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Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.
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INTRODUCTION: Health technology assessment (HTA) is a standardized methodology that allows the assessment technologies' value. By incorporating the perspective of stakeholders in a public consultation process, transparency and quality of decisions can be improved. OBJECTIVE: To describe the active stakeholder consultation process for rapid HTAs in an Argentinean, independent, academic, non-profit HTA agency, assessing its initial five years. METHODS: Since 2017, we have been conducting an active public consultation process for rapid HTA documents, inviting producers, healthcare professionals, and patient organizations to provide comments, and their input may lead to changes in the HTA documents. Changes were classified as major (changes to the coverage recommendation), intermediate (changes in efficacy, net benefit, or cost-effectiveness that did not change coverage recommendations), and minor modifications (other changes). RESULTS: From May 2017-August 2022, 308 rapid HTA (rHTA) reports were published, and 3,438 invitations were sent. 140 rHTA (45.5%) received a total of 228 comments. Comments came from producers in 53% (n = 112) and healthcare professional organizations in 31.2% (n = 66). Technologies evaluated were drugs in 37% (n = 114), procedures in 35.5% (n = 109), diagnostic methods in 15.3% (n = 47), and devices in 12.2% (n = 38). Out of 308 rHTA documents, 120 (39%) were modified-mostly minor adjustments (n = 100; 80%), followed by major (n = 12; 10%) and intermediate modifications (n = 8; 6.4%). CONCLUSION: Implementing an active stakeholder involvement process in HTA is feasible in a low- to middle-income country context and strengthens and improves the HTA process.
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OBJECTIVE: To determine the optimal dose and short-term effectiveness of kinesiotaping (KT) on pain intensity and disability in pregnant women with lumbo-pelvic pain. DATA SOURCES: MEDLINE (via PubMed Central), CINAHL, Epistemonikos, Scopus, and Web of Science from inception to 21st March 2023. STUDY SELECTION: We included randomized controlled trials (RCT) conducted on pregnant women with lumbo-pelvic pain treated with KT. DATA EXTRACTION: The outcomes included pain intensity and disability. ROB-2 and GRADE were used to assess the risk of bias and the certainty of the evidence, respectively. A random effects meta-analysis was performed using the standardized mean difference (SMD) and the corresponding 95% confidence interval (CI). The dose-response association was evaluated using a restricted cubic spline model. DATA SYNTHESIS: Seven RCTs involving 527 patients were included. Meta-analysis revealed a statistically significant effect in favor of KT on pain intensity (SMD = -1.71; 95% CI = -2.51 to -0.90; Pâ¯=â¯<0.001) and on disability (SMD = -1.15; 95% CI = -2.29 to -0.02; Pâ¯=â¯<0.001). The total duration of KT use ranged from 5 to 35 days. It was estimated that a dose of 5-10 days exceeded the minimal clinically important difference (MCID) for pain intensity (mean difference at 10 days = -2.63; 95% CI = -3.05 to -2.22). Low certainty of evidence was identified for both outcomes. CONCLUSIONS: In pregnant women with lumbo-pelvic pain, the use of KT for 5 to 10 days produces a short-term reduction in pain intensity that exceeds the MCID, with a low certainty of evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: Systematic Review Registration Number PROSPERO CRD42023388174. CONTRIBUTION OF PAPER.
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Dolor de la Región Lumbar , Dolor Pélvico , Humanos , Femenino , Embarazo , Dolor de la Región Lumbar/rehabilitación , Dolor de la Región Lumbar/terapia , Dolor Pélvico/terapia , Dimensión del Dolor , Complicaciones del Embarazo , Técnicas de Ejercicio con Movimientos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Cinta AtléticaRESUMEN
COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: "early death" (<15 days until death) and "late death" (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+ epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory-mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.
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COVID-19 , Progresión de la Enfermedad , Pulmón , SARS-CoV-2 , Humanos , COVID-19/sangre , COVID-19/diagnóstico , Pulmón/patología , SARS-CoV-2/aislamiento & purificación , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Análisis de la Célula Individual , Adulto , Brasil , AncianoRESUMEN
This editorial presents a collective vision of unity, innovation and collaboration, and a shared desire for resilient and more equitable health systems worldwide, urging the global health community to harness the collective strength of alliances and international collaboration to guide the health sector into a new era of digital transformation and innovation.
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Tecnología Digital , Salud Digital , Telemedicina , Inteligencia Artificial , Atención Primaria de Salud , Sistemas de Salud , Cooperación InternacionalRESUMEN
BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.
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Anticuerpos Monoclonales Humanizados , Aterosclerosis , Infarto del Miocardio , Prevención Primaria , Receptores de Interleucina-1 , Prevención Secundaria , Factor de Necrosis Tumoral alfa , Humanos , Angina Inestable/prevención & control , Angina Inestable/mortalidad , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Aterosclerosis/prevención & control , Aterosclerosis/mortalidad , Sesgo , Causas de Muerte , Infarto del Miocardio/prevención & control , Infarto del Miocardio/mortalidad , Prevención Primaria/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Receptores de Interleucina-1/antagonistas & inhibidoresRESUMEN
The aims were (i) to determine the effects of Cognitive behavioral therapy for insomnia (CBT-I) on sleep disturbances, pain intensity and disability in patients with chronic musculoskeletal pain (CMP), and (ii) to determine the dose-response association between CBT-I dose (total minutes) and improvements in sleep disorders, pain intensity and disability in patients with CMP. A comprehensive search was conducted in PubMed/MEDLINE, Web of Science, CINAHL, and SCOPUS until December 17, 2023. Randomized clinical trials (RCTs) using CBT-I without co-interventions in people with CMP and sleep disorders were eligible. Two reviewers independently extracted data and assessed risk of bias and certainty of the evidence. A random effects meta-analysis was applied to determine the effects on the variables of interest. The dose-response association was assessed using a restricted cubic spline model. Eleven RCTs (n = 1801 participants) were included. We found a significant effect in favor of CBT-I for insomnia (SMD: -1.34; 95%CI: -2.12 to -0.56), with a peak effect size at 450 min of CBT-I (-1.65, 95%CI: -1.89 to -1.40). A non-significant effect was found for pain intensity. A meta-analysis of disability was not possible due to the lack of data. This review found benefits of CBT-I for insomnia compared to control interventions, with a large effect size. In addition, it was estimated that a 250-min dose of CBT-I had a large effect on reducing insomnia and that the peak effect was reached at 450 min. These novel findings may guide clinicians in optimizing the use of CBT-I in people with CMP and insomnia.
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Dolor Crónico , Terapia Cognitivo-Conductual , Dolor Musculoesquelético , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Dolor Crónico/complicaciones , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Terapia Cognitivo-Conductual/métodos , Dolor Musculoesquelético/complicaciones , Dolor Musculoesquelético/diagnóstico , Dolor Musculoesquelético/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/terapiaRESUMEN
INTRODUCTION: Acne keloidalis nuchae (AKN) is a primary cicatricial alopecia with mixed infiltrate. It is more common in Africans or persons of African descent. OBJECTIVES: Our objective was to describe the epidemiology and clinical and trichoscopic presentations of AKN in a large series of Hispanic patients. METHODS: This was a retrospective study from 10 different dermatological centers in Argentina, Colombia, Mexico, and Peru. Patients with a clinical diagnosis of AKN treated by 12 dermatologists experienced in trichology from 2018 to 2022 were included. The Umar classification system was used to determine severity. RESULTS: We identified 142 patients with AKN: 98% were male (n=140) with a mean age of 32 years; 108 patients had a previous history of trauma to the nuchal area (76%, P < 0.001); and 48 were positive for a history of acne (33.8%, P = 0.021). Patients with >50 months of evolution were mainly classified in classes III and IV compared to patients with an evolution of <50 months (30%, n=9 vs. 14%, n=15; P = 0.019; respectively). CONCLUSION: AKN should be considered in the differential diagnosis in the Hispanic population. Advanced stages of the disease are correlated with chronic evolution.
