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Context. In Europe, during an era of globalization in which traveling and studying abroad is becoming easier and more affordable, an open question remains on whether different European medical schools educate students with a dissimilar level of preparedness and/ or satisfaction. Objective. To develop and validate the EUropean Students' Preparedness and Satisfaction Questionnaire (EUSPSQ), a standardized European tool to assess preparedness and satisfaction in medical education. Materials and methods. 30 participants belonging to the 5th and 6th year of two different European medical schools (Sapienza University of Rome and Universidad Complutense de Madrid) participated in the validation of the study. A standard validation protocol that included item development, test-retesting, and a series of statistical validation analyses, was used. Feasibility, test-retest reliability, inter-item reliability were assessed quantitatively. Face validity was evaluated qualitatively by an expert professor in the field. Results. Test-retest and inter-item reliability were considered satisfactory for all the parts of the questionnaire. Part III and IV presented lower Cohen's kappa values, probably as a consequence of their inherent subjectivity. When one item in Part III was removed, the Cronbach's alpha values of both initial and 48h answers considerably increased (-0.355 to 0.713 and -0.202 to 0.808 respectively). We therefore decided to eliminate the question from the EUSPSQ. Internal and external validity were considered appropriate. The questionnaire was also feasible and viable to complete. Discussion. Preliminary findings indicate that the EUSPSQ can be a valid, viable and reliable questionnaire to measure preparedness and satisfaction of 5th and 6th year medical students across different European Universities. [ABSTRACT FROM AUTHOR]

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. Here, we used single nucleus RNA sequencing and bulk whole genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy. We show that persister cells share common mechanisms of chemotherapy escape including suppression of MYCN activity and activation of NF-κB signaling, the latter is further enhanced by cell-cell communication between the malignant cells and the tumor microenvironment. Overall, our work dissects the transcriptional landscape of cellular persistence in high-risk neuroblastoma and paves the way to the development of new therapeutic strategies to prevent disease relapse.

Objectives: To compare umbilical cord and neonatal blood for chemistry tests upon admission to the neonatal intensive care unit (NICU)., Methods: We designed a prospective, bicentric cohort study enrolling newborns (n = 71) with a planned admission to the NICU. Paired samples of umbilical cord and infant's blood were collected, analyzed, and compared. An intraclass correlation coefficient (ICC) was calculated for a repeatability analysis, and a Bland-Altman analysis was performed to assess the agreement between the 2 methods of sampling. The multivariable coefficient of determination (R2) was reported to quantify the degree of correlation between the methods of measurement., Results: The degree of agreement between the 2 sampling methods for chemistry tests was fair to good for high-sensitivity C-reactive protein (ICC = 0.79 [95% CI, 0.67-0.87]), phosphorus (ICC = 0.83 [95% CI, 0.73-0.90]), and albumin (ICC = 0.76 [95% CI, 0.60-0.86]), while it was good to excellent for γ-glutamyl transpeptidase (ICC = 0.95 [95% CI, 0.88-0.98]) and procalcitonin (ICC = 0.90 [95% CI, 0.76-0.96])., Conclusions: Umbilical cord blood is a reliable replacement source for multiple chemistry tests at birth. This sampling method has the potential to minimize the risk of transfusion-requiring anemia in newborns and its associated complications. Further studies are warranted to assess the efficacy of this strategy in improving neonatal outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Epicardial adipose tissue (EAT) is a visceral fat depot located between the myocardium and visceral epicardium. Emerging evidence suggests that excessive EAT is linked to increased risk of cardiovascular conditions and other metabolic diseases. A literature search was conducted from the earliest studies to the 26th of November 2022 on PubMed, Embase, and the Cochrane. All the studies evaluating changes in EAT, pericardial adipose tissue (PAT), or total cardiac fat loss before and after BS were included. From 623 articles, 35 were eventually included in the systematic review. Twenty-one studies showed a significant reduction of EAT after BS, and only one study showed a non-significant reduction (p = 0.2)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO 2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, biomedical research efforts aimed to unravel the mechanisms involved in motor neuron death that occurs in amyotrophic lateral sclerosis (ALS). While the main causes of disease progression were first sought in the motor neurons, more recent studies highlight the gliocentric theory demonstrating the pivotal role of microglia and astrocyte, but also of infiltrating immune cells, in the pathological processes that take place in the central nervous system microenvironment. From this point of view, microglia-astrocytes-lymphocytes crosstalk is fundamental to shape the microenvironment toward a pro-inflammatory one, enhancing neuronal damage. In this review, we dissect the current state-of-the-art knowledge of the microglial dialogue with other cell populations as one of the principal hallmarks of ALS progression. Particularly, we deeply investigate the microglia crosstalk with astrocytes and immune cells reporting in vitro and in vivo studies related to ALS mouse models and human patients. At last, we highlight the current experimental therapeutic approaches that aim to modulate microglial phenotype to revert the microenvironment, thus counteracting ALS progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Calafatti, Cocozza, Limatola and Garofalo.)

Context: In Europe, during an era of globalization in which traveling and studying abroad is becoming easier and more affordable, an open question remains on whether different European medical schools educate students with a dissimilar level of preparedness and/or satisfaction., Objective: To develop and validate the EUropean Students' Preparedness and Satisfaction Questionnaire (EUSPSQ), a standardized European tool to assess preparedness and satisfaction in medical education., Materials and Methods: 30 participants belonging to the 5th and 6th year of two different European medical schools (Sapienza University of Rome and Universidad Complutense de Madrid) participated in the validation of the study. A standard validation protocol that included item development, test-retesting, and a series of statistical validation analyses, was used. Feasibility, test-retest reliability, inter-item reliability were assessed quantitatively. Face validity was evaluated qualitatively by an expert professor in the field., Results: Test-retest and inter-item reliability were considered satisfactory for all the parts of the questionnaire. Part III and IV presented lower Cohen's kappa values, probably as a consequence of their inherent subjectivity. When one item in Part III was removed, the Cronbach's alpha values of both initial and 48h answers consider-ably increased (-0.355 to 0.713 and -0.202 to 0.808 respectively). We therefore decided to eliminate the question from the EUSPSQ. Internal and external validity were considered appropriate. The questionnaire was also feasible and viable to complete., Discussion: Preliminary findings indicate that the EUSPSQ can be a valid, viable and reliable questionnaire to measure preparedness and satisfaction of 5th and 6th year medical students across different European Universities.

Objective: To evaluate the role and the advantages of nasopharyngeal swabs in the detection of Influenza A and B viruses and Respiratory syncytial virus through a rapid test based upon a nucleic acid amplification reaction in order to avoid improper antibiotics use., Design: Case-control retrospective study., Setting: Emergency Room of "Sandro Pertini" General Hospital, Rome, Italy., Participants: Children (< 14 years old) who consecutively arrived in the Emergency Department (ED) for respiratory tract infections, without obvious signs of bacterial respiratory tract infections and other comorbidities, in the maximal seasonal incidence period of November-to-March of every year between 2016 and 2020., Methods: Medical records of children included in the study were retrospectively examined. Children were subdivided according to the following intervals: 2016-2017 and 2017-2018 (Group 1), 2018-2019 and 2019-2020 (Group 2). Children in Group 2 undertook a nasopharyngeal swab, while those in Group 1 did not undergo any specific diagnostic test., Primary Outcome: Avoidance of improper antibiotics administration., Results: A total of 386 children were included in the study: 174 in Group 1, 212 in Group 2. The Odd Ratio (OR) of prescribing an antibiotic in the groups of children not being swabbed compared to those of children undertaking a swab was 9.21 (CI95% 5.6-15.2, p < 0.001). The overall percentage of hospitalizations, both in the short observation unit or in the pediatric unit, did not differ between the two groups., Conclusions: Nasopharyngeal swabs for the detection of Influenza A and B viruses and Respiratory syncytial virus proved to be a useful means to a correct and timely diagnosis and allowed for a significant reduction in the prescription of antibiotic therapy., Trial Registration: Retrospectively registered., (© 2022. The Author(s).)

While human enteroviruses are generally regarded as a lytic virus, and persistent non-cytolytic enterovirus infection in pancreatic beta cells has been suspected of playing a role in type 1 diabetes pathogenesis. However, it is still unclear how enteroviruses could exit the pancreatic beta cell in a non-lytic manner. This study aimed to investigate the role of beta cell-derived extracellular vesicles (EVs) in the non-lytic enteroviral spread and infection. Size-exclusion chromatography and antibody-based immunoaffinity purification were used to isolate EVs from echovirus 16-infected human beta EndoC-βH1 cells. EVs were then characterized using transmission electron microscopy and Multiplex Bead-Based Flow Cytometry Assay. Virus production and release were quantified by 50% cell culture infectious dose (CCID 50 ) assay and qRT-PCR. Our results showed that EVs from echovirus 16-infected EndoC-βH1 cells harbor infectious viruses and promote their spread during the pre-lytic phase of infection. Furthermore, the EVs-mediated infection was not inhibited by virus-specific neutralizing antibodies. In summary, this study demonstrated that enteroviruses could exit beta cells non-lytically within infectious EVs, thereby thwarting the access of neutralizing antibodies to viral particles. These data suggest that enterovirus transmission through EVs may contribute to viral dissemination and immune evasion in persistently infected beta cells.