scholarly journals Novel genetic constructs for production of recombinant HTLV-1/2 antigens and evaluation of their reactivity to plasma samples from HTLV1-infected patients

2021 ◽  
Author(s):  
Ueriton Dias de Oliveira ◽  
Fred Luciano Neves Santos ◽  
Bernardo Galvão-Castro ◽  
Marco Aurelio Krieger ◽  
Nilson Ivo Tonin Zanchin
Keyword(s):  
High Efficiency ◽  
Viral Envelope ◽  
Structural Proteins ◽  
Serological Tests ◽  
Gag Protein ◽  
Antigenic Proteins ◽  
High Sequence Conservation ◽  
Life Threatening ◽  
High Level ◽  
Genetic Constructs

HTLV-1 can cause life-threatening diseases for which there are no effective treatments. Prevention of HTLV-1 infection requires massive testing of pregnant women, blood for transfusion and, organs for transplantation as well as safe sex. In this context, serological assays are widely used for monitoring HTLV-1 infections. Despite the necessity of recombinant antigens to compose serological tests, there is little information available on procedures to produce recombinant HTLV1/2 antigens for serological diagnostic purposes. In this work, we tested a series of genetic constructions to select those more amenable for production in bacterial systems. To overcome the constraints to express sections of viral envelope proteins in bacteria, we have used the p24 segment of the gag protein as a scaffold to display the immunogenic regions of gp46 and gp21. Nine recombinant antigenic proteins derived from HTLV-1 and five derived from HTLV-2 were successfully purified. The HTLV-1 antigens showed high efficiency in discriminating HTLV-positive from HTLV-negative samples using ELISA. Interestingly, HTLV-1-positive samples showed a high level of cross-reaction with HTLV-2 antigens. This finding is explained by the high sequence conservation between the structural proteins of these two highly related viruses. In summary, the results presented in this work provide a detailed description of the methods used to produce recombinant HTLV-1 and HTLV-2 antigens and demonstrate that the HTLV-1 antigens show strong potential for serological diagnosis of HTLV1 infections.

OPERATIONS FOR ANEURISM OF THE ABDOMINAL AORTIC DEPARTMENT - RESECTION WITH THE FOLLOWING PROSTHETICS AND ENDOPROSTHETICS: A COMPARATIVE ANALYSIS OF COMPLICATIONS

2020 ◽  
pp. 43-49
Author(s):  
Андрей Анатольевич Иванов ◽  
Александр Иванович Жданов ◽  
Максим Сергеевич Шевелин ◽  
Александр Сергеевич Брежнев
Keyword(s):  
Comparative Analysis ◽  
Postoperative Complications ◽  
Statistical Significance ◽  
Aortic Aneurysms ◽  
Surgical Interventions ◽  
Vein Thrombosis ◽  
Scientific Hypothesis ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
High Level

В статье представлены данные оригинального исследования по улучшению хирургического лечения аневризм брюшного отдела аорты. С этой целью произведен сравнительный анализ двух альтернативных друг другу операций: 1) резекции аневризмы с последующим протезированием аорты; 2) эндопротезирования аорты. Сформулировано научное предположение о том, что замена «классических» операций резекции аневризмы на «альтернативные» операции эндопротезирования приведет к принципиальному снижению уровня послеоперационных осложнений. В независимых группах пациентов с использованием сравниваемых хирургических вмешательств произведена точная качественная и количественная оценка послеоперационных осложнений: нетромботических - кардиальных, пульмональных, ренальных и тромботических - тромбозов глубоких вен и тромбозов браншей протеза. После реализации исследования было установлено, что замена «классических» операций на «альтернативные» достоверно приводит к принципиальному снижению уровня наиболее жизнеопасных осложнений - кардиальных (острых форм ишемической болезни сердца, нарушений сердечного ритма), пульмональных (пневмоний, тромбоэмболии легочной артерии, респираторного дистресс-синдрома взрослых) и ренальных (острой почечной недостаточности). Некоторое исключение составили менее жизнеопасные тромботические осложнения. Полученные результаты имеют высокий уровень статистической значимости, что позволяет рекомендовать их к рассмотрению к использованию в практике сосудистой хирургии The article presents data from an original study to improve the surgical treatment of abdominal aortic aneurysms. For this purpose, a comparative analysis of two alternate operations was performed: 1) aneurysm resection followed by aortic prosthetics; 2) aortic endoprosthetics. The scientific hypothesis is formulated that the replacement of the «classical» operations of resection of the aneurysm with «alternative» operations of endoprosthetics will lead to a fundamental decrease in the level of postoperative complications. In independent groups of patients using the compared surgical interventions, an accurate qualitative and quantitative assessment of postoperative complications was made: non-thrombotic - cardiac, pulmonary, renal and thrombotic - deep vein thrombosis and prosthetic jaw thrombosis. After the study was completed, it was found that the fundamental replacement of «classical» operations with «alternative» reliably leads to a fundamental decrease in the level of the most life-threatening complications - cardiac (acute forms of coronary heart disease, cardiac arrhythmias), pulmonary (pneumonia, pulmonary thromboembolism, respiratory distress syndrome of adults) and renal (acute renal failure). Some exceptions were less life-threatening thrombotic complications. The results obtained have a high level of statistical significance, which allows us to recommend them for consideration in the practice of vascular surgery

