Search results for: atrial natriuretic peptide

Authors: Edite Kulmane, Mara Pilmane, Romans Lacis

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Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.

Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin

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Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

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Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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Authors: Neda Valizadeh, Soudabeh Shafiee Ardestani, Arvin Najafi

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Objectives: The aim of this study is to evaluate the association of mid-regional pro-atrial natriuretic peptide (MRproANP), procalcitonin (PCT), proendothelin-1 (proET-1) levels with sepsis severity in Emergency ward patients. Materials and Methods: We assessed the predictive value of MRproANP, PCT, copeptin, and proET-1 in early sepsis among patients referring to the emergency ward with a suspected sepsis. Results-132 patients were enrolled in this study. 45 (34%) patients had a final diagnosis of sepsis. A higher percentage of patients with definite sepsis had systemic inflammatory response syndrome (SIRS) criteria at initial visit in comparison with no-sepsis patients (P<0.05) and were admitted to the hospital (P<0.05). PCT levels were higher in sepsis patients [P<0.05]. There was no significant differences for MRproANP or proET-1 in sepsis patients (P=0.47). Conclusion: A combination of SIRS criteria and PCT levels is beneficial for the early sepsis diagnosis in emergency ward patients with a suspicious infection disease.

Keywords: emergency, prolactin, sepsis, biomarkers

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Authors: Deepshikha Verma, V. N. Rajasekharan Pillai

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The present study reports the synthesis of cyclic PNC-28 peptides with solid-phase peptide synthesis method. In the first step, we synthesize the linear PNC-28 Peptide and in the second step, we cyclize (N-to-C or head-to-tail cyclization) the linear PNC-28 peptide. The molecular formula of cyclic PNC-28 peptide is C64H88N12O16 and its m/z mass is ≈1233.64. Elemental analysis of cyclic PNC-28 is C, 59.99; H, 6.92; N, 13.12; O, 19.98. The characterization of LC-MS, CD, FT-IR, and 1HNMR has been done to confirm the successful synthesis and cyclization of linear PNC-28 peptides.

Keywords: CD, FTIR, 1HNMR, cyclic peptide

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Authors: Abraham J. Rizkalla, Tristan D. Yan

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Atrial myxoma is the most common primary cardiac tumor, and can result in cardiac failure secondary to obstruction, or systemic embolism due to fragmentation. Traditionally, excision of atrial an myxoma has been performed through median sternotomy, however the robotic approach offers several advantages including less pain, improved cosmesis, and faster recovery. Here, we highlight the less well recognized advantages and technical aspects to robotic myxoma resection. This video-presentation demonstrates the resection of a papillary subtype left atrial myxoma using the DaVinci© Xi surgical robot. The 10x magnification and 3D vision allows for the interface between the tumor and the interatrial septum to be accurately dissected, without the need to patch the interatrial septum. Several techniques to avoid tumor fragmentation and embolization are demonstrated throughout the procedure. The tumor was completely excised with clear margins. There was no atrial septal defect or mitral valve injury on post operative transesophageal echocardiography. The patient was discharged home on the fourth post-operative day. This video-presentation highlights the advantages of the robotic approach in atrial myxoma resection compared with sternotomy, as well as emphasizing several technical considerations to avoid potential complications.

Keywords: cardiac surgery, left atrial myxoma, cardiac tumour, robotic resection

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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Authors: Mohammad Obeidat, Ayman Mansour

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In this paper a unique issue rising from feedback control of Atrial Fibrillation monitoring system with embedded communication channels has been investigated. One of the important factors to measure the performance of the feedback control closed loop system is disturbance and noise attenuation factor. It is important that the feedback system can attenuate such disturbances on the atrial fibrillation heart rate signals. Communication channels depend on network traffic conditions and deliver different throughput, implying that the sampling intervals may change. Since signal estimation is updated on the arrival of new data, its dynamics actually change with the sampling interval. Consequently, interaction among sampling, signal estimation, and the controller will introduce new issues in remotely controlled Atrial Fibrillation system. This paper treats a remotely controlled atrial fibrillation system with one communication channel which connects between the heart rate and rhythm measurements to the remote controller. Typical and optimal signal estimation schemes is represented by a signal averaging filter with its time constant derived from the step size of the signal estimation algorithm.

