Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes

Altres ajuts: European Regional Development Fund (FEDER); Gilead. European Union NextGeneration EU/PRTR.Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells. Main methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (C[sbnd]C motif) ligand-2 using Multiplex assays. Key findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir. Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH

Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes.

Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells. Main methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays. Key findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir. Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH

Puerto Rican Karst - A Vital Resource

The limestone region of Puerto Rico covers about 27.5 percent of the island\u27s surface and is subdivided into the northern, southern, and dispersed limestone areas. All limestone areas have karst features. The karst belt is that part of the northern limestone with the most spectacular surficial karst landforms. It covers 142,544 ha or 65 percent of the northern limestone. The karst belt is the focus of this publication, although reference is made to all limestone regions. The northern limestone contains Puerto Rico\u27s most extensive freshwater aquifer, largest continuous expanse of mature forest, and largest coastal wetland, estuary, and underground cave systems. The karst belt is extremely diverse, and its multiple landforms, concentrated in such a small area, make it unique in the world. Puerto Rico\u27s karst forests whether dry, moist, or wet share common physiognomic and structural characteristics. Karst forests contain the largest reported number of tree species per unit area in Puerto Rico. Both fauna and flora are rich in taxa; and many rare, threatened, endangered, and migratory species find refuge in the karst belt. Almost all fossil records of Puerto Rico\u27s extinct flora and fauna come from the karst belt

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

La capacidad de adaptación a peligros naturales desde una perspectiva social-comunitaria.

The risk and vulnerability literature emphasizes the importance of increasing the adaptive capacity of populations exposed to natural hazards. In Puerto Rico, the focus on adaptation has taken particular importance, mainly as related to adaptation to the potential hazards that might result from climate change. This article explores the concept of natural hazard adaptive capacity from a social perspective. Adapting to natural hazards requires tackling the “multiple risks” people are exposed to, not just those risks related to the natural hazard alone. In that respect, augmenting adaptive capacity requires enhancing people’s general well being. Enhancing people’s capacity to deal with present climate conditions will strengthen their adaptive capacity and resilience to longer-term conditions, including those that may result from climate change. The notions of adaptive capacity are exemplified within the context of flood prone communities in Fajardo, Puerto Rico.La literatura de riesgos y vulnerabilidad enfatiza la importancia de aumentar la capacidad de adaptación de las personas expuestas a amenazas naturales. En Puerto Rico, el tema de la adaptación ha adquirido gran importancia, particularmente en lo que se asocia con las amenazas que pueden resultar del cambio climático. En este artículo se examina el concepto de capacidad de adaptación desde una perspectiva social. La capacidad de adaptación ante amenazas naturales requiere abordar los “múltiples riesgos” a los que las personas están expuestas; no solo aquellos relacionados con las amenazas naturales. En este sentido, aumentar capacidad de adaptación requiere mejorar el bienestar general de las personas. Mejorar la capacidad de las personas de lidiar con amenazas actuales aumentará su capacidad de adaptación ante futuras amenazas naturales, incluso aquellas que puedan resultar por el cambio climático. La noción de capacidad de adaptación se ejemplifica en el contexto de comunidades expuestas a inundaciones en Fajardo, Puerto Rico

Efectiveness of mindfulness as a complementary technique in fibromyalgia patients: a systematic review

