The Impact of the COVID-19 Pandemic on Research and Volunteering Activities among Medical Students: A Cross-Sectional Study among Romanian and International Students from One Medical Faculty from Romania.

INTRODUCTION: This study focuses on the influence of the COVID-19 pandemic on medical students in their last year of study at the Faculty of Medicine of the University of Medicine and Pharmacy in Cluj-Napoca, Romania. It analyzes the impact of social distance limits on the conduct of research activities required for the development of the graduation thesis, as well as assesses sixth-year students' attitudes and behaviors toward volunteer activities during the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted in June-July 2021 among sixth-year students. It used an anonymous online questionnaire and was sent to all students from the Faculty of Medicine studying in the Romanian, English, or French sections (n = 606). The response rate was 38.28%, resulting in a final sample of 232 students from both Romanian and international sections. RESULTS: The findings demonstrate that two-thirds of the students in the survey agreed that the COVID-19 pandemic had a substantial impact on their research. Some of the students had to choose another subject for their graduation thesis, while about a quarter of the students gave up collecting personal data, 25% of respondents stated that it was difficult to contact research participants, one-third of them linked the difficulty of doing activities at the hospital to the present outbreak, and almost 30% of the students had difficulty communicating with the coordinator. The disturbance of the research activity seems to be higher among international students in comparison with the Romanian students, while there are limited gender differences. One out of five medical students has been involved in volunteer activities during the pandemic. Most have opted to volunteer at hospitals (especially international students) and contribute to health education activities (especially women). CONCLUSIONS: This is the first study from Romania and one of the few from Europe that presents data regarding the influence of the COVID-19 pandemic on research and volunteering activities among medical students.

Attitudes and Practices Regarding Research among Romanian Medical Undergraduate Students.

OBJECTIVES: This study focuses on the assessment of attitudes and practices regarding research among undergraduate medical students from Cluj-Napoca, Romania. MATERIAL AND METHODS: A cross-sectional study was performed thorough anonymous questionnaires (May-June 2018) among 510 third- and fifth-year students of Iuliu Hatieganu University of Medicine and Pharmacy from Cluj-Napoca, Romania. RESULTS: More than 60% of the third- and fifth-year students declared that they were interested and willing to perform research during medical studies, while more than two-thirds were interested in doing so after graduation. In total, 6% of third-year students and 31% of fifth-year students declared that they had prepared a scientific presentation for a medical congress at least once. Around 9% of the third-year students contributed to the writing of a scientific article and participated in research projects. Among fifth-year students, one-quarter were involved in writing scientific papers, and 21% participated in research projects. CONCLUSIONS: To the best of our knowledge, this study assesses, for the first time in Romania, the perspectives and behaviors of medical undergraduate students with regard to involvement in research activities. The results show that Romanian medical students value opportunities for conducting research, which encourages institutional initiatives that support their involvement in curricular and extracurricular research activities.

Designed Peptide Inhibitors of STEP Phosphatase-GluA2 AMPA Receptor Interaction Enhance the Cognitive Performance in Rats.

Cognitive impairment and learning ability of the brain are directly linked to synaptic plasticity as measured in changes of long-term potentiation (LTP) and long-term depression (LTD) in animal models of brain diseases. LTD reflects a sustained reduction of the synaptic AMPA receptor content based on targeted clathrin-mediated endocytosis. AMPA receptor endocytosis is initiated by dephosphorylation of Tyr876 on the C-terminus of the AMPAR subunit GluA2. The brain-specific striatal-enriched protein tyrosine phosphatase (STEP) is responsible for this process. To identify new, highly effective inhibitors of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization, we performed structure-based design of peptides able to inhibit STEP-GluA2-CT complex formation. Two short peptide derivatives were found as efficient in vitro inhibitors. Our in vivo experiments evidenced that both peptides restore the memory deficits and display anxiolytic and antidepressant effects in a scopolamine-treated rat model. The interference peptides identified and characterized here represent promising lead compounds for novel cognitive enhancers and/or behavioral modulators.

New and Recovered Temporary Anchorage Devices, In Vitro Assessment of Structural and Surface Properties.

The orthodontic miniscrew (TADs) is a device that is fixed into bone in the short term for the purpose of enhancing orthodontic anchorage. The aim of our study was to investigate the structural and surface properties of recovered TADs after orthodontic treatment, and compare them to new TADs. TADs (n = 15) from the same manufacturer (Absoanchor; Dentos, Daegu, Korea) were assessed; n = 10 were recovered from patients after orthodontic treatment and n = 5 were new. We performed electrochemical investigations, scanning electron microscopy (SEM) and microbiological analysis. Qualitative analysis on general electrochemical polarization revealed that the TADs retrieved from the patients provided much lower current densities in the passivity zone, and the oxidative processes taking place on their surface were of lower intensity. The surface morphologies of the tips of the retrieved mini-implants showed less sharp tips and smooth surfaces. Defects in the form of pores or cracks could be identified in both evaluated TAD groups. All retrieved TADs showed signs of biological materials (SEM analysis) and contamination on their surfaces. In conclusion, these results can assist orthodontists in comprehending the complexities of TAD behavior with respect to their design and structure.

State of the art regarding anticoagulant and thrombolytic therapy in dental procedures.

Patients with anticoagulant therapy have a high thromboembolic risk. Due to the rich oro-maxillofacial vasculature and the fact that some dental procedures may cause a bleeding, the physician should be able to correlate this risk with the hemorrhagic risk. Dental procedures are a trigger for psychic stress. One of the most important changes in acute stress is in cardiovascular system. In healthy patients, these changes are reversible and have no significant consequences, but in patients with cardiovascular diseases, the response to the catecholamine stress can cause organic lesions resulting in an acute myocardial infarction or stroke. This review explores in a concise manner the biochemical changes concerning anticoagulation and thrombolytic treatment in dental procedures.

Paradoxical effect of baclofen on social behavior in the fragile X syndrome mouse model.

INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse. Evidence from studies in mice demonstrates that GABA, the major inhibitory neurotransmitter in the brain, and its receptors, is involved in the pathogenesis of FXS. Moreover, several FXS phenotypes, including social behavior deficits, could be corrected in Fmr1 KO mice after acute treatment with GABAB agonists. METHODS: As FXS would probably require a lifelong treatment, we investigated the effect of chronic treatment with the GABAB agonist baclofen on social behavior in Fmr1 KO mice on two behavioral paradigms for social behavior: the automated tube test and the three-chamber sociability test. RESULTS: Unexpectedly, chronic baclofen treatment resulted in worsening of the FXS phenotypes in these behavior tests. Strikingly, baclofen treatment also affected wild-type animals in both behavioral tests, inducing a phenotype similar to that of untreated Fmr1 KO mice. CONCLUSION: Altogether, the disappointing results of recent clinical trials with the R-baclofen enantiomer arbaclofen and our current results indicate that baclofen should be reconsidered and further evaluated before its application in targeted treatment for FXS.

The metabolic syndrome is not correlated with the short-term risk of decompensation in patients with cirrhosis.

BACKGROUND AND AIMS: Obesity proved to favor clinical decompensation in patients with cirrhosis. Our aim was to investigate if metabolic syndrome (MS) in cirrhotic patients represents a risk factor for decompensation. METHODS: 704 cirrhotics, included in a MS prevalence study were considered for evaluation; 121 patients were excluded because they did not complete the follow-up and 303 because they were decompensated at the start of the study. The remaining 280 were followed-up for a median period of 28.1+/-18 months. Patients were censored at the end of follow-up or at occurrence of a liver related event (LRE). Liver related events were considered the following: decompensation (ascites, variceal bleeding, hepatorenal syndrome, jaundice, encephalopathy), hepatocellular carcinoma, portal vein thrombosis and infections. RESULTS: All MS criteria except the abdominal circumference were significantly different between decompensated and compensated patients. HDL-cholesterol levels were lower in decompensated patients. Among the 280 patients who completed the follow-up, 85 (30%) presented LREs. Ascites was the most frequent event. In the univariate analysis of the MS criteria we found a trend to significance of an inverse correlation between MS and LREs. There was no significant difference between patients with or without MS regarding survival free of LREs, 76.7% and 66.5%, respectively. None of the MS criteria reached the level of significance in discriminating patients with and without LREs. CONCLUSIONS: In short term, presence of MS was not a risk factor for LREs. In short term, liver function and lower nutritional status influenced the prognosis. In decompensated patients, the MS defining criteria are not applicable.

Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant.

Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The disease is a result of lack of expression of the fragile X mental retardation protein. Brain tissues of patients with FXS and mice with FMRP deficiency have shown an abnormal dendritic spine phenotype. We investigated the dendritic spine length and density of hippocampal CA1 pyramidal neurons in 2-, 10-, and 25-week-old Fmr1 knockout (KO). Next, we studied the effects of long-term treatment with an mGluR5 antagonist, AFQ056/Mavoglurant, on the spine phenotype in adult Fmr1 KO mice. We observed alterations in the spine phenotype during development, with a decreased spine length in 2-week-old Fmr1 KO mice compared with age-match wild-type littermates, but with increased spine length in Fmr1 KO mice compared with 10- and 25-week-old wild-type controls. No difference was found in spine density at any age. We report a rescue of the abnormal spine length in adult Fmr1 KO mice after a long-term treatment with AFQ056/Mavoglurant. This finding suggests that long-term treatment at later stage is sufficient to reverse the structural spine abnormalities and represents a starting point for future studies aimed at improving treatments for FXS.

Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development.

