On the atrial response to focal discharges in man

INTRODUCTION: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. METHODS AND RESULTS: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value 3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 +/- 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 +/- 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. CONCLUSION: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia.     

Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.     

Magnetic phase transition from paramagnetic in Nb2AlC-MAX to superconductivity-like diamagnetic in Nb2C-MXene: an experimental and computational analysis

Transition metal carbides (TMCs) have recently emerged as competent members among the family of two-dimensional (2D) materials, owing to their promising applications. There are many promising applications of MXenes; however, their magnetic properties lack a wide margin, both experimentally as well as theoretically, which needs to be investigated for potential use in spintronics. In this study, we carried out a comprehensive etching process via selective extraction of Al layers from Nb₂AlC-MAX using a wet electrochemical route under well-optimized conditions to obtain fine 2D-Nb₂C MXene sheets. Structural analysis using X-ray diffraction (XRD) confirms the effective removal of Al followed by confirmation of a 2D layered structure from morphological analysis using scanning electron microscopy (SEM). Zero-field-cooled (ZFC) and field-cooled (FC) measurements of MAX and MXene at different field strengths were performed using a superconducting quantum interference device (SQUID). Magnetic measurements reveal the paramagnetic nature of Nb₂AlC-MAX measured under 5 mT; however, this changes to a clear superconductor-like diamagnetic behavior with a shift of the magnetization from positive to negative values at low temperatures when measured under 5 mT and 10 mT for Nb₂C MXene. The diamagnetism, however, is changed to paramagnetism at 100 mT, which shows the existence of critical fields known typically for a type-II superconductor. To gain an insight into this unusual behavior in MXene, density functional theory (DFT) first-principles calculation was also performed in Wein2K software using spin-polarized generalized gradient approximation (sp-GGA). The magnetic moment of the compound is calculated to be negative, which corresponds well with the experimental finding and suggests that the negative magnetic moment originated from the d-orbital of Nb₂C. The present report provides a pathway to deeply understanding the existence of superconductivity-like diamagnetic behavior in Nb₂C MXene, which is useful for future magnetic applications.

Transition metal carbides (TMCs) have recently emerged as competent members among the family of two-dimensional (2D) materials, owing to their promising applications.

In two-dimensional (2D) materials, magnetism at the nanoscale is at the forefront of many cutting-edge technological applications, such as spintronic devices. Naguib et al. have synthesized a new class of two-dimensional materials, known as MXenes (M_nX_n+1), discovered in 2011, giving a possibility of magnetism in such 2D materials and their promising uses in spintronic devices.¹ These 2D layer structured early transition metal carbides and/or nitrides are known as MXenes, so named to indicate their structural similarities with graphene.² MXenes are derived from 3D MAX phases (space group P6₃/mmc) in which “M” is an early transition metal, e.g., Ti, Ta, V, etc.; “A” is mainly a group 13 or group 14 element (group III-A or IV-A), e.g., Si, Al; “X” is a carbide, nitride or can be both; and n = 1, 2, 3 represents the number of layers, forming 211, 312 and 413 phases.^3–5 Over the past decade, this new material has gained enormous attention, thus developing an entirely new research field to disclose the properties of the 2D state of this material. The materials in the 2D regime own a cluster of astonishing physical properties as compared to the 3D nature, but intrinsic two-dimensional magnetism has proved to be challenging. As 2D semiconductors have revamped the field of electronics, similarly, magnetism in 2D materials could remodel spintronic devices that can employ a spin degree of freedom.^6,7Nb₂C MXene was first synthesized by Naguib et al., but they just reported its electrochemical activity as a promising electrode material.⁴ Further work has been reported in Nb₂C with various biomedical applications, energy storage, supercapacitors, and nanoelectronics.^9–19 As far as the magnetism in such 2D MXenes is concerned, it remains less investigated, and this research void needs to be filled. Recently, Babar et al. reported the observation of superconductivity in as-prepared powdered Nb₂C for the first time, with the highest onset transition temperature T_c,onset = 12.5 K among the MXene family. However, the authors did not discuss the magnetic nature of the parent Nb₂AlC MAX itself and did not reason for the presence of unusual magnetic effects in MXene.⁸ MXenes are favorable members of 2D magnetism, and different magnetic natures are computationally predicted in various carbide and nitride MXenes.^7,20 The existence of novel room-temperature ferromagnetic order in doped MXene and the coexistence of different magnetic phases in MXene, along with experimental evidence, indicate its potential of hosting diverse magnetic natures.^21,22 Considerable research has been focused on these 2D structures due to their importance and favorable applications, such as spintronics. MXene could provide a vast platform for exploring the magnetic properties and is one of the best candidates that can host superconductivity as compared to other members of the 2D family. Experimental studies are generally dependent upon numerous variables, thus affecting the research pace. However, density functional theory-based first principles calculation and theoretical simulations are a successful way to examine and foresee the properties of low-dimensional materials. This provoked us to theoretically explore superconductivity in Nb₂C and their validation through superconductivity measurements of experimentally synthesized Nb₂C MXene. In this work, we report a systematic etching mechanism of Nb₂C MXene to obtain fine 2D sheets via a chemical etching route using hydrofluoric (HF) acid. Structural and morphological studies using the X-ray diffraction technique (XRD), scanning electron microscopy (SEM) and elemental analysis by energy-dispersive X-ray spectroscopy (EDX) show the effective removal of Al from the parent 3D-Nb₂AlC MAX, thus revealing an accordion-like sheet structure. Optical analysis indicates a significant reduction in bandgap after chemical etching. Magnetic properties were carried out to observe the signatures of superconductivity (a perfect diamagnetic state, negative magnetic moment) and its magnetic nature at room temperature. To study the magnetic nature of as-prepared powder-form Nb₂C, density functional theory (DFT) first principles calculation was carried out through Wein2K using spin-polarized generalized gradient approximation (sp-GGA). The magnetic moment of the compound is calculated to be −0.00485, which although but small is important, as the value is negative, which is an indication of the presence of diamagnetism in Nb₂C. Here, the detailed chemical etching process, magnetic properties of Nb₂AlC MAX and its effect on magnetic phase of Nb₂C MXene, and the density functional theory calculation are reported, which were not discussed by Babar et al. in ref. 8.     