Keywords: atrial fibrillation, communication channels, closed loop, estimation

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Authors: Shirin Jalili, Ramin Ghasemi Shayan

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Atrial fibrillation is the foremost common arrhythmia around the world, with expanding recurrence famous with age. Thromboembolic occasions and strokes are the number one cause of mortality and morbidity. For patients who don't react to restorative treatment for rate and beat control, the maze method offers an elective treatment mediation. pharmaco-medical treatment for atrial fibrillation is pointed at the control of rate or cadence, intrusive treatment for atrial fibrillation is pointed at cadence control. An obtrusive approach may comprise of percutaneous catheter treatment, surgery, or a crossover approach. Since the maze method is recognized as the foremost successful way to dispense with AF, combining the maze strategy amid major cardiac surgeries has been received in clinical hone. the maze strategy, moreover known as Cox¬maze iii or the ‘cut¬and¬sew’ method, involves making different incisions within the atria to make an arrangement of scars that dispose of each potential zone of re¬entry. The electrical drive is constrained through a maze of scars that coordinates the electrical drive from the sinus node to the av node. By settling the headstrong period between ranges of scar, re¬entry is disposed of. in this article, we evaluate the Maze surgery method that's the surgical method of choice for the treatment of restorative atrial fibrillation.

Keywords: atrial fibrillation, congenital heart disease, procedure, maze surgery, treatment

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Authors: Tiancheng Lan

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E10A is a kind of replication-defective adenovirus which carries the human endostatin gene to inhibit the growth of tumors. Kringle 5(K5) has almost the same function as angiostatin to also inhibit the growth of tumors since they are all the byproduct of the proteolytic cleavage of plasminogen. Tumor size increasing can be suppressed because both of the endostatin and K5 can restrain the angiogenesis process. Therefore, in order to improve the treatment effect on tumor, 2A peptide is used to construct a fusion gene carrying both E10A and K5. Using 2A peptide is an ideal strategy when a fusion gene is expressed because it can avoid many problems during the expression of more than one kind of protein. The overlap extension PCR is also used to connect 2A peptide with E10A and K5. The final construction of fusion gene E10A-2A-K5 can provide a possible new method of the anti-angiogenesis treatment with a better expression performance.

Keywords: E10A, Kringle 5, 2A peptide, overlap extension PCR

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Authors: Ibrahim Ahmed, Richard Amoateng, Akhil Jain, Mohamed Ahmed

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Alcoholic cardiomyopathy (ACM) is a type of acquired cardiomyopathy caused by chronic alcohol consumption. Frequently ACM is associated with arrhythmias such as atrial flutter. Our aim was to characterize the patient demographics and investigate the effect of atrial flutter (AF) on ACM. This was a retrospective cohort study using the Nationwide Inpatient Sample database to identify admissions in adults with principal and secondary diagnoses of alcoholic cardiomyopathy and atrial flutter from 2019. Multivariate linear and logistic regression models were adjusted for age, gender, race, household income, insurance status, Elixhauser comorbidity score, hospital location, bed size, and teaching status. The primary outcome was all-cause mortality, and secondary outcomes were the length of stay (LOS) and total charge in USD. There was a total of 21,855 admissions with alcoholic cardiomyopathy, of which 1,635 had atrial flutter (AF-ACM). Compared to Non-AF-ACM cohort, AF-ACM cohort had fewer females (4.89% vs 14.54%, p<0.001), were older (58.66 vs 56.13 years, p<0.001), fewer Native Americans (0.61% vs2.67%, p<0.01), had fewer smaller (19.27% vs 22.45%, p<0.01) & medium-sized hospitals (23.24% vs28.98%, p<0.01), but more large-sized hospitals (57.49% vs 48.57%, p<0.01), more Medicare (40.37% vs 34.08%, p<0.05) and fewer Medicaid insured (23.55% vs 33.70%, p=<0.001), fewer hypertension (10.7% vs 15.01%, p<0.05), and more obesity (24.77% vs 16.35%, p<0.001). Compared to Non-AF-ACM cohort, there was no difference in AF-ACM cohort mortality rate (6.13% vs 4.20%, p=0.0998), unadjusted mortality OR 1.49 (95% CI 0.92-2.40, p=0.102), adjusted mortality OR 1.36 (95% CI 0.83-2.24, p=0.221), but there was a difference in LOS 1.23 days (95% CI 0.34-2.13, p<0.01), total charge $28,860.30 (95% CI 11,883.96-45,836.60, p<0.01). In patients admitted with ACM, the presence of AF was not associated with a higher all-cause mortality rate or odds of all-cause mortality; however, it was associated with 1.23 days increase in LOS and a $28,860.30 increase in total hospitalization charge. Native Americans, older age and obesity were risk factors for the presence of AF in ACM.

Keywords: alcoholic cardiomyopathy, atrial flutter, cardiomyopathy, arrhythmia

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Authors: L. C. Prasanna, Antony Sylvan D’Souza, Kumar M. R. Bhat

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Although life as a conjoined twin would seem intolerable, there has recently been an increased interest in this subject because of the increasing number of cases where attempts have been made to separate them surgically. We have reviewed articles on cardiovascular anomalies in conjoined twins and presenting rarest anomaly in dicephalus parapagus fetus having two heads attached to one body from the neck or upper chest downwards, with a pair of limbs and a set of reproductive organs. Both the twins shared a common thoracic cavity with a single sternum. When the thoracic cavity was opened, a common anterior mediastinum was found. On opening the pericardium, two separate, closely apposed hearts were exposed. The two cardia are placed side by side. The left heart was slightly larger than the right and were joined at the atrial levels. Four atrial appendages were present, two for each twin. The atrial complex was a common chamber posterior to the ventricles. A single large tributary which could be taken as inferior vena cava drains into the common atrial chamber. In this case, the heart could not be assigned to either twin and therefore, it is referred to as the shared heart within a common pericardial sac. The right and left descending thoracic aorta have joined with each other just above the diaphragm to form a common descending thoracic aorta which has an opening in the diaphragm to be continued as common abdominal aorta which has a normal branching pattern. Upon an interior dissection, it is observed that the two atria have a wide communication which could be a wide patent foramen ovale and this common atrial cavity has a communication with a remnant of a possible common sinus venosus.

Keywords: atrium, congenital anomaly, conjoined twin, sinus venosus

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Authors: Klaudia Chmielewska, Krystyna Dzierzbicka, Iwona Inkielewicz-Stepniak

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Carnosine, an endogenous peptide consisting of β-alanine and L-histidine has a variety of functions to mention: antioxidant, antiglycation, and reducing the toxicity of metal ions. It has therefore been proposed to act as a therapeutic agent for many pathological states, although its therapeutic index is limited by quick enzymatic cleavage. To overcome this limitation, there’s an urge to create new derivatives which might become less potent to hydrolysis, while preserving the therapeutic effect. The poster summarizes the efficiency of two peptide synthesis methods, which were: (1) the mixed anhydride with isobutyl chloroformate and N-methylmorpholine (NMM) and (2) carbodiimide - mediated coupling method via appropriate reagent condensing, here – CDI. The methods were used to obtain dipeptides which were the derivatives of carnosine. Obtained dipeptides were made in the form of methyl esters and their structures will be confirmed 1H NMR, 13C NMR, MS and elemental analysis techniques. Later on, they will be analyzed for their antioxidant properties, in comparison to carnosine.

Keywords: carnosine, method, peptide, synthesis

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Authors: Hanjun Zhao, Ke Zhang, Bojian Zheng

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Background: So far, there is no universal antiviral agent which can inhibit multiple viral infections. More and more drug-resistant viral strains emerge after the antiviral drug application for treatment. Defensins are the front line of host innate immunity and have broad spectrum antibacterial and antiviral effects. However, there is limited data to show if these defensins have good antiviral activity in vivo and what the antiviral mechanism is. Subjects: To investigate a peptide with widespread antivirus activity in vitro and in vivo and illustrate the antiviral mechanism. Methods: Antiviral peptide library designed from mouse beta defensins was synthesized by the company. Recombinant beta defensin was obtained from E. coli. Antiviral activity in vitro was assayed by plaque assay, qPCR. Antiviral activity in vivo was detected by animal challenge with 2009 pandemic H1N1 influenza A virus. The antiviral mechanism was assayed by western blot, ELISA, and qPCR. Conclusions: We identify a new peptide which has widespread effects against multiple viruses (H1N1, H5N1, H7N9, MERS-CoV) in vitro and has efficient antivirus activity in vivo. This peptide inhibits viral entry into target cells and subsequently blocks viral replication. The in vivo study of the antiviral peptide against other viral infections and the investigation of its more detail antiviral mechanism are ongoing.

