Effect of DNA methylation on impaired Interferon type I signaling as a strategy to escape of SARS-CoV-2 from innate immune response: a hypothesisSomayeh Shokri 1,2 , Shahab Mahmoudvand1,2, *1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran2 Department of Virology, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran.* Corresponding Author: Shahab Mahmoudvand, Department of Virology, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Phone Number: +989188523259,Email: mahmoudvandsh100@yahoo.com

The root tip of a plant is highly sensitive to environmental cues and exerts sensory, chemical and movement responses and has even been likened to an animal’s brain. Yet, the assemblage of microbes at the root tip, the controls governing their diversity, the nature of their recruitment to that particular niche, and their roles in plant phenotypic function, remain poorly understood. This study investigated longitudinal niche differentiation of the root-associated microbiome in chickpeas ( Cicer arietinum L.) and its interactions with both diverse soil types and host plants with genetic variation in phenology, from the exterior to the interior of the root. Compared with late flowering (LF) genotypes, endophyte microbiomes at the apical zone of the early flowering (EF) host were characterised by greater diversity, higher compositional similarity to the basal zone, and closely inhabiting Rhizobacter and Methylotenera across soils. Additionally, EF genotype secreted a specific composition of metabolites from the apical zone, with more carboxylates (benzoic acid) and amino acids (propionic acid) than the LF plant. Our findings demonstrate that longitudinal differentiation within a seedling root is an essential feature shaping the root microbiome and indicative of genetic variation in phenology of host plants.

Climate change-induced variations in temperature and precipitation negatively impact plant growth and development. To ensure future food quality and availability, a critical need exists to identify phenotypic and physiological responses that confer drought tolerance in agronomically important crop plants. In this study, two Sorghum bicolor accessions that differ in their pre-flowering responses to drought were exposed to cycles of drying and rewatering. Morphological, physiological, and histological traits were measured across juvenile and adult developmental stages. Our results suggest that induction of stomatal closure works to prevent hydraulic damage under drought conditions, particularly when morphological and histological adjustments are unable to compensate for this hydraulic risk. These findings demonstrate that morphology, histology, and physiology may work independently over developmental time to achieve a shared goal of regulating transpirational water loss to mitigate the risk of xylem embolism.

Studies on freshwater meiofauna are still enigmatic. This field of research is quite Neglected. Publications on this topic are not increasing as much as the others, showing that there is a certain gap when it comes to this area. This paper contains a brief review of what already exists on freshwater meiofauna around the world, focusing on increasing knowledge on this topic and making it a common study field in science, surveying the research in this little known area of meiofauna. For this, the methodology involved a bibliographic survey carried out from Web of Science (WoS) and SCOPUS bibliographic databases. The search was performed by title and keywords, highlighting Meiofauna (or meiobenthos), hyporheic zone (or freshwater). The results showed a number of 28 documents on freshwater meiofauna around the world, mainly concentrated in Germany. Based on this, a discussion was present given these few articles found, highlighting that the lack of researches on freshwater meiofauna community, its ecology, taxonomy and biology, which are consequently poorly known what imposes a barrier on new researchers and researches to emerge in this area and need increase scientific interest at all. It is hoped that this bibliometric review can be used as an alert about this area of meiofauna that is so important but at the same time is neglected, having a very exclusive group of authors and works, being of extreme importance a direction of research that involve freshwater meiofauna, increasing publications worldwide.

Introduction: Telemedicine is the use of web - based technologies to provide health care services. Case history: A 40 year old conjoined twin, known case of dorsal spine tuberculosis contracted Covid-19 infection following which they were shifted to our center. Several unique challenges were encountered during the course of management.

Multi-phenotypic screening of multiple zebrafish larvae plays an important role in enhancing the quality and speed of biological assays. Many microfluidic devices have been presented for zebrafish phenotypic assays, but multi-organ screening of multiple larvae, from different needed orientations, in a single device that can enable rapid and large-sample testing is yet to be achieved. Here, we propose a multi-phenotypic quadruple-fish microfluidic chip for simultaneous monitoring of fin movement and heart activity of 5–7-day postfertilization zebrafish larvae trapped in the chip. In each experiment, fin movements of four larvae were quantified in the dorsal view in terms of fin beat frequency (FBF). Positioning of four optical prisms next to the traps provided the lateral views of the four larvae and enabled heart rate (HR) monitoring. The device’s functionality in chemical testing was validated by assessing the impacts of ethanol on heart and fin activities. Larvae treated with 3% ethanol displayed a significant drop of 13.2% and 35.8% in HR and FBF, respectively. Subsequent tests with cadmium chloride highlighted the novel application of our device for screening the effect of heavy metals on cardiac and respiratory function at the same time. Exposure to 5 μg/L cadmium chloride revealed a significant increase of 8.2% and 39.2% in HR and FBF, respectively. The device can be employed to improve quantitative multi-phenotypic screening of zebrafish larvae in response to chemical stimuli in various chemical screening assays, in applications such as ecotoxicology and drug discovery.

Primary herpetic gingivostomatitis(PHGS)is a manifestation of primary herpes infection with the simplex virus .It may be preceded by some prodromal symptoms.After the resolution of the primary infection, the virus remains latent in a nervous ganglion. The aim of this paper was to report a case of PHGS in a child

In this report, we discuss how autoimmune conditions and associated immunocompromise may impact diagnostic utility of molecular screening tools for mycobacterial infection. Imaging, molecular screening, and clinical judgment are required to rule out disease in the immunocompromised, especially in an acute setting

Mechanical thrombectomy is the standard of care for acute large vessel occlusion stroke since 2015 . Many studies report pre-intervention distal thrombus migration, especially after intravenous thrombolysis. We report a case of spontaneous intraprocedural thrombus migration during mechanical Thrombectomy with a review of conditions favoring the phenomenon.

This paper is concerned with the existence of mild solutions and approximate controllability for a class of noninstantaneous impulsive fractional neutral measure evolution systems with state-dependent delay. First, the existence of mild solutions for the considered system is obtained by using Kuratowski's measure of noncompactness and the set contraction fixed point theorem. Next, under the assumption that the correlated linear system is approximately controllable, the approximate controllability of the system is studied. Finally, we present two applications to support the practical usefulness of the study

Although most manifestations of coronavirus infection in children are mainly related to the respiratory and gastrointestinal organs, involvement of other organs has also been seen with less prevalence. Because of the expression of virus receptors in male genitalia, this system is regarded as a potential target for this virus.

A document by I. Gökhan AKSOY. Click on the document to view its contents.

Ozonation of cornstarch at pH 13 was performed using a semi-batch reactor to analyse the influence of a continuous ozone-oxygen gas flow (40 NL/h) at different ozone concentrations (0-42.30 g/Nm3) and temperatures (20-60ºC). A pseudofirst-order kinetic model was proposed to elucidate the reaction mechanisms associated with ozone at high pH conditions. The radical concentration remains constant and proportional to the ozone continuous dose, being a non-limiting factor independent of temperature (activation energy 14.2-14.5 KJ/mol). The oxidation kinetic of starch was studied monitoring the Chemical Oxygen Demand, finding a reduction in ozone concentration when both temperature and time increased (activation energy 8.1 KJ/mol). Therefore, the model proposed for the starch ozonation at high alkaline solutions provides a better understanding of the oxidation processes of common product additives such as starch, also making it possible to determine the environmental impact of such solutions by Chemical Oxygen Demand measurement.

Little attention has been given to the bubble temperature problem of a pure component in academic field. A robust methodology for solving the pure saturation temperature (vapor temperature) is proposed by using cubic equations of state. The methodology is based on a Newton-Raphson iterative technique for solving phase equilibrium criteria, coupled with initialization procedures. This methodology is free of numerical pitfalls from the critical point to very low reduced pressure. The fact that the given pressure is equal to the pressure at the inflection point of the initial temperature isotherm yields an automatic initialization of the calculations inside a region of convergence where the EOS can always predict vapor temperatures. In addition, the initialization method can also be used to calculate vapor pressures. Examples for vdW, RK, SRK and PR EOS show that the methodology can give perfect predictions for saturation properties even at very low reduced pressure and temperature.

The production of hydrocarbons for the synthesis of readily available energy and multifunctional materials is of great importance in modern society. Zeolites have proven to be a boon for the targeted regulation of specific hydrocarbon as shape-selective catalyst in converting carbon resources. Yet our mechanistic understanding and quantitative description of shape-selectivity of zeolite catalysis remains rather limited, which restricts the upgrade of zeolite catalysts. Herein, we proposed quantitative principle of shape-selectivity for zeolite catalysis using methanol-to-hydrocarbons (MTH) as model. Combining with molecular simulations and infrared imaging, we unveil the competition of thermodynamic stability, preferential diffusion and favored secondary reactions between different hydrocarbons within zeolite framework are the essence of zeolite shape-selective catalysis. Notably, we provide methodology to in silico search for the optimal combination of framework topology and acidity properties of zeolites with operating conditions that potentially outperform commercial MTH catalysts to achieve high selectivity of desired hydrocarbon products.

The equilibrium CO2 solubility of 2-[2-(dimethylamino)ethoxy]ethanol (DMAEE) was investigated at the temperature range of 298.15-323.15 K with the CO2 partial pressure from 5.0 to 60 kPa. A novel modified Kent-Eisenberg model was proposed to predict the CO2 solubility of DMAEE with the absolute average deviation (ADD) of 3.0% in this work, and this model provides more accurate prediction than the reported Kent-Eisenberg, Austgen, Hu-Chakma, and Li-Shen model. Then four reported tertiary amines were used to validate the universality of the proposed model and the obtained results indicate that the developed model can be applied to the mentioned amines with an acceptable AADs (4.80, 5.47, 8.56, and 3.65 %). In addition, the heat of CO2 absorption and the dissociation constant (pKa) also were systematically evaluated and compared with other reported amines, all obtained results indicates that the DMAEE has a potential to be an alternative absorbent for post-combustion CO2 capture.

According to the explicit propositions by Clausius, in the original publications in the 1850’s, the temperatures of the “reservoirs” are irrelevant for the “second fundamental equation” of the “mechanical theory of heat” to hold true. It is shown that entropy being history independent, i.e., “path independent”, “state function”, is contradictory to “reversibility”, i.e., contradictory to the “second fundamental equation” of the “mechanical theory of heat” holding true for “reversible” phenomena, only. This result is corroborated by experimental evidence. This result only removes the unnecessary restriction posed by “reversibility”, causes no adverse practical consequences, and offers the possibility to unify and simplify continuum entropy modeling. For example, the result removes the dilemma due to “reversibility” from engineering calculations for real physical phenomena, none of which are “reversible”.

1. The western honey bee, Apis mellifera, lives worldwide in approximately 94 million managed hives but also wild throughout much of its native and introduced range. Despite the global importance of A. mellifera as a crop pollinator, wild colonies have received comparatively little attention in the scientific literature and basic information regarding their density and abundance is scattered. 2. Here we review 29 studies that quantified wild colony density directly and analyse a larger dataset including an additional 7 studies that quantified density indirectly using genetic markers. 3. Densities varied from 0.1 to 24.2/km2 at 38 locations worldwide and were 24 times lower in Europe (0.35/km2) than Africa (8.4/km2) on average. Survey area varied from 1.2 to 924km2 and was negatively correlated with density. Survey areas were largest in Europe (average of 70.4km2) and were partly responsible for the low densities reported in this region. 4. After controlling for survey area in a GLM, mean annual temperature and net primary productivity became important predictors of density. This model was used to estimate wild colony numbers at a regional scale, which varied from approximately 135 million in Latin America to 8 million in Europe and 250 million worldwide. 5. Overall, wild colonies were estimated to outnumber managed hives in all regions except Europe and were estimated to be over twice as numerous worldwide. This is a significant result given that A. mellifera is often viewed as a domesticated species that primarily lives under human management.

Actinopterygian fishes display considerable diversity of parental behaviors and forms of parenting. In order to understand the evolutionary history in the ray-finned fishes, both characters were mapped, using parsimony ancestral state reconstruction upon an existing supertree. According to the data, in this subclass, parental care and parenting traits evolved from ancestors devoid of parental care or parenting. The transition from the ancestral state to substrate guarding, and that from the ancestral state to uniparental male care were the most observed ones, whereas the remaining transitions recorded low scores. Concerning the evolution of parental care, the data supported the evolution of mouthbrooding from substrate guarding, whilst external egg carrying arose from both substrate guarding and the ancestral state, which suggested the lack of a unique evolutionary pattern. Regarding the evolution of caregiver sex, the data did not support the stepping-stone model since the complete predicted sequence was not observed. In addition, the evolution of carer sex showed higher diversity of transitions among states than recorded in the evolution of parental care, suggesting the absence of a unique evolutionary pattern fitting the entire subclass.

