New variants of SARS-CoV-2, vaccine immune response and the Brazilian reality

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic β-coronavirus, is the etiologic agent of coronavirus disease 2019 (COVID-19), which gave rise to a difficult to control pandemic, especially in Brazil. Approximately 4,000 mutations have been identified in SARS-CoV-2, with the majority being redundant without having any biological effect on the virus. The aim of the present study was to objectively understand how new SARS-CoV-2 variants can affect vaccine response, in addition to highlighting the current situation in Brazil in the face of the pandemic and considering epidemiological and immunological aspects of COVID-19. The main protective correlate investigated in most vaccines is the neutralizing antibody titer induced by immunizing agents, observed in the pre-clinical phase in animals, whose action is to block the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, preventing infection. Up to the second half of 2021, the variants that are of greatest concern worldwide and require molecular surveillance are Alpha variant (or B.1.1.7 lineage), Beta (or B.1.351 lineage), Gamma (or P1 lineage) and Delta (or B.1.617.2 lineage). Brazil finds itself in a highly unfavorable scenario, with the circulation of variants of concern, mainly Gamma and Delta, with high fatality rates for COVID-19 and low vaccination rate. Given the still latent situation of the COVID-19 pandemic in Brazil, the lack of global planning for action strategies for non-pharmacological prevention measures, there is an imminent risk of the emergence of new variants due to the finding of susceptible hosts and the high proliferative rate of SARS-CoV-2. It is urgent to increase the genotyping of positive samples isolated from infected individuals, the speed of vaccination of the entire population and the unification of non pharmacological preventive measures throughout the country.

Audit on Clinical Competency of Fresh Medical Graduates in a Malaysian Private University Using Kirkpatrick Level-1 Evaluation Model

Clinical competency is the core of the medical curriculum. Careful ongoing evaluation of clinical competency is required to ensure continuous reviewing for curriculum development. The objective of this study was to investigate self-perceptions of clinical competency of fresh medical graduates using the Kirkpatrick framework – the most convenient and widely used model for measuring clinical competency. A cross-sectional study was conducted among 50 fresh medical graduates of Widad University College, Malaysia in 2019 using a standardised questionnaire containing 43-items of competency. Respondents were asked to rate self-perceptions of his/her competency in these attributes using a five-point Likert scale against each attribute, where 5 = always competent and 1 = never competent. The response rate was 92%. Out of 43 items, graduates were always competent in taking clinical history and examining a patient thoroughly; frequently competent in eight attributes; sometimes competent in 29; and occasionally competent in four. The graduates have not yet started their houseman-training; and thus, got fewer chances to practice all the procedures. It is expected that graduates’ competency will improve during their houseman training. There is scope for improvement, as faculty need to pay more attention to improving student competency by arranging additional training. The teaching of clinical competency also needs integration with the pre-clinical phase for early exposure. The findings have direct implications for faculty development towards competency-based education that would bridge the gap between education and practice. This study offers other medical schools a window towards comprehensive use of competency tools to assess the competency of their graduates.

Medical students positions regarding resource allocation in times of crisis

Objective To compare the perspectives of medical students in the preclinical and clinical phases of medical training on the issue of rationing scarce medical resources in times of crisis. Methods Questionnaire-based cross-sectional study. Results A total of 201 participants took part in the study, with 100 participants in the preclinical phase group, and 101 in the clinical phase group. A multivariable analysis found that just 14.9% (n = 34) of the clinical phase students were willing to give a short-supplied blood unit to the first-arrived patient to the emergency department when more patients are expected compared to 63.9% in the preclinical group (n = 62) ( p < 0.001, OR = 0.75 95% CI: 0.029−0.192). Seventy-four percent (n = 74) of the clinical phase students were found to be willing to remove a patient from a respirator to allocate it to an ill child compared to 35.7% (n = 35) in the preclinical phase group ( p < 0.001, OR = 4.168 95% CI: 1.931−8.998). Of the clinical phase group, 46.6% (n = 41) were willing to allocate a short supplied flu medicine to a patient with poor prognosis compared to 57.7% (n = 56) in the preclinical phase group ( p = 0.04, OR = 0.457 95% CI: 0.216−0.966). Conclusion Clinical exposure during training may affect the way medical students make ethical decisions, independent of age, sex, as well as marital and parental status.

ImproveCog, a cognitive stimulation program for people with mild cognitive impairment and dementia: First stage of development

Cognitive stimulation seems to be an important tool to slow the rate of cognitive decline due to dementia. This study describes the development of a cognitive stimulation program (ImproveCog) for people with Mild Cognitive Impairment, Alzheimer’s Disease, and behavioral variant Frontotemporal Dementia, within the Medical Research Council framework. Stage 1 established the theoretical and evidence basis of the program through a review of the existing cognitive stimulation programs as well as cognitive exercises and their efficacy (Pre-Clinical Phase) and includes qualitative testing through five focus group with eighteen health professionals and twelve individual interviews with people with cognitive impairment (Phase I - Modeling). An initial version of the program, which consisted of twelve 90-min weekly sessions and included a manual with cognitive stimulation exercises to be performed at home, was ready to be implemented in a pilot study to create a final version of ImproveCog.

A Glimpse in the Future of Malignant Mesothelioma Treatment

Malignant mesothelioma (MMe) is a rare neoplasm with few therapeutic options available. The landscape of effective therapy for this disease remained unchanged in the last two decades. Recently, however, the introduction of Immune Checkpoint Inhibitors (ICIs) led to small, but nevertheless, promising improvements. However, many efforts are still needed to radically improve the prognosis of MMe. In this review, we analyze all those therapeutic strategies for MMe that are still in a preclinical or early clinical phase of development. In particular, we focus on novel antiangiogenic drugs and their possible combination with immunotherapy. Furthermore, we describe also more complex strategies such as microRNA-loaded vectors, oncolytic viruses, and engineered lymphocytes.

Peripheral Biomarkers in Multiple Sclerosis Patients Treated with Interferon-Beta

Multiple sclerosis is a relapsing and eventually progressive disorder of the central nervous system that continues to challenge researchers who try to understand the pathogenesis of the disease and prevent its progression. Interferon-beta is the most widely prescribed treatment for MS. Peripheral blood seems to mirror the immunological disturbances that underlie MS, which could represent the migration patterns between periphery and other tissues according to the clinical phase of the disease. Based on this assumption, several studies point to significant alterations in peripheral blood homeostasis of different subpopulations of T cells, like γδ T cells or Th1, Th2 and Th17 functional subsets; of B cells subpopulations; and of innate cells like monocytes and dendritic cells. The main goal of this chapter is to make an in-depth review of the major findings described in the literature that correlate specific alterations on different leukocytes subpopulations with disease status, and which therefore have the potential to constitute a peripheral biomarker of disease progression.

Vaccine-induced immune responses against SARS-CoV-2 infections

Vaccination against coronavirus disease 2019 (COVID-19) is one of the most effective tools to curb the pandemic. Multiple vaccine candidates based on different platforms are available for emergency use presently. However, in common all the vaccines target spike protein, which is a dominant immunogen of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Adequate immunogenicity and efficacy are demonstrated by many of the vaccines in clinical phase III trials. The emergence of the new variant of concern is believed to be associated with less susceptibility to the post-infection or post-vaccination mounted immunity. It is a global concern currently threatening the progression of the vaccination drive. Nevertheless, the results of the presently available phase III clinical trials promote COVID-19 vaccination to prevent disease severity and COVID-19 related deaths. Cross-immunity towards the new variants of concern especially against the South African variant is yet to be explored and managed adequately.

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy

Hepatitis B virus (HBV) is a major causative agent of human hepatitis. Its viral genome comprises partially double-stranded DNA, which is complexed with viral polymerase within an icosahedral capsid consisting of a dimeric core protein. Here, we describe the effects of capsid assembly modulators (CAMs) on the geometric or kinetic disruption of capsid construction and the virus life cycle. We highlight classical, early-generation CAMs such as heteroaryldihydropyrimidines, phenylpropenamides or sulfamoylbenzamides, and focus on the chemical structure and antiviral efficacy of recently identified non-classical CAMs, which consist of carboxamides, aryl ureas, bithiazoles, hydrazones, benzylpyridazinones, pyrimidines, quinolines, dyes, and antimicrobial compounds. We summarize the therapeutic efficacy of four representative classical compounds with data from clinical phase 1 studies in chronic HBV patients. Most of these compounds are in phase 2 trials, either as monotherapy or in combination with approved nucleos(t)ides drugs or other immunostimulatory molecules. As followers of the early CAMs, the therapeutic efficacy of several non-classical CAMs has been evaluated in humanized mouse models of HBV infection. It is expected that these next-generation HBV CAMs will be promising candidates for a series of extended human clinical trials.

Lack of residents due to COVID-19 pandemic. Can a mentor–mentee program during medical studies have a positive influence on the choice for specialist training in gynecology and obstetrics? A review of current literature and results of a national wide survey of medical students

Objective The COVID-19 pandemic restricting clinical practice and exacerbating the lack of medical staff. There is currently a lack of young residents who are deciding on further training in gynecology and obstetrics. Design: review and prospective, cross-sectional study. Setting: the aim of this study was to investigate if structured mentoring programs can counteract this deficiency. Population: medical students took part from Germany in the clinical phase. Methods An anonymous questionnaire was developed and distributed to students from January to October 2020. Epidemiological data, questions about mentoring experiences, necessity and their expected influence on career planning were collected and statistically evaluated. Main outcome measures: structured mentoring-programs can influence the choice of subject. In particular, men are still underrepresented. Research on the topic of mentoring during in the field of gynaecology and obstetrics is completely lacking. Results A representative number of 927 medical students took part in the survey. 22% (170/906) of the students had already participated in a mentoring program with a significantly higher proportion of men (69%; 117/170; p < 0.001). Of these, 94% (453/170) said this was helpful. 6% (55/906) wanted to pursue a career in gynecology and obstetrics. When asked about their appreciation for structured mentoring programs in gynecology and obstetrics, 95% (880/906) would participate and 94% agreed (871/906) that this could have an impact on their choice of specialist and career planning. Conclusions An active provision of mentoring programs and more content can be a way of counteracting the shortage of residents in gynecology and obstetrics.