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Abstract This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D‐material integrated hydrogels, with a focus on their performance in bone‐related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near‐infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D‐material‐based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug‐loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D‐materials ‐infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug‐resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio‐imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real‐time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D‐materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials.

This document investigates the relationship between wages and labor productivity in Mexico, considering the territorial dimension and, within it, the impact that the productivity of neighboring entities has on local wages, given the geographical proximity. Results show that an increase in labor productivity impacts remuneration. Moreover, an increase in productivity in a particular state positively impacts the remunerations of neighboring states. The results allow us to understand that territorial productivity has a spillover effect on the remunerations of neighboring territories.

Introducción: La dimensión cognitiva comprende las habilidades para establecer relaciones, analizar, crear, actuar y transformar la realidad; constituyen la base para la formación y desarrollo de las habilidades de aprender a aprender. Objetivo: Caracterizar la dimensión cognitiva de las habilidades de aprender a aprender en estudiantes de Medicina. Métodos: Se empleó un diseño mixto del tipo explicativo secuencial. La investigación se realizó de enero a marzo de 2022 en la Universidad de Ciencias Médicas de Cienfuegos. La muestra no probabilística quedó constituida por 255 estudiantes del primer año de la carrera de Medicina. Se exploraron las variables: planificación, procesamiento y búsqueda de la información y solución de problemas. Se utilizó un cuestionario para evaluar el nivel de formación de las habilidades de aprender a aprender, además de las observaciones a actividades docentes y grupos focales. Resultados: La planificación está presente en el 49,8% de los estudiantes, el procesamiento y búsqueda de la información en el 49,4%, mientras que la solución de problemas en el 42,4%. En los grupos focales los estudiantes reconocen no tener formadas las habilidades y presentan insuficiencias en algunos indicadores, lo que se corresponde con los datos obtenidos en las observaciones a las actividades docentes. Conclusiones: La dimensión cognitiva de las habilidades de aprender a aprender, se caracterizó por presentar dificultades en la planificación de las actividades de aprendizaje y en la búsqueda y procesamiento de la información científica e insuficiencias en la solución de problemas. Palabras clave: búsqueda de la información, planificación, solución de problemas

Background: communication is essential in the process of training and development of learning-to-learn skills in medical students. Objective: to characterize the communication dimension of the skills of learning to learn in medical students. Methods: a descriptive research with a mixed design of the sequential explanatory type was carried out at Cienfuegos University of Medical Sciences from January to March 2022. Theoretical methods were used: analysis-synthesis and historical-logical; empirical ones: questionnaire, observations of teaching activities and focal groups; and mathematical-statistical for the analysis of the data, and the Atla.ti software for the qualitative analysis of the information. Results: it was found that 65.5% of the students affirm that they use assertive communication, while 43.9% express verbal and extraverbal messages in a way that is accessible to other people. In the focal groups, the students accepted that they had deficiencies in the training of skills and had limitations in their indicators, which corresponds to the information obtained in the observations of teaching activities. Conclusions: the communication dimension of skills learning-to-learn was characterized in medical students with a medium level of assertive communication and insufficiencies in the expression of verbal and extraverbal messages in a way that is accessible to other people.

Abstract Background Peritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment of adhesive interactions between cancer cells and the peritoneal membrane. Interrelations between EOC and the mesothelial stroma are critical to facilitate the metastatic process. No data is available so far on the impact of histone acetylation/deacetylation, a potentially relevant mechanism governing EOC metastasis, on mesothelial cells (MCs)-mediated adhesion. Methods Static adhesion and peritoneal clearance experiments were performed pretreating mesenchymal-like MCs and platinum—sensitive/resistant EOC cell lines with MS-275—a Histone deacetylase (HDAC)1–3 pharmacological inhibitor currently used in combination trials. Results were acquired by confocal microscopy and were analyzed with an automated Opera software. The role of HDAC1/2 was validated by genetic silencing. The role of α4-, α5-α1 Integrins and Fibronectin-1 was validated using specific monoclonal antibodies. Quantitative proteomic analysis was performed on primary MCs pretreated with MS-275. Decellularized matrices were generated from either MS-275-exposed or untreated cells to study Fibronectin-1 extracellular secretion. The effect of MS-275 on β1 integrin activity was assessed using specific monoclonal antibodies. The role of Talin-1 in MCs/EOC adhesion was analyzed by genetic silencing. Talin-1 ectopic expression was validated as a rescue tool from MS-275-induced phenotype. The in vivo effect of MS-275-induced MC remodeling was validated in a mouse model of peritoneal EOC dissemination. Results Treatment of MCs with non-cytotoxic concentrations of MS-275 caused a consistent reduction of EOC adhesion. Proteomic analysis revealed several pathways altered upon MC treatment with MS-275, including ECM deposition/remodeling, adhesion receptors and actin cytoskeleton regulators. HDAC1/2 inhibition hampered actin cytoskeleton polymerization by downregulating actin regulators including Talin-1, impairing β1 integrin activation, and leading to abnormal extracellular secretion and distribution of Fibronectin-1. Talin-1 ectopic expression rescued EOC adhesion to MS-275-treated MCs. In an experimental mouse model of metastatic EOC, MS-275 limited tumor invasion, Fibronectin-1 secretion and the sub-mesothelial accumulation of MC-derived carcinoma-associated fibroblasts. Conclusion Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.

Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.

This study delves into the impacts of the 2008 global financial crisis (GFC) and the COVID-19 health crisis on U.S. financial indices, exploring the intricate relationship between economic shocks and these indices during downturns. Using Markov switching regression models and control variables, including GDP, consumer sentiment, industrial production, and the ratio of inventories-to-sale, it quantifies the effects of these crises on the CBOE Volatility Index (VIX), Standard & Poor’s 500 (S&P 500), and the Dow Jones Industrial Average (DJIA) from Q1 2000 to Q2 2023, covering crucial moments of both crises and stable periods (dichotomous variables). Results reveal that the 2008 crisis significantly heightened financial volatility and depreciated the valuation of S&P 500 and DJIA indicators, while the COVID-19 crisis had a diverse impact on market dynamics, particularly negatively affecting specific sectors. This study underscores the importance of consumer confidence and inventory management in mitigating financial volatility and emphasises the need for robust policy measures to address economic shocks, enhance financial stability, and alleviate future crises, especially during endogenous crises such as financial downturns. This research sheds light on the nuanced impact of crises on financial markets and the broader economy, revealing the intricate dynamics shaping market behaviour during turbulent times.

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.

Fundamento: la autonomía permite a los estudiantes pensar por sí mismos, con sentido crítico e independencia, tener en cuenta diferentes puntos de vista y actuar en correspondencia con ellos. Constituye un indicador necesario en el estudio de las habilidades de aprender a aprender.Objetivo: caracterizar la autonomía como indicador de las habilidades de aprender a aprender en estudiantes de medicina. Métodos: se empleó un diseño mixto de investigación del tipo explicativo secuencial. La investigación se realizó de octubre de 2021 a marzo de 2022 en la Universidad de Ciencias Médicas de Cienfuegos. La muestra no probabilística, intencionada, quedó constituida por 255 estudiantes del primer año de la carrera de Medicina. Para la recolección de información se utilizó el cuestionario que evalúa el nivel de formación de las habilidades de aprender a aprender, observaciones a actividades docentes y grupos focales.Resultados: la autonomía está presente en el 45,4 % de los estudiantes, según cuestionario. En los grupos focales algunos estudiantes reconocen presentar insuficiencias en algunos indicadores de la autonomía, lo que se corresponde con los datos obtenidos en las observaciones a las actividades docentes.Conclusiones: la autonomía como indicador clave de las habilidades de aprender a aprender en los estudiantes del primer año de la Universidad de Ciencias Médicas de Cienfuegos se caracterizó por una baja expresión en los procesos de aprendizaje de los estudiantes de medicina.

This article aims to alert about the relevance of nanosciences and nanotechnology accompanied by nanometrology for the nations development in the 21st century. Scielo was used as a database, with the keywords: nanotechnology, nanomedicine, Cuban health units. The article makes an approach to nanotechnology with an international and regional approach. It describes some applications of nanotechnologies, with an emphasis on nanomedicine, as well as the dilemmas and ethical considerations associated with them. It advises about these developments’ harmfulness to human health, also defends the idea that nanometrology is essential for the technological developments achievement, with greater relevance in the nanomedicine field, as well as that nanotechnology should be treated as the 21st century science due to the social, cultural and economic impact that will have, and this can change the world.

Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.

IntroductionNon-profit organizations (NPOs) are a complex working context whose main characteristic resides in the dichotomy between paid staff and volunteers. Despite its benefits for goal achievement, this circumstance can be also a challenge, for both groups' interaction, for their comprehension of their own role and to HR management. The aim of this study was to explore factors that may contribute to promote job satisfaction among NPOs' members.MethodsCombining two different data analyses, serial multiple mediation analyses and cluster analyses, first we analyze whether there are differences between paid staff and volunteers in perceived intrapersonal conflict and performance and its effect on job satisfaction, and second, we analyze whether there is an additional profiles distribution that reflects more adequately the reality of NPOs, despite the formal roles that coexist in these organizations (paid staff and volunteers).ResultsResults confirm that paid staff and volunteers differ on their perceived job satisfaction level, with volunteers being more satisfied. This relationship is serially mediated by role conflict, role ambiguity, and performance. Another characteristic of the NPOs is that the dichotomy between paid staff and volunteers does not capture well the reality of the labor relations between members of both groups and the organization. To explore this phenomenon, we perform a cluster analysis based on paid staff and volunteers' perceptions. Cluster analyses demonstrate the existence of three rather homogenous profiles.DiscussionAdditionally, practical implications for HR management in NPOs and future research lines to understand this organizational context dynamics are also discussed.

En esta investigación se calcula un índice de inclusión financiera para México. Las dimensiones incluidas en el índice son acceso, uso y calidad. Se utiliza una metodología en tres etapas sobre la base del análisis de componentes principales. Los datos provienen de la Encuesta Nacional de Inclusión Financiera. Los resultados del índice nos muestran que existe un bajo nivel de inclusión financiera. La dimensión que más contribuye a la inclusión financiera es el acceso, mientras la más rezagada es la calidad. Se percibe una mayor inclusión financiera de los hombres, así como de los individuos de la Ciudad de México, el Noreste y el Noroeste, en las localidades de más de 100,000 habitantes, y los que trabajan. Esto nos indica que la diversificación impulsa los niveles de inclusión financiera, pero se necesita incentivar el uso, fortalecer capacidades, y mejorar el diseño. Existe un rezago en la información de productos y servicios financieros novedosos, lo que limita el estudio.

Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR’s role as a promising therapeutic target in combating these devastating disorders.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

Esta investigación pretende dilucidar, a partir del análisis de técnicas de inteligencia artificial explicables, la robustez y el nivel de generalización de los métodos de visión por computadora propuestos para identificar COVID-19 utilizando imágenes de radiografías de tórax. Asimismo, alertar a los investigadores y revisores sobre el problema del aprendizaje por atajos. En este estudio se siguen recomendaciones para identificar si los modelos de clasificación automática de COVID-19 se ven afectados por el aprendizaje por atajos. Para ello, se revisaron los artículos que utilizan métodos de inteligencia artificial explicable en dicha tarea. Se evidenció que al utilizar la imagen de radiografía de tórax completa o el cuadro delimitador de los pulmones, las regiones de la imagen que más contribuyen a la clasificación aparecen fuera de la región pulmonar, algo que no tiene sentido. Los resultados indican que, hasta ahora, los modelos existentes presentan el problema de aprendizaje por atajos, lo cual los hace inapropiados para ser usados en entornos clínicos.

La preocupación que tiene la sociedad en todos los países acerca de la salud sigue siendo mayor que sobre cualquier otro aspecto. Una calidad de vida óptima solo es posible con una salud favorable. Ante los recientes eventos de la COVID-19, la importancia de la tecnología médica en la atención del paciente ha resultado evidente. El trabajo pretende mostrar el relevante papel que juega la rama biomédica, su influencia e impacto en los procesos de las unidades de salud. Resume algunos de los desarrollos tecnológicos logrados desde el contexto internacional hasta el local en el complejo escenario epidemiológico en el que se encuentra el planeta. Describe la necesaria cronología del sistema electromédico en Cuba con énfasis en Cienfuegos. Defiende la idea de que es necesario un cambio conceptual acerca del importante papel que juega la rama biomédica, su influencia e impacto en los procesos de las unidades y que los ingenieros biomédicos y electromédicos, así como los licenciados y técnicos en electromedicina, merecen un adecuado reconocimiento ante la comunidad científica por sus tangibles logros en tiempos de Covid-19. Ellos también salvan vidas.

Simple Summary: Approximately 70–80% of patients with epithelial ovarian cancer (OC) experience peritoneal metastasis. Identification of mesothelial-to-mesenchymal transition (MMT) in the peritoneum may guide the accurate treatment and follow-up of patients with advanced OC. The aim of this study was to evaluate whether MMT took place in primary OC biopsies. We suggest the identified mesothelial-derived carcinoma-associated fibroblasts in primary tumors could impact the clinical progression of patients with OC. Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread. [ABSTRACT FROM AUTHOR]

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations. [ABSTRACT FROM AUTHOR]

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). To date, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. Recently, several studies have described that PKAN patient-derived fibroblasts present the main pathological features associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, vitamin E, omega 3, α-lipoic acid L-carnitine or thiamine, improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help optimize therapeutic strategies in individual PKAN patients.

Este artículo estima la Ley de Okun (1962) para México al nivel estatal y por tamaños de localidades. Se utiliza un modelo de Panel de Vectores Autorregresivos (PVAR) para determinar los efectos de corto plazo, mientras que las funciones de Impulso-Respuesta y el Panel de Cointegración se utilizan para determinar los efectos de largo plazo para el período que va de 2005 a 2022. Los resultados verifican la existencia de la Ley de Okun para todos los estados, y para el tamaño de localidad mayor a 100 mil habitantes. Los rezagos de la tasa de crecimiento del capital humano tienen un efecto positivo en la tasa de crecimiento del desempleo, y los rezagos temporales de la tasa de desempleo tienen una incidencia negativa sobre la misma. Además, las innovaciones de estas variables presentan un comportamiento cíclico sobre el desempleo. Para el caso del análisis de largo plazo existe evidencia de una relación de largo plazo entre las variables estacionarias y una relación negativa.

Introducción: Las emociones positivas vinculadas a una adecuada motivación hacia el estudio crean las condiciones para la formación y desarrollo de las habilidades de aprender a aprender. Objetivo: Caracterizar la dimensión afectiva motivacional de las habilidades de aprender a aprender en estudiantes de medicina. Métodos: Se empleó un diseño mixto del tipo explicativo secuencial. La muestra no probabilística, intencionada quedó constituida por 255 estudiantes del primer año de la carrera de medicina. Para la recolección de información se utilizó un cuestionario para evaluar el nivel de formación de las habilidades de aprender a aprender, observaciones a actividades docentes y grupos focales. Resultados: La motivación hacia el estudio está presente en el 68,2 % de los estudiantes, la atribución de sentido al aprendizaje en el 53,5 %, mientras que la percepción del control emocional en el 26,6 %. En los grupos focales los estudiantes reconocen no tener formadas las habilidades y presentar insuficiencias en algunos indicadores, aunque la mayoría asegura gustarle la medicina y esperan ser buenos profesionales, lo que se corresponde con los datos obtenidos en las observaciones a las actividades docentes, en las cuales se aprecia la disposición hacia las tareas, colaboración y armonía durante la actividad. Conclusiones: La dimensión afectiva motivacional de las habilidades de aprender a aprender se caracteriza por una adecuada motivación hacia el estudio, pobre atribución de sentido al aprendizaje e insuficiente percepción del control emocional.

El empleo de pruebas complementarias en que intervienen equipos biomédicos, que llevan implícitos instrumentos de medición, indicadores para corroborar las hipótesis médicas y lograr diagnósticos certeros se hace más cada vez más común. Un error en las mediciones puede acarrear compromiso para la vida del paciente. De ahí la importancia de considerar el riesgo metrológico en la evaluación del Sistema de Gestión de las mediciones en salud. Este trabajo tiene como propósito contribuir a la visualización de la necesidad del enfoque de riesgo metrológico en las unidades de salud. Como criterios para la selección de las 80 fuentes consultadas se tomaron la declaración explícita de los autores referida al posicionamiento acerca del constructo riesgo y su visión de la importancia de este enfoque en las organizaciones de salud, durante el período del 2009 al 2020, que justifica plenamente el nivel de actualización de la información. Aparecen referenciados 21 textos con el 67 % de actualización. Se concluye que el índice de riesgo metrológico constituye un instrumento valioso al que deben acceder los gestores en salud promoviendo así la incorporación de nuevas técnicas en su gestión, lo que resultaría valioso para la toma de decisiones. El enfoque de riesgo en la evaluación del desempeño metrológico en salud es necesario, lo que evidenciaría un pensamiento avanzado científicamente, profundo y práctico.

Background: Peritoneal dialysis (PD) is a renal replacement technique that requires repeated exposure of the peritoneum to hyperosmolar PD fluids (PDFs). Unfortunately, it promotes alterations of the peritoneal membrane (PM) that affects its functionality, including mesothelial-mesenchymal transition (MMT) of mesothelial cells (MCs), inflammation, angiogenesis, and fibrosis. Glucose is the most used osmotic agent, but it is known to be at least partially responsible, together with its degradation products (GDP), for those changes. Therefore, there is a need for more biocompatible osmotic agents to better maintain the PM. Herein we evaluated the biocompatibility of Steviol glycosides (SG)-based fluids.Methods: The ultrafiltration and transport capacities of SG-containing and glucose-based fluids were analyzed using artificial membranes and an in vivo mouse model, respectively. To investigate the biocompatibility of the fluids, Met-5A and human omental peritoneal MCs (HOMCs) were exposed in vitro to different types of glucose-based PDFs (conventional 4.25% glucose solution with high-GDP level and biocompatible 2.3% glucose solution with low-GDP level), SG-based fluids or treated with TGF-β1. Mice submitted to surgery of intraperitoneal catheter insertion were treated for 40 days with SG- or glucose-based fluids. Peritoneal tissues were collected to determine thickness, MMT, angiogenesis, as well as peritoneal washings to analyze inflammation.Results: Dialysis membrane experiments demonstrated that SG-based fluids at 1.5%, 1%, and 0.75% had a similar trend in weight gain, based on curve slope, as glucose-based fluids. Analyzing transport capacity in vivo, 1% and 0.75% SG-based fluid-exposed nephrectomized mice extracted a similar amount of urea as the glucose 2.3% group. In vitro, PDF with high-glucose (4.25%) and high-GDP content induced mesenchymal markers and angiogenic factors (Snail1, Fibronectin, VEGF-A, FGF-2) and downregulates the epithelial marker E-Cadherin. In contrast, exposition to low-glucose-based fluids with low-GDP content or SG-based fluids showed higher viability and had less MMT. In vivo, SG-based fluids preserved MC monolayer, induced less PM thickness, angiogenesis, leukocyte infiltration, inflammatory cytokines release, and MMT compared with glucose-based fluids.Conclusion: SG showed better biocompatibility as an osmotic agent than glucose in vitro and in vivo, therefore, it could alternatively substitute glucose in PDF.

The methods used for the measurement management system range from the verification of the equipment to the application of statistical techniques in the control of the measurement process. In the health sector, metrological confirmation is basically developed. In this sector, it serves to verify that the measurements of the equipment are reliable, both those of diagnosis and those of therapy, which directly results in the safety of the patient. The use of methodologies for the construction and application of a performance indicator with a management approach is the most successful in these times. The objective of this work is to explain how the evaluation of metrological performance is essential for the evaluation of quality in health units, based on updated procedures to contribute to create a metrological culture in organizations of this sector.

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

Polymer nanoclay composites have received significant attention due to their substantially enhanced mechanical, thermal and barrier properties. However, the effect of these nanoclays on the dynamic fracture resistance of a polymer matrix during fast fracture events has not been documented. In this study, the effect of nanoclay addition on the rapid crack propagation (RCP) resistance of high-density polyethylene (HDPE) was investigated through the high-speed double torsion test. Results showed that the addition of 1, 3, and 5% of nanoclays improved the dynamic fracture resistance under the plane strain conditions (Gd1) of HDPE up to 65%. An increase in the storage and loss modulus, and a decrease in crystallinity and melt flow index with nanoclay content was also found. Although the presence of agglomerates can hinder the enhancement of Gd1 as it promotes agglomerate fracture and debonding, the increase in energy consumption through fibrillation and crazing promoted by the nanoclay prevails, suggesting that the nanoclay’s toughening effect that has been extensively reported under quasi-static and impact tests, is also present under RCP conditions, and that the HDPE nanocomposites could be used in applications in which RCP must be prevented.

This study delves into the impacts of the 2008 global financial crisis (GFC) and the COVID-19 health crisis on U.S. financial indices, exploring the intricate relationship between economic shocks and these indices during downturns. Using Markov switching regression models and control variables, including GDP, consumer sentiment, industrial production, and the ratio of inventories-to-sale, it quantifies the effects of these crises on the CBOE Volatility Index (VIX), Standard & Poor's 500 (S&P 500), and the Dow Jones Industrial Average (DJIA) from Q1 2000 to Q2 2023, covering crucial moments of both crises and stable periods (dichotomous variables). Results reveal that the 2008 crisis significantly heightened financial volatility and depreciated the valuation of S&P 500 and DJIA indicators, while the COVID-19 crisis had a diverse impact on market dynamics, particularly negatively affecting specific sectors. This study underscores the importance of consumer confidence and inventory management in mitigating financial volatility and emphasises the need for robust policy measures to address economic shocks, enhance financial stability, and alleviate future crises, especially during endogenous crises such as financial downturns. This research sheds light on the nuanced impact of crises on financial markets and the broader economy, revealing the intricate dynamics shaping market behaviour during turbulent times. [ABSTRACT FROM AUTHOR]

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations. [ABSTRACT FROM AUTHOR]