Quantum tunneling time delay investigation of [Formula: see text] ion in human telomeric G-quadruplex systems.

Guanine-rich quadruplex DNA (G-quadruplex) is of interest both in cell biology and nanotechnology. Its biological functions necessitate a G-quadruplex to be stabilized against escape of the monovalent metal cations. The potassium ion ([Formula: see text]) is particularly important as it experiences a potential energy barrier while it enters and exits the G-quadruplex systems which are normally found in human telomere. In the present work, we analyzed the time it takes for the [Formula: see text] cations to get in and out of the G-quadruplex. Our time estimate is based on entropic tunneling time-a time formula which gave biologically relevant results for DNA point mutation by proton tunneling. The potential energy barrier experienced by [Formula: see text] ions is determined from a quantum mechanical simulation study, Schrodinger equation is solved using MATLAB, and the computed eigenfunctions and eigenenergies are used in the entropic tunneling time formula to compute the time delay and charge accumulation rate during the tunneling of [Formula: see text] in G-quadruplex. The computations have shown that ion tunneling takes picosecond times. In addition, average [Formula: see text] accumulation rate is found to be in the picoampere range. Our results show that time delay during the [Formula: see text] ion tunneling is in the ballpark of the conformational transition times in biological systems, and it could be an important parameter for understanding its biological role in human DNA as well as for the possible applications in biotechnology. To our knowledge, for the first time in the literature, time delay during the ion tunneling from and into G-quadruplexes is computed.

Time delay during intra-base proton tunneling in the guanine base of the single stranded DNA.

Spontaneous point mutations are one of the main actors in evolution, and the tautomerization of organic bases in the DNA is hypothesized to be the underlying mechanism of this crucial process. Tautomerization can be induced by proton tunneling, and if it occurs in single-stranded DNA (ssDNA) during the replication process, tautomerized bases might give rise to a mismatch, which will eventually defect the genetic code. In the present work, we report on the tautomerization time in the guanine base of the ssDNA. The model we use includes an intra-base tunneling mechanism such that time tunneling (delay time) is estimated to be around a few pico-seconds. The time delay is found to be biologically relevant which indicates that it is long enough to induce point mutations. Our results close a gap in the literature and sheds light on the importance of point mutations originating from quantum effects in the ssDNA.

Characteristics and Gender-Related Differences of Patients Admitted to a Large Intensive Cardiac Care Unit: A Single-Center Experience with over 55 000 Patients.

OBJECTIVE: Parallel to the aging of the world population, the complexity of patients with cardiac problems has increased, especially in intensive cardiology care units, and the importance of multidisciplinary care has become more evident. The aim of this study was to analyze the clinical characteristics and gender-related differences of patients hospitalized in a large intensive cardiology care unit. METHODS: This single-center, retrospective, cross-sectional study includes all hospitalizations in a large intensive cardiology care unit between January 2016 and March 2021. All data were obtained using data collection software and transferred to MEDULLA, Turkey's general database system. RESULTS: Of the 55 737 consecutive patients included in the analysis, 16342 (29%) were women. The mean age of males was 59.71 ± 12 years, and the mean age of females was 63.3 ± 14 years (P <.001). Over a period of 5 years, the most common reason for hospitalization in the intensive cardiac care unit was acute coronary syndrome. The number of acute coronary syndrome patients who underwent coronary angiography was found to be 17 478 (31%), of which 12 878 were males and 26.3% were female. The number of patients who underwent at least 1 stent implantation was 13 952 (80% of coronary angiography procedures), and 2960 (21%) were women. The second cause of hospitalization in the intensive cardiology care unit was arrhythmias (5654 patients [10%]) followed by advanced heart failure (932 patients [1.7%]). During follow-up in the intensive cardiology care unit, the percentage of development of multiorgan failure was found to be approximately 18%. The mortality rate was 7% in women, which was higher than in men (4%). While the most common cause of death was acute coronary syndrome, the highest rate of death was found in patients with advanced heart failure. Among the patients who died, the mean age of females was higher than that of males, and the length of hospital stay was longer. CONCLUSION: Although numerically the highest death rate was observed in male acute coronary syndrome patients, the highest mortality rate was found in patients with advanced heart failure. Due to the elderly population and the increase in the number of patients requiring multidisciplinary treatment, the development of multiorgan failure in intensive cardiology care units seems to be one of the most important causes of death. Although the number of females hospitalized in the intensive cardiology care unit is lower than that of males, the mean age and mortality rate were found to be higher than males.

Time delay during the proton tunneling in the base pairs of the DNA double helix.

