Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart.

Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß-adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis. To assess whether isoproterenol-induced cardiomyocyte necrosis triggers an adaptive immune response against the heart, we treated C57BL/6J mice with a single intraperitoneal injection of isoproterenol. We confirmed tissue damage reminiscent of human type 2 myocardial infarction. This is followed by an adaptive immune response targeting the heart as demonstrated by the activation of T cells, the presence of anti-heart auto-antibodies in the serum as late as 12 weeks after initial challenge and IgG deposition in the myocardium. All of these are hallmark signs of an established autoimmune response. Adoptive transfer of splenocytes from isoproterenol-treated mice induces left ventricular dilation and impairs cardiac function in healthy recipients. In summary, a single administration of a high dose of isoproterenol is a suitable high-throughput model for future studies of the pathological mechanisms of anti-heart autoimmunity and to test potential immunomodulatory therapeutic approaches.

The role of humanities in the medical curriculum: medical students' perspectives.

BACKGROUND: The humanities have long been shown to play an important role in the medical school curriculum. However, few studies have looked into the opinions of medical students on the usefulness and necessity of the humanities as well as their extracurricular involvement with them. The aim of this study was to: a) understand medical students' attitude towards the humanities in medical education and b) assess their understanding of the necessary qualities of doctors and how interaction with the humanities affects the development of such attributes. METHODS: A mixed methods survey was designed to elicit demographics, engagement, interest and perspective on curricular positioning, and to explore how students ranked the qualities of a doctor. It was distributed to medical students of all year groups in the 6-year bachelor of medicine, bachelor of surgery (MBBS) course at Imperial College London. RESULTS: One hundred nine fully completed questionnaires were received. No significant difference was found in engagement or interest in the humanities between genders. Students felt strongly that humanities subjects shouldn't be assessed (71:18) though some felt it was necessary for engagement, while no consensus was reached on whether these subjects should be elective or not (38:31). The majority of students wanted more medical humanities to be incorporated into the traditional medical course with a preference of incorporation into the first 3 years. Junior medical students were more likely to rank empathy as a highly desirable attribute than senior students. Students provided qualitative insights into curricular positioning, assessment and value. CONCLUSIONS: This study provides the perspective of medical students on how and whether the humanities should be positioned in medical education. It may be helpful to medical schools that are committed to student involvement in curriculum design.

Structural and functional evaluation of recombinant histidine phosphokinase NisK and response regulator NisR: in silico and experimental approach.

In the two-component system of NisRK from Lactococcus lactis, the production of nisin is affected by transmembrane NisK and activation of intracellular NisR. The transcription of nisin structural genes can be induced by derivatives of nisin. NisR activation leads to the activation of nisA/Z transcription, which encodes the nisin maturation machinery, nisin regulation and activation of the nisFEG operon to confer immunity. The aim of this study was to express the Lactococcus lactis histidine phosphokinase NisK and response regulator NisR in E. coli, and to perform activity assays and in silico analysis. In silico methods were applied to study the properties and structures of the NisK and NisR proteins, including prediction of physicochemical characteristics, secondary and tertiary structure, stability and ligand-receptor interactions.pET32a and pET28a vectors containing synthetic nisK and nisR genes were transformed into E. coli followed by IPTG induction. SDS-PAGE and western blotting methods were applied to confirm the presence and identity of the amplified proteins. Following purification, the proteins were dialyzed and then prepared for activity assay. The CAI index showed that the genes was compatible with the E. coli host and that the proteins have effective expression. Also, the mRNA prediction results suggest that there is enough mRNA stability for efficient translation in the new host. NisK and NisR recombinant proteins were expressed in E. coli with half - lives of around 10 h and were confirmed with molecular weights of 27 kDa and 69 kDa, respectively, by SDS-PAGE and western blotting. The secondary structure of the recombinant proteins as predicted by circular dichroism spectroscopy was similar to the in silico protein structures. Activity assay of recombinant NisK was performed by measuring the amount of consumed ATP according to the light produced by luciferase. Because NisK and NisR have a direct impact on each other, they have an essential role in increasing the production of nisin and they can be used in different research fields. Our results demonstrated that recombinant proteins NisK and NisR preserved their structure and function after expression.

Integrative role of traditional and modern technologies to combat COVID-19.

INTRODUCTION: With the development of various branches of sciences, we will be able to resolve different clinical aspects of various diseases better. The convergence of these sciences can potentially tackle the new corona crisis. AREAS COVERED: In this review, we attempted to explore and describe various scientific branches studying COVID-19. We have reviewed the literature focusing on the prevention, diagnosis, and treatment of COVID-19. The primary databases targeted were Science Direct, Scopus and PubMed. The most relevant reports from the recent two decades were collected utilizing keywords including SARS-CoV, MERS-CoV, COVID-19, epidemiology, therapeutics and diagnosis. EXPERT OPINION: Based on this literature review, both traditional and emerging approaches are vital for the prevention, diagnosis and treatment of COVID-19. The traditional sciences play an essential role in the preventive and supportive care of corona infection, and modern technologies appear to be useful in the development of precise diagnosis and powerful treatment approaches for this disease. Indeed, the integration of these sciences will help us to fight COVID-19 disease more efficiently.

Characterization of Biosynthesized Silver Nanoparticles Using Lactobacillus rhamnosus GG and its In Vitro Assessment Against Colorectal Cancer Cells.

Silver nanoparticles are the most desirable nanoparticles broadly used in diverse fields. This study intends to investigate the anticancer properties of synthesized silver/Lactobacillus rhamnosus GG nanoparticles (Ag-LNPs) as a reducing and stabilizing agent in the synthesis process. To prepare silver/Lactobacillus rhamnosus GG nanoparticles, 1 mg/ml cell lysate of Lactobacillus rhamnosus GG and 1 mM silver nitrate solution were mixed and incubated for 72 h. XRD, FTIR, and TEM methods were used for nanoparticle characterization. MTT assay and annexin/PI staining were employed to analyze the toxicity and apoptotic cells levels of Ag-LNPs, respectively. TEM showed that these nanoparticles are spherical shaped about 233 nm in size. FTIR spectroscopy demonstrated that Ag-LNPs were functionalized with biomolecules. XRD pattern showed high purity and face-centered crystal structure of Ag-LNPs. MTT assay revealed that the percentages of HT-29 live cells significantly reduced in the high concentration of Ag-LNPs. Annexin/PI staining showed that these nanoparticles could lead HT-29 cells to apoptosis. This study showed the new Ag-LNP-synthesizing method using Lactobacillus rhamnosus GG as a cost-effective and efficient approach. Also, it showed that these nanoparticles can be considered as a potential active agent for biomedical applications and drug delivery due to their anticancer activities.

Self-Perceived Confidence of Medical Students Communicating with Pediatric Patients in a 7-Week Pediatric Placement: A Pilot Survey.

BACKGROUND: Pediatrics is a specialty reserved until later stages of the medical curriculum, with many students receiving early exposure via volunteering opportunities. Self-perceived confidence across the pediatric curriculum is crucial, due to limited clinical exposure before qualification. We aimed to assess the impact of a 7-week pediatric placement on medical students' self-perceived confidence and factors that influenced self-perceived confidence. METHODS: We conducted a prospective pilot survey on three cohorts of fifth-year students undertaking pediatric placements in 2018. A two-part questionnaire was distributed before and after the placement, evaluating the level of self-confidence in clinical skills using a 10-point scale. RESULTS: Of 103 students, 62 (60%) students completed both questionnaires. Of these, 34 (55%) students reported previous professional experiences with children. There was a significant increase in self-reported confidence scores across ten questions before (mean 5.4 [IQR 4.1-6.1]) and after the placement (7.6 [6.6-8.5], p<0.0001). Subgroup analyses between students with prior professional experience with children and those without revealed a significant difference in preplacement confidence in four pediatric practices: verbal communication, physical engagement, asking sensitive or probing questions, and explaining medical management (p<0.05). There was no significant difference in postplacement confidence between these two groups. CONCLUSION: Medical students with prior professional experience with children reported higher self-confidence in interacting with pediatric patients prior to placement. However, a large and consistent increase in confidence across the cohort was such that there were no measurable differences at exit. This study supports the value of undergraduate pediatric training in promoting student self-confidence in managing pediatric clinical issues.

Cardiac phenotype in mouse models of systemic autoimmunity.

Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.

Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications.

The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, ß-blockers, and renin⁻angiotensin⁻aldosterone inhibitors.

Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies.