II Congreso Nacional de Pediatría. La lucha contra la mortalidad infantil / II National Congress of Paediatrics: The fight against child mortality

En el presente trabajo se presenta una aproximación a los contenidos de las ponencias del IICongreso Nacional de Pediatría, celebrado en San Sebastián en 1923, con ocasión del centenario del mismo. Se destaca como hilo conductor de las mismas el problema de la mortalidad infantil, que en aquellos años era muy elevada en España y era una preocupación de políticos, de intelectuales y de la clase médica. Se constata que alguna de las propuestas y preocupaciones de los pediatras que asistieron a dicho congreso siguen vigentes hoy en día.(AU)

In this work, we present an overview of the contents of the communications presented at the Second National Congress of Paediatrics, held in San Sebastian in 1923, on the occasion of the 100th year anniversary. The problem of infant mortality stands out as a common thread, which in those years was very high in Spain and was a concern of politicians, intellectuals and the medical profession. It is worth noting that some of the proposals and concerns of the paediatricians who attended that congress continue to be relevant today.(AU)

II National Congress of Paediatrics: The fight against child mortality.

In the present work, we present an overview of the contents of the communications presented at the Second National Congress of Paediatrics, held in San Sebastian in 1923, on the occasion of the 100th year anniversary. The problem of infant mortality stands out as a common thread, which in those years was very high in Spain and was a concern of politicians, intellectuals and the medical profession. It is worth noting that some of the proposals and concerns of the paediatricians who attended that congress continue to be relevant today.

Outcomes after surgical revascularization in diabetic patients.

OBJECTIVES: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG. METHODS: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE. RESULTS: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE. CONCLUSIONS: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM.

Vein graft preservation with an endothelial damage inhibitor in isolated coronary artery bypass surgery: an observational propensity score-matched analysis.

Background: Preservation solutions may be used intraoperatively during coronary artery bypass grafting (CABG) to flush and preserve vein grafts. The aim of this study is to evaluate the effect of DuraGraft, an endothelial damage inhibitor (EDI) preservation solution on major adverse cardiac events (MACEs) after CABG. Methods: We conducted an observational, prospective, longitudinal, single-center study that included patients who underwent isolated CABG. The cohort treated with an EDI was matched 1:1 with a control group treated with conventional vein preservation, and matching was adjusted for possible confounding factors through propensity score (PS) matching. Three years follow-up was conducted, and the occurrence of MACE [defined as all cause-death, acute coronary syndrome (ACS), and new unplanned revascularization] was analyzed using Kaplan-Meier method. Results: The study included 180 patients, 90 in each group. There were no significant differences in baseline characteristics across study groups. The EDI group had a significantly better event-free survival at 3 years (89% vs. 78%, log-rank test P=0.035), with an incidence rate ratio of 0.41 [95% confidence interval (CI): 0.16-0.96]. In the pre-specified subgroups analysis, the use of an EDI was associated with a significantly better event-free survival in diabetic patients (log-rank test P=0.041) and those with two or more saphenous vein grafts (log-rank test P=0.015). Conclusions: The utilization of an EDI for vein flushing and storage after vein harvest in CABG procedures has been shown to significantly decrease the incidence of MACE at 3 years post-surgery. This protective effect is particularly notable in diabetic patients and in individuals who have multiple vein grafts.

Synthesis of High Sn Content Ge1-x-ySixSny (0.1 < y < 0.22) Semiconductors on Si for MWIR Direct Band Gap Applications.

A systematic effort has been described to grow ternary Ge1-x-ySixSny semiconductors on silicon with high Sn concentrations spanning the 9.5-21.2% range. The ultimate goal is not only to produce direct band gap materials well into the infrared region of the spectrum but also to approach a critical concentration (yc) for which further additions of Si would decrease─rather than increase─the band gap. This counterintuitive behavior is expected as a result of the giant bowing parameter in the compositional dependence of the band gap associated with the presence of Si-Sn pairs. The growth approach in this study was based on a chemical vacuum deposition method that uses Si4H10, Ge3H8, and SnD4 or SnH4 as the sources of Si, Ge, and Sn, respectively. A fixed Si concentration near x = 0.05-0.07 was chosen to focus the exploration of the compositional space. A first family of samples was grown of Ge-buffered Si substrates. For Sn concentrations y < 0.12, it was found that the samples relaxed their mismatch strain in situ during growth, resulting in high Sn content films that had relatively low levels of strain and exhibited photoluminescence signals that demonstrated direct band gap behavior for the first time. The device potential of these materials was also demonstrated by fabricating a prototype photodiode with low dark currents. The optical studies suggest that the above-mentioned critical concentration is close to yc = 0.2. As the growth temperature was lowered in an effort to reach such values, Sn concentrations as high as y = 0.15 were obtained, but the films grew fully strained with compressive levels as high as 1.7%. To increase the Sn concentration beyond y = 0.15, a new strategy was adopted, in which the Ge buffer layer was eliminated, and the ternary alloy was grown directly on Si. The much higher lattice mismatch between the Ge1-x-ySixSny layer and the Si substrate caused strain relaxation right at the film/substrate interface, and the subsequent films grew with much lower levels of strain. This made it possible to lower the growth temperatures even further and achieve a comprehensive series of strained relaxed samples with tunable Sn concentrations as high as y = 0.21 (and beyond). The latter represent the highest Sn contents in crystalline Ge1-x-ySixSny attained to date and reach the desired yc = 0.2 range. The synthesized films exhibited significant thickness, allowing a thorough determination of composition, crystallinity, morphology, and bonding properties, indicating the formation of single-phase single-crystal alloys with random cubic structures. Further work will focus on optimizing the latter samples to explore the optical and electronic properties.

[Prevalence of dental and mucosal lesions among the pediatric population who attended the emergency department of a general hospital].

BACKGROUND: The high prevalence of oral pathology in children encourages to gain further understanding on their manifestations and urgent nature, objective of the present study Methodology. Cross-sectional study that included patients aged <14 years of age who attended an emergency department over a one-year period. The relationship between the variables collected and oral pathology was analyzed. RESULTS: Fifty-five patients were included, 45.5% girls, mean age 4.11 years (10 days to 13 years). Overall, mucosal pathology (74.5%) prevailed over dental ones, and lesions of infectious origin (54.6%) over the traumatic ones (14.5%). Dental pathology (50% toothache and 35.7% infections) was significantly associated with being >6 years (66.7 vs 10%), pain (40.7 vs 10.7%) and absence of fever (37.9 vs 11.5%). Mucosal pathology (61% infections: 53.7% viral and 31.7% due to herpangina) was significantly associated with being =6 years (60 vs 6.7%) and having fever (76.9 vs 17.2%). Six traumatic lesions on the mucosa and two on the teeth were observed; significantly more patients attended the emergency room within 24 hours (median =1 hour) than in the case of infection (100 vs 51.7%). Being =6 years was significantly associated with fever, mucosal pathology, mucosal infection, and herpangina, and being >6 years was associated with pain, previous antibiotic treatment and at discharge, and previous NSAID regimen. CONCLUSIONS: The analyzed pediatric oral pathologies treated in the emergency department are of mucosal and infectious origin. Dental disease prevail in children >6 years of age and mucosal lesions in those =6 years; no sex differences are observed.

Prevalencia de patología infantil dental y de la mucosa en un servicio de urgencias hospitalario / Prevalence of dental and mucosal lesions among the pediatric population who attended the emergency department of a general hospital

Fundamento: La elevada prevalencia de la patología oral infantil incentiva a conocer sus manifestaciones y el carácter urgente de las mismas, objetivo del presente estudio. Metodología: Estudio transversal que incluyó pacientes de edad <14 años que acudieron a un servicio de urgencias durante un año. Se analizó la relación entre las variables recogidas y la patología oral. Resultados: Se incluyeron 55 pacientes, 45,5% niñas, edad media 4,11 años (10 días a 13 años). Globalmente, predominó la patología mucosa (74,5%) frente a la dentaria, y el origen infeccioso (54,6%) frente al traumático (14,5%). La patología dentaria (50% odontalgia y 35,7% infecciones) se asoció significativamente a edad >6 años (66,7 vs 10%), dolor (40,7 vs 10,7%) y ausencia de fiebre (37,9 vs 11,5%). La patología mucosa (61% infecciones: 53,7% víricas y 31,7% por herpangina) se asoció significativamente a edad ≤6 años (60 vs 6,7%;) y fiebre (76,9 vs 17,2%). Se observaron seis lesiones traumáticas sobre la mucosa y dos en los dientes; significativamente más pacientes acudieron a urgencias antes de 24 horas (mediana =1 hora) que en caso de infección (100 vs 51,7%). La edad ≤6 años se asoció significativamente a fiebre, patología mucosa, infección de la mucosa y herpangina, y la >6 años se asoció a dolor, tratamiento antibiótico previo y al alta y pauta previa de AINE. Conclusión: La patología oral infantil atendida en el servicio de urgencias analizado fue de la mucosa y origen infeccioso, predominando la dentaria en >6 años y la mucosa en ≤6 años, sin diferencia por sexo.(AU)

Background: The high prevalence of oral pathology in children encourages to gain further understanding on their manifestations and urgent nature, objective of the present study. Methodology: Crosssectional study that included patients aged <14 years of age who attended an emergency department over a oneyear period. The relationship between the variables collected and oral pathology was analyzed. Results: Fifty-five patients were included, 45.5% girls, mean age 4.11 years (10 days to 13 years). Overall, mucosal pathology (74.5%) prevailed over dental ones, and lesions of infectious origin (54.6%) over the traumatic ones (14.5%). Dental pathology (50% toothache and 35.7% infections) was significantly associated with being >6 years (66.7 vs 10%), pain (40.7 vs 10.7%) and absence of fever (37.9 vs 11.5%). Mucosal pathology (61% infections: 53.7% viral and 31.7% due to herpangina) was significantly associated with being ≤6 years (60 vs 6.7%) and having fever (76.9 vs 17.2%). Six traumatic lesions on the mucosa and two on the teeth were observed; significantly more patients attended the emergency room within 24 hours (median =1 hour) than in the case of infection (100 vs 51.7%). Being ≤6 years was significantly associated with fever, mucosal pathology, mucosal infection, and herpangina, and being >6 years was associated with pain, previous antibiotic treatment and at discharge, and previous NSAID regimen. Conclusions: The analyzed pediatric oral pathologies treated in the emergency department are of mucosal and infectious origin. Dental disease prevail in children >6 years of age and mucosal lesions in those ≤6 years; no sex differences are observed.

Novel PWO/ ZnO heterostructured nanocomposites: Synthesis, characterization, and photocatalytic performance.

Photocatalytic degradation is becoming an increasingly attractive method for addressing environmental remediation challenges. In this work, the novel pure PWO/ZnO and doped PWO: Er/ZnO: Ag heterostructure nanocomposites with premier photocatalytic efficiency were synthesized via a simple co-precipitation method followed by a solvothermal procedure. X-ray diffraction (XRD), diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray (EDX), and ultraviolet-visible (UV-Vis) absorbance measurements techniques were employed to characterize the structural and optical properties. HRTEM images prove the possibility of intimate contact formation at the pure and doped PWO/ZnO heterostructure nanocomposite interfaces. The photocatalytic performance of the PWO/ZnO heterostructure nanocomposites in the degradation of the methylene blue (MB) and methyl orange (MO) dyes under UVA light was evaluated. The photocatalysts' ability in the mineralization of organic pollutants was confirmed by the TOC test. BET and zeta potential analyses were used to study the dye adsorption mechanisms. Additionally, adsorption isotherms and kinetics have been investigated to describe the adsorption of MB and MO into the samples. The degradation rates of MB with PWO/ZnO and PWO: Er/ZnO: Ag heterostructure nanocomposites were 4.7 and 6.6 times higher than those of PWO and PWO: Er nanoparticles. This rate for MO degradation is 5.2 and 3.5 times higher than that of pure PWO and PWO: Er nanoparticles, respectively. This study outlines an easy method to develop innovative, highly effective heterostructure nanocomposites capable of converting UVA light into photocatalytic performance.

Validation of the TRI-SCORE in patients undergoing surgery for isolated tricuspid regurgitation.

INTRODUCTION: Estimation of peri-procedural risk in patients with tricuspid regurgitation (TR) undergoing isolated tricuspid valve surgery (ITVS) is of paramount importance. The TRI-SCORE is a new surgical risk scale specifically developed for this purpose, which ranged from 0 to 12 points and included eight parameters: right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin (with a value of 2 points), age ≥70 years, New York Heart Association Class III-IV, left ventricular ejection fraction <60% and moderate/severe right ventricular dysfunction (with a value of 1 point). The objective of the study was to evaluate the performance of the TRI-SCORE in an independent cohort of patients undergoing ITVS. METHODS: A retrospective observational study was performed in four centres, including consecutive adult patients undergoing ITVS for TR between 2005 and 2022. The TRI-SCORE and the traditional risk scores used in cardiac surgery (Logistic EuroScore (Log-ES) and EuroScore-II (ES-II)) were applied for each patient, and discrimination and calibration of the three scores were evaluated in the entire cohort. RESULTS: A total of 252 patients were included. The mean age was 61.5±11.2 years, 164 (65.1%) patients were female, and TR mechanism was functional in 160 (63.5%) patients. The observed in-hospital mortality was 10.3%. The estimated mortality by the Log-ES, ES-II and TRI-SCORE was 8.7±7.3%, 4.7±5.3% and 11.0±16.6%, respectively. Patients with a TRI-SCORE ≤4 and >4 had an in-hospital mortality of 1.3% and 25.0%, p=0.001, respectively. The discriminatory capacity of the TRI-SCORE had a C-statistic of 0.87 (0.81-0.92), which was significantly higher than both the Log-ES (0.65 (0.54-0.75)) and ES-II (0.67 (0.58-0.79)), p=0.001 (for both comparisons). CONCLUSION: This external validation of the TRI-SCORE demonstrated good performance to predict in-hospital mortality in patients undergoing ITVS, which was significantly better than the Log-ES and ES-II, which underestimated the observed mortality. These results support the widespread use of this score as a clinical tool.

Clinical outcomes and quality of life after contemporary isolated coronary bypass grafting: a prospective cohort study.

OBJECTIVES: The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG. METHODS: The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis. RESULTS: A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9-2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72-0.92] at baseline to 0.92 [IQR, 0.82-1.00] at 1 year ( P <0.0001). CONCLUSION: Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL.

Cardiac surgery simulation: Advances in transvenous lead extraction.

The clinical importance of procedures for transvenous lead extraction has increased greatly because the volume of cardiac implantable electronic devices has increased. Consequently, the number of device-related complications requiring lead extraction has also been increasing. Great improvements in lead extraction techniques have occurred in recent years with the development of transvenous lead extraction tools and techniques. Experienced centres can achieve high success rates with infrequent complications. However, even in experienced hands, life-threatening complications can occur, and any physician performing these procedures must be prepared and trained for such eventualities. Moreover, because the occurrence of these stressful situations cannot be accurately predicted, training obtained in simulated environments can be decisive. We have developed a training module that simulates all the ordered steps of a transvenous lead extraction procedure and thus is able to help surgeons refine their surgical techniques and improve their performance.

De la cicloadición de Huisgen a la química bioortogonal. Un comentario al premio Nobel de Química de 2022 / From the Huisgen cycloaddition to bioorthogonal chemistry. A commentary on the 2022 Nobel Prize in Chemistry

El primer logro de los galardonados con el Premio Nobel de Química de 2022, y en particular de Sharpless, es de tipo conceptual, y consistió en la propuesta del concepto de reacción click dentro de un cuerpo de doctrina general. En una segunda fase, tanto Sharpless como Meldal establecieron la catálisis de la cicloadición 1,3-dipolar de Huisgen por Cu(I), lo que llevó a su reconocimiento de como la primera reacción click y a su empleo generalizado en todos los campos de la química. Estos descubrimientos prepararon el terreno para el descubrimiento por Bertozzi de las reacciones click bioortogonales, aprovechando el incremento de reactividad asociado a la tensión anular de los derivados de ciclooctino. La influencia de estas ideas y descubrimientos ha sido enorme y ha conducido a grandes avances en diversos campos de la Química y la Biología. (AU)

The first achievement of the 2022 Chemistry Nobel Prize awardees, Sharpless in particular, was of a conceptual nature and consisted in the proposal of the click chemistry concept, together with its placement in a broader theoretical frame. In a second phase, both Sharpless and Meldal established the copper(I)-catalyzed conditions that allowed the Huisgen 1,3-dipolar cycloaddition to be recognized as the first click reaction, which was broadly employed in all fields of chemistry. These discoveries laid the ground for the development by Bertozzi of bioorthogonal chemistry on the basis of the increased reactivity associated to ring strain in cyclooctyne derivatives. The influence of these ideas and discoveries has been widespread and has led to innumerable advances in many fields of Chemistry and Biology. (AU)

Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease.

Calcific aortic valve disease (CAVD) is highly prevalent during aging. CAVD initiates with endothelial dysfunction, leading to lipid accumulation, inflammation, and osteogenic transformation. Integrin-linked kinase (ILK) participates in the progression of cardiovascular diseases, such as endothelial dysfunction and atherosclerosis. However, ILK role in CAVD is unknown. First, we determined that ILK expression is downregulated in aortic valves from patients with CAVD compared to non-CAVD, especially at the valve endothelium, and negatively correlated with calcification markers. Silencing ILK expression in human valve endothelial cells (siILK-hVECs) induced endothelial-to-mesenchymal transition (EndMT) and promoted a switch to an osteoblastic phenotype; SiILK-hVECs expressed increased RUNX2 and developed calcified nodules. siILK-hVECs exhibited decreased NO production and increased nitrosative stress, suggesting valvular endothelial dysfunction. NO treatment of siILK-hVECs prevented VEC transdifferentiation, while treatment with an eNOS inhibitor mimicked ILK-silencing induction of EndMT. Accordingly, NO treatment inhibited VEC calcification. Mechanistically, siILK-hVECs showed increased Smad2 phosphorylation, suggesting a TGF-ß-dependent mechanism, and NO treatment decreased Smad2 activation and RUNX2. Experiments performed in eNOS KO mice confirmed the involvement of the ILK-eNOS signaling pathway in valve calcification, since aortic valves from these animals showed decreased ILK expression, increased RUNX2, and calcification. Our study demonstrated that ILK endothelial expression participates in human CAVD development by preventing endothelial osteogenic transformation.

Clinical event rate in patients with and without left main disease undergoing isolated coronary artery bypass grafting: results from the European DuraGraft Registry.

OBJECTIVES: Left main coronary artery disease (LMCAD) is considered an independent risk factor for clinical events after coronary artery bypass grafting (CABG). We have conducted a subgroup analysis of the multicentre European DuraGraft Registry to investigate clinical event rates at 1 year in patients with and without LMCAD undergoing isolated CABG in contemporary practice. METHODS: Patients undergoing isolated CABG were selected. The primary end point was the incidence of a major adverse cardiac event (MACE) defined as the composite of death, myocardial infarction (MI) or repeat revascularization (RR) at 1 year. The secondary end point was major adverse cardiac and cerebrovascular events (MACCE) defined as MACE plus stroke. Propensity score matching was performed to balance for differences in baseline characteristics. RESULTS: LMCAD was present in 1033 (41.2%) and absent in 1477 (58.8%) patients. At 1 year, the MACE rate was higher for LMCAD patients (8.2% vs 5.1%, P = 0.002) driven by higher rates of death (5.4% vs 3.4%, P = 0.016), MI (3.0% vs 1.3%, P = 0.002) and numerically higher rates of RR (2.8% vs 1.8%, P = 0.13). The incidence of MACCE was 8.8% vs 6.6%, P = 0.043, with a stroke rate of 1.0% and 2.4%, P = 0.011, for the LMCAD and non-LMCAD groups, respectively. After propensity score matching, the MACE rate was 8.0% vs 5.2%, P = 0.015. The incidence of death was 5.1% vs 3.7%, P = 0.10, MI 3.0% vs 1.4%, P = 0.020, and RR was 2.7% vs 1.6%, P = 0.090, for the LMCAD and non-LMCAD groups, respectively. Less strokes occurred in LMCAD patients (1.0% vs 2.4%, P = 0.017). The MACCE rate was not different, 8.5% vs 6.7%, P = 0.12. CONCLUSIONS: In this large registry, LMCAD was demonstrated to be an independent risk factor for MACE after isolated CABG. Conversely, the risk of stroke was lower in LMCAD patients. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02922088.

Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis.

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 µM) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 µM) might add a piece to the puzzle of its anti-ALS molecular profile.