RESUMEN

This study aimed to investigate the impact of dietary inclusion of babassu oil (BO) associated with sunflower oil (SO) on feeding behavior, water intake, and physiological parameters of feedlot lambs. Thirty-five castrated male lambs (16.6 kg ± 3.9 kg) were distributed in a randomized block design with 5 treatments (diets) and 7 replications. The tested diets were oil-free diet (OF), 45 g/kg BO (BO), 30 g/kg BO with an additional 15 g/kg SO (1.5 SO), 22.5 g/kg BO with an additional 22.5 g/kg SO (2.25 SO), and 30 g/kg SO with an additional 15 g/kg BO (3.0 SO) on dry matter (DM) basis. The experimental period lasted 60 days. Animals that received BO diet and the combination of BO with SO had lower intakes of DM and neutral detergent fiber (NDF) compared to the control diet (P < 0.05). Differences on the respiratory rate (RR) was observed between animals in the control diet and those in the diets containing SO (P=0.001), with a linear increase in RR as the levels of SO in the diets increased (P=0.004). All physiological parameters showed a time effect (P < 0.05). Animals fed with the control diet had higher water intake via drinking fountain (P=0.030) and total water intake (P=0.029) compared to animals fed with diets containing SO. In relation to SO levels, water intake via drinking fountain (P=0.002), total water intake (P=0.002), and total water intake per kg of DM ingested (P=0.001) linearly increased with the levels increase in the composition of the diets. The tested diets did not alter the feeding behavior of the feedlot lambs. However, the combination of BO with different levels of SO reduced DM and water intake via drinking fountain and RR.

RESUMEN

The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.

Asunto(s)

COVID-19 , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/genética , COVID-19/inmunología , COVID-19/virología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Anciano , Adulto , Receptor Toll-Like 7/genética , TYK2 Quinasa/genética , Genotipo , Predisposición Genética a la Enfermedad , 2',5'-Oligoadenilato Sintetasa/genética

RESUMEN

Enhanced oil recovery (EOR) techniques are crucial for maximizing the extraction of residual oil from mature reservoirs. This review explores the latest advancements in surfactant carriers for EOR, focusing on their mechanisms, challenges, and opportunities. We delve into the role of inorganic nanoparticles, carbon materials, polymers and polymeric surfactants, and supramolecular systems, highlighting their interactions with reservoir rocks and their potential to improve oil recovery rates. The discussion includes the formulation and behavior of nanofluids, the impact of surfactant adsorption on different rock types, and innovative approaches using environmentally friendly materials. Notably, the use of metal oxide nanoparticles, carbon nanotubes, graphene derivatives, and polymeric surfacants and the development of supramolecular complexes for managing surfacant delivery are examined. We address the need for further research to optimize these technologies and overcome current limitations, emphasizing the importance of sustainable and economically viable EOR methods. This review aims to provide a comprehensive understanding of the emerging trends and future directions in surfactant carriers for EOR.

RESUMEN

In 2021, the Clinical Pharmacology Department of Hospital Universitario de La Princesa launched the PriME-PGx initiative (Multidisciplinary Initiative of the Hospital Universitario de La Princesa for the Implementation of Pharmacogenetics) to promote the expansion of pharmacogenetics in hospitalized patients. We establish seven pharmacogenetic profiles based on the specific needs of seven departments: Oncology, Pain Unit, Neuropsychiatry, Internal or Infectious Medicine, Cardiology, Gastroenterology and Immunosuppressants. The experience of the last 3 years reflects a total of 1421 reports (37.4% being oncology profiles), with a gradual increase in the number of requests each year. With this project, we aim to expand the availability and utility of pharmacogenetic biomarkers to achieve personalised therapy that avoids adverse drug reactions and therapeutic failure.

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[Box: see text].