RATIONALE: Fragile X syndrome (FXS) is considered the leading inherited cause of intellectual disability and autism. In FXS, the fragile X mental retardation 1 (FMR1) gene is silenced and the fragile X mental retardation protein (FMRP) is not expressed, resulting in the characteristic features of the syndrome. Despite recent advances in understanding the pathophysiology of FXS, there is still no cure for this condition; current treatment is symptomatic. Preclinical research is essential in the development of potential therapeutic agents. OBJECTIVES: This review provides an overview of the preclinical evidence supporting metabotropic glutamate receptor 5 (mGluR5) antagonists as therapeutic agents for FXS. RESULTS: According to the mGluR theory of FXS, the absence of FMRP leads to enhanced glutamatergic signaling via mGluR5, which leads to increased protein synthesis and defects in synaptic plasticity including enhanced long-term depression. As such, efforts to develop agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. Animal models, particularly the Fmr1 knockout mouse model, have become invaluable in exploring therapeutic approaches on an electrophysiological, behavioral, biochemical, and neuroanatomical level. Two direct approaches are currently being investigated for FXS treatment: reactivating the FMR1 gene and compensating for the lack of FMRP. The latter approach has yielded promising results, with mGluR5 antagonists showing efficacy in clinical trials. CONCLUSIONS: Targeting mGluR5 is a valid approach for the development of therapeutic agents that target the underlying pathophysiology of FXS. Several compounds are currently in development, with encouraging results.

Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation.

Cerebellar granule cells (GCs) account for more than half of all neurons in the CNS of vertebrates. Theoretical work has suggested that the abundance of GCs is advantageous for sparse coding during memory formation. Here, we minimized the output of the majority of GCs by selectively eliminating their CaV2.1 (P/Q-type) Ca(2+) channels, which mediate the bulk of their neurotransmitter release. This resulted in reduced GC output to Purkinje cells (PCs) and stellate cells (SCs) as well as in impaired long-term plasticity at GC-PC synapses. As a consequence modulation amplitude and regularity of simple spike (SS) output were affected. Surprisingly, the overall motor performance was intact, whereas demanding motor learning and memory consolidation tasks were compromised. Our findings indicate that a minority of functionally intact GCs is sufficient for the maintenance of basic motor performance, whereas acquisition and stabilization of sophisticated memories require higher numbers of normal GCs controlling PC firing.

Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice.

Fragile X syndrome is caused by lack of FMR1 protein (FMRP) leading to severe symptoms, including intellectual disability, hyperactivity and autistic-like behaviour. FMRP is an RNA binding protein involved in the regulation of translation of specific target mRNAs upon stimulation of metabotropic glutamate receptor 5 (mGluR5) at the synapse. The absence of FMRP leads to enhanced activity of mGluR5 signal transduction pathways. Many conflicting results have been reported regarding social behaviour deficits in Fmr1 knockout mice, and little is known about the involvement of mGluR5 pathways on social behaviour. In this study, a three-chambered task was used to determine sociability and preference for social novelty in Fmr1 knockout mice. Disruption of Fmr1 functioning resulted in enhanced interaction with stranger mouse during sociability while no significant changes were observed during preference for social novelty assay. Chronic administration of a specific mGluR5 antagonist, AFQ056/Mavoglurant, was able to restore sociability behaviour of Fmr1 knockout mice to levels of wild type littermates. These results support the importance of mGluR5 signalling pathways on social interaction behaviour and that AFQ056/Mavoglurant might be useful as potential therapeutic intervention to rescue various behavioural aspects of the fragile X phenotype.

Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO mice.

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by the lack of fragile X mental retardation protein (FMRP). In the brain, spine abnormalities have been reported in both patients with FXS and Fmr1 knockout mice. This altered spine morphology has been linked to disturbed synaptic transmission related to altered signaling in the excitatory metabotropic glutamate receptor 5 (mGluR5) pathway. We investigated hippocampal protrusion morphology in adult Fmr1 knockout mice. Our results show a hippocampal CA1-specific altered protrusion phenotype, which was absent in the CA3 region of the hippocampus. This suggests a subregion-specific function of FMRP in synaptic plasticity in the brain.

AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome.

Fragile X syndrome, the most common form of inherited intellectual disability, is caused by a lack of FMRP, which is the product of the Fmr1 gene. FMRP is an RNA-binding protein and a component of RNA-granules found in the dendrites of neurons. At the synapse, FMRP is involved in regulation of translation of specific target mRNAs upon stimulation of mGluR5 receptors. In this study, we test the effects of a new mGluR5 antagonist (AFQ056) on the prepulse inhibition of startle response in mice. We show that Fmr1 KO mice have a deficit in inhibition of the startle response after a prepulse and that AFQ056 can rescue this phenotype. We also studied the effect of AFQ056 on cultured Fmr1 KO hippocampal neurons; untreated neurons showed elongated spines and treatment resulted in shortened spines. These results suggest that AFQ056 might be a potent mGluR5 antagonist to rescue various aspects of the fragile X phenotype.