DNA undergoes spontaneous point mutations, which are believed to be central to the evolution of the organisms and which are thought to occur by tautomerization of the canonical Guanine-Cytosine (G-C) base pair into non-canonical G∗-C∗ base pair via the double proton tunneling. In the present work, we close a gap in the literature by computing the time delay during the proton tunneling. Our results, based on the well-known dwell time and our model of the entropic time, range from femtoseconds to picoseconds, and completely agree with the time scales of the structural changes in molecules (mutation processes not the complete replication processes). The tunneling delay times are thus nonnegligible and imply that the DNA mutations can be resolved using the attosecond laser technology, if not the femtosecond technology. Our results can be relevant also for other tunneling-enabled biological processes.

The role of tissue Doppler study in the assessment of left ventricular dysfunction in obesity.

PURPOSE: The purpose of this study was to investigate the potential utility of tissue Doppler echocardiography in the assessment of left ventricular systolic and diastolic function in the obese population. METHOD: 96 obese (48 male, 48 female) patients and 50 normal weight (25 male, 25 female) control subjects were enrolled. Obese patients were subgrouped into mild (25-29.9 kg/m2), moderate (30-34.9 kg/m2) and significant (> or =35 kg/m2) according to their body mass index (BMI). Left ventricular systolic and diastolic functions were evaluated by tissue Doppler imaging with conventional transthoracic echocardiography. Peak systolic velocity (Sm) of the lateral mitral annulus, the duration from electrocardiographic Q wave to Sm and early and late diastolic velocities (Em,Am) were recorded with tissue Doppler imaging. RESULTS: The ejection fraction and fractional shortening values were found to be increased in the mildly and moderately obese subjects. Left ventricular diameters were increased in all of the patients in the obesity group; however, relative wall thicknesses were similar to control subjects.The peak systolic velocities of the mitral lateral annular area (Sm) were lower in moderately and significantly obese subjects compared to the control subjects. None of the study patients had systolic dysfunction by conventional echocardiographic assessment while prevalence of diastolic dysfunction was significantly higher in the obese group of which the prevalence proportionally increased with BMI. Diastolic dysfunction was also more prevalent in the subjects with abdominal obesity which was determined by waist circumference (WC). CONCLUSION: The ejection phase indices were increased in mildly and moderately obese subjects. However, in significantly obese subjects they were similar to control subjects by conventional echocardiographic methods. Sm values of the moderately and significantly obese patients were significantly lower when measured by tissue Doppler imaging. Diastolic function was also shown to be impaired in the moderately and significantly obese subjects when measured by tissue Doppler imaging.

Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe pulmonary hypertension: its correlates, clinical impact, and management strategies.

Aims: Although left main coronary artery (LMCA) compression (Co) by pulmonary artery (PA) aneurysm (A) has been reported in some pulmonary hypertension (PH) series, clinical importance and management of this complication remain to be determined. In this single-centre prospective study, we evaluated correlates, clinical impact, and management strategies of LMCA-Co in patients with PH. Methods and results: Our study group comprised 269 (female 166, age 52.9 ± 17.3 years) out of 498 patients with confirmed PH who underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co during diagnostic evaluation with multidetector computed tomography. The LMCA-Co ≥ 50% was documented in 22 patients (8.2%) who underwent CA, and stenosis were between 70% and 90% in 14 of these. Univariate comparisons revealed that a younger age, a D-shaped septum, a higher PA systolic, diastolic, and mean pressures and pulmonary vascular resistance, a larger PA diameter, a smaller aortic diameter and pulmonary arterial hypertension associated with patent-ductus arteriosus, atrial or ventricular septal defects were significantly associated with LMCA-Co. Bare-metal stents were implanted in 12 patients and 1 patient underwent PAA and atrial septal defect surgery and another one declined LMCA stenting procedure. Conclusion: Our study demonstrates that LMCA-Co is one of the most important and potentially lethal complications of severe PH, and alertness for this risk seems to be necessary in specific circumstances related with PAA. However, long-term benefit from stenting in this setting remains as a controversy.

A five-year, single-centre experience on ultrasound-assisted, catheter-directed thrombolysis in patients with pulmonary embolism at high risk and intermediate to high risk.

AIMS: In this single-centre study, we aimed to evaluate the short- and long-term efficacy and safety outcomes of ultrasound-assisted thrombolysis (USAT) performed in patients with acute pulmonary embolism (PE) at intermediate to high risk and high risk (IHR, HR). METHODS AND RESULTS: The study group comprised 141 retrospectively evaluated patients with PE who underwent USAT. Tissue-type plasminogen activator (t-PA) dosage was 36.1±15.3 mg, and infusion duration was 24.5±8.1 hours. USAT was associated with improvements in echocardiographic measures of right ventricle systolic function, pulmonary arterial (PA) obstruction score, right to left ventricle diameter ratio (RV/LV), right to left atrial diameter ratio and PA pressures, irrespective of the risk (p<0.0001 for all). In-hospital mortality, major and minor bleeding rates were 5.7%, 7.8% and 11.3%, respectively. Follow-up data (median 752 days) were available in all patients. Absolute and % changes in RV/LV and % changes in PA mean pressure were significantly higher in patients younger than 65 years compared with older patients, whereas bleeding, 30-day and long-term mortality were not related to age, t-PA dosage or infusion duration. HR versus IHR increased 30-day mortality. CONCLUSIONS: USAT was associated with improvements in thrombolysis and stabilisation of haemodynamics along with relatively low rates of complications in patients with PE, regardless of the risk status. However, HR still confers a higher short-term mortality. Increasing the t-PA dosage and prolongation of infusion may not offer benefit in USAT treatments.