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing,docking and molecular dynamics simulation study

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

Inhibitory potential of ilimaquinone (marine sponge metabolite) against nine essential SARS-CoV-2 target proteins, employing a molecular interaction and dynamics simulation approach.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Development and treatment approaches of bronchopleural fistula after pulmonary resection

Pulmonary resections comprise most of the operations performed in thoracic surgery departments. Diseases like pulmonary cancers, bronchiectasis, pulmonary abscess, tuberculosis and fungal infections are treated surgically by pulmonary resections. One of the important steps of the pulmonary resection is to suture the bronchi through which the air is supplied to the resected pulmonary tissue. Bronchopleural fistula developed in the bronchial stump is encompassed as one of the most important factors affecting mortality and morbidity regarding postoperative complications.     

Low eradication rate of Helicobacter pylori with triple 7-14 days and quadriple therapy in Turkey

AIM:The eradication rate of Helicobacter pylori (H pylon) shows variation among countries and regimens of treatment.We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication.METHODS:One hundred and sixty-four Hpylori positivepatients (68 males, 96 females; mean age:48&#177;12 years)with duodenal or gastric ulcer without a smoking history were included in the study. The patients were divided into three groups according to the treatment regimens. Omeprazole 20mg, clarithromycin 500mg, amoxicillin 1g were given twice daily for 1 week (Group I) and 2 weeks (Group Ⅱ).Patients in Group Ⅲ received bismuth subsitrate 300mg,tetracyline 500 mg and metronidazole 500mg four times daily in addition to Omeprazole 20mg twice daily.Two biopsies each before and after treatment were obtained from antrum and corpus, and histopathologically evaluated.Eradication was assumed to be successful if no Hpylorus was detected from four biopsy specimens taken after treatment. The effects of factors like age, sex, Hpyloridensity on antrum and corpus before treatment, the total Hpylori density, and the inflammation scores on the rate of Hpylori eradication were evaluated.RESULTS:The overall eradication rate was 42%. The rates in groups Ⅱ and Ⅲ were statistically higher than that in group I (P&lt;0.05). The rates of eradication were 24.5%,40.7% and 61.5% in groups Ⅰ, Ⅱ and Ⅲ, respectively. The eradication rate was negatively related to either corpus Hpylori density or total Hpyloridensity (P&lt;0.05).The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55yr vs 39yr, P&lt;0.001). No correlation between sex and Hpylori eradication was found.CONCLUSION: Our rates of eradication were significantly lower when compared to those reported in literature.We believe that advanced age and high Hpyloridensity are negative predictive factors for the rate of Hpylorieradication.