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BACKGROUND: The spread of mosquito-transmitted diseases such as dengue is a major public health issue worldwide. The Aedes aegypti mosquito, a primary vector for dengue, thrives in urban environments and breeds mainly in artificial or natural water containers. While the relationship between urban landscapes and potential breeding sites remains poorly understood, such a knowledge could help mitigate the risks associated with these diseases. This study aimed to analyze the relationships between urban landscape characteristics and potential breeding site abundance and type in cities of French Guiana (South America), and to evaluate the potential of such variables to be used in predictive models. METHODS: We use Multifactorial Analysis to explore the relationship between urban landscape characteristics derived from very high resolution satellite imagery, and potential breeding sites recorded from in-situ surveys. We then applied Random Forest models with different sets of urban variables to predict the number of potential breeding sites where entomological data are not available. RESULTS: Landscape analyses applied to satellite images showed that urban types can be clearly identified using texture indices. The Multiple Factor Analysis helped identify variables related to the distribution of potential breeding sites, such as buildings class area, landscape shape index, building number, and the first component of texture indices. Models predicting the number of potential breeding sites using the entire dataset provided an R² of 0.90, possibly influenced by overfitting, but allowing the prediction over all the study sites. Predictions of potential breeding sites varied highly depending on their type, with better results on breeding sites types commonly found in urban landscapes, such as containers of less than 200 L, large volumes and barrels. The study also outlined the limitation offered by the entomological data, whose sampling was not specifically designed for this study. Model outputs could be used as input to a mosquito dynamics model when no accurate field data are available. CONCLUSION: This study offers a first use of routinely collected data on potential breeding sites in a research study. It highlights the potential benefits of including satellite-based characterizations of the urban environment to improve vector control strategies.
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Aedes , Ciudades , Imágenes Satelitales , Animales , Imágenes Satelitales/métodos , Mosquitos Vectores , Guyana Francesa/epidemiología , Dengue/epidemiología , Dengue/transmisión , Dengue/prevención & control , Humanos , Cruzamiento/métodosRESUMEN
Histidine kinases (HKs) are a central part of bacterial environmental-sensing two-component systems. They provide their hosts with the ability to respond to a wide range of physical and chemical signals. HKs are multidomain proteins consisting of at least a sensor domain, dimerization and phosphorylation domain (DHp), and a catalytic domain. They work as homodimers and the existence of two different autophosphorylation mechanisms (cis and trans) has been proposed as relevant for pathway specificity. Although several HKs have been intensively studied, a precise sequence-to-structure explanation of why and how either cis or trans phosphorylation occurs is still unavailable nor is there any evolutionary analysis on the subject. In this work, we show that AlphaFold can accurately determine whether an HK dimerizes in a cis or trans structure. By modeling multiple HKs we show that both cis- and trans-acting HKs are common in nature and the switch between mechanisms has happened multiple times in the evolutionary history of the family. We then use AlphaFold modeling to explore the molecular determinants of the phosphorylation mechanism. We conclude that it is the difference in lengths of the helices surrounding the DHp loop that determines the mechanism. We also show that very small changes in these helices can cause a mechanism switch. Despite this, previous evidence shows that for a particular HK the phosphorylation mechanism is conserved. This suggests that the phosphorylation mechanism participates in system specificity and mechanism switching provides these systems with a way to diverge.
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Evolución Molecular , Histidina Quinasa , Modelos Moleculares , Fosforilación , Histidina Quinasa/metabolismo , Histidina Quinasa/química , Histidina Quinasa/genética , Proteínas Quinasas/química , Proteínas Quinasas/metabolismo , Multimerización de Proteína , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genéticaRESUMEN
BACKGROUND: Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). METHODS: The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. RESULTS: Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. CONCLUSIONS: The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.
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Hipopituitarismo , Ratones Noqueados , Hipófisis , Hipopituitarismo/genética , Animales , Humanos , Hipófisis/metabolismo , Hipófisis/anomalías , Hipófisis/patología , Ratones , Fenotipo , Femenino , Masculino , Modelos Animales de Enfermedad , Secuenciación del Exoma , Displasia Septo-Óptica/genéticaRESUMEN
Background: Several studies focused on the escalating prevalence of Problematic Use of Internet (PUI) and its consequential impact on mental health globally. This study investigates the relationship between PUI and associated psychological variables across different cultural contexts in Italy, Spain, Ecuador, and Peru. Method: A total of 675 participants, aged 18 to 54 (M = 22.73; SD = 4.05), completed measures assessing Internet addiction, social media addiction, Fear of Missing Out, Internet Gaming Disorder, and Phubbing. Results: Significant cultural variations were found, with Italian participants showing higher levels of Internet addiction but lower levels of social media addiction compared to other countries. Fear of Missing Out was higher in Italy, while the Italian sample exhibited lower Internet Gaming Disorder levels compared to Peru. As regards the communication disturbance caused by Phubbing, the Italian sample demonstrated significantly higher scores than the Peruvian sample. Linear regression analyses revealed distinct predictors for problematic Internet use in each country, emphasizing the importance of considering the cultural context in understanding this phenomenon. Conclusions: These findings contribute valuable insights into the interplay of cultural factors, psychological variables, and problematic Internet use, guiding future research and interventions.
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Resumen Introducción. En Argentina la información sobre la disponibilidad de los recursos en hemostasia y trombosis es muy escasa. El grupo Promoción del Acceso a los Recursos del grupo CAHT (Cooperativo Argentino de Hemostasia y Trombosis) desarrolló un amplio relevamiento de los recursos en Argentina para conocer el estado de situación de la especialidad. Objetivos. Describir la disponibilidad de los recursos humanos y físicos (diagnósticos y terapéuticos) en hemostasia y trombosis en los centros asistenciales de Argentina en 2022 e identificar diferencias regionales y/o entre los sectores privado y público. Materiales y métodos. Estudio de cohorte transversal. Se incluyeron centros asistenciales de la República Argentina: instituciones con internación, centros ambulatorios y laboratorios. Se obtuvieron datos respecto a la disponibilidad de recursos humanos, diagnósticos, y terapéuticos en hemostasia y trombosis, en algún momento del año 2022, mediante una encuesta a profesionales de la salud. En los recursos analíticos se definió disponibilidad cuando la prueba se realizaba en la institución o se derivaba la muestra/paciente. Resultados. En el estudio se incluyeron 215 centros de 77 ciudades argentinas. El 85,5% de los centros contaban con internación. La mediana de especialistas en hematología por institución fue de 3 (RIC 1-5). Se encontraron diferencias entre las medianas de las regiones: CABA-Ciudad Autónoma de Buenos Aires-(5), Centro/Cuyo (3,5) GBA/LP-Gran Buenos Aires/La Plata-(2), NOA-Noroeste Argentino-(2), NEA-Nordeste Argentino-(1) y SUR (1). El 27% de los centros contaban con 1 ("trabajo solitario") o ningún especialista en hematología. El 59% de los centros reportaron que contaban con bioquímicos especialistas en hemostasia/hematología. La región con menor porcentaje de centros con especialistas fue GBA/LP (37%). Se observó una alta disponibilidad de pruebas básicas de la coagulación. Por el contrario, en las estudios de mayor complejidad la disponibilidad fue subóptima y se detectaron marcadas asimetrías regionales (GBA/LP, NOA y NEA presentaron la menor proporción de centros con los recursos). Algunas pruebas, como la agregación plaquetaria o el anti-factor plaquetario 4 / heparina (anti-PF4/hep), no estuvieron disponibles en amplias áreas del país. En la mayoría de los recursos terapéuticos se detectó una mayor disponibilidad en el sector privado. Conclusiones. Detectamos una disponibilidad sub-óptima de los recursos físicos de alta complejidad y disparidades público-privada y regionales. Consideramos que el establecimiento de redes integradas es una estrategia que permitirá reducir las inequidades de acceso. Desde su lugar, las sociedades científicas podrían realizar valiosos aportes para obtener esa meta.
Abstract Introduction. In Argentina, information regarding the availability of resources in hemostasis and thrombosis is very scarce. The "Grupo Promoción del Acceso" del grupo CAHT (Cooperativo Argentino de Hemostasia y trombosis) conducted an extensive survey of resources in Argentina to understand the current state of the specialty. Objectives. To describe the availability of human and physical resources (diagnostic and therapeutic) in hemostasis and thrombosis in healthcare centers across Argentina in 2022 and to identify regional differences or disparities between the private and public sectors. Materials and methods. Cross-sectional cohort study. Healthcare centers from the Argentine Republic were included: institutions with inpatient services, outpatient centers, and laboratories. Data regarding the availability of human, diagnostic, and therapeutic resources in hemostasis and thrombosis were obtained at some point during the year 2022 through surveys conducted among healthcare professionals. Availability in analytical resources was defined when the test was performed within the institution or when the sample/patient was referred elsewhere for testing. Results. The study included 215 centers from 77 cities across Argentina. 85.5% of the centers had inpatient services. The median number of hematologists per institution was 3 (IQR 1-5). Differences were found among the median numbers across regions: CABA-Ciudad Autónoma de Buenos Aires-(5), Centro/Cuyo (3.5), GBA/LP-Gran Buenos Aires/La Plata-(2), NOA-Noroeste Argentino-(2), NEA-Nordeste Argentino-(1), and SUR (1). 27% of the centers had 1 or no hematologist. 59% of the centers reported employing specialized biochemists in hemostasis/ hematology. The region with the lowest percentage of centers with specialists was GBA/LP (37%). There was a high availability of basic coagulation tests observed. Conversely, for more complex tests, availability was suboptimal and marked regional asymmetries were detected (GBA/LP, NOA, and NEA presented the lowest proportion of centers with resources). Some tests, such as platelet aggregation or anti-platelet factor 4/heparin, were not available in wide areas of the country. In most therapeutic resources, greater availability was detected in the private sector. Conclusions. We identified suboptimal availability of high-complexity physical resources and public-private and regional disparities. We believe that the establishment of integrated networks is a strategy that will help reduce access inequities. Scientific societies, from their position, can make valuable contributions to achieve this goal.
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Supernumerary chromosomes (B chromosomes) have been an intriguing subject of study. Our understanding of the molecular differentiation of B chromosomes from an interpopulation perspective remains limited, with most analyses involving chromosome banding and mapping of a few sequences. To gain insights into the molecular composition, origin, and evolution of B chromosomes, we conducted cytogenetic and next-generation sequencing analysis of the repeatome in the grasshopper Abracris flavolineata across various populations. Our results unveiled the presence of B chromosomes in two newly investigated populations and described new satellite DNA sequences. While we observed some degree of genetic connection among A. flavolineata populations, our comparative analysis of genomes with and without B chromosomes provided evidence of two new B chromosome variants. These variants exhibited distinct compositions of various repeat classes, including transposable elements and satellite DNAs. Based on shared repeats, their chromosomal location, and the C-positive heterochromatin content on the B chromosome, these variants likely share a common origin but have undergone distinct molecular differentiation processes, resulting in varying degrees of heterochromatinization. Our data serve as a detailed example of the dynamic and differentiated nature of B chromosome molecular content at the interpopulation level, even when they share a common origin.
Asunto(s)
Cromosomas de Insectos , Saltamontes , Animales , Saltamontes/genética , Cromosomas de Insectos/genética , Heterocromatina/genética , Evolución Molecular , ADN Satélite/genética , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Elementos Transponibles de ADNRESUMEN
We report herein an enantioselective palladium-catalyzed Heck-Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride.
RESUMEN
The basin entropy is a measure that quantifies, in a system that has two or more attractors, the predictability of a final state, as a function of the initial conditions. While the basin entropy has been demonstrated on a variety of multistable dynamical systems, to the best of our knowledge, it has not yet been tested in systems with a time delay, whose phase space is infinite dimensional because the initial conditions are functions defined in a time interval [-τ,0], where τ is the delay time. Here, we consider a simple time-delayed system consisting of a bistable system with a linear delayed feedback term. We show that the basin entropy captures relevant properties of the basins of attraction of the two coexisting attractors. Moreover, we show that the basin entropy can give an indication of the proximity of a Hopf bifurcation, but fails to capture the proximity of a pitchfork bifurcation. The Hopf bifurcation is detected because before the fixed points become unstable, a oscillatory, limit-cycle behavior appears that coexists with the fixed points. The new limit cycle modifies the structure of the basins of attraction, and this change is captured by basin entropy that reaches a maximum before the Hopf bifurcation. In contrast, the pitchfork bifurcation is not detected because the basins of attraction do not change as the bifurcation is approached. Our results suggest that the basin entropy can yield useful insights into the long-term predictability of time-delayed systems, which often have coexisting attractors.
RESUMEN
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi (Chagas, 1909). One of the primary vectors of T. cruzi in South America is Triatoma infestans (Klug, 1834). This triatomine species is distributed across a huge latitudinal gradient, inhabiting domiciliary , peridomiciliary , and wild environments. Its wide geographic distribution provides an excellent opportunity to study the relationships between environmental gradients and intraspecific morphological variation. In this study, we investigated variations in wing size and shape in T. infestans across six ecoregions. We aimed to address the following questions: How do wing size and shape vary on a regional scale, does morphological variation follow specific patterns along an environmental or latitudinal gradient, and what environmental factors might contribute to wing variation? Geometric morphometric methods were applied to the wings of 162 females belonging to 21 T. infestans populations, 13 from Argentina (n = 105), 5 from Bolivia (n = 42), and 3 from Paraguay (n = 15). A comparison of wing centroid size across the 21 populations showed significant differences. Canonical Variate Analysis (CVA) revealed significant differences in wing shape between the populations from Argentina, Bolivia, and Paraguay, although there was a considerable overlap, especially among the Argentinian populations. Well-structured populations were observed for the Bolivian and Paraguayan groups. Two analyses were performed to assess the association between wing size and shape, geographic and climatic variables: multiple linear regression analysis (MRA) for size and Partial Least Squares (PLS) regression for shape. The MRA showed a significant general model fit. Six temperature-related variables, one precipitation-related variable, and the latitude showed significant associations with wing size. The PLS analysis revealed a significant correlation between wing shape with latitude, longitude, temperature-related, and rainfall-related variables. Wing size and shape in T. infestans populations varied across geographic distribution. Our findings demonstrate that geographic and climatic variables significantly influence T. infestans wing morphology.
Asunto(s)
Triatoma , Alas de Animales , Animales , Triatoma/anatomía & histología , Triatoma/fisiología , Triatoma/crecimiento & desarrollo , Triatoma/clasificación , Alas de Animales/anatomía & histología , Femenino , Argentina , Bolivia , Paraguay , Enfermedad de Chagas/transmisiónRESUMEN
CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.
RESUMEN
Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes (Ad). This study aimed to investigate the impact of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from rats on a high-fat sucrose (HFS) diet displayed reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than the control (C) group. Mitochondrial analysis revealed heightened activity in undifferentiated ASC-HFS but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 profile in ASCs on genes related to adipogenesis, mitochondrial function, inflammation, and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations, confirming the upregulation of genes associated with inflammatory and immunomodulatory pathways. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. Overall, the HFS diet induced significant epigenetic and transcriptomic changes in ASCs, impairing differentiation and causing dysfunctional adipocyte formation.NEW & NOTEWORTHY Obesity is associated with the development of chronic diseases like metabolic syndrome and type 2 diabetes, and adipose tissue plays a crucial role. In a rat model, our study reveals how an obesogenic environment primes adipocyte precursor cells, leading to epigenetic changes that affect inflammation, adipogenesis, and mitochondrial activity after differentiation. We highlight the importance of histone modifications, especially the trimethylation of histone H3 to lysine 4 (H3K4me3), showing its influence on adipocyte expression profiles.