Allopreening occurs in many species of birds and is known for providing hygienic and social benefits. While this behavior has been studied between conspecifics, its occurrence among different species remains mysterious. Outside of captivity environment, only a few records of interspecific allopreening exist. In this study, we report the first documented record of a Spot-necked Babbler (Stachyris strialata) allopreening a Nonggang Babbler (Stachyris nonggangensis) in a non-captive environment in southern China. We provide three hypotheses (social dominance, cleaning mutualism, and hybridization) to explain the occurrence of this understudied behavior. We suggest that interspecific allopreening may not be as rare as we assumed if we are in the correct place to study it. This study contributes to our understanding of not only the potential mechanism(s) for interspecific allopreening but also the behavioral ecology of the vulnerable Nonggang Babbler.

Desertification is a problem in regions with arid, semi-arid and dry sub-humid climates and is characterized by the degradation of natural resources. The influence of vegetation cover and rainfall intensity on the dynamics of water infiltration, surface runoff and soil loss was measured in situ in a Desertification Zone in the semi-arid region of Brazil. Twenty-four plots were evaluated in two areas, each with the same type of soil that is predominant in the region: 1) Luvisol with dense vegetation cover (LD) and 2) Luvisol with sparse vegetation cover (LS). Rainfall of 60 and 100 mm h -1 was simulated with a rainfall simulator. Soil hydraulic conductivity, soil water retention curves and soil carbon and nitrogen stocks were also determined. Water infiltration was greater in the LD (53 mm h -1) compared to the LS (15 mm h -1), while the runoff rates were 27 mm h -1 for the LD and 61 mm h -1 for the LS. Rainfall intensity significantly influenced when runoff started and the runoff rate, accelerating soil loss. Vegetation cover significantly influenced the total soil carbon and nitrogen stocks, as well as the saturated hydraulic conductivity of the soil. This is the first study in the semi-arid desertification region of Brazil that used simulated rainfall to assess the effects rain intensity on soil properties. The results of this study can be used as a reference for calibrating erosion models in areas undergoing a desertification process