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

scholarly journals Clinicians’ Knowledge and Attitudes About Delirium Detection and Management

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 519-520
Author(s):  
Priyanka Shrestha ◽  
Erica Husser ◽  
Diane Berish ◽  
Long Ngo ◽  
Marie Boltz ◽  
...  
Keyword(s):  
Rating Scale ◽  
P Value ◽  
Clinical Implementation ◽  
Chi Square ◽  
Response Options ◽  
Knowledge And Attitudes ◽  
Point Rating Scale ◽  
Life Threatening ◽  
Strongly Agree ◽  
High Level

Abstract Delirium is a serious and potentially life-threatening problem, but it remains clinically under-recognized. Various factors contribute to this under-recognition, including limited understanding of delirium, insufficient training and application of delirium assessments, potential stigma for the patient and increased workload for the clinician. As a part of an NIH funded study testing a rapid two-step delirium identification protocol at two hospitals in the U.S. (one urban and one rural), clinicians completed a 12-item survey to assess their knowledge and attitudes about delirium and their confidence in preventing and managing delirium. Survey response options followed a 5-point rating scale (strongly disagree, disagree, undecided, agree, strongly agree). The sample for this analysis included 399 clinicians (MDs=53; RNs=235; CNAs=111). Chi-square was used to test for group differences between clinician types. Less than half of the clinicians reported agreeing with the statement, “delirium is largely preventable” (MDs: 47%; RN: 44%; CNA: 41%, p-value=0.021). MDs and RNs indicated a high level of confidence in recognizing delirium while CNAs endorsed lower levels of confidence (MDs: 87%; RN: 81%; CNA: 65%, p-value=0.001). All types of clinicians reported lower confidence in managing delirium (MDs: 29%; RN: 36%; CNA: 44%, p-value=0.117). 47% of CNAs and 37% of RNs agreed there is a need for additional training in caring for persons with delirium while only 21% of MDs agreed (p = 0.031). Understanding how different types of clinicians think and feel about delirium will inform training and communication initiatives, clinical implementation, and research on best practices for delirium identification and management.

scholarly journals A fatal toxic shock-like syndrome post COVID-19 infection in a child

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Houda Ajmi ◽  
Wissem Besghaier ◽  
Wafa Kallala ◽  
Abdelhalim Trabelsi ◽  
Saoussan Abroug
Keyword(s):  
Ejection Fraction ◽  
Pediatric Intensive Care ◽  
Fresh Frozen Plasma ◽  
Multiple Organ ◽  
Clinical Feature ◽  
Fresh Frozen ◽  
Life Threatening ◽  
High Doses ◽  
Definition Of ◽  
High Level

Abstract Background Children affected by Coronavirus disease 2019 (COVID-19) showed various manifestations. Some of them were severe cases presenting with multi-system inflammatory syndrome (MIS-C) causing multiple organ dysfunction. Case presentation We report the case of a 12-year-old girl with recent COVID-19 infection who presented with persistent fever, abdominal pain and other symptoms that meet the definition of MIS-C. She had lymphopenia and a high level of inflammatory markers. She was admitted to pediatric intensive care unit since she rapidly developed refractory catecholamine-resistant shock with multiple organ failure. Echocardiography showed a small pericardial effusion with a normal ejection fraction (Ejection Fraction = 60%) and no valvular or coronary lesions. The child showed no signs of improvement even after receiving intravenous immunoglobulin, fresh frozen plasma, high doses of Vasopressors and corticosteroid. His outcome was fatal. Conclusion Pediatric patients affected by the new COVID-19 related syndrome may show severe life-threatening conditions similar to Kawasaki disease shock syndrome. Hypotension in these patients results from heart failure and the decreased cardiac output. We report a new severe clinical feature of SARS-CoV-2 infection in children in whom hypotension was the result of refractory vasoplegia.

scholarly journals The YadA Protein of Yersinia pseudotuberculosis Mediates High-Efficiency Uptake into Human Cells under Environmental Conditions in Which Invasin Is Repressed

2002 ◽  
Vol 70 (9) ◽  
pp. 4880-4891 ◽  
Author(s):  
Julia Eitel ◽  
Petra Dersch
Keyword(s):  
Extracellular Matrix ◽  
Mammalian Cells ◽  
Yersinia Pseudotuberculosis ◽  
High Efficiency ◽  
Environmental Parameters ◽  
Infection Process ◽  
Nutrient Concentrations ◽  
Integrin Receptors ◽  
Uptake Process ◽  
High Level

ABSTRACT The YadA protein is a major adhesin of Yersinia pseudotuberculosis that promotes tight adhesion to mammalian cells by binding to extracellular matrix proteins. In this study, we first addressed the possibility of competitive interference of YadA and the major invasive factor invasin and found that expression of YadA in the presence of invasin affected neither the export nor the function of invasin in the outer membrane. Furthermore, expression of YadA promoted both bacterial adhesion and high-efficiency invasion entirely independently of invasin. Antibodies against fibronectin and β1 integrins blocked invasion, indicating that invasion occurs via extracellular-matrix-dependent bridging between YadA and the host cell β1 integrin receptors. Inhibitor studies also demonstrated that tyrosine and Ser/Thr kinases, as well as phosphatidylinositol 3-kinase, are involved in the uptake process. Further expression studies revealed that yadA is regulated in response to several environmental parameters, including temperature, ion and nutrient concentrations, and the bacterial growth phase. In complex medium, YadA production was generally repressed but could be induced by addition of Mg2+. Maximal expression of yadA was obtained in exponential-phase cells grown in minimal medium at 37°C, conditions under which the invasin gene is repressed. These results suggest that YadA of Y. pseudotuberculosis constitutes another independent high-level uptake pathway that might complement other cell entry mechanisms (e.g., invasin) at certain sites or stages during the infection process.

scholarly journals Population-Predicted MHC Class II Epitope Presentation of SARS-CoV-2 Structural Proteins Correlates to the Case Fatality Rates of COVID-19 in Different Countries

2021 ◽  
Vol 22 (5) ◽  
pp. 2630
Author(s):  
Chunguang Liang ◽  
Elena Bencurova ◽  
Eric Psota ◽  
Priya Neurgaonkar ◽  
Martina Prelog ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Case Fatality Rate ◽  
Case Fatality ◽  
Class Ii ◽  
Viral Envelope ◽  
Structural Proteins ◽  
P Value ◽  
Fatality Rate ◽  
Different Populations ◽  
Infection Spread

We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.

High Efficiency Combined Aggregate – Submerged Combustion Melter–Electric Furnace for Vitrification of High-Level Radioactive Wastes

2004 ◽  
Author(s):  
L. S. Pioro ◽  
I. L. Pioro
Keyword(s):  
Electric Furnace ◽  
High Efficiency ◽  
High Capacity ◽  
Main Idea ◽  
Melting Process ◽  
Radioactive Wastes ◽  
Single Stage ◽  
Interface Surface ◽  
High Level ◽  
Submerged Combustion

It is well known that high-level radioactive wastes (HLRAW) are usually vitrified inside electric furnaces. Disadvantages of electric furnaces are their low melting capacity and restrictions on charge preparation. Therefore, a new concept for a high efficiency combined aggregate – submerged combustion melter (SCM)–electric furnace was developed for vitrification of HLRAW. The main idea of this concept is to use the SCM as the primary high-capacity melting unit with direct melt drainage into an electric furnace. The SCM employs a single-stage method for vitrification of HLRAW. The method includes concentration (evaporation), calcination, and vitrification of HLRAW in a single-stage process inside a melting chamber of the SCM. Specific to the melting process is the use of a gas-air or gas-oxygen-air mixture with direct combustion inside a melt. Located inside the melt are high-temperature zones with increased reactivity of the gas phase, the existence of a developed interface surface, and intensive mixing, leading to intensification of the charge melting and vitrification process. The electric furnace clarifies molten glass, thus preparing the high-quality melt for subsequent melt pouring into containers for final storage.

PROCEDURE IN PATIENTS WITH HEART FAILURE (UPDATE 2019) – NON-PHARMACOLOGICAL THERAPY

2020 ◽  
Vol 4 (53) ◽  
pp. 19-22
Author(s):  
Przemysław Mitkowski
Keyword(s):  
Heart Failure ◽  
Meta Analysis ◽  
Pharmacological Therapy ◽  
Functional Mitral Regurgitation ◽  
Pharmacological Management ◽  
Device Implantation ◽  
Patients With Heart Failure ◽  
Life Threatening ◽  
Treatment Analysis ◽  
High Level

Up-date of ESC Guidelines on management of patients with heart failure was published last year. Beside topics related to pharmacological treatment one can find also chapters dedicated to non-pharmacological management. In the field of ICD therapy Authors propose one may consider not to implant the device in patients over 70 years old, especially when they suffer from advanced heart failure and life-threatening comorbidities. It is in contra with meta-analysis presented after results of DANISH trial has been published, which underlined benefits of ICD treatment in such patients. Moreover in patients randomized to treatment without ICD almost 60% received CRTP. It is also important that 24 patients randomized to no-ICD group finally received ICD because of appearance of life-threatening ventricular arrhythmia. In such situation additional on-treatment analysis would be beneficial. One can get an impression that pulmonary vein ablation in patients with heart failure and atrial fibrillation achieve enough high level of recommendation despite favourable results of CASTLE-AF and on-treatment analysis of CABANA trials. Analysis of data according to received treatment seemed to be beneficial especially when the percentage of crossover is significant. Functional mitral regurgitation should be managed after meaningful analysis of each case and referral to MitraClip implantation should be based on the protocol of COAPT trial which proves benefits of a such device implantation.

scholarly journals The Nature of Post-Traumatic Stress in Life-Threatening Diseases

Vestnik RFFI ◽  
2019 ◽  
pp. 49-58
Author(s):  
Natalia E. Kharlamenkova ◽  
Daria A. Nikitina
Keyword(s):  
Traumatic Stress ◽  
Post Traumatic Stress ◽  
Paranoid Ideation ◽  
Special Configuration ◽  
Psychological Study ◽  
Psychopathological Symptoms ◽  
Life Threatening ◽  
Post Traumatic ◽  
The Individual ◽  
High Level

This article presents the results of theoretical and empirical study of the psychological problems, which are arisen on the influence of high-intensity stressors on a personality. The post-traumatic stress, as a delayed complex response to a stress- or – a life-threatening disease, is considered as one of such consequences. On a sample of people (n = 39) diagnosed with meningioma (a benign tumor of the arachnoid mater), in the post-surgical period, a comprehensive psychological study was conducted using the interviewing and testing methods. The authors verified the hypothesis of a special configuration of personality characteristics and psychopathological symptoms at different levels of post-traumatic stress (PTS), caused by the reaction of the individual to the diagnosis of meningioma. The investigation demonstrates that at the high level of PTS such personality traits as depression, emotional lability, shyness and irritability are diagnosed, that are the most likely prerequisites for the development of psychopathological symptoms – depression, anxiety, paranoid ideation and psychoticism. It is concluded that the severe experience of post-traumatic stress, caused by the diagnosis of a life-threatening illness, systematically manifests itself at all levels of the individual functioning – organismal, psychological and social.

scholarly journals High-Level Aminoglycoside Resistance in Human Clinical Klebsiella pneumoniae Complex Isolates and Characteristics of armA-Carrying IncHI5 Plasmids

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueya Zhang ◽  
Qiaoling Li ◽  
Hailong Lin ◽  
Wangxiao Zhou ◽  
Changrui Qian ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Conjugative Plasmid ◽  
Comparative Genomic ◽  
Aminoglycoside Resistance ◽  
Life Threatening ◽  
Aminoglycoside Resistance Genes ◽  
High Level

Aminoglycosides are important options for treating life-threatening infections. However, high levels of aminoglycoside resistance (HLAR) among Klebsiella pneumoniae isolates have been observed to be increasing frequently. In this study, a total of 292 isolates of the K. pneumoniae complex from a teaching hospital in China were analyzed. Among these isolates, the percentage of HLAR strains was 13.7% (40/292), and 15 aminoglycoside resistance genes were identified among the HLAR strains, with rmtB being the most dominant resistance gene (70%, 28/40). We also described an armA-carrying Klebsiella variicola strain KP2757 that exhibited a high-level resistance to all aminoglycosides tested. Whole-genome sequencing of KP2757 demonstrated that the strain contained one chromosome and three plasmids, with all the aminoglycoside resistance genes (including two copies of armA and six AME genes) being located on a conjugative plasmid, p2757-346, belonging to type IncHI5. Comparative genomic analysis of eight IncHI5 plasmids showed that six of them carried two copies of the intact armA gene in the complete or truncated Tn1548 transposon. To the best of our knowledge, for the first time, we observed that two copies of armA together with six AME genes coexisted on the same plasmid in a strain of K. variicola with HLAR. Comparative genomic analysis of eight armA-carrying IncHI5 plasmids isolated from humans and sediment was performed, suggesting the potential for dissemination of these plasmids among bacteria from different sources. These results demonstrated the necessity of monitoring the prevalence of IncHI5 plasmids to restrict their worldwide dissemination.

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