Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic.

This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction.

Partial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model. An EMT-specific quantitative polymerase chain reaction (qPCR) array was used to screen for deregulated genes, leading to the establishment of an in silico gene signature that was correlated with poor disease-free survival in CRC patients along with the CRC consensus molecular subtype CMS4. Among the significantly deregulated p-EMT genes, a triple-gene signature consisting of SERPINE1, SOX10, and epidermal growth factor receptor (EGFR) was identified. Starvation-induced p-EMT was characterised by increased migratory potential and chemoresistance, as well as E-cadherin processing and internalisation. Both gene signature and E-cadherin alterations could be reversed by the proteasomal inhibitor MG132. Spatially resolving EGFR expression with high-resolution immunofluorescence imaging identified a proliferation stop in starved CRC cells caused by EGFR internalisation. In conclusion, we have gained insight into a previously undiscovered EMT mechanism that may become relevant when tumour cells are under nutrient stress, as seen in early stages of metastasis. Targeting this process of tumour cell dissemination might help to prevent EMT and overcome drug resistance. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Estudio comparativo del control cistoscópico vs control radiológico para el tratamiento endoscópico del megauréter obstructivo primario / Comparative study of cystoscopic control vs. radiological control in the endoscopic treatment of primary obstructive megaurater

Objetivo: La dilatación neumática con balón de alta presión para el tratamiento del megauréter obstructivo primario (MOP) fue descrita inicialmente bajo control cistoscópico y radioscópico. Sin embargo, algunos grupos utilizan únicamente el control cistoscópico, con la intención de evitar la radiación ionizante asociada al procedimiento. Material y métodos: Estudio retrospectivo que incluye los MOP tratados mediante dilatación neumática en nuestro servicio entre 2008 y 2021. Comparamos tasa de éxito, complicaciones y seguimiento entre dos grupos: dilatación bajo control cistoscópico exclusivo (CS) vs control radioscópico exclusivo (RX). Resultados: Intervenimos 23 pacientes: 9 CS y 14 RX. Ambos grupos fueron demográficamente comparables. La estancia media hospitalaria fue significativamente menor en el grupo CS (1 vs 2 días; p0,009). El tiempo quirúrgico fue mayor en el grupo RX (78 vs 30 min; p0,001). La dilatación de la unión vesicoureteral (UVU) fue satisfactoria 100% CS vs 79% RX: RR 3,87 (0,51-26,99). Las complicaciones postoperatorias fueron similares para ambos grupos, RR 3,87 (0,51-26,99). La migración del catéter doble J ocurrió en un caso en ambos grupos: RR 0,64 (0,05-9,03). A largo plazo, la tasa de éxito del tratamiento fue mayor para el grupo CS (100% vS 71%); RR 3,87 (0,51-26,99). Conclusión: La dilatación neumática del MOP bajo control cistoscópico exclusivo es más rápida de realizar, sin aumentar por ello el riesgo de complicaciones. Basándonos en nuestra experiencia, proponemos eliminar la radiación ionizante a los pacientes durante el procedimiento, ya que la consideramos innecesaria.(AU)

Objective: High-pressure balloon pneumatic dilatation for the treatment of primary obstructive megaureter (POM) was initially described under cystoscopic and radiological control. However, some groups use cystoscopic control only, in an attempt to avoid the ionizing radiation associated with the procedure. Materials and methods: A retrospective study of POM patients treated with pneumatic dilatation in our unit from 2008 to 2021 was carried out. Success rates, complications, and follow-up were compared between two groups –dilatation under cystoscopic control alone (CS) vs. dilatation under radiological control only (RX). Results: 23 patients –9 CS and 14 RX– underwent surgery. Both groups were demographically comparable. Mean hospital stay was significantly shorter in the CS group (1 vs. 2 days; p = 0.009). Operating time was longer in the RX group (78 vs. 30 min; p = 0.001). Ureterovesical junction (UVJ) dilatation was successful in 100% of CS vs. 79% of RX cases; RR: 3.87 (0.51-26.99). Postoperative complications were similar in both groups; RR: 3.87 (0.51-26.99). Double J stent migration occurred in one case in both groups; RR: 0.64 (0.05-9.03). In the long-term, treatment success rate was higher in the CS group (100% vs. 71%); RR: 3.87 (0.51-26.99). Conclusion: POM pneumatic dilatation under cystoscopic control alone is faster, without increasing the risk of complications. Based on our experience, we suggest ionizing radiation be removed, since we consider it to be unnecessary.(AU)

Comparative study of cystoscopic control vs. radiological control in the endoscopic treatment of primary obstructive megaurater. / Estudio comparativo del control cistoscópico vs control radiológico para el tratamiento endoscópico del megauréter obstructivo primario.

OBJECTIVE: High-pressure balloon pneumatic dilatation for the treatment of primary obstructive megaureter (POM) was initially described under cystoscopic and radiological control. However, some groups use cystoscopic control only, in an attempt to avoid the ionizing radiation associated with the procedure. MATERIALS AND METHODS: A retrospective study of POM patients treated with pneumatic dilatation in our unit from 2008 to 2021 was carried out. Success rates, complications, and follow-up were compared between two groups -dilatation under cystoscopic control alone (CS) vs. dilatation under radiological control only (RX). RESULTS: 23 patients -9 CS and 14 RX- underwent surgery. Both groups were demographically comparable. Mean hospital stay was significantly shorter in the CS group (1 vs. 2 days; p = 0.009). Operating time was longer in the RX group (78 vs. 30 min; p = 0.001). Ureterovesical junction (UVJ) dilatation was successful in 100% of CS vs. 79% of RX cases; RR: 3.87 (0.51-26.99). Postoperative complications were similar in both groups; RR: 3.87 (0.51-26.99). Double J stent migration occurred in one case in both groups; RR: 0.64 (0.05-9.03). In the long-term, treatment success rate was higher in the CS group (100% vs. 71%); RR: 3.87 (0.51-26.99). CONCLUSION: POM pneumatic dilatation under cystoscopic control alone is faster, without increasing the risk of complications. Based on our experience, we suggest ionizing radiation be removed, since we consider it to be unnecessary.

OBJETIVO: La dilatación neumática con balón de alta presión para el tratamiento del megauréter obstructivo primario (MOP) fue descrita inicialmente bajo control cistoscópico y radioscópico. Sin embargo, algunos grupos utilizan únicamente el control cistoscópico, con la intención de evitar la radiación ionizante asociada al procedimiento. MATERIAL Y METODOS: Estudio retrospectivo que incluye los MOP tratados mediante dilatación neumática en nuestro servicio entre 2008 y 2021. Comparamos tasa de éxito, complicaciones y seguimiento entre dos grupos: dilatación bajo control cistoscópico exclusivo (CS) vs control radioscópico exclusivo (RX). RESULTADOS: Intervenimos 23 pacientes: 9 CS y 14 RX. Ambos grupos fueron demográficamente comparables. La estancia media hospitalaria fue significativamente menor en el grupo CS (1 vs 2 días; p 0,009). El tiempo quirúrgico fue mayor en el grupo RX (78 vs 30 min; p 0,001). La dilatación de la unión vesicoureteral (UVU) fue satisfactoria 100% CS vs 79% RX: RR 3,87 (0,51-26,99). Las complicaciones postoperatorias fueron similares para ambos grupos, RR 3,87 (0,51-26,99). La migración del catéter doble J ocurrió en un caso en ambos grupos: RR 0,64 (0,05-9,03). A largo plazo, la tasa de éxito del tratamiento fue mayor para el grupo CS (100% vS 71%); RR 3,87 (0,51-26,99). CONCLUSION: La dilatación neumática del MOP bajo control cistoscópico exclusivo es más rápida de realizar, sin aumentar por ello el riesgo de complicaciones. Basándonos en nuestra experiencia, proponemos eliminar la radiación ionizante a los pacientes durante el procedimiento, ya que la consideramos innecesaria.

Neurophobia among resident physicians in the emergency service. / Neurofobia entre médicos residentes en los servicios de urgencias.

INTRODUCTION: Neurophobia is defined as the fear towards clinical neurology caused by the inability to apply theoretical knowledge to practical clinical situations. This phenomenon is not restricted to medical students and has never been studied before in the Emergency Department. We aimed to study how resident doctors perceive their knowledge in neurology and urgent neurological conditions as well as possible causes for said fears. MATERIALS AND METHODS: Cross-sectional multicentric study using self-administered surveys sent to medical residents within the Aragon Health Service. They were questioned about their fear of neurology and other medical specialties, possible causes, and perception of knowledge in neurological pathologies and subareas in the emergency service. RESULTS: We obtained 134 responses. 27.6% (37) suffered from neurophobia. Despite neurology being considered the most difficult discipline, it did also arouse the third most interest among the students. The areas where they showed the most confidence were headaches and vascular pathology. The areas where they felt the most insecure were neuromuscular diseases, neuro-ophthalmology, and spinal cord injury. In none of the areas surveyed, the percentage of respondents who felt secure exceeded 50%. CONCLUSIONS: Neurophobia is prevalent among trainee doctors working in the emergency department. Their confidence correlates with the degree of exposure to patients. Neurologist must play an active role in the education of new specialist and promote the collaboration with emergency departments.

TITLE: Neurofobia entre médicos residentes en los servicios de urgencias.Introducción. La neurofobia se define como el miedo hacia la neurología que surge de la incapacidad para aplicar los conocimientos teóricos a situaciones clínicas prácticas. Este fenómeno parece no limitarse únicamente a estudiantes de medicina, pero no se dispone de estudios previos en el ámbito de urgencias. Este trabajo valora la percepción de conocimientos en las distintas patologías neurológicas urgentes por parte de médicos en formación y posibles motivos de neurofobia. Material y métodos. Se trata de un estudio transversal multicéntrico mediante encuestas autoadministradas a médicos en formación de todo el Servicio Aragonés de Salud. Se interrogó sobre su miedo a la neurología y otras especialidades médicas, posibles causas y percepción de conocimientos en patologías neurológicas en el servicio de urgencias. Resultados. Se obtuvieron 134 respuestas. El 27,6% (37) sufría neurofobia. La neurología fue la tercera disciplina que mayor interés despertó, pero se considera la de mayor dificultad. Las áreas en las que mayor seguridad mostraron fueron las cefaleas y la patología vascular. Donde mayor inseguridad existía fue en la neuromuscular, la neurooftalmología y la lesión medular aguda. En ninguna de las áreas hubo un porcentaje mayor del 50% que se sintiera seguro o muy seguro. Conclusiones. La neurofobia está presente entre los médicos en formación que desempeñan su labor en los servicios de urgencias. Su distribución depende del grado de exposición a los pacientes. Los neurólogos debemos desempeñar un papel activo en la formación de nuevos especialistas y promover la colaboración con los servicios de urgencias.

Neurofobia entre médicos residentes en los servicios de urgencias / Neurophobia among resident physicians in the emergency service

Introducción La neurofobia se define como el miedo hacia la neurología que surge de la incapacidad para aplicar los conocimientos teóricos a situaciones clínicas prácticas. Este fenómeno parece no limitarse únicamente a estudiantes de medicina, pero no se dispone de estudios previos en el ámbito de urgencias. Este trabajo valora la percepción de conocimientos en las distintas patologías neurológicas urgentes por parte de médicos en formación y posibles motivos de neurofobia. Material y métodos. Se trata de un estudio transversal multicéntrico mediante encuestas autoadministradas a médicos en formación de todo el Servicio Aragonés de Salud. Se interrogó sobre su miedo a la neurología y otras especialidades médicas, posibles causas y percepción de conocimientos en patologías neurológicas en el servicio de urgencias. Resultados Se obtuvieron 134 respuestas. El 27,6% (37) sufría neurofobia. La neurología fue la tercera disciplina que mayor interés despertó, pero se considera la de mayor dificultad. Las áreas en las que mayor seguridad mostraron fueron las cefaleas y la patología vascular. Donde mayor inseguridad existía fue en la neuromuscular, la neurooftalmología y la lesión medular aguda. En ninguna de las áreas hubo un porcentaje mayor del 50% que se sintiera seguro o muy seguro. Conclusiones La neurofobia está presente entre los médicos en formación que desempeñan su labor en los servicios de urgencias. Su distribución depende del grado de exposición a los pacientes. Los neurólogos debemos desempeñar un papel activo en la formación de nuevos especialistas y promover la colaboración con los servicios de urgencias. (AU)

INTRODUCTION Neurophobia is defined as the fear towards clinical neurology caused by the inability to apply theoretical knowledge to practical clinical situations. This phenomenon is not restricted to medical students and has never been studied before in the Emergency Department. We aimed to study how resident doctors perceive their knowledge in neurology and urgent neurological conditions as well as possible causes for said fears. MATERIALS AND METHODS Cross-sectional multicentric study using self-administered surveys sent to medical residents within the Aragon Health Service. They were questioned about their fear of neurology and other medical specialties, possible causes, and perception of knowledge in neurological pathologies and subareas in the emergency service. RESULTS We obtained 134 responses. 27.6% (37) suffered from neurophobia. Despite neurology being considered the most difficult discipline, it did also arouse the third most interest among the students. The areas where they showed the most confidence were headaches and vascular pathology. The areas where they felt the most insecure were neuromuscular diseases, neuro-ophthalmology, and spinal cord injury. In none of the areas surveyed, the percentage of respondents who felt secure exceeded 50%. CONCLUSIONS Neurophobia is prevalent among trainee doctors working in the emergency department. Their confidence correlates with the degree of exposure to patients. Neurologist must play an active role in the education of new specialist and promote the collaboration with emergency departments. (AU)

Differences and similarities between COVID-19 related-headache and COVID-19 vaccine related-headache. A case-control study. / Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles.

INTRODUCTION: Headache is a frequent symptom at the acute phase of coronavirus disease 2019 (COVID-19) and also one of the most frequent adverse effects following vaccination. In both cases, headache pathophysiology seems linked to the host immune response and could have similarities. We aimed to compare the clinical phenotype and the frequency and associated onset symptoms in patients with COVID-19 related-headache and COVID-19 vaccine related-headache. SUBJECTS AND METHODS: A case-control study was conducted. Patients with confirmed COVID-19 infection and COVID-19-vaccine recipients who experienced new-onset headache were included. A standardised questionnaire was administered, including demographic variables, prior history of headaches, associated symptoms and headache-related variables. Both groups were matched for age, sex, and prior history of headache. A multivariate regression analysis was performed. RESULTS: A total of 238 patients fulfilled eligibility criteria (143 patients with COVID-19 related-headache and 95 subjects experiencing COVID-19 vaccine related-headache). Patients with COVID-19 related-headache exhibited a higher frequency of arthralgia, diarrhoea, dyspnoea, chest pain, expectoration, anosmia, myalgia, odynophagia, rhinorrhoea, cough, and dysgeusia. Further, patients with COVID-19 related-headache had a more prolonged daily duration of headache and described the headache as the worst headache ever experienced. Patients with COVID-19 vaccine-related headache, experienced more frequently pain in the parietal region, phonophobia, and worsening of the headache by head movements or eye movements. CONCLUSION: Headache caused by SARS-CoV-2 infection and COVID-19 vaccination related-headache have more similarities than differences, supporting a shared pathophysiology, and the activation of the innate immune response. The main differences were related to associated symptoms.

TITLE: Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles.Introducción. La cefalea es un síntoma frecuente en la fase aguda de la enfermedad por coronavirus 2019 (COVID-19) y también uno de los efectos adversos más comunes tras la vacunación. En ambos casos, la fisiopatología de la cefalea parece estar relacionada con la respuesta inmunitaria del huésped y podría presentar similitudes. Nuestro objetivo fue comparar el fenotipo clínico y la frecuencia de los síntomas asociados y los síntomas de inicio en pacientes con cefalea relacionada con la COVID-19 y cefalea relacionada con la vacuna de la COVID-19. Sujetos y métodos. Se realizó un estudio de casos y controles. Se incluyó a pacientes con infección confirmada por COVID-19 y receptores de la vacuna de la COVID-19 que experimentaron un nuevo inicio de cefalea. Se administró un cuestionario estandarizado que incluyó variables demográficas, antecedentes previos de cefaleas, síntomas asociados y variables relacionadas con la cefalea. Ambos grupos se emparejaron por edad, sexo y antecedentes previos de cefaleas. Se realizó un análisis de regresión multivariante. Resultados. Un total de 238 pacientes cumplieron con los criterios de elegibilidad (143 pacientes con cefalea relacionada con la COVID-19 y 95 sujetos con cefalea relacionada con la vacuna de la COVID-19). Los pacientes con cefalea relacionada con la COVID-19 presentaron una mayor frecuencia de artralgia, diarrea, disnea, dolor torácico, expectoración, anosmia, mialgia, odinofagia, rinorrea, tos y disgeusia. Además, los pacientes con cefalea relacionada con la COVID-19 experimentaron una duración diaria más prolongada de la cefalea y describieron la cefalea como la peor que habían experimentado. Los pacientes con cefalea relacionada con la vacuna de la COVID-19 experimentaron con más frecuencia dolor en la región parietal, fonofobia y empeoramiento de la cefalea por movimientos de la cabeza o de los ojos. Conclusión. La cefalea causada por la infección por el SARS-CoV-2 y la cefalea relacionada con la vacunación de la COVID-19 presentan más similitudes que diferencias, lo que respalda una fisiopatología compartida y la activación de la respuesta inmunitaria innata. Las principales diferencias estuvieron relacionadas con los síntomas asociados.

Neurology teaching difficulties and the academic consequences of the COVID-19 pandemic. Reply. / Dificultades en la enseñanza de la neurología y las consecuencias académicas de la pandemia de la COVID-19. Réplica.

TITLE: Dificultades en la enseñanza de la neurología y las consecuencias académicas de la pandemia de la COVID-19. Réplica.

Coronary computed tomography in emergencies: The importance of the radiologist's experience.

INTRODUCTION: Incorporating coronary computed tomography angiography (CTA) in the hospital workup for suspected acute coronary syndrome requires appropriate skills for interpreting this imaging test. Radiologists' skills can affect the interobserver agreement in evaluating these studies. OBJECTIVE: To determine the interobserver agreement according to radiologists' experience in the interpretation of coronary CTA studies done in patients who present at the emergency department with acute chest pain and low-to-intermediate probability of acute coronary syndrome. MATERIALS AND METHODS: We studied the interobserver agreement in the urgent evaluation of coronary CTA studies in which CAD-RADS was used to register the findings. We created pairs of observers among a total of 8 assessors (4 attending radiologists and 4 radiology residents). We used the kappa coefficient to estimate the overall concordance and the concordance between subgroups according to their experience. RESULTS: The agreement was substantial between experienced radiologists and residents (k=0.627; 95%CI: 0.436-0.826) as well as between all the pairs of observers (k=0.661; 95%CI: 0.506-0.823) for all the CAD-RADS together. The degree of agreement within the group of experienced radiologists was greater than that within the group of residents in all the analyses. The agreement was excellent for the overall CAD-RADS (k=0.950; 95% CI: 0.896-1) and for CAD-RADS ≥ 4 (k=1); the agreement was lower for CAD-RADS ≥ 3 (k=0.754; 95% CI: 0.246-1.255). The agreement for the residents for these categories was k=0.623, k=0.596, and k=0.473, respectively. CONCLUSION: The agreement among attending radiologists regarding the assessment of urgent coronary CTA studies is excellent. The agreement is lower when residents are paired with attending radiologists. These findings should be taken into consideration when implementing coronary CTA in emergency departments and in the organisation of radiological staff for interpreting and reporting this imaging test.

Implementing an outpatient surgical management in moderated-high risk patients with groin hernia repair.

PURPOSE: There is a growing trend to expand Ambulatory Surgery (AS) criteria in abdominal wall surgery. No Admission (NOADS) circuit. The present study aimed to assess the impact of classification criteria on postoperative results and hospital stays in a NOADS versus a conventional admission circuit to throw some light on surgical circuit inclusion. METHODS: A retrospective analysis of a prospective;y maintained database was performed comparing groin hernia's interventions in a NOADS vs Admission circuit in our center in 2018-2021. A multiple regression predictive model followed by a retrospective retest were dessigned to assess the impact of each criterion on hospital stay. In total, 743 patients were included, 399 in the Admission circuit (ADC) and 344 in NOADS circuit (NOADS). RESULTS: There were no statistical differences in complication or readmission rates (p = 0.343 and p = 0.563), nevertheless, a shorter hospital stay was observed in NOADS (p = 0.000). A hierarchical multiple regression predictive model proposed two opposite scenarios. The best scenario, not likely to need admission, was a female patient operated via the laparoscopic approach of a unilateral primary hernia (Estimated Postoperative Stay: 0.049 days). The worst scenario, likely to need admission, was a male patient operated via the open approach of a bilateral and recurrent hernia (Estimated Postoperative Stay: 1.505 Days). CONCLUSION: Groin hernia patients could safely benefit from a No Admission (NOADS) circuit. Our model could be useful for surgical circuit decision-making, especially for best/worst scenarios.

Neurofobia entre los estudiantes de medicina de una universidad española: experiencias más allá de la anglosfera / Neurophobia among undergraduate medical students: a European experience beyond the Anglosphere

Introducción: Definimos neurofobia como el miedo a las neurociencias y la neurología clínica, fundamentalmente asociado a la falta de capacidad del estudiante para aplicar sus conocimientos teóricos. Esta sensación, bien contrastada en el sistema anglosajón, ha sido poco estudiada en otros territorios europeos y nunca en nuestro país. Nuestro objetivo es analizar si este miedo hacia la neurología también existe entre estudiantes de una universidad española. Material y métodos. Estudio mediante encuestas autoadministradas a estudiantes de segundo, cuarto y sexto año de medicina de la Universidad de Zaragoza durante los cursos académicos 2020-2021 y 2021-2022. Cuestionario de 18 preguntas que recoge la percepción hacia la neurología y el resto de las neurociencias y su comparación con respecto a otras especialidades médicas. Resultados: De los 320 encuestados, el 34,1% sufriría neurofobia y tan sólo el 31,2% tendría claro a qué se dedica un neurólogo. A pesar de ser la especialidad considerada más difícil, es también la que mayor interés despierta. Los principales motivos para ese miedo son una enseñanza eminentemente teórica (59,4%), la neuroanatomía (47,8%) y una falta de integración entre las asignaturas de neurociencias (39,5%). Las soluciones consideradas de mayor peso por los alumnos para revertir esta situación irían en esa línea. Conclusiones: La neurofobia es también un problema en la formación universitaria española. Identificada la metodología docente como una de sus causas fundamentales, los neurólogos tenemos la oportunidad y la obligación de intentar revertir esta situación. Para ello, será necesario participar activamente en la formación de los futuros médicos desde las etapas más tempranas del grado.(AU)

Introduction: Neurophobia is defined as the fear of the neural sciences and clinical neurology that is due to the students’ inability to apply their knowledge of basic sciences to clinical situations. This phenomenon, well documented in the Anglosphere, has seldom been studied in other European countries and never in our country. Our study aimed to determine whether said fear existed among Spanish medical students. Material and methods: A self-administered questionnaire with 18 items was sent to medical students in the second, fourth and sixth years of medical school at a Spanish university during the academic years 2020-2021 and 2021-2022. They were questioned about their fears regarding neurology and neurosciences, causes and potential solutions. Results: Out of 320 responses, 34.1% suffered from neurophobia and only 31.2% felt confident they knew what neurologists do. Despite Neurology being considered the most difficult discipline, it did also arouse the most interest among the students. Main reasons identified for neurophobia were too theoretical lectures (59.4%), neuroanatomy (47.8%), and a lack of integration between neuroscience subjects (39.5%). Solutions considered most important by the students to reverse this situation went along those lines. Conclusion: Neurophobia is prevalent among Spanish medical students too. Having identified the teaching methodology as one of its fundamental causes, neurologists have the opportunity and obligation to reverse this situation. We should strive for more proactive involvement of neurologists at earlier stages of medical education.

Expression of Mn-sod, PAL1, aos1 and HPL genes in soybean plants overexpressing the NmDef02 defensin.

Plant defensins are a potential tool in crop improvement programs through biotechnology. Their antifungal action makes them attractive molecules for the production of transgenic plants. Information is currently lacking on what happens to the expression of defense genes in transgenic plants that overexpress a defensin. Here we show the relative expression of four defense-related genes: Mn-sod, PAL1, aos1 and HPL evaluated in two transgenic soybean events (Def1 and Def17) constitutively expressing the NmDef02 defensin gene from Nicotiana megalosiphon. The expression of these defense genes showed a differential profile in the transgenic events, with the increased expression of the aos1 gene and the repression of the Mn-sod gene in both events, when compared to the non-transgenic control. Furthermore, the expression of the PAL1 gene only increased in the Def17 event. The results indicate that although there were some changes in the expression of defense genes in transgenic plants overexpressing the defensin NmDef02; the morphoagronomic parameters evaluated were similar to the non-transgenic control. Understanding the molecular changes that occur in these transgenic plants could be of interest in the short, medium and long term.

Neurophobia among undergraduate medical students: a European experience beyond the Anglosphere. / Neurofobia entre los estudiantes de medicina de una universidad española: experiencias más allá de la anglosfera.

INTRODUCTION: Neurophobia is defined as the fear of the neural sciences and clinical neurology that is due to the students' inability to apply their knowledge of basic sciences to clinical situations. This phenomenon, well documented in the Anglosphere, has seldom been studied in other European countries and never in our country. Our study aimed to determine whether said fear existed among Spanish medical students. MATERIAL AND METHODS: A self-administered questionnaire with 18 items was sent to medical students in the second, fourth and sixth years of medical school at a Spanish university during the academic years 2020-2021 and 2021-2022. They were questioned about their fears regarding neurology and neurosciences, causes and potential solutions. RESULTS: Out of 320 responses, 34.1% suffered from neurophobia and only 31.2% felt confident they knew what neurologists do. Despite Neurology being considered the most difficult discipline, it did also arouse the most interest among the students. Main reasons identified for neurophobia were too theoretical lectures (59.4%), neuroanatomy (47.8%), and a lack of integration between neuroscience subjects (39.5%). Solutions considered most important by the students to reverse this situation went along those lines. CONCLUSION: Neurophobia is prevalent among Spanish medical students too. Having identified the teaching methodology as one of its fundamental causes, neurologists have the opportunity and obligation to reverse this situation. We should strive for more proactive involvement of neurologists at earlier stages of medical education.

TITLE: Neurofobia entre los estudiantes de medicina de una universidad española: experiencias más allá de la anglosfera.Introducción. Definimos neurofobia como el miedo a las neurociencias y la neurología clínica, fundamentalmente asociado a la falta de capacidad del estudiante para aplicar sus conocimientos teóricos. Esta sensación, bien contrastada en el sistema anglosajón, ha sido poco estudiada en otros territorios europeos y nunca en nuestro país. Nuestro objetivo es analizar si este miedo hacia la neurología también existe entre estudiantes de una universidad española. Material y métodos. Estudio mediante encuestas autoadministradas a estudiantes de segundo, cuarto y sexto año de medicina de la Universidad de Zaragoza durante los cursos académicos 2020-2021 y 2021-2022. Cuestionario de 18 preguntas que recoge la percepción hacia la neurología y el resto de las neurociencias y su comparación con respecto a otras especialidades médicas. Resultados. De los 320 encuestados, el 34,1% sufriría neurofobia y tan sólo el 31,2% tendría claro a qué se dedica un neurólogo. A pesar de ser la especialidad considerada más difícil, es también la que mayor interés despierta. Los principales motivos para ese miedo son una enseñanza eminentemente teórica (59,4%), la neuroanatomía (47,8%) y una falta de integración entre las asignaturas de neurociencias (39,5%). Las soluciones consideradas de mayor peso por los alumnos para revertir esta situación irían en esa línea. Conclusiones. La neurofobia es también un problema en la formación universitaria española. Identificada la metodología docente como una de sus causas fundamentales, los neurólogos tenemos la oportunidad y la obligación de intentar revertir esta situación. Para ello, será necesario participar activamente en la formación de los futuros médicos desde las etapas más tempranas del grado.

Bilateral absence of the deep brachial artery.

The aim of the following study was to present and comprehensively describe a case of a bilateral absence of the deep brachial artery (DBA). Furthermore, its embryology and clinical significance will also be discussed. During routine dissection, a 71-year-old male cadaver with a bilateral abnormality in the DBA and its branches was found. The first branch of the brachial artery (BA) was found to be the radial collateral artery, which passed behind the radial nerve. Furthermore, the middle collateral artery originated distal to the radial collateral artery and gave off first a singular, minor muscular branch and then the superior ulnar collateral artery. Later, the preceding nutrient arteries of the humerus and the deltoid branch consecutively branched off from the middle collateral artery. Subsequently, the middle ulnar collateral artery, the inferior ulnar collateral artery, the deltoid artery, the radial artery, and the ulnar artery branched off from the BA, as adapted in the current knowledge regarding the anatomy of the upper extremity. Furthermore, detailed measurements of the distances between the mentioned arteries were carried out. In the present study, a bilateral absence of the DBA was demonstrated. Meta-analysis focusing on the anatomy of this artery has shown how variable its characteristics are. However, our case report is the first in the literature to present this extremely rare variation. Having adequate knowledge regarding the anatomy of the arteries of the proximal arm is of immense importance when performing orthopaedic and reconstructive surgeries in this area.

Determination of the appropriate concentration of sodium alginate used for in vitro culture of cat preantral follicles in a serum-free medium containing FSH, EGF and IGF-I.

Culture of domestic cat preantral follicles can be a suitable technology to assist oocyte conservation strategies in the family Felidae. This research was aimed to comparatively analyse cat preantral follicular development of follicles directly seeded on growth surface or encapsulated in 0.5 or 1% of sodium alginate in a serum-free medium containing FSH, EGF and IGF-I. Preantral follicles were isolated from cat ovarian cortical tissue after ovariectomy. Alginate was dissolved at 0.5 or 1% in PBS. Follicles, 4 per well, with 0% (G-0%), 0.5% (G-0.5%) or 1% (G-1%) of sodium alginate were cultured in M199 with FSH (100 ng/mL), EGF (100 ng/mL) and IGF-I (100 ng/mL) for 7 days at 37°C, 5% CO2 and 99% humidity. Culture medium was replaced every 48 h and samples were stored at -20°C until ELISA of steroid hormones. Morphometric evaluation of follicles was performed every 24 h. G-0% follicles showed granulosa cell migration away from the oocyte and disrupted morphology, whereby they reached apparently larger diameters (203.70 ± 5.82 µm; p < .05) than G-0.5% and G-1% follicles (157.89 ± 8.47 µm and 95.23 ± 1.67 µm, respectively) which maintained three-dimensional organization, being larger in G-0.5% than in G-1% (p < .05). G-0.5% follicles attained the multi-layer preantral follicle stage on day 7 of culture, whereas G-1% follicles underwent progressive atresia. On day 6, steroid concentrations were higher (p < .05) in G-0% than in G-1%: 60 ± 19 vs 0.88 ± 0.32 pg/mL oestradiol; 2.6 ± 0.84 vs 0.04 ± 0.02 ng/mL progesterone; 1.3 ± 0.22 vs 0.61 ± 0.04 ng/mL testosterone and 1.6 ± 0.54 vs 0.22 ± 0.07 ng/mL androstenedione respectively. Steroid concentrations in G-0.5% were comprised between those of G-0% and G-1% (p > .05). In conclusion, two-layer cat preantral follicles encapsulated in 0.5% alginate cultured in medium containing FSH, EGF and IGF-I can develop up to the multi-layer preantral stage in 7 days of culture, whereas follicles directly seeded on growth surface or encapsulated in 1% alginate lost their three-dimensional organization, and experienced regression with compromised steroidogenesis, respectively.

Natural Products as a Major Source of Candidates for Potential Senolytic Compounds obtained by in silico Screening.

BACKGROUND: Preclinical studies suggest that senolytic compounds such as quercetin (a natural product) and dasatinib (a synthetic product) decrease senescent cells, reduce inflammation, and alleviate human frailty. This evidence has opened a new field of research for studying the effect of these compounds on age-related dysfunction and diseases. OBJECTIVE: The present study performed in silico and we identified new potential senolytic candidates from an extensive database that contains natural products (NPs) and semi-synthetic products (SMSs). METHODS: Computer programs Chemminer and rcdk packages, which compared the fingerprints of numerous molecules (40,383) with reference senolytics, and the creation of a pharmacological network built with signaling pathways and targets involved in senescence processes were used to identify compounds with a potential activity. RESULTS: Six drug-like candidates (3,4'-dihydroxypropiophenone, baicalein, α, ß-dehydrocurvularin, lovastatin, luteolin, and phloretin) were identified. CONCLUSION: To our knowledge, this is the first time that these six natural molecules have been proposed to have senolytic activity. To validate the methodology employed in the identification of new drug-like senolytics, experimental evidence is needed with models that evaluate senolytic activity.

Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults.

OBJECTIVE: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. METHODS: 82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. RESULTS: The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ - 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18F-FDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality. CONCLUSION: Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov no. NCT02365129 (registered 18 February 2015).

Cronotaraxis como síntoma guía de un infarto talámico medial / Chronotaraxis as a harbinger of medial thalamic infarction

La cronotaraxis es una afectación de la percepción de la secuencia temporal. Esta alteración de la temporalidad se ha descrito asociada de forma característica a la afectación talámica, concretamente al núcleo dorsomediano. Casos clínicos. Presentamos los casos clínicos de dos pacientes con ictus isquémicos agudos de localización en dicho territorio, con una clínica basada en este síntoma y cuyo reconocimiento resultó esencial en el abordaje terapéutico. Tanto en el primero como en el segundo caso se describe cómo la percepción de la temporalidad fue esencial para el diagnóstico de la patología isquémica de ambos pacientes. Discusión. El conocimiento y la divulgación de esta asociación pueden resultar fundamentales en el manejo de los pacientes con alteraciones talámicas. Esto se debe a la posibilidad que surge de influir y modificar el abordaje inicial, puesto que el reconocimiento de un síntoma específico, como es la cronotaraxis, puede evitar la extensión del daño talámico, y prevenir de esta manera las secuelas, sobre todo cognitivas, que ocasiona a largo plazo.(AU)

Introduction: Chronotaraxis is an impairment of the perception of the sequencing of time. This alteration of temporality has been described as being characteristically associated with thalamic involvement, specifically in the dorsomedial nucleus. Case reports: We report the clinical cases of two patients with acute ischaemic strokes located in said territory, with a clinical presentation based on this symptom and the recognition of which was essential in the therapeutic approach. In the first and second cases, it is described how the perception of temporality was essential for the diagnosis of the ischaemic condition in both patients. Discussion: Awareness and dissemination of this association may be vital in the management of patients with thalamic disorders. This is due to the possibility of influencing and modifying the initial approach, since the recognition of a specific symptom, such as chronotaraxis, can prevent the spread of thalamic damage, in addition to the long-term sequelae that it causes, especially those of a cognitive nature.(AU)

[Chronotaraxis as a harbinger of medial thalamic infarction]. / Cronotaraxis como síntoma guía de un infarto talámico medial.

INTRODUCTION: Chronotaraxis is an impairment of the perception of the sequencing of time. This alteration of temporality has been described as being characteristically associated with thalamic involvement, specifically in the dorsomedial nucleus. CASE REPORTS: We report the clinical cases of two patients with acute ischaemic strokes located in said territory, with a clinical presentation based on this symptom and the recognition of which was essential in the therapeutic approach. In the first and second cases, it is described how the perception of temporality was essential for the diagnosis of the ischaemic condition in both patients. DISCUSSION: Awareness and dissemination of this association may be vital in the management of patients with thalamic disorders. This is due to the possibility of influencing and modifying the initial approach, since the recognition of a specific symptom, such as chronotaraxis, can prevent the spread of thalamic damage, in addition to the long-term sequelae that it causes, especially those of a cognitive nature.

TITLE: Cronotaraxis como síntoma guía de un infarto talámico medial.Introducción. La cronotaraxis es una afectación de la percepción de la secuencia temporal. Esta alteración de la temporalidad se ha descrito asociada de forma característica a la afectación talámica, concretamente al núcleo dorsomediano. Casos clínicos. Presentamos los casos clínicos de dos pacientes con ictus isquémicos agudos de localización en dicho territorio, con una clínica basada en este síntoma y cuyo reconocimiento resultó esencial en el abordaje terapéutico. Tanto en el primero como en el segundo caso se describe cómo la percepción de la temporalidad fue esencial para el diagnóstico de la patología isquémica de ambos pacientes. Discusión. El conocimiento y la divulgación de esta asociación pueden resultar fundamentales en el manejo de los pacientes con alteraciones talámicas. Esto se debe a la posibilidad que surge de influir y modificar el abordaje inicial, puesto que el reconocimiento de un síntoma específico, como es la cronotaraxis, puede evitar la extensión del daño talámico, y prevenir de esta manera las secuelas, sobre todo cognitivas, que ocasiona a largo plazo.