High Density Pace-Mapping for Scar-related Ventricular Tachycardia AblationTravis D. Richardson MD and William G. Stevenson MD.1 Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USARunning Title: High Density Pace MappingCorresponding Author:Travis D. Richardson, MDDivision of Cardiovascular MedicineVanderbilt University Medical Center1211 Medical Center DrNashville, TN 37232USAEmail: travis.d.richardson@vumc.orgWord Count: 2,225Conflicts of Interest :Dr. Stevenson has received speaking Honoria from: Boston Scientific, Medtronic, Abbott, Johnson and Johnson, and Biotronik; he is co-holder of a patent for irrigated needle ablation that is consigned to Brigham and Women’s Hospital.Dr. Richardson has received research funding from Medtronic Inc, Abbott Inc and served as a consultant for Philips Inc and Johnson and Johnson.This work did not receive any funding.Despite advances in medical and interventional therapies, ventricular tachycardia (VT) due to reentrant activity within complex regions of myocardial scar remains a common late complication of myocardial infarction.1 While implantable defibrillators (ICD) may prevent sudden death, ICD shocks are painful and impact quality of life2. Catheter ablation reduces the likelihood of ICD therapies and it’s role early in the course of disease is expanding3–5. However, several factors limit the success and safety of catheter ablation procedures. Scar-related reentry circuits can be large with a critical isthmus shared by multiple loops. Ablation of the isthmus is associated with a low risk of recurrence of that VT6,7. The critical isthmus can be identified during VT by detailed activation mapping and entrainment. However, prolonged mapping during VT is often not feasible or desired. Patients undergoing VT ablation often have severe systolic heart failure as well as other comorbid conditions. VT is often not hemodynamically tolerated and even when tolerated, prolonged time in VT may lead to decompensation. Strategies to limit initiation and mapping of VT may improve procedural safety8. Methods to guide ablation based on characterization of the sinus rhythm substrate alone have generally shown good results9. A number of approaches have been applied, including ablation over the entire low voltage area (scar homogenization)10. While this is often successful, areas of scar can be quite extensive, and undoubtedly this technique leads to ablation of more areas than absolutely necessary for success. This approach is also more effective if epicardial ablation is routinely included, which has the potential to increase procedural risk. A strategy to focus on the critical regions, particularly when a clinically relevant VT is known, remains a reasonable first step in the procedure. A variety of electrogram markers of critical regions have been described including late potentials, potentials that display variable coupling to surrounding tissue during programmed stimulation11 , and areas of slow conduction identified by high density mapping 12,13. While these are likely to increase the specificity of ablation targets compared to electrogram voltage alone, they are also seen at bystander areas14.Pace-mapping during sinus rhythm is useful to help identify the general location of focal arrhythmia sources,15 and can also be used in scar related reentry.16,17 At the reentry circuit exit region the paced QRS morphology often resembles the VT QRS, and this will also occur at sites proximal to the exit provided that the stimulated wavefront follows the reentry path to the exit. A stimulus – QRS > 40 ms is also consistent with slow conduction away from the pacing site, that can be a marker for reentry substrate17.In this issue of the Journal of Cardiovascular Electrophysiology,Guenancia et al. review their technique of using high density pace mapping to guide VT ablation18. Their method takes advantage of software available in electroanatomic mapping systems that assigns a measure of correlation between two different QRS morphologies; in this case the VT and the paced QRS morphology.19 A pacing correlation map is generated by pacing multiple sites within the ventricle and color coding the algorithmically derived score for display at each point on the anatomic map. Sites near the exit from the reentry circuit isthmus, typically along the border of a scar, will display good correlation with induced VT. As one moves along the isthmus deeper into the low voltage scar the S-QRS prolongs due to the conduction time between the pacing site and the exit region. If the isthmus is anatomically defined, such that it is present during VT and sinus rhythm, the QRS morphology remains similar to the VT as long as the paced wavefront follows the isthmus out to the exit. Moving to the entrance or adjacent sites outside the isthmus can produce an abrupt transition to a markedly different paced QRS because the wavefront can propagate away without following the path of the isthmus.20 Thus, the pace-map correlation maps can outline the location of a reentry circuit isthmus during sinus rhythm, as they illustrate.Their method can also help identify cases in which the critical isthmus is not located on the surface being mapped. When the VT circuit is epicardial or intramural, the earliest endocardial activation may appear focal. Similarly, the pace-map correlation maps may reveal a concentric or focal pattern of matching, potentially allowing recognition of this situation without the need for activation mapping during VT.We agree with the fundamental principles described, and feel this technique can be a helpful substrate mapping approach. There are several caveats. Evaluation to clarify its specificity and sensitivity is limited. The authors report that in their unpublished experience an abrupt transition is seen in the majority of post-infarct cases, they have also published a series of 10 post-infarct patients undergoing VT ablation during which the pacing correlation maps visually matched VT activation maps.21This technique is likely to be effective in cases where the VT isthmus is confined to the ventricular surface being mapped. Pacing can capture deep to the endocardium depending on current strength.22 Whether this technique can detect intramural isthmuses and whether deep tissue that can be captured with pacing can also be ablated from the pacing site is not clear.It is important to point out that very good correlations with VT can be observed pacing in an outer loop immediately adjacent to the exit where one would not anticipate RF ablation delivery would be effective. If a focal pattern is seen on both the endocardial and epicardial surfaces very little can be inferred about the VT circuit; the site with better correlation would be expected to be closer to the exit. In this setting entrainment during a brief episode of induced VT with assessment of the post-pacing interval can potentially clarify the proximity to the reentry circuit.During VT, areas of functional conduction block may be present that are absent during sinus rhythm. Functional block can also occur remote from the reentry isthmus and alter activation wavefronts during VT changing the QRS