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1.
Curr Obes Rep ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356455

RESUMO

PURPOSE: To develop Mexico's first methodologically rigorous clinical practice guideline for the management of adult overweight and obesity. The target audiences are interdisciplinary healthcare professionals across healthcare systems who are the first point of contact for patients with obesity in Mexico, patients, and health system decision makers. RECENT FINDINGS: A review of recent international obesity clinical practice guidelines and an expert consensus process identified: i) common recommendations appropriate for implementation in Mexico and ii) knowledge gaps requiring the formulation of new recommendations. In all, 20 new recommendations and 20 good practice statements were developed using the GRADE Evidence-to-Decision Framework and expert consensus. Overweight and obesity negatively impact the health and well-being of individuals and populations in Mexico. This guideline aims to establish a new evidence-based, patient-centered, non-stigmatizing, and practical treatment and management framework, based on the fundamental principles of chronic disease prevention and management.

2.
Cureus ; 16(9): e68729, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39376871

RESUMO

Medical education worldwide has undergone numerous stages of reform. Cultural and financial restraints have decelerated progress in developing countries. Current reforms should focus on creating integrated, competency-based, and student-centered curricula that emphasize patient-centered care. The following review of literature published between 2014 and 2023 on global curricular reforms highlighted key components, challenges, and strategies for implementing or evaluating undergraduate medical programs that prioritize student-centered approaches and competency-based models. This review also compared the current curriculum at the National Autonomous University of Honduras (UNAH) with these international experiences to suggest strategies in order to encourage significant reform. The following review identified 47 articles that provided insights into ideal contexts for curricular reforms, while 15 publications detailed the current state of the UNAH medical curriculum and its potential weaknesses. Additionally, 25 articles discussed specific reforms in other countries, offering valuable results and conclusions for consideration. Drawing from these models and experiences, strategies were proposed for UNAH's curriculum reform, including identifying basic needs, defining project vision, training teaching staff and students, and integrating multidisciplinary teams of experts. Although training all teaching staff abroad may be financially unfeasible, selecting and training key individuals to train others could be a viable alternative. Successful reform requires a comprehensive, periodic, and systematic evaluation. Despite the challenges faced by developing countries, global experiences with alternative reform models offer promising solutions, providing an opportunity for the Faculty of Medical Sciences at UNAH to overcome local limitations and fulfill the primary task of training professionals who are clinically, ethically, and adaptively competent, with a focus on patient-centered and primary care approaches.

3.
Front Immunol ; 15: 1431403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224589

RESUMO

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed. Results: Multivariate regression analysis showed anti-cd20 (ß= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (ß=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Discussion: Findings regarding humoral and cellular response are consistent with previous reports.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunossupressores , Esclerose Múltipla , SARS-CoV-2 , Humanos , Masculino , Feminino , Imunossupressores/uso terapêutico , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/tratamento farmacológico , COVID-19/imunologia , COVID-19/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Argentina , Adenoviridae/genética , Adenoviridae/imunologia , Imunidade Humoral , Glicoproteína da Espícula de Coronavírus/imunologia
4.
Sci Rep ; 14(1): 20416, 2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223259

RESUMO

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.


Assuntos
Transtorno do Espectro Autista , Histona Desmetilases com o Domínio Jumonji , Camundongos Knockout , Transmissão Sináptica , Animais , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Transmissão Sináptica/genética , Transtorno do Espectro Autista/genética , Camundongos , Encéfalo/metabolismo , Plasticidade Neuronal/genética , Comportamento Animal , Hipocampo/metabolismo , Epigênese Genética , Masculino , Sinapses/metabolismo
6.
Front Oncol ; 14: 1397613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099684

RESUMO

Chimeric Antigen Receptor T-cell (CAR-T) therapies are transforming the treatment of B-cell lymphoproliferative disorders and multiple myeloma, yet global access challenges and barriers for their implementation persist. Global access disparities persist, particularly for persons living in low and middle-income countries and for underserved populations in high income countries. In this review we address patient-related factors including age, comorbidities, fitness, race and ethnicity, and geographic location for CAR-T access. Also, we review disease-related and health system barriers like disease biology, potential for short and long-term toxicity, insurance access, referrals, supply and manufacturing, regulation, costs and treatment center capacity. Lastly, alternatives for overcoming these barriers exemplified by research efforts worldwide are discussed, emphasizing the need for a multifaceted approach from all stakeholders to improve global accessibility and ensure equitable access and improved outcomes for patients worldwide.

7.
Viruses ; 16(8)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39205276

RESUMO

The rabies virus (RABV) is the exclusive lyssavirus affecting both wild and domestic mammalian hosts in the Americas, including humans. Additionally, the Americas stand out as the sole region where bat rabies occurs. While carnivore rabies is being increasingly managed across the region, bats are emerging as significant reservoirs of RABV infection for humans and domestic animals. Knowledge of the bat species maintaining rabies and comprehending cross-species transmission (CST) and host shift processes are pivotal for directing surveillance as well as ecological research involving wildlife reservoir hosts. Prior research indicates that bat RABV CST is influenced by host genetic similarity and geographic overlap, reflecting host adaptation. In this study, we compiled and analyzed a comprehensive nucleoprotein gene dataset representing bat-borne RABV diversity in Argentina and the broader Americas using Bayesian phylogenetics. We examined the association between host genus and geography, finding both factors shaping the global phylogenetic structure. Utilizing a phylogeographic approach, we inferred CST and identified key bat hosts driving transmission. Consistent with CST determinants, we observed monophyletic/paraphyletic clustering of most bat genera in the RABV phylogeny, with stronger CST evidence between host genera of the same family. We further discuss Myotis as a potential ancestral spreader of much of RABV diversity.


Assuntos
Quirópteros , Filogenia , Filogeografia , Vírus da Raiva , Raiva , Quirópteros/virologia , Raiva/transmissão , Raiva/epidemiologia , Raiva/virologia , Raiva/veterinária , Animais , Vírus da Raiva/genética , Vírus da Raiva/classificação , Vírus da Raiva/isolamento & purificação , América/epidemiologia , Reservatórios de Doenças/virologia , Teorema de Bayes , Humanos , Argentina/epidemiologia
8.
Drug Saf ; 47(10): 991-1010, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39009928

RESUMO

BACKGROUND: Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal. OBJECTIVE: This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website. METHODS: We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters. RESULTS: We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively). CONCLUSIONS: We found a large body of evidence supporting the safety and effectiveness of COVID-19 vaccines during pregnancy. While the certainty of evidence is not high, it stands as the most reliable option available, given the current absence of pregnant individuals in clinical trials. Results are shared in near real time in an accessible and interactive format for scientists, decision makers, clinicians, and the general public. This living systematic review highlights the relevance of continuous vaccine safety and effectiveness monitoring, particularly in at-risk populations for COVID-19 impact such as pregnant persons, during the introduction of new vaccines. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42021281290.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Gravidez , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Feminino , COVID-19/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2 , Vacinação
9.
Heliyon ; 10(14): e34336, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39082007

RESUMO

Environmental pollution associated with the petroleum industry is a major problem worldwide. Microbial degradation is extremely important whether in the extractive process or in bioremediation of contaminants. Assessing the local microbiota and its potential for degradation is crucial for implementing effective bioremediation strategies. Herein, contaminated soil samples of onshore oil fields from a semiarid region in the Northeast of Brazil were investigated using metagenomics and metataxonomics. These soils exhibited hydrocarbon contamination and high salinity indices, while a control sample was collected from an uncontaminated area. The shotgun analysis revealed the predominance of Actinomycetota and Pseudomonadota, while 16S rRNA gene amplicon analysis of the samples showed Actinomycetota, Bacillota, and Pseudomonadota as the most abundant. The Archaea domain phylotypes were assigned to Thermoproteota and Methanobacteriota. Functional analysis and metabolic profile of the soil microbiomes exhibited a broader metabolic repertoire in the uncontaminated soil, while degradation pathways and surfactant biosynthesis presented higher values in the contaminated soils, where degradation pathways of xenobiotic and aromatic compounds were also present. Biosurfactant synthetic pathways were abundant, with predominance of lipopeptides. The present work uncovers several microbial drivers of oil degradation and mechanisms of adaptation to high salinity, which are pivotal traits for sustainable soil recovery strategies.

10.
Rev Argent Microbiol ; 56(3): 227-231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38871623

RESUMO

The aim of this study was to detect vector-borne pathogens (Anaplasmataceae family, Rickettsia genus, and Bartonella genus) in bats from Misiones (Argentina). Thirty-three specimens were captured over 8 days using mist nets. Twenty (60.6%) blood samples were positive (11/13 Artibeus lituratus, 4/10 Desmodus rotundus, 4/8 Carollia perspicillata, and 1/2 Myotis nigricans) by PCR for the gltA gene fragment of Bartonella. All samples were negative by PCR for the Anaplasmataceae family and Rickettsia genus. The phylogenetic analysis showed seven Bartonella genotypes. The three genotypes obtained from A. lituratus, 2 from C. perspicillata, and 1 from D. rotundus were related to Bartonella spp. from New World bats, while the sequence obtained from M. nigricans was related to Old World bats. We identified a considerable diversity of Bartonella genotypes in a small number of bats, thus further research is required to better understand the complex bat-pathogen interaction.


Assuntos
Infecções por Bartonella , Bartonella , Quirópteros , Animais , Quirópteros/microbiologia , Bartonella/genética , Bartonella/isolamento & purificação , Bartonella/classificação , Infecções por Bartonella/microbiologia , Infecções por Bartonella/veterinária , Infecções por Bartonella/transmissão , Infecções por Bartonella/epidemiologia , Argentina , Filogenia , Genótipo , Especificidade da Espécie
11.
BMC Biol ; 22(1): 142, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926759

RESUMO

BACKGROUND: The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown. RESULTS: To examine the role of VPS50 in mammalian brain function and behavior, we used the CRISPR/Cas9 system to generate knockouts of VPS50 in both cultured murine cortical neurons and living mice. In cultured neurons, KO of VPS50 did not affect the number of synaptic vesicles but did cause mislocalization of the V-ATPase V1 domain pump and impaired synaptic activity, likely as a consequence of defects in vesicle acidification and vesicle content. In mice, mosaic KO of VPS50 in the hippocampus altered synaptic transmission and plasticity and generated robust cognitive impairments. CONCLUSIONS: We propose that VPS50 functions as an accessory protein to aid the recruitment of the V-ATPase V1 domain to synaptic vesicles and in that way plays a crucial role in controlling synaptic vesicle acidification. Understanding the mechanisms controlling behaviors and synaptic function in ASD-associated mutations is pivotal for the development of targeted interventions, which may open new avenues for therapeutic strategies aimed at ASD and related conditions.


Assuntos
Camundongos Knockout , Vesículas Sinápticas , Animais , Camundongos , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Sinapses/metabolismo , Sinapses/fisiologia , Transmissão Sináptica , Vesículas Sinápticas/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
12.
Medicina (B Aires) ; 84 Suppl 2: 1-32, 2024 May.
Artigo em Espanhol | MEDLINE | ID: mdl-38823037

RESUMO

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.


La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.


Assuntos
Guias de Prática Clínica como Assunto , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevenção & controle , Medição de Risco , Fidelidade a Diretrizes , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Fatores de Risco
13.
Medicina (B.Aires) ; Medicina (B.Aires);84(supl.2): 1-32, jun. 2024. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1569349

RESUMO

Resumen La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.


Abstract Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital´s reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

14.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 40-47, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814236

RESUMO

Periodontal ligament stem cells (PDLSCs) show plasticity towards the adipogenic lineage; however, little has been done on the participation of epigenetic mechanisms. Histone acetylation is a dynamic process, though balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) activities. This process can be halted by HDACs inhibitors, such as trichostatin A (TSA) and valproic acid (VPA). This study aimed to determine the role of HDACs class I in adipogenic differentiation of PDL cells. PDLSCs were treated with TSA at concentrations of 100, 200, and 250 nM, or VPA at 1, 4 and 8 mM. Cell viability was assessed using MTT assays. Gene expression of pluripotency markers (NANOG, OCT4, SOX2), HAT genes (p300, GCN5), and HDACs genes (HDAC1-3) was analyzed by RT-qPCR. Adipogenic differentiation was evaluated via oil red O staining, and acetylation of histone H3 lysine 9 (H3K9ac) was examined by Western blot. VPA treatment resulted in a 60% reduction in cell proliferation, compared to a 50% when using TSA. Cell viability was not affected by either inhibitor. Furthermore, both TSA and VPA induced adipogenic differentiation, through an increase in the deposition of lipid droplets and in GCN5 and p300 expression were observed. Western blot analysis showed that TSA increased H3K9ac levels on adipogenic differentiation of PDLSCs. These findings highlight the potential of HDAC inhibitors as a tool for modulating H3K9 acetylation status and thus influencing adipogenic differentiation of PDLCs.


Assuntos
Adipogenia , Diferenciação Celular , Sobrevivência Celular , Inibidores de Histona Desacetilases , Ligamento Periodontal , Ácido Valproico , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Ácido Valproico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Ácidos Hidroxâmicos/farmacologia , Células Cultivadas , Histonas/metabolismo , Proliferação de Células/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo
15.
Diabetol Metab Syndr ; 16(1): 106, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769575

RESUMO

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

16.
J Community Health ; 49(5): 887-899, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38575835

RESUMO

Community health promotion offers a potential solution to persistent healthcare challenges, with community health workers playing a pivotal role. The Community Training Institute for Health Disparities (CTIHD) implemented a problem-solving curriculum in Community Health Promotion, integrating a competency-based learning model through two courses: Introduction to Community Health Promotion and Design of an Action Plan for the Promotion of Community Health. Each course comprised ten three-hour sessions, featuring pre/post-tests, evaluations, and a cognitive debriefing. Knowledge change was assessed using pre/post-test scores among 27 community leaders from southern Puerto Rico. Cohort 1 and Cohort 2 demonstrated an overall retention rate of 62.6% and 96.7%, respectively. Although differences in knowledge gained between cohorts and courses weren't statistically significant, a trend toward increased knowledge was noted. Cohort 1 experienced a 22% knowledge increase in Course 1 and a 24% increase in Course 2. Cohort 2 demonstrated a 41% knowledge increase in Course 1 and a 25% increase in Course 2. The CTIHD's Community Health Promotion Program has made significant strides in elevating awareness and knowledge, marking a positive step toward reducing health disparities and fostering healthier, empowered communities in southern Puerto Rico.


Assuntos
Agentes Comunitários de Saúde , Promoção da Saúde , Humanos , Porto Rico , Promoção da Saúde/métodos , Promoção da Saúde/organização & administração , Agentes Comunitários de Saúde/educação , Agentes Comunitários de Saúde/organização & administração , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Área Carente de Assistência Médica , Currículo , Empoderamento
17.
Front Mol Neurosci ; 17: 1009404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660384

RESUMO

Brain-derived neurotrophic factor (BDNF) and its tropomyosin receptor kinase B (TrkB) are important signaling proteins that regulate dendritic growth and maintenance in the central nervous system (CNS). After binding of BDNF, TrkB is endocytosed into endosomes and continues signaling within the cell soma, dendrites, and axon. In previous studies, we showed that BDNF signaling initiated in axons triggers long-distance signaling, inducing dendritic arborization in a CREB-dependent manner in cell bodies, processes that depend on axonal dynein and TrkB activities. The binding of BDNF to TrkB triggers the activation of different signaling pathways, including the ERK, PLC-γ and PI3K-mTOR pathways, to induce dendritic growth and synaptic plasticity. How TrkB downstream pathways regulate long-distance signaling is unclear. Here, we studied the role of PLC-γ-Ca2+ in BDNF-induced long-distance signaling using compartmentalized microfluidic cultures. We found that dendritic branching and CREB phosphorylation induced by axonal BDNF stimulation require the activation of PLC-γ in the axons of cortical neurons. Locally, in axons, BDNF increases PLC-γ phosphorylation and induces intracellular Ca2+ waves in a PLC-γ-dependent manner. In parallel, we observed that BDNF-containing signaling endosomes transport to the cell body was dependent on PLC-γ activity and intracellular Ca2+ stores. Furthermore, the activity of PLC-γ is required for BDNF-dependent TrkB endocytosis, suggesting a role for the TrkB/PLC-γ signaling pathway in axonal signaling endosome formation.

18.
Curr Opin Crit Care ; 30(3): 239-245, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38525875

RESUMO

PURPOSE OF REVIEW: Herein, we conducted a review of the literature to better understand the issue of prolonged emergency department (ED) boarding by providing an overview of the current evidence on the available causes, consequences, and mitigation strategies. RECENT FINDINGS: Severely ill patients awaiting transfer to intensive care units (ICU) imposes additional burdens on the emergency care team from both a clinical and management perspective. The reasons for prolonged ED boarding are multifactorial. ED boarding compromises patients' safety and outcomes, and is associated with increased team burnout and dissatisfaction. Mitigation strategies include the optimization of patients' flow, the establishment of resuscitative care units, deployment of mobile critical care teams, and improvements in training. Staffing adjustments, changes in hospital operations, and quality improvement initiatives are required to improve this situation, while active bed management and implementation of capacity command centers may also help. SUMMARY: Considering the characteristics of healthcare systems, such as funding mechanisms, organizational structures, delivery models, access and quality of care, the challenge of ED boarding of critically ill patients requires a nuanced and adaptable approach. Solutions are complex but must involve the entirety of the hospital system, emergency department, staff adjustment, and education.


Assuntos
Serviço Hospitalar de Emergência , Transferência de Pacientes , Humanos , Serviço Hospitalar de Emergência/organização & administração , Transferência de Pacientes/organização & administração , Unidades de Terapia Intensiva/organização & administração , Aglomeração , Estado Terminal/terapia , Tempo de Internação/estatística & dados numéricos , Melhoria de Qualidade , Admissão do Paciente , Equipe de Assistência ao Paciente/organização & administração , Cuidados Críticos/organização & administração
19.
Viruses ; 16(3)2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38543768

RESUMO

LTR-retrotransposons are transposable elements characterized by the presence of long terminal repeats (LTRs) directly flanking an internal coding region. They share genome organization and replication strategies with retroviruses. Steamer-like Element-1 (MchSLE-1) is an LTR-retrotransposon identified in the genome of the Chilean blue mussel Mytilus chilensis. MchSLE-1 is transcribed; however, whether its RNA is also translated and the mechanism underlying such translation remain to be elucidated. Here, we characterize the MchSLE-1 translation mechanism. We found that the MchSLE-1 5' and 3'LTRs command transcription of sense and antisense RNAs, respectively. Using luciferase reporters commanded by the untranslated regions (UTRs) of MchSLE-1, we found that in vitro 5'UTR sense is unable to initiate translation, whereas the antisense 5'UTR initiates translation even when the eIF4E-eIF4G interaction was disrupted, suggesting the presence of an internal ribosomal entry site (IRES). The antisense 5'UTR IRES activity was tested using bicistronic reporters. The antisense 5'UTR has IRES activity only when the mRNA is transcribed in the nucleus, suggesting that nuclear RNA-binding proteins are required to modulate its activity. Indeed, heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as an IRES trans-acting factor (ITAF) of the MchSLE-1 IRES. To our knowledge, this is the first report describing an IRES in an antisense mRNA derived from a mussel LTR-retrotransposon.


Assuntos
Sítios Internos de Entrada Ribossomal , Mytilus , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sítios Internos de Entrada Ribossomal/genética , Retroelementos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Regiões 5' não Traduzidas , Mytilus/genética , Mytilus/metabolismo , Biossíntese de Proteínas
20.
Thorax ; 79(8): 788-795, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38448221

RESUMO

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.


Assuntos
Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/terapia , Progressão da Doença , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como Assunto
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