The frequency of angiotensin-converting enzyme genotype and left ventricular functions in the obese population.

The authors investigated the relationship between angiotensin-converting enzyme (ACE) genotype and left ventricular functions in an obese population and compared their findings with controls. Ninety-six obese patients and 50 controls were enrolled. Obesity was subgrouped into mild (body mass index [BMI] 25-29.9 kg/m(2)), moderate (BMI 30-34.9 kg/m(2)), and significant (BMI > or =35 kg/m(2)). Body fat distribution was categorized according to waist-to-hip ratio and waist circumference. Left ventricular systolic and diastolic functions were evaluated by echocardiography. ACE gene polymorphism was investigated by standard polymerase chain reaction, and frequency distributions were calculated for the subgroups. Systolic functional indices were found to be increased in mild and moderate obesity subgroups. The obese population had increased left ventricular diameters. None of the patients had systolic dysfunction, while diastolic dysfunction was significantly more common in the obese group; the frequency of diastolic dysfunction was proportionally increased with body mass index. Diastolic dysfunction was more common in persons with abdominal obesity. ACE DD genotype frequency was increased in moderately and significantly obese subgroups and also in all obese patients with diastolic dysfunction.

Increased urinary albumin excretion rates can be a marker of coexisting coronary artery disease in patients with peripheral arterial disease.

Coexisting coronary artery disease (CAD) is an important cause of morbidity and mortality in patients with peripheral arterial disease (PAD). Clinical evaluation and noninvasive tests have some important limitations for the detection of CAD in patients with PAD. The purpose of this study was to investigate whether urinary albumin excretion (UAE) was a sign of atherosclerotic involvement of coronary arteries in patients with PAD. Our study consisted of 65 consecutive patients (56 men, 9 women, mean age; 59.7+/-7.9 years) with PAD who underwent coronary angiography. Urinary albumin excretion was measured in 24-hour urine samples by immunoprecipitation technique. PAD was defined as the presence of > or =50% stenotic lesions in at least 1 of the iliac, femoral, popliteal, tibialis anterior, tibialis posterior, or peroneal arteries. CAD was defined as > or =25% diameter stenosis in at least 1 coronary artery. Patients without any coronary lesions were accepted as having normal coronaries. Age, sex, distributions of coronary risk factors, and UAE rates were compared between patients with and without CAD. Mean UAE was 17.9+/-15.6 mg/day in the total population. Thirty-seven percent of patients had CAD, and 63% had no coronary lesion. UAE rates were 22.33+/-18.74 and 15.32+/-13.01 mg/day in patients with CAD and those with normal coronary arteries, respectively (p = 0.021). Microalbuminuria was detected in 25% in patients with CAD and 12% in those without coronary artery lesions (p = 0.184). The difference was not statistically significant. The distributions of other risk factors and sex were not different between the 2 groups. These data suggest that in patients with PAD, urinary albumin excretion rates may be used to determine those with a high probability of CAD. Further studies are required to decide whether this noninvasive testing is appropriate in detecting high-risk patients.

[Risk factor distribution according to the obesity degree in patients with coronary artery disease]. / Koroner arter hastaligi bulunan olgularda obezite derecelerinin diger risk faktörleriyle iliskisi.

OBJECTIVE: World Health Organization and other international guide committees defined different obesity categories according to the body mass index (BMI) and waist circumferences. The purpose of our study was (i) to compare the dispersion of other coronary risk factors in patients with coronary artery disease (CAD) with different obesity categories that were defined according to the body mass index (BMI) and the waist circumference, (ii) to determine to which extent these cut-off values effect the dispersion of other coronary risk factors. METHODS: The study group included 617 consecutive subjects (516 male, mean age - 57.2+/-10.8 years) who underwent their first angiography between January 2000 and May 2000 and in whom significant coronary lesions were detected. The distribution of risk factors such as, age, smoking, hypertension, diabetes mellitus, high LDL-C, low HDL-C, total cholesterol/HDL-C ratio, triglycerides, family history of premature CAD was compared between overweight and obese cases defined according to BMI values. The same risk factors were compared among the cases grouped as action level 1 and action level 2 defined by the waist circumference. RESULTS: In male patients; smoking was found to be higher in overweight individuals than in obese cases (71% vs. 56%) (p<0.05). In female patients; the only difference was the ratio of total-C/HDL-C as being greater in obese group than overweight group (p<0.05). In male and female patients there was no significant difference between obese and overweight cases regarding the number of total risk factors. According to the waist circumference, in male patients, smoking was more prevalent in action level 1 group than in action level 2 group. In female patients risk factors prevalence was similar in both groups. CONCLUSION: In patients with CAD, the amount of total risk factors doesn't differ between overweight and obese cases and between patients with action level 1 and action level 2 of the waist circumference. These findings indicate the necessity of using the same secondary prevention approaches in patients with CAD and different levels of obesity.

[Distribution of therapeutic procedures and choice of drug therapies in patients with angiographically confirmed coronary artery disease]. / Koroner arter hastaligi anjiyografik olarak kanitlanmis olgularda tedavi prosedürlerinin dagilimi ve hastaneden cikista ilaç seçimi.

OBJECTIVE: The aims of our study were to assess the distribution of interventional and other therapeutic procedures performed on subjects who had proven CAD by angiography in our clinic; to determine the groups of therapeutic agents prescribed at the time of discharge; and to compare these with the results of EUROASPIRE II, which examined the prophylactic drug therapy upon discharge of CAD patients in 15 European countries. METHODS: Our patients comprises of 617 subjects (516 male, 101 female; mean age 57.2 +/- 10.8 years) who underwent coronary angiography for the first time in our clinic and who were found to have a 50% lesion in at least one of the coronary arteries. In all patients distribution of risk factors on admission, distribution of therapeutic procedures and the use of drug therapies at the hospital discharge were recorded. RESULTS: We found that, 68% of our cases were considered to be eligible for a percutaneous or surgical intervention, while 27% were assessed not as requiring such an intervention and consequently were discharged being prescribed appropriate medications. For the remaining 5% of the subjects, tests for detection of viable myocardium were advised, before selecting the proper type of management. At discharge, prescription rates for antiplatelets, beta-blockers, nitrates, statins, angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers and anticoagulants were detected to be %99, 86%, 86%, 63%, 40%, 16%, and 2% respectively. CONCLUSION: Compared with the results of EUROASPIRE II study, these data show that, antiplatelet, beta-blocker, ACE-I and lipid-lowering treatments our subjects received upon discharge were higher, whereas anticoagulant treatment was lower than the averages of the fifteen European countries consisting the EUROASPIRE II study.

Dirac neutrino masses from generalized supersymmetry breaking.

We demonstrate that Dirac neutrino masses in the experimentally preferred range are generated within supersymmetric gauge extensions of the standard model with a generalized supersymmetry breaking sector. If the superpotential neutrino Yukawa terms are forbidden by the gauge symmetry [such as a U(1)'], sub-eV scale effective Dirac mass terms can arise at tree level from hard supersymmetry breaking Yukawa couplings, or at one loop due to nonanalytic soft supersymmetry breaking trilinear scalar couplings. The radiative neutrino magnetic and electric dipole moments vanish at one-loop order.

Distribution of risk factors and prophylactic drug usage in Turkish patients with angiographically established coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of adult deaths in our country. In clinical practice, an adequate level of secondary prevention towards CAD primarily requires full recognition of the distribution of risk factors. The aim of our study was to determine the prevalence of coronary risk factors and the use of prophylactic drugs among patients who have an angiographically proven CAD in our centre, and to compare it with those of the EUROASPIRE I and II studies. DESIGN: Cross-sectional, observational study. METHODS: Our patients comprise 617 subjects (516 male, mean age 57.2 +/- 10.8 years) who underwent an angiography between January 2000 and May 2000 for the first time and in whom significant coronary lesions were detected. Age, gender, family history of premature CAD (FH), diabetes mellitus (DM), hypertension (HT), lipid profile, smoking, body mass index, waist circumference, hip circumference and physical activity data were recorded prior to angiography. The medical treatments received by these cases at discharge from hospital were investigated. Data thus obtained were compared with the results of the EUROASPIRE I and II trials, which studied the frequency of existing risk factors and prophylactic drug use among CAD patients in European countries. RESULTS: Hyperlipidaemia, FH, DM, HT, smoking, obesity, central obesity were found in 52, 26, 20, 41, 65, 18 and 29% of patients, respectively. The use of antiplatelets, beta-blockers, ACE inhibitors, statins and calcium antagonists were 99, 86, 40, 63 and 16%, respectively. CONCLUSION: Upon comparison of the risk factors, prevalence of obesity and DM was found to be similar to the average of nine European countries among our subjects. Smoking was found to be considerably higher, whereas HT, hyperlipidaemia and family history of premature CAD were lower than the European average within our subjects. In our cases the frequency of prophylactic drug usage at discharge was higher than the European means.