morphology. Theoretically it is then possible to have poor correlation between the VT and paced QRS at its exit. In animal models of post-infarction VT exit regions have been shown to harbor very slow areas of conduction which could be prone to altering total ventricular activation during VT.23.We would caution against generalizing these techniques to patients with dilated cardiomyopathies where confluent regions of low voltage scar are absent. Diffuse interstitial fibrosis may play a greater role in some of these VT circuit and anatomically fixed isthmus sites are less likely to be present.Further study is needed before utilizing this technique when anatomical structures within the ventricle are involved in the VT circuit. Structures such as the moderator band may by definition have multiple exits and varied QRS morphologies24, and papillary muscles may display large areas of similar paced morphology25, potentially distorting pacing correlation maps.This technique is unlikely to correctly characterize VT circuits that involve a portion of the cardiac conduction system as occurs in some scar-related VTs and in bundle-branch reentry.26 These circuits may demonstrate a focal pattern at the left or right ventricular apical septum on pacing correlation maps due to the long, insulated nature of the reentrant circuit itself, and ablation at the exit site is very unlikely to be effective.This strategy of high density pace mapping adds to the available substrate mapping methods for guiding VT ablation while limiting VT induction. This strategy does not rely on electrogram interpretation, making it of particular interest in regions of very low voltage. Indeed, when utilizing larger recording electrodes, such as an ablation catheter, pacing will often reveal the presence of excitable tissue where a local electrogram is not always apparent. In post-infarct ventricular tachycardia circuits with a well-defined scar and a short anatomically bounded isthmus, pacing correlation maps are likely to be revealing. More study is warranted to further assess this method in relation to other substrate mapping methods, in complex substrate with intramural components, and in other disease substrates. It is useful to have multiple tools in the tool box. More studies are needed to further define which tools work best for which substrate.References:1. Stevenson WG: Ventricular Tachycardia After Myocardial Infarction: From Arrhythmia Surgery to Catheter Ablation. J Cardiovasc Electrophysiol 1995; 6:942–950.2. Moss AJ, Schuger C, Beck CA, et al.: Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012; 367:2275–2283.3. Sapp JL, Wells GA, Parkash R, et al.: Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med 2016; 375:111–121.4. Cronin EM, Bogun FM, Maury P, et al.: 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias: Executive summary. Heart Rhythm 2020; 17:e155–e205.5. Della Bella P, Baratto F, Vergara P, et al.: Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial. Circulation 2022; .6. Hadjis A, Frontera A, Limite LR, et al.: Complete Electroanatomic Imaging of the Diastolic Pathway Is Associated With Improved Freedom From Ventricular Tachycardia Recurrence. Circ Arrhythm Electrophysiol 2020; 13:e008651.7. Tokuda M, Kojodjojo P, Tung S, et al.: Characteristics of Clinical and Induced Ventricular Tachycardia Throughout Multiple Ablation Procedures. J Cardiovasc Electrophysiol 2016; 27:88–94.8. Yu R, Ma S, Tung R, et al.: Catheter ablation of scar-based ventricular tachycardia: Relationship of procedure duration to outcomes and hospital mortality. Heart Rhythm 2015; 12:86–94.9. Irie T, Yu R, Bradfield JS, et al.: Relationship between sinus rhythm late activation zones and critical sites for scar-related ventricular tachycardia: systematic analysis of isochronal late activation mapping. Circ Arrhythm Electrophysiol 2015; 8:390–399.10. Di Biase L, Santangeli P, Burkhardt DJ, et al.: Endo-Epicardial Homogenization of the Scar Versus Limited Substrate Ablation for the Treatment of Electrical Storms in Patients With Ischemic Cardiomyopathy. J Am Coll Cardiol 2012; 60:132–141.11. de Riva M, Naruse Y, Ebert M, et al.: Targeting the Hidden Substrate Unmasked by Right Ventricular Extrastimulation Improves Ventricular Tachycardia Ablation Outcome After Myocardial Infarction. JACC Clin Electrophysiol 2018; 4:316–327.12. Anter E, Neuzil P, Reddy VY, et al.: Ablation of Reentry-Vulnerable Zones Determined by Left Ventricular Activation From Multiple Directions: A Novel Approach for Ventricular Tachycardia Ablation: A Multicenter Study (PHYSIO-VT). Circ Arrhythm Electrophysiol 2020; 13:e008625.13. Tung R: Substrate Mapping in Ventricular Arrhythmias. Card Electrophysiol Clin 2019; 11:657–663.14. Nayyar S, Wilson L, Ganesan AN, et al.: High-density mapping of ventricular scar: a comparison of ventricular tachycardia (VT) supporting channels with channels that do not support VT. Circ Arrhythm Electrophysiol 2014; 7:90–98.15. Bennett R, Campbell T, Kotake Y, et al.: Catheter ablation of idiopathic outflow tract ventricular arrhythmias with low intraprocedural burden guided by pace mapping. Heart Rhythm O2 2021; 2:355–364.16. Brunckhorst CB, Delacretaz E, Soejima K, Maisel WH, Friedman PL, Stevenson WG: Identification of the ventricular tachycardia isthmus after infarction by pace mapping. Circulation 2004; 110:652–659.17. Stevenson WG, Sager PT, Natterson PD, Saxon LA, Middlekauff HR, Wiener I: Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars. J Am Coll Cardiol 1995; 26:481–488.18. Guenancia C, Supple GE, Sellal J-M, et al.: How to use pace mapping for ventricular tachycardia ablation in post-infarct patients. J Cardiovasc Electrophysiol .19. de Chillou C, Sellal J-M, Magnin-Poull I: Pace Mapping to Localize the Critical Isthmus of Ventricular Tachycardia. Card Electrophysiol Clin 2017; 9:71–80.20. Hanaki Y, Komatsu Y, Nogami A, et al.: Combined endo- and epicardial pace-mapping to localize ventricular tachycardia isthmus in ischaemic and non-ischaemic cardiomyopathy. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol 2022; 24:587–597.21. de Chillou C, Groben L, Magnin-Poull I, et al.: Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm. Heart Rhythm 2014; 11:175–181.22. Itoh T, Yamada T: Excellent Pace Maps Recorded from Two Remote Sites Inside and Outside the Scar in a Patient with Ischemic VT: What Is the Mechanism? Pacing Clin Electrophysiol 2017; 40:72–74.23. Anter E, Tschabrunn CM, Buxton AE, Josephson ME: High-Resolution Mapping of Postinfarction Reentrant Ventricular Tachycardia: Electrophysiological Characterization of the Circuit. Circulation 2016; 134:314–327.24. Jiang C-X, Long D-Y, Li M-M, et al.: Evidence of 2 conduction exits of the moderator band: Findings from activation and pace mapping study. Heart Rhythm 2020; 17:1856–1863.25. Itoh T, Yamada T: Usefulness of pace mapping in catheter ablation of left ventricular papillary muscle ventricular arrhythmias with a preferential conduction. J Cardiovasc Electrophysiol 2018; 29:889–899.26. Bogun F, Good E, Reich S, et al.: Role of Purkinje fibers in post-infarction ventricular tachycardia. J Am Coll Cardiol 2006; 48:2500–2507.

