP and PCWP, p=0.065. Pulmonary vascular resistance was decreased in 15 patients and the pulmonary shunt was increased in 19. Two patients with CI < 2L/min/m² received circulatory support. CONCLUSION: Patients in the POP of cardiac surgery frequently have a mixed shock due to the systemic inflammatory response syndrome (SIRS). Therefore, invasive hemodynamic monitoring is useful in handling blood volume, choice of vasoactive drugs, and indication for circulatory support.

Cardiac abnormalities in the acquired immunodeficiency syndrome. A prospective study with a clinical-pathological correlation in twenty-one adult patients

OBJECTIVE - To evaluate the cardiac abnormalities and their evolution during the course of the acquired immunodeficiency syndrome, as well as to correlate clinical and pathological data. METHODS - Twenty-one patients, admitted to the hospital with the diagnosis of acquired immunodeficiency syndrome, were prospectively studied and followed until their death. Age ranged from 19 to 42 years (17 males). ECG and echocardiogram were also obtained every six months. After death, macro- and microscopic examinations were also performed. RESULTS - The most frequent causes of referral to the hospital were: diarrhea or repeated pneumonias, tuberculosis, toxoplasmosis or Kaposi sarcoma. The most frequent findings were acute or chronic pericarditis (42%) and dilated cardiomyopathy (19%). Four patients died of cardiac problems: infective endocarditis, pericarditis with pericardial effusion, bacterial myocarditis and infection by Toxoplasma gondii. CONCLUSION - Severe cardiac abnormalities were the cause of death in some patients. In the majority of the patients, a good correlation existed between clinical and anatomical-pathological data. Cardiac evaluation was important to detect early manifestations and treat them accordingly, even in asymptomatic patients.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52±14 years). The average duration of the siesta was 118±58 minutes. RESULTS: (average ± standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138±16/85±11 vs 139±16/86±11 mmHg, p<0.05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION: The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

Mediastinitis after cardiac transplantation

OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6%) of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3±10.0 years) and 10 (83.3%) patients were males. Seven (58.3%) patients showed sternal stability on palpation, 4 (33.3%) patients had pleural empyema, and 2 (16.7%) patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7%) patients. Staphylococcus epidermidis was identified in 2 (16.7%) patients, Enterococcus faecalis in 1 (8.3%) patient, and the cause of mediastinitis could not be determined in 1 (8.3%) patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7%) patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3%) patient. Out of this series, 5 (41.7%) patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3%) patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

Reduction of QTc interval dispersion. Potential mechanism of cardiac protection of pyridostigmine bromide

OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886±27 ms vs after: 1054±37 ms) and decreased QTc dispersion (before: 72±9ms vs after: 45±3ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.

Cardiac involvement in total generalized lipodystrophy (Berardinelli- Seip syndrome)

Total generalized lipodystrophy (Berardinelli--Seip Syndrome) is a rare hereditary disease characterized by insulin-resistant diabetes mellitus and a small quantity of adipose tissue and is of unknown origin. Common cardiovascular alterations related to this syndrome are cardiac hypertrophy and arterial hypertension. This article reports a case of Berardinelli--Seip syndrome and reviews the literature with special emphasis on the cardiovascular manifestations of this syndrome.

Outcome of acute renal failure associated with cardiac surgery in infants

OBJECTIVE: To analyze the impact of acute renal failure (ARF) on the evolution of infants undergoing cardiac surgery. METHODS: We assessed 15 infants undergoing cardiac surgery who developed (ARF). Their demographic, clinical and surgical data, and evolution were analyzed. RESULTS: Their mean age was 4.4±4.0 months (8 days to 24 months). Twelve infants were males, and 4 patients already had ARF at surgery. The primary cause of ARF was immediate acute cardiac dysfunction in 10 infants, cardiac dysfunction associated with sepsis in 2 infants, and isolated sepsis in 3 infants. All children depended on mechanical ventilation during their postoperative period, 14 infants used vasoactive drugs, and 11 had an infectious process associated with ARF. Thirteen infants required dialytic treatment. Eleven infants developed oluguric ARF, and all had to undergo peritoneal dialysis; of the 4 patients with non-oliguric, 2 required dialysis, the main indication being hypervolemia. Of these 13 dialyzed infants, 4 died in the first 24 hours because of the severity of the underlying cardiac disease (mean urea level of 49±20 mg/dl). The mortality rate for the entire group was 60% , and it was higher among the patients with oliguria ARF (73% vs 25%, p<0.001). The cause of death was acute cardiac dysfunction in 6 infants (early type-1ARF) and sepsis in the 3 remaining infants (late type-2 ARF). CONCLUSION: The mortality rate of ARF associated with cardiac surgery in infants was hight, being higher among children with oliguria; peritoneal dialysis was indicated due to clinically uncontrolled hypervolemia and not to the uremic hypercatabolic state.

Cardiac findings in 31 patients with Noonan's syndrome

OBJECTIVE: To evaluate cardiac findings in 31 Noonan syndrome patients. METHODS: Thirty-one (18 males and 13 females)patients from 26 families affected with Noonan's syndrome were evaluated from the cardiac point of view with electrocardiography and echodopplercardiography. RESULTS: Twenty patients had some type of cardiac abnormality. The most frequent was pulmonary valve stenosis followed by hypertrophic myocardiopathy, commonly associated with valve defects. Upper deviation of the QRS axis was observed in 80% of these patients. CONCLUSION: In view of the high frequency and diversity of cardiac abnormalities present in Noonan syndrome, cardiac evaluation with electrocardiography and echocardiography should be performed in all patients diagnostically suspected of having this disease.

Analysis of the risk factors for allograft vasculopathy in asymptomatic patients after cardiac transplantation

OBJECTIVE: To study the influence of immune and nonimmune risk factors on the development of allograft vasculopathy after cardiac transplantation. METHODS: We studied 39 patients with a mean age of 46±12 years. The following variables were analyzed: weight (kg), body mass index (kg/m²), donor's age and sex, rejection episodes in the first and second years after transplantation, systolic and diastolic blood pressures (mmHg), total cholesterol and fractions (mg/dL), triglycerides (mg/dL), diabetes, and cytomegalovirus infection. The presence of allograft vasculopathy was established through coronary angiography. RESULTS: Allograft vasculopathy was observed in 15 (38%) patients. No statistically significant difference was observed between the two groups in regard to hypertension, cytomegalovirus infection, diabetes, donor's sex and age, rejection episodes in the first and second years after transplantation, and cholesterol levels. We observed a tendency toward higher levels of triglycerides in the group with disease. Univariate and multivariate analyses showed statistically significant differences between the two groups when we analyzed the body mass index (24.53±4.3 versus 28.11±4.6; p=0.019). CONCLUSION: Body mass index was an important marker of allograft vasculopathy in the population studied.