Decreased DNA Disruption in the Porcine Neocortex with Erythromycin Preconditioning during Prolonged Hypothermic Circulatory Arrest: Evidence for Neuroprotection.

BACKGROUND AND AIM OF THE STUDY: We have previously reported that the neocortex is selectively vulnerable to injury in an acute porcine model of hypothermic circulatory arrest (HCA) at 18°C. In view of recent evidence showing that pharmacologic preconditioning with a single dose of erythromycin induces tolerance against transient global cerebral ischemia in rats, we hypothesized that erythromycin would reduce the number of apoptotic neurons in the neocortex in an acute porcine model of HCA at 18°C. METHODS: Fourteen piglets underwent 75 min of HCA at 18°C following pretreatment with erythromycin (25 mg/kg, IV) (n = 8) or vehicle (Normal Saline 0.9%) (n = 6), applied 12 hr before arrest. Three served as normal controls. After gradual rewarming to a temperature of 36°C, treatment animals were sacrificed and brains were perfusion-fixed and cryopreserved. Neuronal apoptosis after HCA was observed morphologically with hematoxylin and eosin staining, and characterized by in situ DNA fragmentation using terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry. RESULTS: Pre-ischemic conditioning with a single dose of the antibiotic erythromycin reduced neuronal apoptosis in the neocortex of the porcine brain. TUNEL-positive cells indicating DNA fragmentation and neuronal injury were significantly greater in the neocortex of animals treated with 18°C HCA (2.55 ± 1.17) compared to animals undergoing HCA after erythromycin preconditioning (1.76 ± 0.91) (p ≤ 0.001). CONCLUSIONS: These results suggest that cerebral protection during HCA may be achieved with erythromycin pharmacological preconditioning in the porcine model.

Burnout and motivation to study medicine among students during the COVID-19 pandemic.

Aim: To investigate medical students' burnout and motivation levels in each of the six years of their studies during the COVID-19 pandemic and identify independent predictors of burnout and motivation. Methods: An anonymous cross-sectional survey was sent to the students of all six years within our school. Burnout was measured with the adapted Oldenburg Burnout Inventory questionnaire (OLBI-S) and motivation with the updated Strength of Motivation for Medical School (SMMS-R) questionnaire. Univariate analysis was performed with the Kruskal-Wallis test and Spearman's correlation, while multivariable analysis with linear regression models. Results: A total of 333 medical students (52% of student body) responded. Higher burnout levels correlated with lower motivation to study medicine (rho = -0.30, p < 0.001). Burnout levels differed between the six years of medical studies, peaking in years two and four whereas being the lowest in year one (p = 0.01). Motivation levels differed significantly as well, peaking in years one and four whereas being the lowest in years five and six (p = 0.012). In the multivariable linear regression models, being a female (b = 2.22, p = 0.016), studying in the fourth year vs. first year (b = 2.54, p = 0.049), having a perceived beginner/intermediate vs. advanced/expert technology level (b = 2.05, p = 0.032) and a perceived poor school support system (b = 6.35, p < 0.001) were independently associated with higher burnout levels. Furthermore, studying in the fifth year vs. first year (b = -5.17, p = 0.019) and a perceived poor school support system (b = -3.09, p = 0.01) were independently associated with a reduced motivation to study medicine. Conclusion: Our study highlighted potential areas for intervention to decrease the rate of burnout and low motivation among medical students. However, further research is needed to unravel the full effect of the pandemic on medical students.

Shift to emergency remote preclinical medical education amidst the Covid-19 pandemic: A single-institution study.

The Covid-19 pandemic disrupted medical education, shifting it towards emergency remote delivery. This cross-sectional study aimed to assess the impact of the pandemic on preclinical medical education and identify predictors of the virtual learning experience and perceived stress. An anonymous survey was delivered electronically to the students of the authors' medical school that attended either histology or pathology. This survey contained two scales, the virtual learning experience (VLE) and the perceived stress scale-10 (PSS-10). A total of 173/255 (68%) responded, showing a positive perception towards the remote delivery of both courses. An exploratory factor analysis was performed on the VLE scale items and four new dimensions were formed: "course quality and learning outcomes", "student motivation", virtual against F2F learning", and "virtual laboratory sessions". The following significant predictors of enhanced VLE, in at least one dimension, were identified: female gender, pathology course, final examination grade >80%, lower perceived stress levels, studying in home country, and holding of another degree before medical school. In addition, the following predictors were significantly associated with higher levels of student perceived stress: female gender, pathology course, studying away from home, and suboptimal internet connection. Notably, the quality of internet connection was significantly associated with the students' final examination performance. Concerning the best mode for future delivery of both courses, most students proposed a blended, rather than an entirely on-campus or online approach. In conclusion, despite its problems, a high-quality remote preclinical medical education was possible in the authors' school and offered tremendous opportunities for future improvement.

Glutamate receptors in human caudate nucleus in normal aging and Alzheimer's disease.

Neostriatum is one of the brain areas that are not primarily affected in Alzheimer's disease, according to classic regard of the disease. However, recent data emphasize the involvement of neostriatum, especially the head of the caudate nucleus, in the emergence of characteristic symptoms of the disease. Glutamatergic neurotransmission is a key component of striatal pathways. The present study is focused on glutamate receptors of striatal neurons on human caudate nucleus in normal aging and Alzheimer's disease. Immunohistochemical studies were carried out for N-methyl-D-aspartate receptor subunit 1 (NMDAR1), α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit 2 (GluR2) and metabotropic glutamate receptor 5 (mGluR5). Ionotropic receptors (NMDAR1 and GluR2) were found to be expressed by 82% - 93% of striatal neurons with no significant alterations in aging and Alzheimer's disease. On the other hand, metabotropic receptor mGluR5 was found to be expressed by just 40% of striatal neurons in young individuals, with significant intensity variations among the neurons. This percent was increased in elderly individuals and Alzheimer's disease patients to 80% and 92% of striatal neurons, respectively. The up-regulation of mGluR5 both in normal aging and Alzheimer's disease is possibly associated with reorganization of neuronal connections, indicates the complexity of this receptor function and renders quite unpredictable the intervention and treatment of dementia with mGluR5 inhibitors or modulators.

Students' physical and psychological reactions to forensic dissection: Are there risk factors?

The reactions of students to forensic dissection encompass psychologico-emotional and physical components. This exploratory study aimed to determine risk factors for students' adverse physical and psychological reactions to forensic dissection. All sixth-year medical students (n = 304) attending the compulsory practical course in forensic medicine in the 2005-2006 academic year were asked to complete a questionnaire at the conclusion of the five-day course. The questionnaire surveyed physical and psychological reactions (outcomes) and 47 student traits, beliefs, and behaviors (risk factors) that might predispose to adverse reactions. Multivariate ordinal logistic regression yielded five independent risk factors for negative psychological reactions: female gender, stereotypic beliefs about forensic pathologists, a less cognitive and more emotional frame of mind relative to forensic dissection, more passive coping strategies, and greater fear of death. The sole independent risk factor for physical symptoms was a less cognitive/more emotional approach to dissection. Students' reactions to forensic dissection integrate a host of inherent and dissection-related risk factors, and future interventions to improve this aspect of medical education will need to take into account the complexities underlying students' experiences with dissection.

Neuropathological findings in Dandy Walker variant.

OBJECTIVE: Dandy-Walker malformation is a congenital malformation that is characterized by hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of the posterior fossa. The aim of the study is to describe the morphological and morphometric alterations of neurons (in various regions of the brain) in a case of Dandy-Walker Variant. METHODS: By Golgi method and routine techniques, the alterations in the brain of a 23 years old case of Dandy-Walker Variant who died accidentally were studied. Furthermore, a detailed morphometric analysis of neuronal parameters and a statistical comparison with an age-matched control were applied. RESULTS: In the cerebellum the morphological study, apart from gliosis, revealed reduction of the size of cell body and poverty of dendritic arborization with loss of dendritic branches and spines. In the cerebral cortex and the hippocampus the most prominent findings were the tortuous configuration of the apical dendrites of the pyramidal neurons, the focal swellings of the axons and the dendrites and significant gliosis. CONCLUSION: Although the gross anatomical examination of the brain demonstrated only mild neurodevelopmental anomalies (except the key features of the syndrome), the microscopic examination revealed significant morphological alterations of neurons and dendrites.