Comparing the performance of artificial intelligence learning models to medical students in solving histology and embryology multiple choice questions.

INTRODUCTION: The appearance of artificial intelligence language models (AI LMs) in the form of chatbots has gained a lot of popularity worldwide, potentially interfering with different aspects of education, including medical education as well. The present study aims to assess the accuracy and consistency of different AI LMs regarding the histology and embryology knowledge obtained during the 1st year of medical studies. METHODS: Five different chatbots (ChatGPT, Bing AI, Bard AI, Perplexity AI, and ChatSonic) were given two sets of multiple-choice questions (MCQs). AI LMs test results were compared to the same test results obtained from 1st year medical students. Chatbots were instructed to use revised Bloom's taxonomy when classifying questions depending on hierarchical cognitive domains. Simultaneously, two histology teachers independently rated the questions applying the same criteria, followed by the comparison between chatbots' and teachers' question classification. The consistency of chatbots' answers was explored by giving the chatbots the same tests two months apart. RESULTS: AI LMs successfully and correctly solved MCQs regarding histology and embryology material. All five chatbots showed better results than the 1st year medical students on both histology and embryology tests. Chatbots showed poor results when asked to classify the questions according to revised Bloom's cognitive taxonomy compared to teachers. There was an inverse correlation between the difficulty of questions and their correct classification by the chatbots. Retesting the chatbots after two months showed a lack of consistency concerning both MCQs answers and question classification according to revised Bloom's taxonomy learning stage. CONCLUSION: Despite the ability of certain chatbots to provide correct answers to the majority of diverse and heterogeneous questions, a lack of consistency in answers over time warrants their careful use as a medical education tool.

Small Interfering Ribonucleic Acid as Lipid-Lowering Therapy: Inclisiran in Focus.

The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) enzyme interferes with the metabolism of low-density lipoprotein (LDL) cholesterol. Inhibition of PCSK9 results in lower LDL cholesterol levels, which can be achieved by different molecular pathways. Monoclonal antibodies targeting circulating PCSK9 have shown strong and persistent effects on lowering the LDL cholesterol level, while reducing the risk of future cardiovascular events. However, this therapy requires once- or twice-monthly administration in the form of subcutaneous injection. This dosing regimen might impact the therapy adherence in cardiovascular patients who often require multiple drugs with different dosing intervals. Small interfering ribonucleic acid (siRNA) represents a promising therapy approach for patients with elevated LDL cholesterol level despite optimized background statin therapy. Inclisiran is a synthesized siRNA which inhibits PCSK9 synthesis in the liver and provides sustained and durable lowering of LDL cholesterol with twice-yearly application and a good tolerability profile. Herein, we present an overview of the current available data and critical review of the major clinical trials which assessed safety and efficacy of inclisiran in different groups of patients with elevated LDL cholesterol level.

Knowledge, attitudes and practices and fear of COVID-19 among medical students in Serbia.

INTRODUCTION: The outbreak of the disease caused by the novel coronavirus, SARS-CoV-2 named COVID-19 has spread throughout the world. The number of registered cases is increasing and almost no country or territory worldwide has been without any COVID-19 patient. The aim of this study was to examine the level of knowledge on the SARS-COv-2 and COVID-19 among medical students and to explore the differences in attitudes, practices and fear of COVID-19 among students with sufficient and students with insufficient knowledge. METHODOLOGY: The cross-sectional study among the 1,722 medical students was conducted through an online platform of the Faculty of Medicine, University of Belgrade. The instrument used was a questionnaire with sections on socio-demographic characteristics, knowledge, attitudes and practices towards COVID-19 and the Fear of COVID-19 scale. RESULTS: Total of 1576 (91.50%) students were in the sufficient knowledge group. The multivariate logistic regression analysis showed that there was a significant association between the sufficient knowledge on COVID-19 and female sex (OR = 1.70, 95% CI = 1.18-2.45), age (OR = 1.10, 95% CI = 1.02-1.18), considering the preventive measures enforced in Serbia as good (OR = 2.57, 95% CI = 1.18-5.56), wearing the surgical mask outside of the household in the past 14 days (OR = 1.87, 95% CI = 1.22-2.87) and score on Fear of COVID-19 scale (OR = 0.94, 95% CI = 0.91-0.98). CONCLUSIONS: Medical students showed good knowledge of COVID-19 and could be a part of the promotion of health education messages as a part of preventive measures.