RESUMEN

BACKGROUND: Major depressive disorder (MDD) represents a sizable economic burden in Spain. Pharmacogenetic (PGx) screening to guide the choice of antidepressant medication (ADM) in MDD patients yields higher response and remission rates, which could reduce both healthcare and indirect costs. METHODS: We built a cost-effectiveness probabilistic Markov model with microsimulation using Tree Age Pro 2022, simulating a patient cohort from the SNHS starting ADM for MDD, and comparing PGx screening before starting ADM versus no screening (No PGx). We carried out a probabilistic sensitivity analysis using the Monte Carlo simulation with microsimulation, set for 1000 iterations and 1000 microsimulation trials, both from societal and healthcare provider perspectives, for a time horizon of 3 years. RESULTS: From a societal perspective, the model estimated a mean cost of 3172.85€ and effectiveness of 2.64 quality-adjusted life years (QALYs) for the No PGx strategy, and a mean cost of 1687.02€ and effectiveness of 2.84 QALYs for the PGx strategy. The mean ICER was -7820.56 €/QALY. From a healthcare provider perspective (no indirect costs considered), the mean cost was 662.62€ for the No PGx strategy, and 446.60€ for the PGx strategy. The mean ICER was -1130.16 €/QALY. LIMITATIONS: The heterogeneity of input data from the literature, the need for assumptions of homogeneous distribution of variables and events across population and time, and the inherent limitations of cost-effectiveness analysis should be considered. The model omits combined therapies (ADMs with mood stabilizers, antipsychotics, cognitive behavioral therapy…). CONCLUSIONS: PGx screening in MDD prior to ADM start is a dominant strategy in the SNHS.

Asunto(s)

Antidepresivos , Análisis Costo-Beneficio , Trastorno Depresivo Mayor , Cadenas de Markov , Pruebas de Farmacogenómica , Años de Vida Ajustados por Calidad de Vida , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/economía , Trastorno Depresivo Mayor/genética , España , Antidepresivos/uso terapéutico , Antidepresivos/economía , Pruebas de Farmacogenómica/economía , Costos de la Atención en Salud/estadística & datos numéricos , Femenino , Masculino , Adulto

RESUMEN

Due to the increasing prevalence of articular cartilage diseases and limitations faced by current therapeutic methodologies, there is an unmet need for new materials to replace damaged cartilage. In this work, poly(vinyl alcohol) (PVA) hydrogels were reinforced with different amounts of Nomex® (known for its high mechanical toughness, flexibility, and resilience) and sterilized by gamma irradiation. Samples were studied concerning morphology, chemical structure, thermal behavior, water content, wettability, mechanical properties, and rheological and tribological behavior. Overall, it was found that the incorporation of aramid nanostructures improved the hydrogel's mechanical performance, likely due to the reinforcement's intrinsic strength and hydrogen bonding to PVA chains. Additionally, the sterilization of the materials also led to superior mechanical properties, possibly related to the increased crosslinking density through the hydrogen bonding caused by the irradiation. The water content, wettability, and tribological performance of PVA hydrogels were not compromised by either the reinforcement or the sterilization process. The best-performing composite, containing 1.5% wt. of Nomex®, did not induce cytotoxicity in human chondrocytes. Plugs of this hydrogel were inserted in porcine femoral heads and tested in an anatomical hip simulator. No significant changes were observed in the hydrogel or cartilage, demonstrating the material's potential to be used in cartilage replacement.

RESUMEN

Groundwater is the main source of water for more than 2 billion people worldwide. In southern Brazil, the Crystalline Basement Aquifer System is composed of strategic groundwater reservoirs. Groundwater is mostly taken from shallow wells, and it is often used without any treatment, which poses a risk to public health. The present study aims to evaluate shallow groundwater quality and the geochemistry of shallow and deep groundwater located in the municipality of Canguçu, southern Brazil. The physicochemical and microbiological parameters of groundwater samples collected from shallow wells were monitored and analyzed using ANOVA variance analysis and water quality index (CCME WQI) approaches. Also, the results were compared with secondary data from deep wells. The monitored shallow wells had thermotolerant coliforms, Escherichia coli, pH, potassium, manganese, iron, and nitrate in disagreement with the guidelines of the World Health Organization. Moreover, variance analysis showed that the parameters temperature, dissolved oxygen, pH, chloride, and magnesium were the most influenced by seasonal variations. According to the CCME WQI, most samples had good quality (60%), 28% had fair quality, and 12% had poor quality. In addition, the field campaigns with higher precipitation rates also presented fair quality. Therefore, most of the shallow groundwater quality is affected by surface pollutants from the urban area, aggravated in rainy periods. Whereas deep groundwater is influenced by geochemistry mechanisms. The results revealed the risk of water consumption for public health and the urgent need for better maintenance of these wells and water treatment implementation.

Asunto(s)

Monitoreo del Ambiente , Agua Subterránea , Calidad del Agua , Agua Subterránea/química , Brasil , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Concentración de Iones de Hidrógeno , Microbiología del Agua , Estaciones del Año , Pozos de Agua , Nitratos/análisis

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Mirabegron is a drug used in overactive bladder (OAB) treatment. Genetic variation in pharmacogenes might alter its pharmacokinetics, affecting its efficacy and safety. This research aimed to analyze the impact of genetic variation on mirabegron pharmacokinetics and safety. Volunteers from three bioequivalence trials (n = 79), treated with a single or a multiple dose of mirabegron 50 mg under fed or fasting conditions, were genotyped for 115 variants in pharmacogenes and their phenotypes were inferred. A statistical analysis was performed, searching for associations between genetics, pharmacokinetics and safety. CYP2D6 intermediate metabolizers showed a higher elimination half-life (t1/2) (univariate p-value (puv) = 0.018) and incidence of adverse reactions (ADRs) (puv = 0.008, multivariate p (pmv) = 0.010) than normal plus ultrarapid metabolizers. The UGT1A4 rs2011425 T/G genotype showed a higher t1/2 than the T/T genotype (puv = 0.002, pmv = 0.003). A lower dose/weight corrected area under the curve (AUC/DW) and higher clearance (CL/F) were observed in the SLC6A2 rs12708954 C/C genotype compared to the C/A genotype (puv = 0.015 and 0.016) and ADR incidence was higher when the SLCO1B1 function was decreased (puv = 0.007, pmv = 0.010). The lower elimination and higher ADR incidence when CYP2D6 activity is reduced suggest it might be a useful biomarker in mirabegron treatment. UGT1A4, SLC6A2 and SLCO1B1 might also be involved in mirabegron pharmacokinetics.

RESUMEN

Ramipril is an angiotensin-converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty-nine healthy volunteers who had participated in a single-dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype-informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7-fold higher dose/weight-corrected area under the curve (AUC/DW) than volunteers with the normal function (NF) phenotype (univariate p-value [puv] < 0.001, multivariate p-value [pmv] < 0.001, ß = 0.533, R2 = 0.648). Similarly, volunteers with ABCG2 DF + poor function (PF) phenotypes presented around 1.6-fold higher AUC/DW than those with the NF phenotype (puv = 0.011, pmv < 0.001, ß = 0.259, R2 = 0.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance.

Asunto(s)

Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Inhibidores de la Enzima Convertidora de Angiotensina , Genotipo , Transportador 1 de Anión Orgánico Específico del Hígado , Proteínas de Neoplasias , Fenotipo , Ramipril , Humanos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Ramipril/farmacocinética , Ramipril/administración & dosificación , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Masculino , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Adulto Joven , Femenino , Voluntarios Sanos , Área Bajo la Curva , Variantes Farmacogenómicas , Farmacogenética

RESUMEN

Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. KEY POINTS: • Several T- and B-cell epitopes were identified in all the three proteins. • Four different adjuvants were used in vaccine formulations. • Immunization stimulated significant levels of IgG2/3 in vaccinated animals.

Asunto(s)

Anticuerpos Antibacterianos , Vacunas Bacterianas , Leptospirosis , Lipoproteínas , Animales , Leptospirosis/prevención & control , Leptospirosis/inmunología , Lipoproteínas/inmunología , Lipoproteínas/genética , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/genética , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Cricetinae , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/genética , Adyuvantes Inmunológicos/administración & dosificación , Inmunoglobulina G/sangre , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Leptospira interrogans/inmunología , Leptospira interrogans/genética , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Vacunación , Inmunidad Humoral , Leptospira/inmunología , Leptospira/genética , Inmunogenicidad Vacunal

RESUMEN

The Yanomami population, residing in Brazil's largest indigenous reserve in the Amazon Rainforest, face significant health challenges exacerbated by external threats such as infectious diseases, malnutrition, and mercury contamination from illegal mining. These issues, coupled with inadequate healthcare provision, have led to an alarming increase in mortality rates and potentially threaten the long-term survival of the Yanomami community. This ecological study utilized demographic data from the Special Secretariat of Indigenous Health to explore the demographic evolution and natural increase of the Yanomami Indigenous population in Brazil from 2003 to 2022. Employing population pyramids, crude rates of natural increase, the Mann-Kendall test for trend analysis, and linear regression modeling, the study analyzed vital statistics to forecast demographic trends, with analysis conducted using the R statistical software. Our findings showed a substantial growth of the Yanomami population, yet with a decreasing natural increase rate (τ = -0.33; p = 0.047), suggesting a shift toward population stagnation or decline within the next century. These results call for urgent, coordinated actions to address the complex demographic trends and health challenges faced by Yanomami Indigenous people, ensuring their demographic sustainability and the preservation of their traditional ways of life amidst ongoing environmental and health crises.

Asunto(s)

Indígenas Sudamericanos , Humanos , Brasil/epidemiología , Masculino , Femenino , Indígenas Sudamericanos/estadística & datos numéricos , Adulto , Adolescente , Persona de Mediana Edad , Pueblos Indígenas/estadística & datos numéricos , Lactante , Preescolar , Niño , Demografía/métodos , Demografía/estadística & datos numéricos , Adulto Joven , Anciano , Crecimiento Demográfico , Recién Nacido

RESUMEN

OBJECTIVE: To describe the clinical and radiographic performance and survival rate of a new two-piece ceramic implant system after at least 12 months of follow-up. MATERIALS AND METHODS: Sixty-five implants were placed and followed up for at least 12 months (12.3 ± 1.5), in 50 patients. The implants were installed both in fresh extraction sockets and in healed sites and received provisional restoration when the clinical insertion torque was greater than 35Ncm. The primary results describe the survival rate of these implants. Clinical performance was evaluated through the evaluation of the Pink Esthetic Score (PES) and the degree of satisfaction of the patients. Bone loss was measured through radiographic measurements of the marginal bone loss in the mesial (MBLM) and distal (MBLD) sites. RESULTS: The survival rate was 98.5%. The average MBLM was 0.24 mm (± 0.53) and the MBLD was 0.27 mm (± 0.57). A statistical difference was observed only when comparing immediate implants with delayed ones (MBLM - p = 0.046 and MBLD - p = 0.028) and when they received immediate provisionalization or not (MBLM - p = 0.009 and MBLD - p = 0.040). The PES before the intervention (T0) was 13.4 (± 0.8) and the PES at T2 (12-month follow-up) was 12.9 (± 1.5) (p = 1.14). CONCLUSION: The new two-piece ceramic implant used in the present study showed predictable and reliable results, similar to those found with titanium implants after one year of follow-up. CLINICAL RELEVANCE: These implants can be used as an alternative to titanium implants in terms of the marginal bone loss and the degree of patient satisfaction.

Asunto(s)

Cerámica , Diseño de Prótesis Dental , Humanos , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Cerámica/química , Resultado del Tratamiento , Adulto , Satisfacción del Paciente , Anciano , Estética Dental , Pérdida de Hueso Alveolar/diagnóstico por imagen , Alveolo Dental/cirugía , Alveolo Dental/diagnóstico por imagen , Fracaso de la Restauración Dental , Implantes Dentales

RESUMEN

Introduction: Bioequivalence clinical trials are conducted in healthy volunteers whose blood tests should be within normal limits; individuals with Gilbert syndrome (GS) are excluded from these studies on suspicion of any liver disease, even if the change is clinically insignificant. GS is a benign genetic disorder characterized by elevated bilirubin levels, the primary cause of which is the presence of polymorphisms in UGT1A1 gene. In this work, subjects with UGT1A1 intermediate (IM) or poor (PM) metabolizer genotype-informed phenotypes were investigated to determine whether they have a higher incidence of liver disease or other biochemical parameters. Methods: The study population comprised 773 healthy volunteers who underwent biochemical analysis at baseline and at the end of the study which were genotyped for UGT1A1*80 (rs887829), as an indicator of UGT1A1*80+*28 (rs887829 and rs3064744), and UGT1A1*6 (rs4148323). Results: Bilirubin levels were higher in subjects IMs and PMs compared to normal metabolizers (NMs). Decreased uric acid levels was observed in PMs compared to NMs. No associations were observed in liver enzyme levels according to UGT1A1 phenotype. Discussion: Considering that there is no hepatic toxicity in subjects with UGT1A1 IM or PM phenotype, who are more likely to develop GS, this study suggests that they could be included in bioequivalence clinical trials as their biochemical parameters are not affected outside normal ranges.

RESUMEN

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

RESUMEN

Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17ß-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.

Asunto(s)

Tejido Adiposo Pardo , Estrógenos , Hipotálamo , Hígado , Ratones Noqueados , Olanzapina , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteína Desacopladora 1 , Animales , Femenino , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Ratones , Hígado/metabolismo , Hígado/efectos de los fármacos , Estrógenos/metabolismo , Estrógenos/farmacología , Olanzapina/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/genética , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Masculino , Metabolismo Energético/efectos de los fármacos , Inyecciones Intraperitoneales , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Ratones Endogámicos C57BL , Estradiol/farmacología , Ovariectomía

RESUMEN

SARS-CoV-2 virus emerged as a new threat to humans and spread around the world, leaving a large death toll. As of January 2023, Brazil is among the countries with the highest number of registered deaths. Nonpharmacological and pharmacological interventions have been heterogeneously implemented in the country, which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics. Here, we investigate the spatiotemporal dispersion of SARS-CoV-2 lineages in the Pernambuco state (Northeast Brazil) throughout the distinct epidemiological scenarios that unfolded in the first 2 years of the pandemic. We generated a total of 1,389 new SARS-CoV-2 genomes from June 2020 to August 2021. This sampling captured the arrival, communitary transmission, and the circulation of the B1.1, B.1.1.28, and B.1.1.33 lineages; the emergence of the former variant of interest P.2; and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma). Based on the incidence and lineage spread pattern, we observed an East-to-West to inner state pattern of transmission, which is in agreement with the transmission of more populous metropolitan areas to medium- and small-size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Our results highlight that the fine-grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future nonpharmacological intervention for air-borne transmissible human pathogens.IMPORTANCEDuring the COVID-19 pandemic, Brazil was one of the most affected countries, mainly due its continental-size, socioeconomic differences among regions, and heterogeneous implementation of intervention methods. In order to investigate SARS-CoV-2 dynamics in the state of Pernambuco, we conducted a spatiotemporal dispersion study, covering the period from June 2020 to August 2021, to comprehend the dynamics of viral transmission during the first 2 years of the pandemic. Throughout this study, we were able to track three significant epidemiological waves of transmission caused by B1.1, B.1.1.28, B.1.1.33, P.2, and P.1 lineages. These analyses provided valuable insights into the evolution of the epidemiological landscape, contributing to a deeper understanding of the dynamics of virus transmission during the early years of the pandemic in the state of Pernambuco.

Asunto(s)

COVID-19 , SARS-CoV-2 , COVID-19/transmisión , COVID-19/epidemiología , COVID-19/virología , Humanos , Brasil/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/clasificación , Análisis Espacio-Temporal , Genoma Viral , Filogenia , Pandemias

RESUMEN

OBJECTIVE: This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. METHODS: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. RESULTS: Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (-1.02 days; 95% CI = -2.00 to -0.03) and increased exercise capacity (6-minute walk distance) (+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6-minute walk distance (45.84 m; 95% CI = 10.89 to 80.80), MIP (-23.19 cm H2O; 95% CI = -31.31 to -15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (-11.17; 95% CI = -17.98 to -4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. CONCLUSION: IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. IMPACT: IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits.

Asunto(s)

Ejercicios Respiratorios , Rehabilitación Cardiaca , Puente de Arteria Coronaria , Tiempo de Internación , Fuerza Muscular , Calidad de Vida , Músculos Respiratorios , Humanos , Puente de Arteria Coronaria/rehabilitación , Ejercicios Respiratorios/métodos , Rehabilitación Cardiaca/métodos , Músculos Respiratorios/fisiopatología , Músculos Respiratorios/fisiología , Tiempo de Internación/estadística & datos numéricos , Fuerza Muscular/fisiología , Tolerancia al Ejercicio/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Asunto(s)

Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/genética , Inhibidores de la Bomba de Protones/uso terapéutico , Factor de Transcripción STAT6/genética , Comorbilidad

RESUMEN

Since financial assets on stock exchanges were created, investors have sought to predict their future values. Currently, cryptocurrencies are also seen as assets. Machine learning is increasingly adopted to assist and automate investments. The main objective of this paper is to make daily predictions about the movement direction of financial time series through classification models, financial time series preprocessing methods, and feature selection with genetic algorithms. The target time series are Bitcoin, Ibovespa, and Vale. The methodology of this paper includes the following steps: collecting time series of financial assets; data preprocessing; feature selection with genetic algorithms; and the training and testing of machine learning models. The results were obtained by evaluating the models with the area under the ROC curve metric. For the best prediction models for Bitcoin, Ibovespa, and Vale, values of 0.61, 0.62, and 0.58 were obtained, respectively. In conclusion, the feature selection allowed the improvement of performance in most models, and the input series in the form of percentage variation obtained a good performance, although it was composed of fewer attributes in relation to the other sets tested.

RESUMEN

Polarization is common in politics and public opinion. It is believed to be shaped by media as well as ideologies, and often incited by misinformation. However, little is known about the microscopic dynamics behind polarization and the resulting social tensions. By coupling opinion formation with the strategy selection in different social dilemmas, we reveal how success at an individual level transforms to global consensus or lack thereof. When defection carries with it the fear of punishment in the absence of greed, as in the stag-hunt game, opinion fragmentation is the smallest. Conversely, if defection promises a higher payoff and also evokes greed, like in the prisoner's dilemma and snowdrift game, consensus is more difficult to attain. Our research thus challenges the top-down narrative of social tensions, showing they might originate from fundamental principles at individual level, like the desire to prevail in pairwise evolutionary comparisons.