Purinergic receptors are the ones that use nucleotides as their agonists or antagonists. They have crucial role in platelets. Their physiological role as well as pharmacological target for antiplatelet drugs are well established and they have immense applications in clinical practice. But today the same purinergic receptors over platelets were identified elsewhere and they have been implicated in various health conditions. So, this review focuses to explain the non-thrombotic uses of platelet purinergic receptors

Background and purpose The translation of new injectable anaesthetic drugs from rodent to humans remains slow, despite the realisation that reliance on the volatile agents is unsustainable from an environmental perspective. The aim of this study was to investigate the influence of rat sex and strain on the PK and PD of the anaesthetic neurosteroid alfaxalone. Experimental approach Forty rats had cannulas inserted under isoflurane anaesthesia for drug administration and sampling. Carotid artery blood samples were collected for blood gas analysis, haematology, biochemistry, and plasma concentrations of alfaxalone. Plasma samples were assayed using liquid chromatography-mass spectrometry. Compartmental non-linear mixed effects methods (NLME) models were applied to two rat populations to determine whether body weight, sex and strain influenced PK parameters Key Results There were significant differences between the sexes for plasma clearance, half-life and mean residence time in Lewis rats and mean arterial blood pressure was significantly lower in the female rats at 120 minutes. An initial NLME PK population model was used to design an adjusted alfaxalone infusion for SD females matching plasma concentrations in males and minimising cardiopulmonary depression but maintaining an appropriate hypnotic effect. A final NLME population model showed that alfaxalone clearance was dependent on both bodyweight and sex whereas volume of distribution was influenced by strain. Conclusion and implications NLME PK models offer the advantage of having a single model that describes a population and therefore shares data interpretation between animals unlike the standard deterministic PK approach. This approach can be used to propose bespoke dosing regimens for optimal use of alphaxalone.