Keywords: antiviral peptide, defensin, Influenza A virus, mechanism

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Authors: Taha Kadir Yesin, Hanyu Liu, Zhangfan Ding, Amit Singh, Qi Tian, Yuheng Zhang, Biswajyoti Borah, Junyu Chen, Anjali P. Kusumbe

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The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent endogenous anabolic NCAM1-14.3.3. ζδ-derived- Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

Keywords: endothelial cell, NCAM1, Clec14a, 14.3.3.ζδ

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Authors: Y. A. Prada, Fanny Guzman, Rafael Cabanzo, John J. Castillo, Enrique Mejia-Ospino

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In this work, we show the important results about of synthesis of photoluminiscents gold nanoclusters using a small peptide as template for biosensing applications. Interestingly, we design one peptide (NBC2854) homologue to conservative domain from 215 250 residue of a galactolectin protein which can recognize the proteophosphoglycans (PPG) from Leishmania. Peptide was synthetized by multiple solid phase synthesis using FMoc group methodology in acid medium. Finally, the peptide was purified by High-Performance Liquid Chromatography using a Vydac C-18 preparative column and the detection was at 215 nm using a Photo Diode Array detector. Molecular mass of this peptide was confirmed by MALDI-TOF and to verify the α-helix structure we use Circular Dichroism. By means of the methodology used we obtained a novel fluorescents gold nanoclusters (AuNC) using NBC2854 as a template. In this work, we described an easy and fast microsonic method for the synthesis of AuNC with ≈ 3.0 nm of hydrodynamic size and photoemission at 630 nm. The presence of cysteine residue in the C-terminal of the peptide allows the formation of Au-S bond which confers stability to Peptide-based gold nanoclusters. Interactions between the peptide and gold nanoclusters were confirmed by X-ray Photoemission and Raman Spectroscopy. Notably, from the ultrafine spectra shown in the MALDI-TOF analysis which containing only 3-7 KDa species was assigned to Au₈-₁₈[NBC2854]₂ clusters. Finally, we evaluated the Peptide-gold nanocluster as an optical biosensor based on fluorescence spectroscopy and the fluorescence signal of PPG (0.1 µg-mL⁻¹ to 1000 µg-mL⁻¹) was amplified at the same wavelength emission (≈ 630 nm). This can suggest that there is a strong interaction between PPG and Pep@AuNC, therefore, the increase of the fluorescence intensity can be related to the association mechanism that take place when the target molecule is sensing by the Pep@AuNC conjugate. Further spectroscopic studies are necessary to evaluate the fluorescence mechanism involve in the sensing of the PPG by the Pep@AuNC. To our best knowledge the fabrication of an optical biosensor based on Pep@AuNC for sensing biomolecules such as Proteophosphoglycans which are secreted in abundance by parasites Leishmania.

Keywords: biosensing, fluorescence, Leishmania, peptide-gold nanoclusters, proteophosphoglycans

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Authors: D. J. Kalita

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Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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Authors: Sharon Li, Zhonghang Xia

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Post-database search is an essential phase in peptide identification using tandem mass spectrometry (MS/MS) to refine peptide-spectrum matches (PSMs) produced by database search engines. These engines frequently face difficulty differentiating between correct and incorrect peptide assignments. Despite advances in statistical and machine learning methods aimed at improving the accuracy of peptide identification, challenges remain in selecting critical features for these models. In this study, two machine learning models—a random forest tree and a support vector machine—were applied to three datasets to enhance PSMs. SHAP values were utilized to determine the significance of each feature within the models. The experimental results indicate that the random forest model consistently outperformed the SVM across all datasets. Further analysis of SHAP values revealed that the importance of features varies depending on the dataset, indicating that a feature's role in model predictions can differ significantly. This variability in feature selection can lead to substantial differences in model performance, with false discovery rate (FDR) differences exceeding 50% between different feature combinations. Through SHAP value analysis, the most effective feature combinations were identified, significantly enhancing model performance.

Keywords: peptide identification, SHAP value, feature selection, random forest tree, support vector machine

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Authors: Sirilak Kongkaew, Pathumwadee Yodmanee, Nopporn Kaiyawet, Arthitaya Meeprasert, Thanyada Rungrotmongkol, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuch, Nawee Kungwan, Supot Hannongbua

Abstract:

Behçet’s disease (BD) is a genetic autoimmune expressed by multisystemic inflammatory disorder mostly occurred at the skin, joints, gastrointestinal tract, and genitalia, including ocular, oral, genital, and central nervous systems. Most BD patients in Japan and Korea were strongly indicated by the genetic factor namely HLA-B*51 (especially, HLA-B*51:01) marker in HMC class I, while HLA-A*26:01 allele has been detected from the BD patients in Greek, Japan, and Taiwan. To understand the selective binding of the MICA-TM peptide towards the HLAs associated with BD, the molecular dynamics simulations were applied on the four HLA alleles (B*51:01, B*35:01, A*26:01, and A*11:01) in complex with such peptide. As a result, the key residues in the binding groove of HLA protein which play an important role in the MICA-TM peptide binding and stabilization were revealed. The Van der Waals force was found to be the main protein-protein interaction. Based on the binding free energy prediction by MM/PBSA method, the MICA-TM peptide interacted stronger to the HLA alleles associated to BD in the identical class by 7-12 kcal/mol. The obtained results from the present study could help to differentiate the HLA alleles and explain a source of Behçet’s disease.

Keywords: Behçet’s disease, MD simulations, HMC class I, autoimmune

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Authors: Hanjun Zhao

Abstract:

Limited efficacy of current antivirals and antiviral-resistant mutations impair anti-influenza treatment. Here, we evaluated the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Virus replication was significantly reduced in 293T and A549 cells transfected with DIG-3. Mice transfected with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus respectively, had significantly better survivals (80% and 50%) than control mice (0%). We further developed a dual-functional peptide TAT-P1, which delivers DIG-3 with high transfection efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification. TAT-P1/DIG-3 was more effective than jetPEI/DIG-3 in treating A(H7N7) or A(H1N1)pdm09-infected mice and showed potent prophylactic protection on A(H7N7) or A(H1N1)pdm09-infected mice. The addition of P1 peptide, preventing endosomal acidification, could enhance the protection of TAT-P1/DIG-3 on A(H1N1)pdm09-infected mice. Dual-functional TAT-P1 with DIG-3 can effectively protect or treat mice infected by avian and seasonal influenza virus infection.

Keywords: antiviral peptide, dual-functional peptide, defective interfering genes, influenza virus

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Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

Abstract:

OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

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Authors: Shah Abbas

Abstract:

Rheumatoid arthritis is a systemic, inflammatory autoimmune disease, affecting an overall 1% of the global population. Despite being tremendous efforts by scientists, early diagnosis of RA still has not been achieved. In the current study, a Graphene oxide (GO) based electrochemical sensor has been developed for early diagnosis of RA through Cyclic voltammetry. Chitosan (CHI), a CPnatural polymer has also been incorporated along with GO in order to enhance the biocompatibility and functionalization potential of the biosensor. CCPs are known antigens for Anti Citrullinated Peptide Antibodies (ACPAs) which can be detected in serum even 14 years before the appearance of symptoms, thus they are believed to be an ideal target for the early diagnosis of RA. This study has yielded some promising results regarding the binding and detection of ACPAs through changes in the electrochemical properties of biosensing material. The cyclic voltammogram of this biosensor reflects the binding of ACPAs to the biosensor surface, due to its shifts observed in the current flow (cathodic current) as compared to the when no ACPAs bind as it is absent in RA negative patients.

Keywords: rheumatoid arthritis, peptide sensor, graphene oxide, anti citrullinated peptide antibodies, cyclic voltammetry

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Authors: Wei-Ting Kuo, Feng-Huei Lin

Abstract:

Epidermal growth factor receptor (EGFR) is often constitutively stimulated in cancer owing to the binding of ligands such as epidermal growth factor (EGF), so it is necessary to investigate the interaction between EGFR and its targeting biomolecules which were over ligands binding. This study would focus on the binding affinity and adhesion force of two targeting products anti-EGFR monoclonal antibody (mAb) and peptide A to EGFR comparing with EGF. Surface plasmon resonance (SPR) was used to obtain the equilibrium dissociation constant to evaluate the binding affinity. Atomic force microscopy (AFM) was performed to detect adhesion force. The result showed that binding affinity of mAb to EGFR was higher than that of EGF to EGFR, and peptide A to EGFR was lowest. The adhesion force between EGFR and mAb that was higher than EGF and peptide A to EGFR was lowest. From the studies, we could conclude that mAb had better adhesion force and binding affinity to EGFR than that of EGF and peptide A. SPR and AFM could confirm the interaction between receptor and targeting ligand easily and carefully. It provide a platform to screen ligands for receptor targeting and drug delivery.

Keywords: adhesion force, binding affinity, epidermal growth factor receptor, target molecule

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Authors: Yongrong Liu, Xin Tang

Abstract:

Background: Persistent atrial fibrillation is a common arrhythmia closely related to heart failure. Heart rate control is an essential strategy for treating persistent atrial fibrillation. Still, the understanding of the relationship between different heart rate control levels and the risk of heart failure rehospitalization is limited. Objective: The objective of the study is to determine the relationship between different levels of heart rate control in patients with persistent atrial fibrillation and the risk of readmission for heart failure. Methods: We conducted a retrospective dual-centre cohort study, collecting data from patients with persistent atrial fibrillation who received outpatient treatment at two tertiary hospitals in central and western China from March 2019 to March 2020. The collected data included age, gender, body mass index (BMI), medical history, and hospitalization frequency due to heart failure. Patients were divided into three groups based on their heart rate control levels: Group I with a resting heart rate of less than 80 beats per minute, Group II with a resting heart rate between 80 and 100 beats per minute, and Group III with a resting heart rate greater than 100 beats per minute. The readmission rates due to heart failure within one year after discharge were statistically analyzed using propensity score matching in a 1:1 ratio. Differences in readmission rates among the different groups were compared using one-way ANOVA. The impact of varying levels of heart rate control on the risk of readmission for heart failure was assessed using the Cox proportional hazards model. Binary logistic regression analysis was employed to control for potential confounding factors. Results: We enrolled a total of 1136 patients with persistent atrial fibrillation. The results of the one-way ANOVA showed that there were differences in readmission rates among groups exposed to different levels of heart rate control. The readmission rates due to heart failure for each group were as follows: Group I (n=432): 31 (7.17%); Group II (n=387): 11.11%; Group III (n=317): 90 (28.50%) (F=54.3, P<0.001). After performing 1:1 propensity score matching for the different groups, 223 pairs were obtained. Analysis using the Cox proportional hazards model showed that compared to Group I, the risk of readmission for Group II was 1.372 (95% CI: 1.125-1.682, P<0.001), and for Group III was 2.053 (95% CI: 1.006-5.437, P<0.001). Furthermore, binary logistic regression analysis, including variables such as digoxin, hypertension, smoking, coronary heart disease, and chronic obstructive pulmonary disease as independent variables, revealed that coronary heart disease and COPD also had a significant impact on readmission due to heart failure (p<0.001). Conclusion: The correlation between the heart rate control level of patients with persistent atrial fibrillation and the risk of heart failure rehospitalization is positive. Reasonable heart rate control may significantly reduce the risk of heart failure rehospitalization.

Keywords: heart rate control levels, heart failure rehospitalization, persistent atrial fibrillation, retrospective cohort study

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Authors: Hamad Rafique

Abstract:

The bioactive peptide RDFPITWPW (RW-9) identified from oat protein has been reported to be positive in memory deficits. However, no clarity on the mechanisms responsible for the neuroprotective effects of RW-9 peptide against AD-like symptoms. Herein, it found that RW-9 intervention showed various improving effects in cognitive-behavioral tests and alleviated oxidative stress and inflammation in the scopolamine-induced mice model. The hippocampus proteomics analysis revealed the upregulation of memory-related proteins, including Grin3a, Ppp2r1b, Stat6, Pik3cd, Slc5a7, Chrm2, mainly involved in cAMP signaling, PI3K-Akt signaling, and JAK-STAT signaling pathways. The administration of RW-9 significantly upregulated the neurotransmitters, including 5-HT, DA, and Arg, in mice brains. Moreover, it regulated the serum metabolic profile and increased the expression levels of ABC transporters, biosynthesis of amino acids, and Amino acyl-tRNA biosynthesis, among others. The 16s-rRNA results illustrated that the RW-9 restored the abundance of Muribaculaceae, Lachnospiraceae, Lactobacillus, Clostridia and Bactericides. Taken together, our results suggest that the RW-9 may prevent the AD-like symptoms via modulation of the gut-serum-brain axis.