Introducción: La fibromialgia (FM) es una enfermedad caracterizada por dolor crónico sin alteraciones orgánicas demostrables y que sigue siendo difícil de manejar, no solo para paliar síntomas físicos sino también aquellos aspectos que pueden deteriorar la calidad de vida de los pacientes y aquellos que les rodean. Los resultados obtenidos mediante distintas terapias son muy diferentes y limitados hasta la fecha, entre ellas destaca el mindfulness . El mindfulness consiste en prestar atención de manera consciente en el momento presente sin juzgar y que se utiliza en técnicas para trabajar ciertos síntomas como son los de la FM. Si bien hay evidencia del tratamiento con mindfulness para la FM, a día de hoy los estudios se han centrado principalmente en el dolor y por lo tanto se cree necesario tener en cuenta y evaluar otros aspectos más sociales, psicológicos y emocionales. Objetivos: El objetivo general de este estudio es realizar una revisión sistemática para conocer la efectividad del mindfulness en pacientes con fibromialgia, con el fin de mejorar la calidad de vida. Metodología: Se realizó una revisión sistemática mediante un protocolo de revisión de acuerdo con el método PRISMA y se examinó la literatura publicada entre octubre de 2010 y noviembre de 2019. Se utilizaron términos relevantes, palabras claves y descriptores. Se revisaron 243 resúmenes de tres bases de datos (Medline, Scielo, WoS). Resultados: 19 estudios cumplieron los criterios de inclusión, los cuales demostraron la mejora de los síntomas de la FM como el dolor, sueño, estrés, ansiedad y depresión entre otros. Conclusiones: Aunque la evidencia demuestra que hay una mejora en aspectos como el dolor, sueño, depresión y ansiedad mediante mindfulness en pacientes con FM, también se ha de tener en cuenta que los resultados son a corto plazo y que estas terapias por sí solas no demuestran una mejora sustancial.Introduction: Fibromyalgia (FM) is a disease characterized by chronic pain without de - monstrable organic alterations and which is still difficult to manage, not only to alleviate physical symptoms but also those aspects that can impair the quality of life of patients and those around them. The results obtained through different therapies are quite different and extremely limited to date, among which is mindfulness. Mindfulness consists in paying atten - tion in a conscious way to the present moment without judging it and it is used in techniques to work certain symptoms such as those of FM. Although there is evidence of mindfulness treatment for FM, studies to date have mainly focused on pain and therefore it is considered necessary to consider and evaluate other more social, psychological and emotional aspects. Objective: The general aim of this study is to conduct a systematic review to know the ef - fectiveness of mindfulness in fibromyalgia patients, in order to improve the quality of their lives. Methodology: A systematic review was performed using a review protocol according to the PRISMA method and the literature published between October 2010 and November 2019 was examined. Relevant terms, keywords, and descriptors were used. 243 abstracts from three databases (Medline, Scielo, WoS) were reviewed. Results: 19 studies met the inclusion criteria. The studies demonstrated the improvement of the symptoms of FM such as pain, sleep, stress, anxiety and depression, among others. Conclusion: Although the evidence shows that there is an improvement in aspects such as pain, sleep, depression and anxiety in FM patients who use mindfulness, it must also be considered that the results are short-term and that these therapies alone do not demonstrate a substantial improvement.Medicin

Efectividad del mindfulness como técnica complementaria en pacientes con fibromialgia: una revisión sistemática

Introduction: Fibromyalgia (FM) is a disease characterized by chronic pain without demonstrable organic alterations and which is still difficult to manage, not only to alleviate physical symptoms but also those aspects that can impair the quality of life of patients and those around them. The results obtained through different therapies are quite different and extremely limited to date, among which is mindfulness. Mindfulness consists in paying attention in a conscious way to the present moment without judging it and it is used in techniques to work certain symptoms such as those of FM. Although there is evidence of mindfulness treatment for FM, studies to date have mainly focused on pain and therefore it is considered necessary to consider and evaluate other more social, psychological and emotional aspects. Objective: The general aim of this study is to conduct a systematic review to know the effectiveness of mindfulness in fibromyalgia patients, in order to improve the quality of their lives. Methodology: A systematic review was performed using a review protocol according to the PRISMA method and the literature published between October 2010 and November 2019 was examined. Relevant terms, keywords, and descriptors were used. 243 abstracts from three databases (Medline, Scielo, WoS) were reviewed. Results: 19 studies met the inclusion criteria. The studies demonstrated the improvement of the symptoms of FM such as pain, sleep, stress, anxiety and depression, among others. Conclusion: Although the evidence shows that there is an improvement in aspects such as pain, sleep, depression and anxiety in FM patients who use mindfulness, it must also be considered that the results are short-term and that these therapies alone do not demonstrate a substantial improvement.Introducción: La fibromialgia (FM) es una enfermedad caracterizada por dolor crónico sin alteraciones orgánicas demostrables y que sigue siendo difícil de manejar, no solo para paliar síntomas físicos sino también aquellos aspectos que pueden deteriorar la calidad de vida de los pacientes y aquellos que les rodean. Los resultados obtenidos mediante distintas terapias son muy diferentes y limitados hasta la fecha, entre ellas destaca el mindfulness. El mindfulness consiste en prestar atención de manera consciente en el momento presente sin juzgar y que se utiliza en técnicas para trabajar ciertos síntomas como son los de la FM. Si bien hay evidencia del tratamiento con mindfulness para la FM, a día de hoy los estudios se han centrado principalmente en el dolor y por lo tanto se cree necesario tener en cuenta y evaluar otros aspectos más sociales, psicológicos y emocionales. Objetivos: El objetivo general de este estudio es realizar una revisión sistemática para conocer la efectividad del mindfulness en pacientes con fibromialgia, con el fin de mejorar la calidad de vida. Metodología: Se realizó una revisión sistemática mediante un protocolo de revisión de acuerdo con el método PRISMA y se examinó la literatura publicada entre octubre de 2010 y noviembre de 2019. Se utilizaron términos relevantes, palabras claves y descriptores. Se revisaron 243 resúmenes de tres bases de datos (Medline, Scielo, WoS). Resultados: 19 estudios cumplieron los criterios de inclusión, los cuales demostraron la mejora de los síntomas de la FM como el dolor, sueño, estrés, ansiedad y depresión entre otros. Conclusiones: Aunque la evidencia demuestra que hay una mejora en aspectos como el dolor, sueño, depresión y ansiedad mediante mindfulness en pacientes con FM, también se ha de tener en cuenta que los resultados son a corto plazo y que estas terapias por sí solas no demuestran una mejora sustancial

Utilización de técnicas complementarias en niños con trastornos del espectro autista: una revisión sistemática

Introduction: The treatment of autism is complicated, that is why many parents look for different alternatives among which are complementary techniques because they offer a different approach to conventional medicine. The different therapies used in children with autism spectrum disorder (ASD) are electro-acupuncture, animal therapy, music therapy, game therapy, among others. Additionally, those that used technology such as augmented reality or iPads were included. Objectives: The general objective of this study was to carry out a systematic review of complementary therapies in a population of 1 to 18 years old with ASD, as well as to analyze the benefits of using these therapies. Methodology: In this study, searches were restricted to publications available in English and Spanish, the search years were 10 years, that is, from 2010 to 2020. We included articles that used complementary techniques in children with autism spectrum disorder aged from the first year to 18 years old. The PRISMA guide was used to develop search terms and strategies. In addition, the following bibliographic databases specialized in health sciences were consulted: PubMed and Web of Science. Results: All the complementary therapies used in children with ASD had positive benefits, such as an increase in social skills, affective skills, non-verbal skills, and affective ties between the family, decrease of irritability and decrease of stress. In addition, it should be noted that electro-acupuncture therapy also has negative effects such as, for example, the child’s crying after puncture. Conclusions: Each parent must choose the most appropriate therapies for their child according to their symptoms and personalities since each child has different characters.Introducción: El tratamiento del autismo es complicado, por lo que muchos padres buscan diferentes alternativas, entre las que se encuentran las técnicas complementarias debido a que ofrecen un enfoque diferente a la medicina convencional. Las diferentes terapias utilizadas en niños con trastorno del espectro autista (TEA) son electroacupuntura, terapias con animales, musicoterapia y juegoterapia, entre otras. También se incluyeron aquellas que usaban tecnología como realidad aumentada o iPads. Objetivos: El objetivo general de este estudio fue realizar una revisión sistemática sobre las terapias complementarias en población de 1 a 18 años con TEA, así como analizar los beneficios de utilizar estas terapias. Metodología: En este estudio, las búsquedas se restringieron a publicaciones disponibles en los idiomas inglés y español y con una antigüedad máxima de diez años, englobando publicaciones del año 2010 hasta el año 2020. Se incluyeron artículos que utilizaban técnicas complementarias en pacientes infantiles con TEA en edades comprendidas entre 1-18 años. Se utilizó la guía PRISMA para desarrollar términos y estrategias de búsquedas consultando las siguientes bases de datos bibliográficas especializadas en ciencias de la salud: PubMed y Web of Science. Resultados: Todas las terapias complementarias utilizadas en niños con TEA tuvieron beneficios positivos entre los que se encuentran: un aumento en habilidades sociales, habilidades afectivas, habilidades no verbales y vínculos afectivos entre la familia, disminución de la irritabilidad y disminución del estrés. Además, cabe destacar que en la terapia de electroacupuntura, aparte de dar efectos positivos, también tiene efectos negativos como, por ejemplo, el llanto del niño por punción. Conclusiones: Cada padre debe elegir las terapias más adecuadas para su hijo mediante sus síntomas y personalidades ya que cada niño tiene un carácter diferente

Use of complementary techniques in children with autism spectrum disorders: a systematic review

Introducción: El tratamiento del autismo es complicado, por lo que muchos padres buscan diferentes alternativas, entre las que se encuentran las técnicas complementarias debido a que ofrecen un enfoque diferente a la medicina convencional. Las diferentes terapias utilizadas en niños con trastorno del espectro autista (TEA) son electroacupuntura, terapias con animales, musicoterapia y juegoterapia, entre otras. También se incluyeron aquellas que usaban tecnolo - gía como realidad aumentada o iPads. Objetivos : El objetivo general de este estudio fue realizar una revisión sistemática sobre las terapias complementarias en población de 1 a 18 años con TEA, así como analizar los beneficios de utilizar estas terapias. Metodología : En este estudio, las búsquedas se restringieron a publicaciones disponibles en los idiomas inglés y español y con una antigüedad máxima de diez años, englobando publicaciones del año 2010 hasta el año 2020. Se incluyeron artículos que utilizaban técnicas complementarias en pacientes infantiles con TEA en edades comprendidas entre 1-18 años. Se utilizó la guía PRISMA para desarrollar términos y estrategias de búsquedas consultando las siguientes bases de datos bibliográficas especializadas en ciencias de la salud: PubMed y Web of Science. Resultados: Todas las terapias complementarias utilizadas en niños con TEA tuvieron beneficios positivos entre los que se encuentran: un aumento en habilidades sociales, habilidades afectivas, habilidades no verbales y vínculos afectivos entre la familia, disminución de la irritabilidad y disminución del estrés. Además, cabe destacar que en la terapia de electroacupuntura, aparte de dar efectos positivos, también tiene efectos negativos como, por ejemplo, el llanto del niño por punción. Conclusiones : Cada padre debe elegir las terapias más adecuadas para su hijo mediante sus síntomas y personalidades ya que cada niño tiene un carácter diferente.Introduction : The treatment of autism is complicated, that is why many parents look for different alternatives among which are complementary techniques because they offer a different approach to conventional medicine. The different therapies used in children with autism spec - trum disorder (ASD) are electro-acupuncture, animal therapy, music therapy, game therapy, among others. Additionally, those that used technology such as augmented reality or iPads were included. Objectives: The general objective of this study was to carry out a systematic review of complementary therapies in a population of 1 to 18 years old with ASD, as well as to analyze the benefits of using these therapies. Methodology : In this study, searches were restricted to publications available in English and Spanish, the search years were 10 years, that is, from 2010 to 2020. We included articles that used complementary techniques in children with autism spectrum disorder aged from the first year to 18 years old. The PRISMA guide was used to develop search terms and strategies. In addition, the following bibliographic databases specialized in health sciences were consulted: PubMed and Web of Science. Re - sults : All the complementary therapies used in children with ASD had positive benefits, such as an increase in social skills, affective skills, non-verbal skills, and affective ties between the family, decrease of irritability and decrease of stress. In addition, it should be noted that electro-acupuncture therapy also has negative effects such as, for example, the child’s crying after puncture. Conclusions : Each parent must choose the most appropriate therapies for their child according to their symptoms and personalities since each child has different characters.Medicin

Monitoring Ada Tasking Programs Correctly

Serotonin 5-HT 6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer's disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT 6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT 6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT 6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT 2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit