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Abstract Background Formal education surrounding abortion care during pre-clinical years of medical school is limited and will likely decrease with the overturning of Roe v. Wade. This study describes and evaluates the impact of an original abortion didactic session implemented during the pre-clinical years of medical school. Methods We implemented a didactic session at the University of California Irvine outlining abortion epidemiology, pregnancy options counseling, standard abortion care, and the current legislative landscape surrounding abortion. The preclinical session also included an interactive, small group case-based discussion. Pre-session and post-session surveys were obtained to evaluate changes in participants’ knowledge and attitudes and to collect feedback for future sessions. Results 92 matched pre- and post-session surveys were completed and analyzed (response rate 77%). The majority of the respondents identified themselves as more “pro-choice” compared to “pro-life” on the pre-session survey. Results reflected significantly increased comfort discussing abortion care and significantly increased knowledge about abortion prevalence and techniques after the session. Qualitative feedback was overwhelmingly positive and reflected participants’ appreciation for the focus on the medical aspects of abortion care as opposed to an ethical discussion. Conclusions Abortion education targeted to preclinical medical students can be implemented effectively by a medical student cohort with institutional support.

Mobile electrocardiogram (ECG) devices are valuable tools for teaching ECG interpretation. The primary purpose of this follow-up study was to determine if an ECG active learning session could be safely and effectively performed during the coronavirus disease 2019 (COVID-19) pandemic using a newly developed mobile 6-lead ECG device. Additionally, we examined the educational impact of these active learning sessions on student knowledge of cardiovascular physiology and the utility of the mobile 6-lead ECG device in a classroom setting. In this study, first-year medical students (MS1) performed four active learning activities using the new mobile 6-lead ECG device. Data were collected from 42 MS1s through a quantitative survey administered in September 2020. Overall, students felt the activity enhanced their understanding of the course material and that the activity was performed safely and in compliance with local COVID-19 guidelines. These results emphasize student preference for hands-on, small group learning activities in spite of the pandemic.

Antioxidant activity is one of the most studied properties of coffee as a beverage, and is mainly ascribed to its polyphenol content, although there is limited scientific literature regarding its mechanism of action at the molecular level. In recent years, epigenetics has been featured as a promising approach in many studies for explaining the mechanisms of action involved in its effects on health exerted by foods and food components. To investigate such an epigenetic contribution toward the antioxidant properties of coffee, an in vivo study was performed on healthy C57BL/6 mice fed with a normal diet supplemented with a low-molecular-weight (MW) fraction (MW < 3500 Da) obtained from regular and decaffeinated coffee. Regular coffee supplementation induced a downregulation of microRNA-124-3p, and its validated target, mRNA coding for glutathione peroxidase (GPX), was upregulated. Decaffeinated coffee was not found to induce any significant changes in the expression levels of microRNA-124-3p and its validated target mRNA. It may be concluded from the results that regular intake of coffee exerts its antioxidant activity through an epigenetic mechanism of action, at least in part, being able to influence the expression levels on a miRNA and an mRNA involved in antioxidant defenses, with caffeine playing a crucial role.

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells.Analysing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene ATG7, increased the cell death rate induced by GVS. Altogether these findings suggest that autophagy represents a pro-survival mechanism activated by GBM CSCs to counteract the efficacy of the anti-proliferative activity of GVS. In conclusion, we demonstrate that GVS is a novel pharmacological tool able to target GBM CSC viability and its efficacy can be enhanced by autophagy inhibitory strategies.

A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons other than PV or SOM.

Many investigations were carried out on the association between viruses and multiple sclerosis (MS). Indeed, early studies reported the detections of neurotropic virus footprints in the CNS of patients with MS. In this study, sera from patients affected by MS, other inflammatory (OIND) and non-inflammatory neurologic diseases (NIND) were analyzed for antibodies against the polyomavirus, Simian Virus 40 (SV40). An indirect enzyme-linked immunosorbent assay (ELISA), with two synthetic peptides, which mimic SV40 antigens, was employed to detect specific antibodies in sera from patients affected by MS, OIND, NIND and healthy subjects (HS). Immunologic data indicate that in sera from MS patients antibodies against SV40 mimotopes are detectable with a low prevalence, 6%, whereas in HS of the same mean age, 40 yrs, the prevalence was 22%. The difference is statistically significant (P = 0.001). Significant is also the difference between MS vs. NIND patients (6% vs. 17%; P = 0.0254), whereas no significant difference was detected between MS vs OIND (6% vs 10%; P>0.05). The prevalence of SV40 antibodies in MS patients is 70% lower than that revealed in HS.

Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types. Beginning with the appearance of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors evolved. Originally, these cell surface proteins were thought to merely mediate the traffic of lipids and nutrients between cells and, in some cases, by functioning as scavenger receptors, remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular space and the cell surface. Over the last decade, this picture has fundamentally changed. We now appreciate that many of these receptors are not mere cargo transporters; they are deeply embedded in the machinery by which cells communicate with each other. By physically interacting and coevolving with fundamental signaling pathways, lipoprotein receptors have occupied essential and surprisingly diverse functions that are indispensable for integrating the complex web of cellular signal input during development and in differentiated tissues.