Keywords: oat protein, active peptide, neuroprotective, gut-brain axis

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Authors: Sayanti Kar, Amitava Ghosh, Pritam Aitch, Gupinath Bhandari

Abstract:

An extensive seasonal analysis of wastewater had been done from outfalls of river Ganga in Howrah, Hooghly, 24 PGS (N) District, West Bengal, India during 2017. The morphological parameters of Bitter gourd (Momordica charantia L.) were estimated under wastewater treatment. An approach to study the activity within the range of low molecular weight peptide 3-0.5 kDa were taken through its extraction and purification by ion exchange resin column, cation, and anion exchanger. HPLC analysis had been done for both in wastewater treated and untreated plants. The antioxidant activity by using DPPH and germination percentage in control and treated plants were also determined in relation to wastewater effect. The inhibition of growth and its parameters were maximum in pre-monsoon in comparing to post-monsoon and monsoon season. The study also helped to explore the effect of wastewater on the peptidome of Bitter gourd (Momordica charantia L.). Some of these low molecular weight peptide(s) (3-0.5 kDa) also inhibited during wastewater treatment. Expression of particular peptide(s) or absence of some peptide(s) in chromatogram indicated the adverse effects on plants which may be the indication of stressful condition. Pre monsoon waste water was found to create more impact than other two.

Keywords: bitter gourd (Momordica charantia l.), low molecular weight peptide, river ganga, waste water

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Authors: Terentes Printzios Dimitrios, Loanna Gourgouli, Vlachopoulos Charalambos

Abstract:

Aims: Atrial fibrillation (AF) remains one of the major causes of stroke, heart failure, sudden death and cardiovascular morbidity. Ablation techniques are becoming more appealing after the latest results of randomized trials showing the overall clinical benefit. On the other hand, imaging techniques and the frontier application of 3D printing are emerging as a valuable ally for cardiac procedures. However, no randomized trial has directly assessed the impact of preprocedural imaging and especially 3D printing guidance for AF ablation. The present study is designed to investigate for the first time the effect of 3D printing of the heart on the safety and effectiveness of the ablation procedure. Methods and design: The 3D-GALA trial is a randomized, open-label, controlled, multicentre clinical trial of 2 parallel groups designed to enroll a total of 100 patients undergoing ablation using cryo-balloon for paroxysmal and persistent AF. Patients will be randomized with a patient allocation ratio of 1: 1 to preprocedural MRI scan of the heart and 3D printing of left atrium and pulmonary veins and cryoablation versus standard cryoablation without imaging. Patients will be followed up to 6 months after the index procedure. The primary outcome measure is the reduction of radiation dose and contrast amount during pulmonary veins isolation. Secondary endpoints will include the percentage of atrial fibrillation relapse at 24h-Holter electrocardiogram monitoring at 6 months after initial treatment. Discussion: To our knowledge, the 3D-GALA trial will be the first study to provide evidence about the clinical impact of preprocedural imaging and 3D printing before cryoablation.

Keywords: atrial fibrillation, cardiac MRI, cryoablation, 3-d printing

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Authors: Palwinder Singh

Abstract:

Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

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Authors: Mohammad A. Obeidat, Ayman M. Mansour

Abstract:

Capturing the dynamic behavior of the heart to improve control performance, enhance robustness, and support diagnosis is very important in establishing real time models for the heart. Control Techniques and strategies have been utilized to improve system costs, reliability, and estimation accuracy for different types of systems such as biomedical, industrial, and other systems that required tuning input/output relation and/or monitoring. Simulations are performed to illustrate potential applications of the technology. In this research, a new control technology scheme is used to enhance the performance of the Af system and meet the design specifications.

Keywords: atrial fibrillation, dynamic behavior, closed loop, signal, filter

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