Differentiation of Amyloid Plaques Between Alzheimer's Disease and Non-Alzheimer's Disease Individuals Based on Gray-Level Co-occurrence Matrix Texture Analysis.

Amyloid plaques, one of the main hallmarks of Alzheimer's disease (AD), are classified into diffuse (associated with cognitive impairment) and dense-core types (a common finding in brains of people without Alzheimer's disease (non-AD) and without impaired cognitive function) based on their morphology. We tried to determine the usability of gray-level co-occurrence matrix (GLCM) texture parameters of homogeneity and heterogeneity for the differentiation of amyloid plaque images obtained from AD and non-AD individuals. Images of amyloid-ß (Aß) immunostained brain tissue samples were obtained from the Aging, Dementia and Traumatic Brain Injury Project. A total of 1,039 plaques were isolated from different brain regions of 69 AD and non-AD individuals and used for further GLCM analysis. Images of Aß stained plaques show higher values of heterogeneity parameters and lower values of homogeneity parameters in AD patients, and vice versa in non-AD patients. Additionally, GLCM analysis shows differences in Aß plaque texture between different brain regions in non-AD patients and correlates with variables that characterize patient's dementia status. The present study shows that GLCM texture analysis is an efficient method to discriminate between different types of amyloid plaques based on their morphology and thus can prove as a valuable tool in the neuropathological investigation of dementia.

Relevance and attitudes toward histology and embryology course through the eyes of freshmen and senior medical students: Experience from Serbia.

Histology and embryology are prerequisite for understanding the complexity of cell and tissue organization, function and development. The aim of this study was to examine the attitudes of medical students toward relevance of histology and embryology in their pre-clinical and clinical medical practice. The study sample consisted of 900 undergraduate students of 1st and 6th study year at the School of Medicine in Belgrade, Serbia. Data were collected using an anonymous questionnaire. Senior students reported the relevance of histology and embryology knowledge for learning pathology, dermatology, physiology, gynecology and obstetrics, pathophysiology and pediatrics. Examination of students' attitudes revealed that 1st year participants more often acknowledged histology and embryology as being of great importance for their professional career. Analysis according to gender indicated that female students consider embryology as of greater importance for further medical education and future clinical practice than male students. Overall, study results suggest that medical students have a positive attitude toward histology and embryology undergraduate course. This evidence could be used as an additional motive for the development of histology and embryology courses, with special emphasis on practical application of knowledge in clinically-oriented setting.

Skin and sural nerve biopsies: ultrastructural findings in the first genetically confirmed cases of CADASIL in Serbia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2-6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

INTRODUCTION: Fast and precise diagnostics of the disease from the large group of adult leukoencephalopathy is difficult but responsible job, because the outcome of the disease is very often determined by its name. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by the mutation of Notch 3 gene on chromosome locus 19p13. Beside the brain arterioles being the main disease targets, extracerebral small blood vessels are affected by the pathological process. Clinically present signs are recurrent ischemic strokes and vascular dementia. CADASIL in its progressive form shows a distinctive pattern of pathological changes on MRI of endocranium. The diagnosis is confirmed by the presence of granular osmiophilic material (GOM) in histopathological skin biopsies. CASE REPORTS: Two young adult patients manifested ischemic strokes of unknown etiology, cognitive deterioration, migraine and psychopathological phenomenology. MRI of endocranium pointed on CADASIL. Ultrastructural examination of skin biopsy proved the presence of GOM in the basal lamina and near smooth muscle cells of arteriole dermis leading to CADASIL diagnosis. The presence of GOM in histopathological preparation is 100% specific for CADASIL. The patients were not searched for mutation in Notch 3 gene on chromosome 19, because some other leukoencephalopathy was disregarded. CONCLUSION: Suggestive clinical picture, distinctive finding of endocranium MRI, the presence of GOM by ultrastructural examination of histopathological skin biopsies are sufficient to confirm CADASIL diagnosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with severe factor XII deficiency.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited adult-onset microangiopathy caused by missense mutations in the Notch3gene on chromosome 19. However, common vascular risk factors may additionally modify clinical expression and progression of the disease. The role of various prothrombotic factors has also been implied. We report a case of a middle-aged man with typical clinical, neuroimaging and histological features of CADASIL, but with notably prolonged activated partial thromboplastin time. Hematological investigations revealed severe clotting Factor XII deficiency. This case illustrates that the occurrence of vascular risk factors should not be overlooked in patients with CADASIL.

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia].

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middle-aged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors--diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. CONCLUSION: Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.