The importance of heart rate recovery in patients with heart failure or left ventricular systolic dysfunction

BACKGROUND: The ability to better predict outcome with exercise testing in patients with heart failure (HF) and left ventricular systolic dysfunction (LVSD) may prove extremely valuable in determining which patients are at increased risk. This study evaluated the ability of heart rate recovery (HRR) to predict outcome in patients with HF and validate previous findings in LVSD. METHODS AND RESULTS: HRR was measured at 1-, 2-, 3-, and 5-minute time points after treadmill testing in 2,193 males being evaluated for chest pain at the Palo Alto and Long Beach VA Hospitals. Left ventricular ejection fraction (LVEF) was calculated using biplane ventriculography and patients were considered to have LVSD if they had an LVEF <50%. Angiographic and clinical data was available for all patients. Of the 2,193 patients, 314 patients had LVSD and 109 had a history of HF. Both HF patients and patients with LVSD with a normal HRR at 2 minutes had improved survival compared with patients that had an abnormal HRR at 2 minutes when adjusted for age and beta-blocker use (HF adjusted odds ratio 0.25, 95% CI 0.10-0.66, P < .006; LVSD alone adjusted odds ratio 0.25, 95% CI 0.13-0.47, P < .0001). Stepwise proportional hazard regression analysis revealed that only 2-minute HRR, age, LVEF, and chronic obstructive pulmonary disorder were significant predictors of mortality in patients with LVSD and only HRR at 2 minutes and LV hypertrophy were significant predictors of mortality in patients with HF. CONCLUSION: HRR is a significant predictor of mortality in patients with HF and patients with LVSD and may be useful in better determining prognosis.     

A mechanistic approach for the calculation of intervertebral mobility in mammals based on vertebrae osteometry

In this paper, we develop and validate an osteometry-based mechanistic approach to calculation of available range of motion (aROM) in presacral intervertebral joints in sagittal bending (SB), lateral bending (LB), and axial rotation (AR). Our basic assumption was the existence of a mechanistic interrelation between the geometry of zygapophysial articular facets and aROM. Trigonometric formulae are developed for aROM calculation, of which the general principle is that the angle of rotation is given by the ratio of the arc length of motion to the radius of this arc. We tested a number of alternative formulae against available in vitro data to identify the most suitable geometric ratios and coefficients for accurate calculation. aROM values calculated with the developed formulae show significant correlation with in vitro data in SB, LB, and AR (Pearson r = 0.900) in the reference mammals (man, sheep, pig, cow). It was found that separate formulae for different zygapophysial facet types (radial (Rf), tangential (Tf), radial with a lock (RfL)) give significantly greater accuracy in aROM calculation than the formulae for the presacral spine as a whole and greater accuracy than the separate formulae for different spine regions (cervical, thoracic, lumbar). The advantage of the facet-specific formulae over the region-specific ones shows that the facet type is a more reliable indicator of the spine mobility than the presence or absence of ribs. The greatest gain in calculation accuracy with the facet-specific formulae is characteristic in AR aROM. The most important theoretical outcome is that the evolutionary differentiation of the zygapophysial facets in mammals, that is the emergence of Tf joints in the rib cage area of the spine, was more likely associated with the development of AR rather than with SB mobility and, hence, with cornering rather than with forward galloping. The AR aROM can be calculated with the formulae common for man, sheep, pig, and cow. However, the SB aROM of the human spine is best calculated with different coefficient values in the formulae than those for studied artiodactyls. The most suitable coefficient values indicate that the zygapophysial articular facets tend to slide past each other to a greater extent in the human thoracolumbar spine rather than in artiodactyls. Due to this, artiodactyls retain relatively greater facet overlap in extremely flexed and extremely extended spine positions, which may be more crucial for their quadrupedal gallop than for human bipedal locomotion. The SB, LB, and AR aROMs are quite separate in respect of the formulae structure in the cervical region (radial facet type). However, throughout the thoracolumbar spine (tangential and radial with lock facets), the formulae for LB and AR are basically similar differing in coefficient values only. This means that, in the thoracolumbar spine, the greater the LB aROM, the greater the AR aROM, and vice versa. The approach developed promises a wide osteological screening of extant and extinct mammals to study the sex, age, geographical variations, and disorders.     

Survival and prognostic factors in patients with oral squamous cell carcinoma

Background This study aimed to evaluate sociodemographic and clinical factors influencing overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). Material and Methods Medical charts of 547 patients with OSCC from a public hospital in northeastern Brazil seen between 1999 and 2013 were evaluated. Survival analysis was performed using the Kaplan-Meier method. The influence of age, sex, ethnicity, clinical stage, anatomical location, type of treatment, and comorbidities on the patients’ prognosis was evaluated. Cox proportional hazards regression model was used to identify independent prognostic factors. Results The 5-year OS was 39%. Multivariate analysis showed that age < 40 years (HR = 2.20; 95%CI: 1.02-4.72) and a single treatment modality (HR = 1.91; 95%CI: 1.37-2.67) were associated with a poor prognosis, while early clinical stage resulted in better outcomes (HR = 0.38; 95%CI: 0.25-0.58). Conclusions OSCC patients in advanced clinical stages, diagnosed at a younger age, and submitted to a single therapeutic modality have a poorer prognosis. Key words:Head and neck cancer, oral cancer, oral squamous cell carcinoma, survival, prognosis.     

Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor

S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325-355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus. Because the trafficking of p53 depends on its oligomerization state, we suggest that S100B and S100A4 could regulate the subcellular localization of p53. But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control.     

Pathology of the endometrium in women with chronic hepatitis C and HIV infection as a cause of unsuccessful in vitro fertilization attempts

Abstract

Aim: The purpose of the study is to detect endometrial pathology in individuals with blood-borne infections (hepatitis C virus [HCV] and HIV) and to assess the impact of quality of the endometrium on the efficiency of assisted reproductive technologies (ART).

Materials and methods of research: The study involved 56 women of reproductive age, 33 women with HCV, 22 with HIV infection (stages 3 and 4A) and 1 patient with co-infection of HCV and HIV, which was excluded from the further study. Ultrasound investigation of the small pelvic organs, hysteroscopy with biopsy of the mucosa of the uterine cavity, histological examination of the endometrium, determination of HCV RNA and HIV RNA in serum and endometrial tissue by PCR method were conducted.

Results: Ultrasound and histological studies of the endometrium revealed a high incidence of development of hyperplastic and inflammatory processes of the endometrium in women with HCV (86% and 100%) and HIV (51% and 99%). When molecular biological examination of endometrial tissue of these patients was performed with the use of a set of reagents “AmpliSens HCV/HBV/HIV-FL” produced by Federal Budgetary Institution of Science (FBUN) Central Research Institute of Epidemiology of Rospotrebnadzor of Russia, HCV was detected in 16.7% and HIV in 14.3% of cases. In 5% of patients with HCV infection and 7% with HIV, pathogens were detected in the endometrium under the non-detectable viral load in the blood plasma. Lower effectiveness of IVF in women with HIV and HCV is defined compared to the women without blood-borne infections.

Conclusion: Detected HIV and HCV replications in the endometrium is the likely cause of hyperplastic and inflammatory processes of the endometrium leading to reduced efficiency of the ART programs in patients with chronic hepatitis C and HIV.     

High-sensitivity heat-capacity measurements on Sr2RuO4 under uniaxial pressure

A key question regarding the unconventional superconductivity of Sr2RuO4 remains whether the order parameter is single- or two-component. Under a hypothesis of two-component superconductivity, uniaxial pressure is expected to lift their degeneracy, resulting in a split transition. The most direct and fundamental probe of a split transition is heat capacity. Here, we report measurement of heat capacity of samples subject to large and highly homogeneous uniaxial pressure. We place an upper limit on the heat-capacity signature of any second transition of a few percent of that of the primary superconducting transition. The normalized jump in heat capacity, ΔC/C, grows smoothly as a function of uniaxial pressure, favoring order parameters which are allowed to maximize in the same part of the Brillouin zone as the well-studied van Hove singularity. Thanks to the high precision of our measurements, these findings place stringent constraints on theories of the superconductivity of Sr2RuO4.

Obtaining a full understanding of the superconductivity of Sr2RuO4 is a core challenge for condensed-matter physics. Since soon after its discovery over a quarter of a century ago (1), the superconducting order parameter of Sr2RuO4 has been known to be unconventional (2, 3) and to condense from a well-understood and fairly simple quasi-two-dimensional Fermi liquid metallic state (4–7). Given the profound advances in theoretical techniques in recent decades a full understanding of its superconductivity is an important, and attainable, challenge for the field. The form of the wave-vector-dependent susceptibility of Sr2RuO4 leads to the prediction of a rich superconducting phase diagram in weak-coupling calculations which aim to perform a bias-free estimate of the condensation energies of different order parameters. A notable feature of the results is how close a number of different odd- and even-parity solutions are seen to be in energy (8–10). On the one hand, this emphasizes the potential of Sr2RuO4 as a test-bed material on which to refine the predictive capabilities of modern theories of unconventional superconductivity (11). On the other hand, realizing this potential will likely first require a conclusive experimental determination of which of the many possible order parameters wins out in the real material. This is a particularly exciting stage of the quest to complete this empirical determination, for reasons that we will now outline.For over 20 y the large majority of attention was paid to odd-parity order parameter candidates for Sr2RuO4 (12), because of NMR measurements of spin susceptibility in the superconducting state that seemed to be inconsistent with any even-parity order parameter (13). However, thanks to the discovery of a systematic error in the original NMR measurements (14, 15), that situation has now been more or less completely reversed. Taking into account the most recent measurements of the magnetic field dependence of the spin susceptibility (16), it seems clear that the order parameter must be even-parity or at least dominated by an even-parity component. The spin susceptibility results would be most easily describable in terms of a single-component, likely d-wave, order parameter, but recent thermodynamic evidence from ultrasound experiments is most straightforwardly interpreted in terms of an order parameter with two degenerate components (17, 18). Such order parameters do not of necessity break time-reversal symmetry, but they can, if the two degenerates have the appropriate phase relationship. In the context it is significant that long-standing muon-spin relaxation (μSR) (19, 20) and magneto-optic Kerr rotation measurements (21) have indicated time-reversal symmetry breaking in the superconducting state.To investigate any order parameter with two degenerate components, whether or not it breaks time-reversal symmetry, uniaxial pressure is a powerful probe because it can split the degeneracy, creating a split superconducting phase transition (22). In a significant experimental advance, the muon-spin relaxation experiments have recently been extended to high uniaxial pressures (23). In line with naive expectation, the temperature at which time-reversal symmetry is broken (TTRSB) splits from the main superconducting transition (Tc), with TTRSB remaining nearly pressure-independent while Tc increases under the application of the pressure. However, there has been a long-standing question about whether the Kerr and muon signals correspond to bulk thermodynamic transitions, so it is highly desirable to compare the new muon-spin relaxation data with those from a bulk thermodynamic probe. In this context, it is natural to look at heat capacity, because it has an intrinsic sensitivity to transitions within the superconducting state, as is well known from work on UPt3 (24, 25).     

Repolarization in perfused myocardium predicts reperfusion ventricular tachyarrhythmias

Background

Aim of the study was to find out which myocardial repolarization parameters predict reperfusion ventricular tachycardia and fibrillation (VT/VF) and determine how these parameters express in ECG.