A clinical study of arrhythmias associated with acute myocardial infarction and thrombolysis

Background: Arrhythmias are a common occurrence in ACS. This study was undertaken to analyze the incidence, frequency and type of arrhythmias in relation to the site of infarction to aid in timely intervention to modify the outcome in MI and to study the significance of Reperfusion arrhythmias.Methods: 100 patients were evaluated. ECG and cardiac enzymes were studied. Arrhythmias complicating AMI in terms of their incidence, timing, severity, type, relation, reperfusion and results were studied.Results: Of the 100 cases, 74% were males and 26% females of which incidence being common between 4th to 7th decades of life. AMI was common in patients with Diabetes and Hypertension (23% each). Incidence of AWMI (58%) is higher than IWMI (40%). Out of all arrhythmias, Ventricular Tachycardia was seen in 24% cases with 50% mortality and preponderance to Antero Lateral Myocardial Infarction. Sinus Tachycardia was seen in 23% of cases with preponderance to Antero Lateral Myocardial Infarction and persistence of Sinus Tachycardia was a prognostic sign, mortality being 22%. Complete Heart Block and Sinus Bradycardia were seen with IWMI, incidence being 53.8% and 100% respectively. Bundle Branch Block was common in AWMI (31%) than IWMI (10%). Among 64 thrombo-lysed cases, 21 had Reperfusion Arrhythmias without any mortality, whereas remaining 43 without Reperfusion Arrhythmias had mortality of 18.6%.Conclusions: According to the study, Tachy-arrhythmias are common with Anterior Wall Myocardial Infarction and Brady-arrhythmias in Inferior Wall Myocardial Infarction. Reperfusion Arrhythmias are a benign phenomenon and good indicator of successful reperfusion

Design of the strut braced wing aircraft in the agile collaborative MDO framework

The paper describes the deployment of the AGILE Development Framework to investigate the Strut Braced Wing aircraft configuration. The design process consists of a multilevel multidisciplinary architecture, progressing from the initial conceptual synthesis to the physics based analysis. All the main disciplinary domains, including on board system design and cost assessment, are accounted for in the assembled workflow. Due to the specific characteristics of the Strut Braced Wing configuration, the aeroelastic analysis is the main focus of the study and it is addressed at both high and low fidelity levels. The integration of the engine-wing system is also included in the design process. All the design competences, which are hosted at the different partners, communicate via CPACS (Common Parametric Aircraft Configuration Schema) data schema. All the results generated, including the multidisciplinary design process itself, will be published and made available as part of the AGILE Overall Aircraft Design database

First urology simulation boot camp in the United Kingdom

Objective: Simulation is now firmly established in modern surgical training and is applicable not only to acquiring surgical skills but also to non-surgical skills and professionalism. A 5-day intensive Urology Simulation Boot Camp was run to teach emergency procedural skills, clinical reasoning, and communication skills using clinical scenario simulations, endoscopic and laparoscopic trainers. This paper reports the educational value of this first urology boot camp. Subjects and methods: Sixteen urology UK trainees completed pre-course questionnaires on their operative experience and confidence level in common urological procedures. The course included seven modules covering basic scrotal procedures, laparoscopic skills, ureteroscopy, transurethral resection of the prostate and bladder tumour, green light laser prostatectomy, familiarisation with common endoscopic equipment, bladder washout to remove clots, bladder botox injection, setting up urodynamics. Emergency urological conditions were managed using scenarios on SimMan®. The main focus of the course was hands-on training using animal models, bench-top models and virtual reality simulators. Post-course assessment and feedback on the course structure and utility of knowledge gained together with a global outcome score was collected. Results: Overall all the sections of feedback received score of over 4.5/5, with the hands-on training on simulators getting the best score 4.8/5. When trainees were asked “The training has equipped me with enhanced knowledge, understanding and skills,” the average score was 4.9/5.0. The vast majority of participants felt they would recommend the boot camp to future junior trainees. Conclusion: This first UK Urology Simulation Boot Camp has demonstrated feasibility and effectiveness in enhancing trainee’s experience. Given these positive feedbacks there is a good reason to expect that future courses will improve the overall skills of a new urology trainee

Metagenomics reveals impact of geography and acute diarrheal disease on the Central Indian human gut microbiome

© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Background: The Central Indian gut microbiome remains grossly understudied. Herein, we sought to investigate the burden of antimicrobial resistance and diarrheal diseases, particularly Clostridioides difficile, in rural-agricultural and urban populations in Central India, where there is widespread unregulated antibiotic use. We utilized shotgun metagenomics to comprehensively characterize the bacterial and viral fractions of the gut microbiome and their encoded functions in 105 participants. Results: We observed distinct rural-urban differences in bacterial and viral populations, with geography exhibiting a greater influence than diarrheal status. Clostridioides difficile disease was more commonly observed in urban subjects, and their microbiomes were enriched in metabolic pathways relating to the metabolism of industrial compounds and genes encoding resistance to 3rd generation cephalosporins and carbapenems. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, phage variation could be directly related to shifts in bacterial populations, with the auxiliary metabolic potential of rural-associated phages enriched for carbon and amino acid energy metabolism. Conclusions: We report distinct differences in antimicrobial resistance gene profiles, enrichment of metabolic pathways and phage composition between rural and urban populations, as well as a higher burden of Clostridioides difficile disease in the urban population. Our results reveal that geography is the key driver of variation in urban and rural Indian microbiomes, with acute diarrheal disease, including C. difficile disease exerting a lesser impact. Future studies will be required to understand the potential role of dietary, cultural, and genetic factors in contributing to microbiome differences between rural and urban populations

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2×106 CFU) and low doses (2×102 CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNγ, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in futur

Grain and seed protein functionality

Editado por Jiménez-López, José Carlos (CSIC

Exploring the Dynamic Range of the Kinetic Exclusion Assay in Characterizing Antigen-Antibody Interactions

Therapeutic antibodies are often engineered or selected to have high on-target binding affinities that can be challenging to determine precisely by most biophysical methods. Here, we explore the dynamic range of the kinetic exclusion assay (KinExA) by exploiting the interactions of an anti-DKK antibody with a panel of DKK antigens as a model system. By tailoring the KinExA to each studied antigen, we obtained apparent equilibrium dissociation constants (KD values) spanning six orders of magnitude, from approximately 100 fM to 100 nM. Using a previously calibrated antibody concentration and working in a suitable concentration range, we show that a single experiment can yield accurate and precise values for both the apparent KD and the apparent active concentration of the antigen, thereby increasing the information content of an assay and decreasing sample consumption. Orthogonal measurements obtained on Biacore and Octet label-free biosensor platforms further validated our KinExA-derived affinity and active concentration determinations. We obtained excellent agreement in the apparent affinities obtained across platforms and within the KinExA method irrespective of the assay orientation employed or the purity of the recombinant or native antigens

Resistance of Foxp3+ Regulatory T Cells to Nur77-Induced Apoptosis Promotes Allograft Survival

The NR4A nuclear receptor family member Nur77 (NR4A1) promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg) cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by ∼80% compared to wild-type (WT) mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT) and secondary lymphoid organs (40–50% of CD4+Foxp3+ T cells vs. 7–8% in WT) of Nur77 transgenic (Nur77Tg) mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival