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Abstract Neratinib is a tyrosine kinase inhibitor that is used for the therapy of patients with HER2+ breast tumors. However, despite its clinical benefit, resistance to the drug may arise. Here we have created cellular models of neratinib resistance to investigate the mechanisms underlying such resistance. Chronic neratinib exposure of BT474 human HER2+ breast cancer cells resulted in the selection of several clones resistant to the antiproliferative action of the drug. The clones were characterized biochemically and biologically using a variety of techniques. These clones retained HER2 levels similar to parental cells. Knockdown experiments showed that the neratinib-resistant clones retained oncogenic dependence on HER2. Moreover, the tyrosine phosphorylation status of BT474 and the resistant clones was equally sensitive to neratinib. Transcriptomic and Western analyses showed that peptidylarginine deiminase 3 was overexpressed in the three neratinib-resistant clones studied but was undetectable in BT474 cells. Experiments performed in the neratinib-resistant clones showed that reduction of PADI3 or inhibition of its function restored sensitivity to the antiproliferative action of neratinib. Moreover, overexpression of FLAG-tagged PADI3 in BT474 cells provoked resistance to the antiproliferative action of neratinib. Together, these results uncover a role of PADI3 in the regulation of sensitivity to neratinib in breast cancer cells overexpressing HER2 and open the possibility of using PADI3 inhibitors to fight resistance to neratinib.

María I Quiñones-Vico,1– 4,* Ana Ubago-Rodríguez,1– 3,* Ana Fernández-González,1– 3 Raquel Sanabria-de la Torre,2,5 Álvaro Sierra-Sánchez,1– 3,5 Trinidad Montero-Vilchez,2,6 Manuel Sánchez-Díaz,2,6 José L Arias,2,7,8 Salvador Arias-Santiago1– 4,6 1Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, Granada, 18014, Spain; 2Instituto de Investigación Biosanitaria Granada ibs.GRANADA, Granada, 18014, Spain; 3Andalusian Network of Design and Translation of Advanced Therapies, Sevilla, 41092, Spain; 4Medicine Department, School of Medicine, University of Granada, Granada, 18016, Spain; 5Department of Biochemistry and Molecular Biology IIi and Immunology, School of Medicine, University of Granada, Granada, 18016, Spain; 6Dermatology Department, Virgen de las Nieves University Hospital, Granada, 18014, Spain; 7Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Granada, 18071, Spain; 8Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, 18100, Spain*These authors contributed equally to this workCorrespondence: Ana Fernández-González, Email ana.fernandez.gonzalez@juntadeandalucia.esAbstract: Pseudomonas aeruginosa (P. aeruginosa) is a common nosocomial pathogen that can cause severe infections in critically ill patients. Due to its resistance to multiple drugs, it is challenging to treat, which can result in serious illness and death. Conventional treatments for infected wounds often involve the topical or systemic application of antibiotics, which can lead to systemic toxicity and the development of drug resistance. The combination of wound dressings that promote wound healing with nanoparticles (NPs) represents a revolutionary strategy for optimizing the safety and efficacy of antibiotics. This review assesses a systematic search to identify the latest approaches where the evaluation of wound dressings loaded with antibiotic NPs is conducted. The properties of NPs, the features of wound dressings, the antimicrobial activity and biocompatibility of the different strategies are analyzed. The results indicate that most research in this field is focused on dressings loaded with silver NPs (57.1%) or other inorganic materials (22.4%). Wound dressings loaded with polymeric NPs and carbon-based NPs represent 14.3% and 6.1% of the evaluated studies, respectively. Nevertheless, there are no clinical trials that have evaluated the efficacy of NPs-loaded wound dressings in patients. Further research is required to ensure the safety of these treatments and to translate the findings from the bench to the bedside. Keywords: hydrogel, skin infection, wound dressing, P. aeruginosa, nanoparticles

Background Silicosis is an occupational respiratory disease linked to silica dust inhalation. The main driver was traditional coal mining, but in recent decades, new sources of exposure have emerged. Our aim in this study was to assess the temporal and spatial distribution of mortality due to this disease over a 22-year period in Spain. Methods Silicosis records, as an Underlying Cause of Death, were extracted from the National Institute of Statistics from 1999 to 2020 using the International Classification of Diseases 10th revision (code J62.8). Age- and sex-adjusted mortality rates per 1,000,000 inhabitants were calculated for the territory and by province. A geographic analysis was performed, and clusters of deaths were identified at the municipal level, and then the outcomes were compared in two periods of 11 years. Results There were 2618 deaths due to silicosis in Spain. The mean age of death increased significantly by 0.66% annually from 1999 to 2013. The age-adjusted mortality rate decreased by 7.30% per year, falling from 3.00 to 0.65 per 1,000,000 inhabitants. The temporal pattern showed a significant decrease of mortality rate in 31% of the provinces (16 out of 52), while it increased in Pontevedra. Regarding the spatial analysis, 11 clusters were found in both periods, but some variations were observed in terms of their distribution in the Spanish territory, as well as in the affected municipalities. Conclusions The decrease in mortality due to Silicosis could be related to less exposure to silica dust over the years and an improvement in the survival of those affected. It is thus essential to analyze the role of preventive measures for this occupational disease.

Resumen: El pueblo Kankuamo es uno de los 102 pueblos originarios de Colombia, que se encuentran en el proceso de desarrollo de estrategias para la autogestión de salud individual y colectiva. Este artículo tiene como objetivo investigar, identificar y analizar, de forma colaborativa e intercultural, los factores que influyen en el bienestar del pueblo Kankuamo, utilizando el Enfoque de Capacidades propuesto por Amartya Sen. Con este fin, se llevaron a cabo tres grupos focales con la participación de 37 personas de las 15 comunidades del resguardo Kankuamo. Las transcripciones fueron analizadas mediante un análisis temático. De los grupos focales surgieron tres temas centrales para el bienestar de los Kankuamo: (i) armonía entre la naturaleza y los seres humanos, (ii) convivencia social y (iii) autodeterminación. Estos temas reflejan los principios y valores fundamentales que guían a la comunidad hacia el bienestar, la expansión de sus capacidades, la armonía y el desarrollo integral. Los resultados sugieren que los aspectos materiales desempeñan un papel secundario en el concepto de bienestar de la comunidad Kankuamo, y además confirman que es fundamental considerar una visión colectiva de capacidades, no solo individuales, en contextos indígenas. Estudios como este pueden contribuir al desarrollo de enfoques más contextualmente apropiados para evaluar y medir la calidad de vida y el bienestar de las comunidades indígenas, incluyendo el pueblo Kankuamo.

Resumen: Antecedentes y objetivo: La calidad de vida profesional se define como el bienestar derivado del equilibrio entre las exigencias del ámbito laboral y los recursos para afrontarlas, el deterioro de la calidad de vida profesional puede contribuir en el síndrome de burnout o del profesional quemado. El objetivo de este estudio consiste en evaluar mediante cuestionario validado la calidad de vida profesional de los dermatólogos españoles. Material y métodos: Se diseñó un estudio transversal que incluyó dermatólogos españoles que respondieran a un formulario autoadministrado enviado a través de aplicaciones de mensajería online. El formulario incluyó datos sociodemográficos, 3 preguntas de respuestas abiertas y el Cuestionario de Calidad de Vida Profesional (CVP-35). Resultados: Se incluyó a 106 participantes en este estudio, siendo un 58% (62/106) mujeres. La edad media fue de 41 años (intervalo de confianza [IC] del 95%: 43,3-38,8). Las puntuaciones para el dominio «carga de trabajo» de CVP-35 fueron superiores en las mujeres (p = 0,02) y en los jefes de servicio (p = 0,005). La presión asistencial fue el tema tratado con más frecuencia como factor limitante de la calidad de vida laboral, y el principal cambio identificado tras la pandemia de COVID-19. Conclusiones: En nuestro estudio las mujeres refirieron una mayor carga de trabajo. El incremento de carga asistencial y de trabajo a distancia fueron los principales cambios por la pandemia de COVID-19. La presión asistencial es una gran limitante de la calidad de vida profesional de nuestros compañeros, reducirla mejoraría la satisfacción diaria y la calidad asistencial. Abstract: Background and objective: Quality of professional life (QPL) is defined as a sense of well-being derived from a balance between the challenges of work and the resources available to deal with them. Impaired QPL can contribute to burnout. The aim of this study was to evaluate QPL in Spanish dermatologists using a validated questionnaire. Material and methods: We designed a cross-sectional study in which Spanish dermatologists were invited to complete an online questionnaire sent out by messaging applications. The dermatologists were asked to provide sociodemographic information, answer 3 open questions, and complete the 35-item Spanish QPL questionnaire (Spanish abbreviation, CVP-35). Results: We analyzed the information submitted by 106 dermatologists (62 women, 58%) with a mean age of 41 years (95% CI, 43.3-38.8 years). Women and department heads scored significantly higher in the workload domain of the questionnaire (P = .02 and P = .005, respectively). A heavy caseload was mentioned as the main factor contributing to impaired QPL and the main change in the wake of the COVID-19 pandemic. Conclusions: Female dermatologists reported heavier workloads. Heavy caseloads and more remote work were the main changes identified after the COVID-19 pandemic. Heavy caseloads have a significant impact on the QPL of dermatologists in Spain. Reducing caseloads would improve general job satisfaction and quality of care provision.

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p = 0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future. Resumen: Antecedentes: La pandemia de COVID-19 ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo: Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p = 0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro.

Resumen: Antecedentes: En España, aunque el Ministerio de Sanidad elabora el informe de posicionamiento terapéutico (IPT) y las condiciones de reembolso de los fármacos, las Comunidades Autónomas (CC. AA.) gestionan los servicios de salud y deciden sobre las condiciones de prescripción en su ámbito territorial. El objetivo del estudio EQUIDAD fue describir los condicionantes para la prescripción de los nuevos fármacos en Dermatología en las CC. AA. y sus posibles diferencias. Material y métodos: Estudio transversal realizado en abril-mayo del 2023. Dos dermatólogos con responsabilidades directivas de cada Comunidad Autónoma (C. A.) informaron sobre los condicionantes autonómicos y locales en la prescripción de los fármacos cuyo IPT para el tratamiento de enfermedades dermatológicas fue publicado en los años 2016-2022. Los datos fueron recogidos mediante un cuestionario online. Resultados: Un total de 33 investigadores de 17 CC. AA. participaron en el estudio. Se observaron inequidades entre CC. AA. para el acceso a los nuevos fármacos. Existieron condicionantes autonómicos adicionales al IPT en psoriasis en el 64,7% de las CC. AA., siendo este porcentaje menor en dermatitis atópica (35,3%) o melanoma (11,8%). El más frecuente fue el requisito de un orden de prescripción previo para el uso del fármaco. En algunas CC. AA. se detectaron además variaciones y condicionantes locales (diferencias entre centros de una misma C. A.). Conclusiones: Existe una multiplicidad de criterios tanto a nivel autonómico como local que añade restricciones adicionales a las establecidas por los IPT y que plantean una situación de inequidad entre los pacientes y los profesionales de las diferentes CC. AA. en el acceso a los nuevos fármacos. Abstract: Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. Material and methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected atthe local level (i.e., differences between hospitals within the same autonomous community). Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Background: Sleep is essential for health, especially during adolescence. However, most adolescents do not obtain the recommended 8 to 10 h of sleep, and their health is significantly affected. While both physical activity (PA) and diet have been shown to help improve the sleep quality and duration, the combined association of these two factors with sleep has yet to be analysed. Objectives: Therefore, the main objective of this study was to assess the evidence on the combined association of PA and diet with the quality and duration of sleep in adolescents. Secondary objectives were to analyse the evidence on the single association of PA with the quality and duration of sleep in adolescents and to analyse the single association of diet with the quality and duration of sleep in adolescents. Methods: To this end, a scoping review was conducted with a structured search in four online databases (PubMed, Scopus, Web of Science and ERIC). Results: The findings suggest that the amount of PA (time/week) and healthy dietary patterns, characterised by meal regularity and high consumption of fruits and vegetables, favour a better quality and a longer duration of sleep. Conversely, less weekly PA and the intake of less healthy foods, such as ultra-processed foods, are associated with decreasing the sleep quality and duration. Conclusions: In conclusion, the results underscore the importance of considering PA and diet as an appropriate approach to investigating sleep quality and duration in adolescents. Studies analysing the interplay between PA, diet and sleep in adolescents are scarce.

Antecedentes: El COVID persistente se define como la persistencia de síntomas de COVID-19 después de cuatro semanas de cursar con un cuadro agudo, según la definición más reciente de los Centers for Disease Control and Prevention. Se estima que existen 65 millones de personas afectadas por esta entidad, aunque algunos reportes indican 200 millones. Objetivo: Caracterizar a la población afectada por COVID persistente en México. Material y métodos: Se incluyeron pacientes mayores de 18 años que consintieron responder a una encuesta en línea y que cumplían los criterios de COVID persistente. Resultados: Se incluyeron los datos de 203 sujetos. Se identificó que 138 (68.0 %) contestaron ser del sexo femenino, con una media de edad de 41.8 años; 29.6 % presentó enfermedad grave y 70.4 %, enfermedad leve a moderada; 89.7 % había recibido vacunas previas para COVID-19: 6.9 %, una dosis; 31.5 %, dos dosis; y 51.2 %, tres o más dosis. Los principales factores de riesgo fueron diabetes, sobrepeso u obesidad e hipertensión arterial sistémica. El principal síntoma reportado fue fatiga, seguido de otras manifestaciones neuropsiquiátricas. Conclusión: Es importante caracterizar a la población para generar protocolos de diagnóstico y tratamiento.

La orientación para profesionales que se vinculan con la educación de las personas sordas debe considerar especialistas competentes en la lengua de señas y el diseño de materiales visuales. Por lo tanto, este artículo de investigación tiene como objetivo explorar el valor de las historias de personas sordas líderes para la construcción de un prototipo pedagógico visual (PPV) que contribuya al desarrollo de la lectura y la escritura en educación primaria. La investigación se aborda desde un enfoque cualitativo y considera las epistemologías de los sordos con un diseño narrativo. De esta forma, se recopilaron historias de vida por medio de entrevistas semiestructuradas a 6 adultos líderes sordos de 3 ciudades de Chile. La información fue codificada con el software Atlas ti. La categoría central es el prototipo pedagógico visual, que engloba 4 subcategorías: identidad sorda, comunidad sorda, comunicación y aprendizaje. Estas conforman el sustento para el diseño del cómic Cata Plum-Cata Plam, cuya historia pone de relieve elementos desde las experiencias lingüístico-culturales de los participantes con su entorno familiar y escolar, que visibilizan la importancia de la lengua de señas chilena, así como la lectura y escritura a través de un material significativo.

Resumen: Antecedentes: La pandemia de COVID-19 ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo: Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p = 0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro. Abstract: Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p = 0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Background and objective: Quality of professional life (QPL) is defined as a sense of well-being derived from a balance between the challenges of work and the resources available to deal with them. Impaired QPL can contribute to burnout. The aim of this study was to evaluate QPL in Spanish dermatologists using a validated questionnaire. Material and methods: We designed a cross-sectional study in which Spanish dermatologists were invited to complete an online questionnaire sent out by messaging applications. The dermatologists were asked to provide sociodemographic information, answer 3 open questions, and complete the 35-item Spanish QPL questionnaire (Spanish abbreviation, CVP-35). Results: We analyzed the information submitted by 106 dermatologists (62 women, 58%) with a mean age of 41 years (95% CI, 43.3-38.8 years). Women and department heads scored significantly higher in the workload domain of the questionnaire (P = .02 and P = .005, respectively). A heavy caseload was mentioned as the main factor contributing to impaired QPL and the main change in the wake of the COVID-19 pandemic. Conclusions: Female dermatologists reported heavier workloads. Heavy caseloads and more remote work were the main changes identified after the COVID-19 pandemic. Heavy caseloads have a significant impact on the QPL of dermatologists in Spain. Reducing caseloads would improve general job satisfaction and quality of care provision. Resumen: Antecedentes y objetivo: La calidad de vida profesional se define como el bienestar derivado del equilibrio entre las exigencias del ámbito laboral y los recursos para afrontarlas, el deterioro de la calidad de vida profesional puede contribuir en el síndrome de burnout o del profesional quemado. El objetivo de este estudio consiste en evaluar mediante cuestionario validado la calidad de vida profesional de los dermatólogos españoles. Material y métodos: Se diseñó un estudio transversal que incluyó dermatólogos españoles que respondieran a un formulario autoadministrado enviado a través de aplicaciones de mensajería online. El formulario incluyó datos sociodemográficos, 3 preguntas de respuestas abiertas y el Cuestionario de Calidad de Vida Profesional (CVP-35). Resultados: Se incluyó a 106 participantes en este estudio, siendo un 58% (62/106) mujeres. La edad media fue de 41 años (intervalo de confianza [IC] del 95%: 43,3-38,8). Las puntuaciones para el dominio «carga de trabajo» de CVP-35 fueron superiores en las mujeres (p = 0,02) y en los jefes de servicio (p = 0,005). La presión asistencial fue el tema tratado con más frecuencia como factor limitante de la calidad de vida laboral, y el principal cambio identificado tras la pandemia de COVID-19. Conclusiones: En nuestro estudio las mujeres refirieron una mayor carga de trabajo. El incremento de carga asistencial y de trabajo a distancia fueron los principales cambios por la pandemia de COVID-19. La presión asistencial es una gran limitante de la calidad de vida profesional de nuestros compañeros, reducirla mejoraría la satisfacción diaria y la calidad asistencial.

Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. Material and methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain. Resumen: Antecedentes: En España, aunque el Ministerio de Sanidad elabora el informe de posicionamiento terapéutico (IPT) y las condiciones de reembolso de los fármacos, las Comunidades Autónomas (CC. AA.) gestionan los servicios de salud y deciden sobre las condiciones de prescripción en su ámbito territorial. El objetivo del estudio EQUIDAD fue describir los condicionantes para la prescripción de los nuevos fármacos en Dermatología en las CC. AA. y sus posibles diferencias. Material y métodos: Estudio transversal realizado en abril-mayo del 2023. Dos dermatólogos con responsabilidades directivas de cada Comunidad Autónoma (C. A.) informaron sobre los condicionantes autonómicos y locales en la prescripción de los fármacos cuyo IPT para el tratamiento de enfermedades dermatológicas fue publicado en los años 2016-2022. Los datos fueron recogidos mediante un cuestionario online. Resultados: Un total de 33 investigadores de 17 CC. AA. participaron en el estudio. Se observaron inequidades entre CC. AA. para el acceso a los nuevos fármacos. Existieron condicionantes autonómicos adicionales al IPT en psoriasis en el 64,7% de las CC. AA., siendo este porcentaje menor en dermatitis atópica (35,3%) o melanoma (11,8%). El más frecuente fue el requisito de un orden de prescripción previo para el uso del fármaco. En algunas CC. AA. se detectaron además variaciones y condicionantes locales (diferencias entre centros de una misma C. A.). Conclusiones: Existe una multiplicidad de criterios tanto a nivel autonómico como local que añade restricciones adicionales a las establecidas por los IPT y que plantean una situación de inequidad entre los pacientes y los profesionales de las diferentes CC. AA. en el acceso a los nuevos fármacos.

ABSTRACTSerratia spp. is a well-recognized pathogen in neonates; however, limited data are available in adults. We studied microbiological and clinical characteristics of Serratia spp. causing bloodstream infections (BSI) in our institution (January 2005–July 2020). Overall, 141 BSI episodes affecting 139 patients were identified and medical records reviewed. Antimicrobial susceptibility was recovered from our informatics system and 118 isolates from 116 patients were available for further microbiological studies. Whole genome sequencing (WGS) was completed in 107 isolates. Incidence of Serratia BSI was 0.3/1000 overall admissions (range 0.12–0.60), with maximum prevalence (27 episodes, 19.1%) during 2017–2018. Relevant patients’ clinical characteristics were 71.9% ≥60 years (n = 100), with high comorbidity rates (49%, ≥2), 23 (74.2%) of them died within 1 month of the BSI episode. WGS identified all isolates as Serratia marcescens when Kraken bioinformatics taxonomic tool was used despite some which were identified as Serratia nematodiphila (32/118) or Serratia ureilytica (5/118) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Nevertheless, when using MASH distance, Serratia nevei (63/107), S. ureilytica (38/107), and S. marcescens (6/107) were assigned. Carbapenemase (blaVIM-1) and extended-spectrum β-lactases (ESBL) (blaSHV-12) genes were found in seven and three isolates, respectively, one of them expressing both genes. The worldwide-disseminated IncL/M scaffold plasmid was identified in six VIM producers. Four genotypes were established based on their virulence factors and resistome. Serratia spp. emerged as a relevant nosocomial pathogen causing BSI in elderly patients in our hospital, particularly in recent years with a remarkable increase in antibiotic resistance. ESBL and carbapenemases production related to plasmid dissemination are particularly noteworthy.IMPORTANCESerratia spp. is the third most frequent pathogen involved in outbreaks at neonatal facilities and is primarily associated with bacteremia episodes. In this study, we characterized all causing bloodstream infection (BSI) in patients admitted to our hospital during a 16-year period (2005–2020). Despite having no neonatal intensive care unit in our hospital, this study revealed that Serratia spp. is a relevant pathogen causing BSI in elderly patients with high comorbidity rates. A significant increase of antimicrobial resistance was detected over time, particularly in 2020 and coinciding with the coronavirus disease (COVID-19) pandemic and nosocomial spread of multidrug-resistant Serratia spp. isolates. extended-spectrum β-lactases and carbapenemases genes associated with plasmid dissemination, typically detected in other Enterobacterales species, were also identified, reinforcing the role of Serratia spp. in the antimicrobial resistance landscape. Additionally, this work highlights the need to reclassify the species of Serratia, since discrepancies were observed in the identification when using different tools.

The aim of this study was to analyse the effects of sprint and power performance on physical fitness and small-sided game-related physical performance in youth male soccer players, using a median split analysis to separate faster and slower players, and powerful and weaker ones. Thirty youth male soccer players (age = 16.9 ± 1.4 years; height = 174.1 ± 7.1 cm; body mass = 63.1 ± 7.9 kg; % body fat = 15.5 ± 3.2) completed the following physical tests: 40 m linear sprint test, repeated sprint ability (RSA) test, countermovement jump (CMJ), horizontal jump (HJ) and a half-squat (HS) power test. In addition, players completed a 4 vs. 4 with goalkeepers small-sided game while external loads were recorded. According to their sprint and HS power performance, players were divided into fast and slow, and powerful and weak. Faster players performed better in 5 m sprint (p = 0.004, Effect Size (ES) = −1.158), 10 m sprint (p < 0.001, ES = −1.722), 40 m sprint (p < 0.001, ES = −3.268), RSAbest (p < 0.001, ES = −2.415), RSAtotal (p < 0.001, ES = −2.785), CMJ height (p = 0.032, ES = 0.823) and HJ distance (p < 0.001, ES = 1.589), but no significant differences (p > 0.05) were found in external loads during small-side games (SSG). In addition, no significant differences (p > 0.05) were observed between powerful and weaker players in the fitness tests and SSG-related physical performance. These results highlight the importance of grouping youth soccer players by their sprinting capacity to design specific and individualized training strategies and suggest that SSG-related physical performance is not influenced by their sprint or power performance.

Abstract Background Alactic base excess (ABE) is a novel biomarker that estimates the renal capability of handling acid–base alterations during the sepsis. Hence, the aim of this study was to evaluate the use of ABE to predict the renal replacement therapy (RRT) in patients with septic shock. Methods A total of 164 patients admitted to the intensive care units with a diagnosis of septic shock according to the third international consensus on sepsis and septic shock (Sepsis-3) were included. This study was retrospective, single center, and conducted between January 1, 2016, and December 31, 2020. The individuals were stratified in patients who did [n = 68] or did not [n = 96] receive the RRT. The diagnostic performed of the variables for the classification into patients who required RRT was evaluated by receiver operating characteristic (ROC) analysis and area under curve (AUC) was calculated. Univariate and multivariate logistic regression models were used to identify risk factors for RRT. Results The median age of the patients was 59 years and female sex (51.8%) predominated. ABE (odds ratio [OR] 1.2270, [95% confidence interval [CI] 1.0453–1.4403], p = 0.0124) and urea (OR 1.0114, [95% CI 1.0053–1.0176], p = 0.0002) were associated with risk of RRT. HCO3− (OR 0.6967, [95% CI 0.5771–0.8410], p = 0.0002) was a protective factor of RRT. ABE (AUC = 0.649, p 75 mg/dL, respectively. Conclusion Although HCO3− is associated with low risk, ABE and urea are independent risk factors for RRT in the patients with septic shock.

Introducción: Para calcular el crecimiento de las plantas se emplean funciones alométricas que consideran ciertos parámetros físicos del árbol, tales como el diámetro a la altura del pecho, la altura y el diámetro de la copa. El objetivo: estimar el crecimiento del mangle blanco (Laguncularia racemosa L. Gaertn) en parcelas de validación durante la época seca del año 2023. Materiales y métodos: Se realizaron mediciones en tres parcelas durante la época de seca del año de las variables alométricas del mangle blanco (Laguncularia racemosa). Resultados: La altura presentó medias de 1.26 m, 1.37 m y 1.43 m, el DAP presento medias de 0.37 cm, 0.28 cm y 0.41 cm, y el diámetro de copa valores de la media de 41.81 cm, 37.17 cm y 51.60 cm, todos estos valores para las mediciones de febrero, abril y junio respectivamente. Conclusión: el estudio confirma que la época seca tiene un impacto significativo en el crecimiento del mangle blanco, ya que se demostró diferencias significativas en el crecimiento de las plantas evaluadas en términos de altura, diámetro a la altura del pecho (DAP) y diámetro de copa, lo cual sugiere que factores estacionales y ambientales influyen notablemente en su desarrollo.

The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.

Abstract Introduction Hidradenitis suppurativa (HS) has been linked to higher cardiovascular risk (CVR) due to its inflammatory burden. There is little evidence on how biologic treatment could modify the cardiovascular risk of patients with HS. The aims of the present study were to explore the modification of CVR in patients under adalimumab treatment and to explore the potential factors associated with CVR improvement. Methods A prospective longitudinal study was performed. A cohort of patients with HS treated with adalimumab was followed up. Carotid intima–media thickness (IMT) and other clinical and biochemical CVR factors were collected at baseline and 32 weeks after starting the treatment. Results Twenty-seven patients with severe HS were included. Overall, there were no differences in IMT between baseline (633 μm) and 32 weeks follow-up (634 μm). However, 40.7% (11/27) of the patients presented an improvement in IMT. This group (IMT responders) had a higher prevalence of dyslipidemia, diabetes mellitus, higher HbA1c levels, consumed more tobacco, and had higher BMI at baseline. Moreover, these patients had lower IHS4 scores at baseline and tended to have a greater IMT basal value, indicating a higher burden of subclinical atherosclerosis. Conclusions Adalimumab treatment might benefit a subset of patients with HS in terms of cardiovascular risk reduction. In light of the results of the present study patients with classical cardiovascular risk factors, and those with higher burden of subclinical atherosclerosis and with less inflammatory load, may be more likely to improve their IMT during adalimumab treatment.

Introduction: Mechanical ventilation is a common practice in intensive care units and anesthesiology with both therapeutic and potentially harmful implications for the respiratory system and distant organs, that is why it is of utmost importance to continually monitor ventilation parameters. Objective: To describe the equation of motion of the respiratory system and its clinical applications in the patient under invasive mechanical ventilation. Main: The equation of motion of the respiratory system integrates the dynamic forces generated by the ventilator with the intrinsic properties of the lung and chest wall. It expresses the pressure in the respiratory system in relation to volume, elastance, resistance, air flow and pressures generated by the ventilator and the patient. Elevated pressures in the respiratory system during mechanical ventilation are associated with greater mortality, that is why the identification of the components responsible for elevation of pressures through the equation of motion of the respiratory system allows to modify ventilator programmed parameters to maintain a protective ventilation. Conclusion: Decision-making based on the equation of motion of the respiratory system allows to modify ventilatory parameters according to the characteristics and diseases of the patient under mechanical ventilation.

El artículo nos presenta un análisis de la eficacia de los derechos humanos de las mujeres, particularmente, del derecho a una vida libre de violencia enfocándolo en la violencia digital, un tipo de violencia que va en aumento y cuya complejidad está en gran medida en la determinación de la competencia jurídica en el mundo digital, donde el establecimiento de fronteras digitales no existe, al menos en Latinoamérica, a diferencia de Europa que sí, ha ido avanzando en esa situación. El uso indebido de la tecnología ya sea por ignorancia o por dolo conlleva consecuencias que pueden ser irreparables, nos referimos a que la desesperación en la que puede colocarse la víctima la puede llevar a cometer suicidio o a buscar venganza de propia mano. Lo anterior va de la mano con la inoperancia de los sistemas de procuración y administración de justicia que contribuyen a que, al menos en el caso de México, se tenga una impunidad que alcanza casi el 100% y una cifra negra que se encuentra entre el 93% de delitos no denunciados, donde podemos ubicar perfectamente a las víctimas de los delitos cibernéticos. De esta forma, en el artículo podrán conocer las reformas que se han realizado en México, que podríamos pensar que han llegado de manera tardía y ante exigencias de la sociedad, principalmente de víctimas que hicieron ver la necesidad de tipificar las conductas que se cometen en Internet, donde las mujeres y las niñas son las más vulnerables.

ABSTRACT: Objectives: This work aimed to isolate bacterial strains with antagonist activity against Vibrio parahaemolyticus, the causative agent of acute hepatopancreatic necrosis disease (VPAHPND) that was isolated from outbreaks in Mexico. Here, we report the draft genome sequences of two antagonistic strains, isolated from saline sediment in Sonora, Mexico. Methods: Cross-streak and well diffusion tests were employed to find the bacterial strains with higher inhibitory activity against VPAHPND. The whole genomes of B. pumilus 36R ATNSAL and B. safensis 13L LOBSAL were sequenced using Ion TorrentTM (PGM) and Illumina MiseqTM platforms, respectively. Annotation was performed using the RAST server, and the genes involved in the biosynthesis of bacterial secondary metabolites were predicted using antiSMASH. Results: Two bacterial isolates, B. safensis 13L LOBSAL and B. pumilus 36R ATNSAL, were chosen based on their strong antagonistic profiles. The genome of 36R ATNSAL was 3.94 Mbp in length and contained 3824 genes and a total of 4116 coding sequences (CDSs); the genome of 13L LOBSAL was 3.68 Mbp and contained 3619 genes and 3688 CDSs. Twenty-eight and 32 biosynthetic gene clusters responsible for putative antimicrobial metabolite production were identified in 36R ATNSAL and 13L LOBSAL, respectively. Conclusions: The two strains 13L LOBSAL and 36R ATNSAL showed excellent probiotic profiles in vitro. The genome sequences will help with the mining and reconstruction of metabolic pathways in Bacillus strains. Genome sequence–guided strain improvement could augment the probiotic potential of Bacillus strains for applications in shrimp aquaculture.

Abstract Background Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography–computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. Results The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. Conclusions Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.

Objetivo: analizar la experiencia de una empresa de alta tecnología en la planificación empresarial, a partir del ejemplo del Centro Nacional de Biopreparados. Métodos y técnicas: se realizó un estudio cuasi experimental (2018-2022), basado en un enfoque cualitativo, cuantitativo, de nivel descriptivo; se utiliza la observación directa, encuestas, la tormenta de ideas para obtener la matriz DAFO; se implica a especialistas de diferentes áreas, grupos temporales de trabajo y comités técnicos. Principales resultados: se lograron establecer las políticas; estrategias; objetivos institucionales; planes temáticos, anuales y mensuales de las actividades, a partir de las particularidades de una empresa de alta tecnología, a través de la retroalimentación para valorar el cumplimiento y trazar las estrategias de mejora continua. Los resultados de la planificación empresarial fueron validados durante el enfrentamiento exitoso a la pandemia de COVID-19 en Cuba. Conclusiones: la identificación de deficiencias en la planificación empresarial en aras de lograr su mayor flexibilidad y orientarla a la innovación, constituye un punto de partida en la proyección de las acciones estratégicas y su implementación para consolidar esta actividad, con el objetivo de mantener a la empresa siempre adaptada al entorno cambiante, para alcanzar los objetivos de desarrollo y crecimiento planeados en una empresa de alta tecnología. La evaluación de la eficacia del proceso de planificación empresarial permitió validar la adecuación de la estrategia como elemento de mejora continua, reforzar los ajustes en el proceso y pertinencia de sus etapas, logrando una mayor coordinación entre las funciones para el cumplimiento de los objetivos de trabajo en situaciones desafiantes como el enfrentamiento a la epidemia de COVID-19.

Objetivo: Proyectar acciones para el desarrollo del potencial tecnológico en una empresa de alta tecnología, sobre la base del análisis del comportamiento y de las limitantes en la categorización tecnológica, tomando como caso de estudio al Centro Nacional de Biopreparados, de la Organización Superior de Dirección Empresarial BioCubaFarma. Métodos y técnicas: Se recopilaron las estadísticas de categorización y formación del potencial humano entre 2002 y 2020; se consultó la legislación vigente, la política de ciencia, tecnología e innovación y la bibliografía internacional. Además, se compilaron los criterios de expertos y fueron identificadas las debilidades, amenazas, fortalezas y oportunidades de la formación y categorización tecnológica. Principales resultados: Se diseñaron las acciones para la captación, desarrollo y renovación del potencial tecnológico, acelerar la formación doctoral, diversificar la formación en gerencia y economía de la producción, incrementar los incentivos morales y materiales con mira a lograr los requisitos para obtener las categorías. Conclusiones: La concepción del Comandante en Jefe Fidel Castro de la formación integral del personal, su consagración, principios éticos y morales y de servir al pueblo, sentó las bases para la constitución de empresas de alta tecnología. La categorización tecnológica es clave para la conversión de resultados de la ciencia en productos y servicios con alto contenido en conocimientos y crecido valor agregado, con gran impacto en salud y en la economía y para alcanzar la condición de empresa de alta tecnología. Organizaciones de este tipo deben dirigirse a la captación, desarrollo y renovación del capital tecnológico como vía principal para su ulterior desarrollo.

Objetivo: analizar la experiencia de una empresa de alta tecnología en la planificación empresarial, a partir del ejemplo del Centro Nacional de Biopreparados. Métodos y técnicas: se realizó un estudio cuasi experimental (2018-2022), basado en un enfoque cualitativo, cuantitativo, de nivel descriptivo; se utiliza la observación directa, encuestas, la tormenta de ideas para obtener la matriz DAFO; se implica a especialistas de diferentes áreas, grupos temporales de trabajo y comités técnicos. Principales resultados: se lograron establecer las políticas; estrategias; objetivos institucionales; planes temáticos, anuales y mensuales de las actividades, a partir de las particularidades de una empresa de alta tecnología, a través de la retroalimentación para valorar el cumplimiento y trazar las estrategias de mejora continua. Los resultados de la planificación empresarial fueron validados durante el enfrentamiento exitoso a la pandemia de COVID-19 en Cuba. Conclusiones: la identificación de deficiencias en la planificación empresarial en aras de lograr su mayor flexibilidad y orientarla a la innovación, constituye un punto de partida en la proyección de las acciones estratégicas y su implementación para consolidar esta actividad, con el objetivo de mantener a la empresa siempre adaptada al entorno cambiante, para alcanzar los objetivos de desarrollo y crecimiento planeados en una empresa de alta tecnología. La evaluación de la eficacia del proceso de planificación empresarial permitió validar la adecuación de la estrategia como elemento de mejora continua, reforzar los ajustes en el proceso y pertinencia de sus etapas, logrando una mayor coordinación entre las funciones para el cumplimiento de los objetivos de trabajo en situaciones desafiantes como el enfrentamiento a la epidemia de COVID-19.

Objetivo: Proyectar acciones para el desarrollo del potencial tecnológico en una empresa de alta tecnología, sobre la base del análisis del comportamiento y de las limitantes en la categorización tecnológica, tomando como caso de estudio al Centro Nacional de Biopreparados, de la Organización Superior de Dirección Empresarial BioCubaFarma. Métodos y técnicas: Se recopilaron las estadísticas de categorización y formación del potencial humano entre 2002 y 2020; se consultó la legislación vigente, la política de ciencia, tecnología e innovación y la bibliografía internacional. Además, se compilaron los criterios de expertos y fueron identificadas las debilidades, amenazas, fortalezas y oportunidades de la formación y categorización tecnológica. Principales resultados: Se diseñaron las acciones para la captación, desarrollo y renovación del potencial tecnológico, acelerar la formación doctoral, diversificar la formación en gerencia y economía de la producción, incrementar los incentivos morales y materiales con mira a lograr los requisitos para obtener las categorías. Conclusiones: La concepción del Comandante en Jefe Fidel Castro de la formación integral del personal, su consagración, principios éticos y morales y de servir al pueblo, sentó las bases para la constitución de empresas de alta tecnología. La categorización tecnológica es clave para la conversión de resultados de la ciencia en productos y servicios con alto contenido en conocimientos y crecido valor agregado, con gran impacto en salud y en la economía y para alcanzar la condición de empresa de alta tecnología. Organizaciones de este tipo deben dirigirse a la captación, desarrollo y renovación del capital tecnológico como vía principal para su ulterior desarrollo.

Los coagulantes naturales a base de plantas se han usado para el tratamiento de aguas desde tiempos remotos y son amigables con el medio ambiente. El objetivo de este trabajo fue evaluar la capacidad de remoción de turbiedad y color de una mezcla coagulante de polvo Crotaloria longirostrata y sulfato de aluminio vs sulfato de aluminio. Se evaluó la dosis optima de sulfato de aluminio comercial y las mezclas coagulantes natural de polvo de C. longirostrata y sulfato de aluminio (tratamientos) que tuvieran la mayor remoción de turbiedad y color (variable respuesta) de un agua residual doméstica. Se utilizó un equipo de prueba de jarras marca PhilesMR para la determinación de las dosis optimas de coagulantes. La turbiedad y color se midieron con un turbidímetro marca LamoteMR. Se usó un diseño simple completamente aleatorizado de un factor y un análisis de varianza seguido de un contraste múltiple de Tukey para encontrar diferencias estadísticas significativas entre los diferentes tratamientos. Las mezclas de polvo de C. longirostrata con sulfato de aluminio (75 mg/L de polvo de C. longirostrata + 175 mg/L de sulfato) removieron una mayor cantidad de turbiedad y color que la dosis optima de sulfato de aluminio (250 mg/L), con remociones de 83.4% de turbiedad y 64.9% de color respectivamente. Los resultados lograron reducir un 30% el uso del sulfato de aluminio. El uso de polvo C. longirostrata como coadyuvante en la remoción de turbiedad y color no tiene efectos tóxicos ya que es un arbusto comestible.

Abstract Muscular dystrophies (MD) are a group of rare hereditary degenerative diseases. Our aim was to analyze the mortality pattern in Spain from 1981 to 2016 to assess the temporal trend and discern possible geographic differences using population-based data. Annual deaths related to MD were obtained from the National Statistics Institute with codes 359.1 of the ICD-9 (1981–1998) and G71.0 of the ICD-10 (1999–2016). Age-adjusted mortality rates were calculated and changes in mortality trends were identified. The standardized mortality ratios (SMR) and their respective 95% confidence intervals were calculated by district for 1999–2016. Smoothed SMRs and posterior probability were also assessed and then mapped to look for patterns or geographic distribution. All rates were expressed per 1,000,000 inhabitants. A total of 2,512 deaths (73.8% men) were identified. The age-adjusted mortality rates varied from 0.63 (95% CI 0.40–0.95) in 1981 to 1.51 (95% CI 1.17–1.93) in 2016. MD mortality showed a significant increase of 8.81% per year (95% CI 5.0–12.7) from 1981 to 1990, remaining stable afterwards. Areas with risk of death higher than expected for Spain as a whole were identified, not showing a specific regional pattern. In conclusion, the rising trend in MD mortality might be attributable to advanced improvements in diagnostic techniques leading to a rise in prevalence. Further research on the districts with the highest mortality would be necessary.

The transit service in a city should be the most efficient, least polluting, most accessible, and sustainable means of transportation for its citizens. However, serious shortcomings have been detected, mainly in medium-sized cities in developing countries. These shortcomings are related to a lack of user information, insecurity, low service availability, and repeated stops in inappropriate and/or unauthorized places. Some of these shortcomings contribute to high accident rates and traffic congestion. The development of tools to improve the characteristics and conditions of transit service in cities has become an imperative need to improve the quality of life of citizens and city sustainability. Transit service tracking is relevant in aspects such as online location information to travelers and control by transport companies for compliance with speed limits, schedules, routes, and stops. This research proposes a transit vehicle tracking system based on the Internet of Vehicles (IoV) in Vehicle-to-Roadside (V2R) classification. The proposed system is ideal for the use of electric vehicles due to the low power consumption of the tracking device. This system uses Intelligent Transportation Systems (ITS) tracking service architecture, Long Range (LoRa) communication technology, and its LoRa Wide Area Network (LoRaWAN) protocol. Additionally, the system offers real-time location prediction in the absence of position data. The IoV tracking device integrates a GPS-LoRa module card with an Inertial Measurement Unit (IMU). A location prediction algorithm was implemented to train and store a prediction model with previously collected data from tracking devices. To evaluate the developed model, a case study in the city of Popayán (Colombia) was implemented, using three routes for testing. The results of the system implementation were satisfactory, obtaining an average coverage of 60.4% of the routes in the final field tests through LoRa communication. For the remaining 39.6% of the routes, location data prediction was used, with an average accuracy of 177 m with respect to the real location. Considering the obtained results, a tracking system such as the one proposed in this article can be used in the transit systems of medium-sized cities in developing countries to improve service quality and fleet control.

Resumen: Introducción: El instrumento utilizado habitualmente para valorar la autoeficacia de la lactancia materna (LM) es la breastfeeding self-efficacy scale-short form (BSES-SF). Este estudio valora la relación entre la puntuación de la BSES-SF y el riesgo de abandono de la lactancia. También se determina el punto de corte en la puntuación de la escala que optimiza la detección de este riesgo desde la atención primaria. Métodos: Análisis secundario de datos del estudio Lactancia y Desarrollo Infantil (LAyDI). Ensayo de cohorte única realizado a través de la red de investigación de pediatras de atención primaria (PAPenRed). Cada especialista reclutó un recién nacido cada mes durante un año. Se siguió la cohorte durante 24 meses. Las madres respondieron la BSES-SF en la primera visita. Se recogieron datos generales de el embarazo y el parto y se valoró la LM (suplementada o exclusiva) hasta los seis meses. Resultados: n = 1.845. El área bajo la curva ROC para la LM exclusiva fue al primer mes de 0,79 (0,77 a 0,82) y al segundo mes de 0,760 (0,734 a 0,786). Para los cuatro y seis meses, así como para cualquier edad en las madres que dan LM suplementada, el área bajo la curva fue menor de 0,75 y su capacidad predictiva no se consideró adecuada. Para una sensibilidad del 80% en la detección de las mujeres en riesgo de abandono de la lactancia, la puntuación de corte fue 58. Conclusiones: Las madres que en atención primaria presenten una puntuación en la BSES-SF por debajo de 58 tienen riesgo de abandono de la LM exclusiva antes de los dos meses. Abstract: Introduction: The most widely used tool for assessing breastfeeding self-efficacy is the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). This study asses the relationship between the BSES-SF score and the risk of breastfeeding (BF) cessation and determine the cut-off point in the scale score that optimizes detection of this risk in primary health care pediatric consultations. Methods: Secondary data analysis of the LAyDI study. It is a cohort study. It was carried out through a research network of primary care pediatricians (PAPenRed). A newborn was recruited every month for one year by 210 pediatricians. The cohort was followed for 24 months. Mothers responded to the BSES-SF at the first visit. General pregnancy and delivery data were collected and assessed to determine whether breastfeeding was exclusive or supplemented during the first six months. Results: n = 1,845. The area under the ROC curve for the exclusive BF was 0.790 (0.765-0.815) the first month and 0.760 (0.734-0.786) the second month. For four and six months, as well as for any age in mothers who give supplemented BF, the Area Under the Curve was less than 0.75 and its predictive capacity was not considered to be good. For a sensitivity of 80% in detecting mothers at risk of BF cessation with the BSES-SF, the cut-off score was 58. Conclusions: Mothers with a BSES-SF score below 58 points in primary health care, are at risk of early withdrawal of exclusive BF within two months.

Introduction: The most widely used tool for assessing breastfeeding self-efficacy is the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). This study assesses the relationship between the BSES-SF score and the risk of breastfeeding (BF) cessation and determines the cut-off point in the scale score that optimizes detection of this risk in primary health care pediatric consultations. Methods: Secondary data analysis of the LAyDI study. Cohort study carried out through a research network of primary care pediatricians (PAPenRed). A newborn was recruited every month for one year by 210 pediatricians. The cohort was followed for 24 months. Mothers responded to the BSES-SF at the first visit. General pregnancy and delivery data were collected and assessed to determine whether breastfeeding was exclusive or supplemented during the first 6 months. Results: N = 1845. The Area Under the ROC Curve for the exclusive BF was 0.790 (0.765-0.815) the first month and 0.760 (0.734-0.786) the second month. For 4 and 6 months, as well as for any age in mothers who give supplemented BF, the Area Under the Curve was less than 0.75 and its predictive capacity was not considered to be good. For a sensitivity of 80% in detecting mothers at risk of BF cessation with the BSES-SF, the cut-off score was 58. Conclusions: Mothers with a BSES-SF score below 58 points in primary health care, are at risk of early withdrawal of exclusive BF within two months. Resumen: Introducción: El instrumento utilizado habitualmente para valorar la autoeficacia de la lactancia materna es la Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). Este estudio valora la relación entre la puntuación de la BSES-SF y el riesgo de abandono de la lactancia. También se determina el punto de corte en la puntuación de la escala que optimiza la detección de este riesgo desde Atención Primaria. Métodos: Análisis secundario de datos del estudio LAyDI. Estudio de cohorte única realizado a través de la red de investigación de pediatras de Atención Primaria (PAPenRed). Cada pediatra reclutó un recién nacido cada mes durante un año. Se siguió la cohorte 24 meses. Las madres respondieron la BSES-SF en la primera visita. Se recogieron datos generales de embarazo y parto y se valoró la lactancia materna (suplementada o exclusiva) hasta los 6 meses. Resultados: n = 1845. El Área Bajo la Curva ROC para la LM exclusiva fue al primer mes de 0,79 (0,77–0,82) y al segundo mes de 0,760 (0,734-0,786). Para los 4 y 6 meses, así como para cualquier edad en madres que dan LM suplementada, el Área Bajo la curva fue menor de 0,75 y su capacidad predictiva no se consideró adecuada. Para una sensibilidad del 80% en la detección de madres en riesgo de abandono de la lactancia la puntuación de corte fue 58. Conclusiones: Las madres que en Atención Primaria presenten una puntuación en la BSES-SF por debajo de 58 puntos tienen riesgo de abandono de la lactancia materna exclusiva antes de los dos meses.

El presente estudio tiene como objetivo identificar las diferencias de género en la vivencia de emociones positivas y negativas, así como en las principales preocupaciones y necesidades identificadas en relación a las clases a distancia durante las primeras semanas del confinamiento por COVID-19. La muestra estuvo constituida por estudiantes de pregrado de diez universidades públicas de México con un total de 13,704 participantes con un rango de edad de 18 a 30 años. Los resultados obtenidos destacan que la principal diferencia entre géneros es la necesidad de estabilidad emocional, obteniendo una puntuación significativamente más baja en la mayoría de los estados afectivos positivos en las mujeres. Respecto a la problemática principal en relación a las clases a distancia durante las primeras semanas del confinamiento, se observan diferencias especialmente en el hecho de que hay más mujeres que deben compartir equipo de cómputo con otros integrantes de la familia. Así mismo se mostró una mayor experimentación de emociones negativas y puntajes más bajos en emociones positivas. Se discuten los resultados evidenciando las desigualdades percibidas por el género e insistiendo en la educación socioemocional como medio para afrontar las demandas cotidianas y relacionarse con las otras personas de manera satisfactoria.

ObjectiveTo evaluate the central venous-to-arterial carbon dioxide difference combined with arterial-to-venous oxygen content difference (∆Pv-aCO2/∆Ca-vO2 ratio) as a predictor of mortality in patients with COVID-19-related severe acute respiratory distress syndrome (ARDS).MethodsPatients admitted to the intensive care unit with severe ARDS secondary to SARS-CoV-2, and invasive mechanical ventilation were included in this single-center and retrospective cohort study performed between April 18, 2020, and January 18, 2022. The tissue perfusion indexes (lactate, central venous oxygen saturation [ScvO2], and venous-to-arterial carbon dioxide pressure difference [∆Pv-aCO2]), anaerobic metabolism index (∆Pv-aCO2/∆Ca-vO2 ratio), and severity index (Simplified Acute Physiology Score II [SAPSII]) were evaluated to determine its association with the mortality through Cox regression analysis, Kaplan-Meier curve and receiver operating characteristic (ROC) curve.ResultsOne hundred fifteen patients were included in the study and classified into two groups, the survivor group (n = 54) and the non-survivor group (n = 61). The lactate, ScvO2, ∆Pv-aCO2, and ∆Pv-aCO2/∆Ca-vO2 ratio medians were 1.6 mEq/L, 75%, 5 mmHg, and 1.56 mmHg/mL, respectively. The ∆Pv-aCO2/∆Ca-vO2 ratio (Hazard Ratio (HR) = 1.17, 95% confidence interval (CI) = 1.06-1.29, p = 0.001) was identified as a mortality biomarker for patients with COVID-19-related severe ARDS. The area under the curve for ∆Pv-aCO2/∆Ca-vO2 ratio was 0.691 (95% CI 0.598-0.774, p = 0.0001). The best cut-off point for ∆Pv-aCO2/∆Ca-vO2 ratio was >2.14 mmHg/mL, with a sensitivity of 49.18%, specificity of 85.19%, a positive likelihood of 3.32, and a negative likelihood of 0.6. The Kaplan-Meier curve showed that survival rates were significantly worse in patients with values greater than this cut-off point.ConclusionsThe ∆Pv-aCO2/∆Ca-vO2 ratio could be used as a predictor of mortality in patients with severe ARDS secondary to SARS-CoV-2.

Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson’s disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.

Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson's disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.

Type D personality is characterized by social inhibition and negative affectivity. Poorer outcomes and worse quality of life have been linked to type D personality in patients with a variety of non-dermatological diseases. Despite increasing evidence of the importance of type D personality in skin diseases, there are no reviews on this subject. The aim of this review is to summarize the current evidence regarding type D personality and skin diseases. A systematic search was performed using Medline and Web of Science databases from inception to 11 October 2022. Studies addressing the presence of type D personality, its associated factors, its impact on the outcomes of the disease or the quality of life of the patients were included in the systematic review. A total of 20 studies, including 3,124 participants, met the eligibility criteria and were included in the review. Acne, hidradenitis suppurativa, psoriasis, melanoma, atopic dermatitis, chronic spontaneous urticaria and pruritic disorders were the main diseases assessed. Type D personality was more frequent among patients with skin diseases than among controls. Type D personality was found to be associated with poorer quality of life and higher rates of psychological comorbidities in patients with skin diseases. In conclusion, type D personality appears to be a marker of patients with increased risk of poorer quality of life and higher rates of psychological comorbidities. Screening for type D personality in specialized dermatology units might be beneficial to identify patients who are more psychologically vulnerable to the consequences of chronic skin diseases.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69–/– mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69–/– mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

Objetivo: Proyectar acciones para el desarrollo del potencial tecnológico en una empresa de alta tecnología, sobre la base del análisis del comportamiento y de las limitantes en la categorización tecnológica, tomando como caso de estudio al Centro Nacional de Biopreparados, de la Organización Superior de Dirección Empresarial BioCubaFarma. Métodos y técnicas: Se recopilaron las estadísticas de categorización y formación del potencial humano entre 2002 y 2020; se consultó la legislación vigente, la política de ciencia, tecnología e innovación y la bibliografía internacional. Además, se compilaron los criterios de expertos y fueron identificadas las debilidades, amenazas, fortalezas y oportunidades de la formación y categorización tecnológica. Principales resultados: Se diseñaron las acciones para la captación, desarrollo y renovación del potencial tecnológico, acelerar la formación doctoral, diversificar la formación en gerencia y economía de la producción, incrementar los incentivos morales y materiales con mira a lograr los requisitos para obtener las categorías. Conclusiones: La concepción del Comandante en Jefe Fidel Castro de la formación integral del personal, su consagración, principios éticos y morales y de servir al pueblo, sentó las bases para la constitución de empresas de alta tecnología. La categorización tecnológica es clave para la conversión de resultados de la ciencia en productos y servicios con alto contenido en conocimientos y crecido valor agregado, con gran impacto en salud y en la economía y para alcanzar la condición de empresa de alta tecnología. Organizaciones de este tipo deben dirigirse a la captación, desarrollo y renovación del capital tecnológico como vía principal para su ulterior desarrollo.

ABSTRACT: Objective: Men have been considered to have a higher incidence of infectious diseases, with controversy over the possibility that sex could influence the prognosis of the infection. This study aimed to explore this assumption in patients admitted to the intensive care unit (ICU) with septic bacteremia. Methods: A retrospective analysis (2006-2017) of septic patients with microbiologically confirmed bacteremia (n=440) was performed. Risk of ICU and in-hospital mortality in males versus females was compared by univariate analysis and a propensity score analysis integrating their clinical characteristics. Results: Sepsis more frequently occurred in males (80.2% vs 76.1%) as well as in-hospital (48.0% vs 41.3%) and ICU (39.9% vs 36.5%) mortality. Univariate analyses showed that males had a higher Charlson comorbidity index and worse McCabe prognostic score. However, the propensity score in 296 matched patients demonstrated that females had higher risk of both ICU (OR 1.39; 95% CI 0.89-2.19) and in-hospital mortality (OR 1.18; 95% CI 0.77-1.83), but without statistical significance. Conclusion: Males with sepsis had worse clinical characteristics when admitted to the ICU, but sex had no influence on mortality. These data contribute to helping reduce the sex-dependent gap present in healthcare provision.

La pandemia del siglo XXI, ha traído transformaciones en todos los niveles, entre ellos el uso de la tecnología en las organizaciones, generando cambios beneficiosos; sin embargo, también puede tener consecuencias negativas en el deterioro de la satisfacción en el trabajo, la productividad, así como un aumento de la sobrecarga laboral y el conflicto entre la vida laboral y personal. La presente investigación analiza el teletrabajo como estrategia emergente en las organizaciones de educación universitaria ante la situación de la pandemia de los inicios del año 2020 en Santiago de Chile. La investigación es descriptiva, se aplicó un cuestionario con escala dicotómica, con 29 ítems dirigido a 384 docentes de universidades de la Región Metropolitana de Chile, fue sometido a validación de contenido, constructo y discriminante con un nivel de confianza 0,92 (Muy alta), se utilizó la estadística descriptiva a través del SPSS25. Los resultados permiten considerar la necesidad de buscar el balance del mantenimiento del profesionalismo, la mística de trabajo, el compromiso y la vida personal y familiar de los colaboradores, el mejoramiento del trabajo remoto, manteniendo los estándares de calidad y productividad, acompañados del bienestar y calidad de vida en las comunidades universitarias en tiempo de pandemia.

ABSTRACT Bloodstream infections are associated with high rates of morbidity and mortality. Blood culture remains the gold standard for the diagnosis of BSIs. We report a prospective crossover diagnostic clinical trial comparing the performances of two blood culture incubation systems: Virtuo and Bactec FX. The primary outcome was the time to detection (TTD) (from the loading of the sample into the incubator to the positivity signal). Patients over 16 years old suspected of having bacteremia/fungemia were included. They were divided into two strata with a total of 9,957 blood extractions. Initially, each stratum was randomly assigned to one of the incubators and then alternated every 2 weeks for 6 months. Each sample was inoculated into an aerobic bottle and an anaerobic bottle. All bottles were processed equally according to the laboratory’s standard procedures after they were flagged positive. We analyzed 4,797 samples in the Virtuo system and 5,160 in the Bactec FX system. The median TTD was significantly lower for the Virtuo group (Virtuo, 15.2 h; Bactec FX, 16.3 h [P

Abstract The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-β-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n = 142), liver (n = 98) or kidney/pancreas (n = 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4–6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended-spectrum β-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4–6 weeks post-transplantation. E. coli producing bla CTX-M-G1 and K. pneumoniae harbouring bla OXA-48 alone or with bla CTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients.

Los derechos humanos muchas personas ya los dan por sentado, nos hemos acostumbrado a verlos en los textos constitucionales y pensamos que la autoridad sin ningún problema los respetará y hará todo lo que esté en sus manos para que sean efectivos. No obstante lo anterior, la pandemia generada por el coronavirus demostró lo difícil que es como gobierno tomar decisiones que pueden afectar el ejercicio de algunos derechos humanos, pero dicha decisión es para salvaguardar un derecho más importante como es la vida.

Type D personality (TDp) is a stable personality type that has been associated with poor quality of life in the general population and in patients with a variety of diseases, such as cancer, cardiac diseases, and dermatological diseases (e.g. psoriasis). To date, the potential association between chronic spontaneous urticaria and TDp has not been studied. The aim of this study is to analyse the impact of TDp on patients with chronic spontaneous urticaria, regarding mood disturbances, quality of life, sexuality, and sleep disturbances. A cross-sectional study including 75 patients with chronic spontaneous urticaria was performed. Data on socio- demographic variables and disease activity, quality of life, sleep, sexual dysfunction, anxiety, depression and TDp were collected using validated questionnaires. TDp was present in 28% (21/75) of the patients. Although TDp was not related to worse disease control, the presence of anxiety and depression was higher in patients with TDp. Regarding quality of life, TDp was associated with poorer quality of life and higher frequency of sleep disturbances. Prevalence of TDp in patients with chronic spontaneous urticaria is similar to that in the general population. It is associated with mood status disturbances and worse quality of life regardless of disease severity, especially in the emotional and psychological domains. This group of patients could benefit from additional psychological support as a complement to their medical treatment.