IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.

BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. RESULTS: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. CONCLUSIONS: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.

Mentha spp. essential oils: toxicity to Alphitobius diaperinus, activity against poultry pathogenic bacteria, and Beauveria bassiana compatibility.

The botanical insecticide market is growing because of limitations placed on the use of certain synthetic chemical insecticides. In this sense, the lesser mealworm Alphitobius diaperius (Coleoptera: Tenebrionidae) is the main poultry pest. The insect causes weight loss and damage to the digestive system of poultry, and it is a vector and reservoir of pathogens. Consequently, this study explored the following hypotheses: (i) essential oils (EOs) derived from Mentha spp. are toxic to A. diaperius; (ii) these EOs are compatible with Beauveria bassiana, the natural enemy of the poultry pest, that parasite A. diaperinus; (iii) these EOs also exhibit activity against bacteria that are pathogenic to poultry. In topical applications and ingestion tests, EOs from Mentha arvensis, Mentha spicata, and Mentha piperita were toxic to A. diaperinus. Chromatographic analyses revealed that menthol is the predominant compound in M. arvensis and M. piperita, whereas carvone is the major compound in M. spicata. Both (-)- and (+)-menthol, along with (-)- and (+)-carvone, underwent testing with A. diaperinus. Nevertheless, their activity was not as potent as those of the EOs, suggesting a possible synergistic and/or additive effect. The EOs did not have any adverse effects on the conidial germination, vegetative growth, or conidia production per colony of the entomopathogenic fungus B. bassiana. Consequently, these EOs are compatible with this natural enemy. The EO extracted from M. spicata exhibited significant toxicity against Staphylococcus aureus (ATCC 25923), whereas the remaining EOs displayed moderate toxicity against this bacterium. The EOs derived from Mentha spp., as assessed in this study, hold promise for the development of botanical insecticides tailored for the control of A. diaperinus. These insecticides are selective in favor of the natural enemy B. bassiana and can also serve as effective sanitizers, thanks to their antibacterial properties.

IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma

Background Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. Results miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. Conclusions These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.

The role of TNF receptors as mediators of chronic vasculitis in possible milder forms of the CNS tuberculosis.

INTRODUCTION: Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB due to its high mortality and functional sequelae. There are several differential diagnoses for TB; and, it can also cause secondary conditions, such as vasculitis. METHODOLOGY: 155 biopsies, corresponding to 155 different patients out of 5,386 registered biopsies from 2008-2013, met the criteria of unknown etiology vasculitis and evidence of cerebral vascular disease. These were analyzed to assess the presence of central nervous system TB. The selected cases were assessed with Suzaan Marais (SM) criteria for clinical tuberculosis. After that, Ziehl-Neelsen (ZN) staining and polymerase chain reaction (PCR) were performed to amplify a fragment of the insertion sequence IS6110 of M. tuberculosis. 21 patients met the criteria for definitive tuberculosis by ZN staining and PCR, and 2 met the criteria for possible tuberculosis. Tumor necrosis factor (TNF)-α, TNF-R1, and TNF-R2 were determined by immunohistochemistry in histological sections from formalin-fixed paraffin-embedded (FF-PE) tissues in the 23 selected patients. RESULTS: Granulomatous TB was present in almost half of the cases. TNF-R1 and TNF-R2 were expressed mainly in blood vessels, histiocytes, and macrophages. TNF-R2 expression was higher than the other markers, which suggests an anti-inflammatory response against M. tuberculosis. CONCLUSIONS: The histopathological presentation of TB is not always limited to granulomas, abscesses, or meningitis; there are also clinical presentations characterized only with chronic inflammation of nervous and vascular tissue.

Unveiling the Role of Sorghum RPAP3 in the Function of R2TP Complex: Insights into Protein Assembly in Plants.

The chaperone R2TP has multiple subunits that assist in the proper folding, assembly, and stabilization of various protein complexes in cells and its study can offer valuable insights into the regulation and maintenance of protein assemblies in plant systems. The 'T' component of R2TP is Tah1 in yeast, consisting of 111 residues, while its counterpart in humans is RPAP3, with 665 residues. RPAP3 acts as a co-chaperone of Hsp90 and facilitates interactions between RUVBL proteins and other complex components, enhancing the recruitment of client proteins by the R2TP complex. These facts further underscore the relevance of studying this complex in different organisms. The putative gene corresponding to the RPAP3 in Sorghum bicolor, a monocotyledon plant, was cloned, and the protein (396 residues) purified for biochemical characterization. SbRPAP3 exists as a folded monomer and has a RPAP3 domain, which is present in human RPAP3 but absent in yeast Tah1. SbRPAP3 retains its functional capabilities, including binding with RUVBLs, Hsp90, and Hsp70. By elucidating the role of RPAP3 in plant R2TP complex, we can further comprehend the molecular mechanisms underlying plant-specific protein assembly and contribute to advancements in plant biology and biotechnological applications.

Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis.

BACKGROUND: Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes. METHODS: We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM. RESULTS: Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM. CONCLUSIONS: Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.

Sweet Taste Receptor Gene and Caries Trajectory in the Life Course.

This study aims to investigate whether the trajectory of dental caries in the life course is associated with rs307355 (TAS1R3) and rs35874116 (TAS1R2) and if there is an epistatic association between rs307355 (TAS1R3) and rs35874116 (TAS1R2). A representative sample of all 5,914 births from the 1982 Pelotas birth cohort was prospectively investigated, and the decayed, missing, and filled teeth (DMF-T) components were assessed at ages 15 (n = 888), 24 (n = 720), and 31 (n = 539) y. Group-based trajectory modeling was used to identify groups with similar trajectories of DMF-T components in the life course. Genetic material was collected, and rs307355 (TAS1R3) and rs35874116 (TAS1R2) were genotyped. Ethnicity was evaluated using ADMIXTURE. Generalized multifactor dimensionality reduction software was used to investigate epistatic interactions. Considering rs307355 (TAS1R3) in the additive effect, the genotype TT was associated with the high decayed trajectory group (odds ratio [OR] = 4.52; 95% confidence interval [CI], 1.15-17.74) and the high missing trajectory group (OR = 3.35; 95% CI, 1.09-10.26). In the dominant effect, the genotype CT/TT was associated with the high decayed trajectory group (OR = 1.64; 95% CI, 1.14-2.35). Allele T was associated with an increased odds of 64% (OR = 1.64; 95% CI, 1.20-2.25) for the decayed component and 41% (OR = 1.41; 95% CI, 1.04-1.92) for the missing component. No associations were observed between rs307355 (TAS1R3) and the filled component. rs35874116 (TAS1R2) was not associated with DMF-T components. Positive epistatic interactions were observed involving rs307355 (TAS1R3) and rs35874116 (TAS1R2) with the decayed component (OR = 1.72; 95% CI, 1.04-2.84). Thus, rs307355 (TAS1R3) genotypes and alleles seem positively associated with the trajectory of decayed and missing components in the life course. Epistatic interaction between rs307355 and rs35874116 may increase the decayed caries trajectory.

PIK3R2 predicts poor outcomes for patients with melanoma and contributes to the malignant progression via PI3K/AKT/NF-κB axis.

BACKGROUND: Melanoma is an aggressive form of skin cancer worldwide. Phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) exerts carcinogenic roles in various tumors. So far, the function and mechanism of PIK3R2 in melanoma are not been fully clarified. OBJECTIVE: We aimed to clarify the role of PIK3R2 in melanoma. METHODS: PIK3R2 expressions in melanoma clinical tissues and melanoma cells were measured using quantitative real-time PCR and Western blot. In addition, PIK3R2 expressions in different tumor stages of melanoma were determined by immunohistochemistry assay. Meanwhile, PIK3R2 function was evaluated using loss or gain-of-function assays, Cell Counting Kit-8 assay, flow cytometry, and Transwell analysis. Furthermore, PIK3R2 mechanism in melanoma was assessed by a series of rescue experiments. RESULTS: PIK3R2 was highly expressed in melanoma tissues and cells, and PIK3R2 expressions were the highest in Stage IV. Functionally, PIK3R2 knockdown repressed melanoma cell proliferation, invasion, epithelial-mesenchymal transition, and facilitated cell apoptosis. Also, PIK3R2 overexpression produced an opposite trend. Mechanistically, PIK3R2 facilitated melanoma progression by activating PI3K/AKT/NF-κB pathway. Furthermore, PIK3R2 knockdown restrained the melanoma tumor growth in vivo. CONCLUSIONS: PIK3R2 aggravated melanoma by activating PI3K/AKT/NF-κB pathway, prompting that PIK3R2 might be a therapeutic target for melanoma.

Generic Pheromones Identified from Northern Hemisphere Cerambycidae (Coleoptera) Are Attractive to Native Longhorn Beetles from Central-Southern Chile.

We conducted field bioassays with several known cerambycid pheromones in two zones of central-southern Chile: (1) Las Trancas (Ñuble region) and Coñaripe (Los Rios region) (Study 1) and (2) Rucamanque and Maquehue (La Araucania region) (Study 2). Up to eight compounds were tested individually, including 3-hydroxy-2-hexanone, (2R*,3S*)- and (2R*,3R*)-2,3-hexanediol, fuscumol, fuscumol acetate, monochamol, 2-methylbutanol, and geranylacetone. Compounds were loaded in plastic sachets placed in either multiple funnel or cross-vane panel traps hung in trees in a randomized block design (n = 3 or 4). The number of treatments and bioassay periods varied depending on the study. A total of 578 specimens belonging to 11 native species were collected, with the three captured in the highest numbers being Eryphus laetus (292 specimens), Calydon submetallicum (n = 234), and Chenoderus testaceus (n = 20). The three species are of economic importance: E. laetus is considered a minor pest in apple orchards, and the other two species infest Nothophagus hosts, including some timber species. Traps baited with 3-hydroxy-2-hexanone collected significant numbers of both sexes of the two most abundant species, and this compound was the only treatment that attracted C. submetallicum. (2R*,3R*)- and (2R*,3S*)-2,3-Hexanediols were also significantly attractive to E. laetus. Our results suggested that 3-hydroxy-2-hexanone and 2,3-hexanediols, which are known pheromone components of cerambycid species worldwide, are also likely to be conserved aggregation pheromone components among some species in western South America.

Compressive strength of premolars restored with ceramic crowns and supported with a glass fiber post using different luting agents.

Objective: The retention of glass fiber post (GFP) is considered a key factor for the long-term success of restorations of endodontically treated teeth. This study aimed to compare the compressive strength of a ceramic crown supported by a GFP using different luting agents. Methods: Forty single-rooted premolars were randomly divided into four groups (n = 10 each): control group (teeth without a GFP), Ketac Cem group (glass ionomer), RelyX ARC group (conventional dual-curing resin), and RelyX U200 group (self-adhesive dual-curing resin). After luting of the posts and placement of all-ceramic crowns made using feldspathic porcelain (Noritake EX-3), they were exposed to thermocycling for 1000 cycles and compressive strength tests. Statistical analysis included Kruskal-Wallis test with Dunn's multi-comparison test. Results: The Ketac Cem group and RelyX U200 group showed significantly greater fracture resistance to compressive loading than the control group. Conclusion: This study indicates a possible role of the luting agent used with the GFP in influencing the compressive strength of the restored teeth. In this study, the self-adhesive dual-curing resin and glass ionomer both offered resistance to fractures.

Regulation of Anthocyanin Biosynthesis by Drought and UV-B Radiation in Wild Tomato (Solanum peruvianum) Fruit.

Anthocyanins are plant pigments derived from the phenylpropanoid pathway which are produced in many different species, contributing to defense against stresses by their antioxidant properties. Cultivated tomatoes cannot synthesize flavonoids; however, wild tomatoes such as Solanum chilense and Solanum lycopersicoides have anthocyanin pigmented skin. Other wild tomato species such as Solanum peruvianum have been poorly studied concerning anthocyanin accumulation in the fruit. This research is the first to address the regulation of anthocyanin biosynthesis mediated by drought stress and light radiation in S. peruvianum fruit. Transcript accumulation of SpAN2, encoding for a key MYB type transcription factor for the regulation of anthocyanin biosynthesis, was induced in the fruit of plants exposed to drought treatment. In addition, fruit peel accumulates a greater anthocyanin content in water deficit-treated plants. The expression of SpAN2 was also regulated according to sunlight exposure, reaching a higher expression during maximal daily UV radiation and under controlled UV-B treatments. Similar results were observed for the expression of the late flavonoid biosynthetic gene dihydroflavonol 4-reductase (SpDFR). These results suggest that SpAN2 and SpDFR are involved in anthocyanin biosynthesis under drought stress and UV radiation in S. peruvianum.

Hospital-Acquired SARS-CoV-2 infection among patients admitted to a university hospital.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency, as it is a highly contagious disease, health services had to adapt to the high demand for hospitalizations in order to contain hospital outbreaks. We aimed to identify the impact of nosocomial transmission of severe acute respiratory coronavirus virus 2 among inpatients at a university hospital in São Paulo, Brazil. Among 455 inpatients diagnosed with coronavirus disease 2019 in March-May, 2020, nosocomial infection was implicated in 42 (9.2%), of whom 23 (54.7%) died. becoming routine, especially when community transmission occur with high levels of incidence. It was possible to observe with this study that the nosocomial transmission by SARS-CoV-2 was present even with these measures instituted, and some of the damages caused by these infections are intangible.

Evolution of the Subgroup 6 R2R3-MYB Genes and Their Contribution to Floral Color in the Perianth-Bearing Piperales.

Flavonoids, carotenoids, betalains, and chlorophylls are the plant pigments responsible for floral color. Anthocyanins, a class of flavonoids, are largely responsible for the red, purple, pink, and blue colors. R2R3-MYB genes belonging to subgroup 6 (SG6) are the upstream regulatory factors of the anthocyanin biosynthetic pathway. The canonical members of these genes in Arabidopsis include AtMYB75, AtMYB90, AtMYB113, and AtMYB114. The Aristolochiaceae is an angiosperm lineage with diverse floral groundplans and perianth colors. Saruma henryi exhibits a biseriate perianth with green sepals and yellow petals. All other genera have sepals only, with colors ranging from green (in Lactoris) to a plethora of yellow to red and purple mixtures. Here, we isolated and reconstructed the SG6 R2R3-MYB gene lineage evolution in angiosperms with sampling emphasis in Aristolochiaceae. We found numerous species-specific duplications of this gene lineage in core eudicots and local duplications in Aristolochiaceae for Saruma and Asarum. Expression of SG6 R2R3-MYB genes examined in different developmental stages and plant organs of four Aristolochiaceae species, largely overlaps with red and purple pigments, suggesting a role in anthocyanin and flavonoid synthesis and accumulation. A directed RNA-seq analysis corroborated our RT-PCR analyses, by showing that these structural enzymes activate during perianth development in Aristolochia fimbriata and that the regulatory genes are expressed in correlation with color phenotype. Finally, the reconstruction of the flavonoid and anthocyanin metabolic pathways using predicted peptides from transcriptomic data show that all pivotal enzymes are present in the analyzed species. We conclude that the regulatory genes as well as the biosynthetic pathway are largely conserved across angiosperms. In addition, the Aristolochiaceae emerges as a remarkable group to study the genetic regulatory network for floral color, as their members exhibit an outstanding floral diversity with elaborate color patterns and the genetic complement for SG6 R2R3-MYB genes is simpler than in core eudicot model species.

The tip of the iceberg: emerging roles of TORC1, and its regulatory functions in plant cells.

Target of Rapamycin (TOR) is an evolutionarily conserved protein kinase that plays a central role in coordinating cell growth with light availability, the diurnal cycle, energy availability, and hormonal pathways. TOR Complex 1 (TORC1) controls cell proliferation, growth, metabolism, and defense in plants. Sugar availability is the main signal for activation of TOR in plants, as it also is in mammals and yeast. Specific regulators of the TOR kinase pathway in plants are inorganic compounds in the form of major nutrients in the soils, and light inputs via their impact on autotrophic metabolism. The lack of TOR is embryo-lethal in plants, whilst dysregulation of TOR signaling causes major alterations in growth and development. TOR exerts control as a regulator of protein translation via the action of proteins such as S6K, RPS6, and TAP46. Phytohormones are central players in the downstream systemic physiological TOR effects. TOR has recently been attributed to have roles in the control of DNA methylation, in the abundance of mRNA splicing variants, and in the variety of regulatory lncRNAs and miRNAs. In this review, we summarize recent discoveries in the plant TOR signaling pathway in the context of our current knowledge of mammalian and yeast cells, and highlight the most important gaps in our understanding of plants that need to be addressed in the future.

Dissecting protein domain variability in the core RNA interference machinery of five insect orders.

RNA interference (RNAi)-mediated gene silencing can be used to control specific insect pest populations. Unfortunately, the variable efficiency in the knockdown levels of target genes has narrowed the applicability of this technology to a few species. Here, we examine the current state of knowledge regarding the miRNA (micro RNA) and siRNA (small interfering RNA) pathways in insects and investigate the structural variability at key protein domains of the RNAi machinery. Our goal was to correlate domain variability with mechanisms affecting the gene silencing efficiency. To this end, the protein domains of 168 insect species, encompassing the orders Coleoptera, Diptera, Hemiptera, Hymenoptera, and Lepidoptera, were analysed using our pipeline, which takes advantage of meticulous structure-based sequence alignments. We used phylogenetic inference and the evolutionary rate coefficient (K) to outline the variability across domain regions and surfaces. Our results show that four domains, namely dsrm, Helicase, PAZ and Ribonuclease III, are the main contributors of protein variability in the RNAi machinery across different insect orders. We discuss the potential roles of these domains in regulating RNAi-mediated gene silencing and the role of loop regions in fine-tuning RNAi efficiency. Additionally, we identified several order-specific singularities which indicate that lepidopterans have evolved differently from other insect orders, possibly due to constant coevolution with plants and viruses. In conclusion, our results highlight several variability hotspots that deserve further investigation in order to improve the application of RNAi technology in the control of insect pests.

Evidências de validade convergente Raven e R-2 em crianças com TEA / Evidence of convergent validity Raven and R-2 in children with ASD / Evidencia de validez convergente Raven y R-2 en niños con TEA

Visando ampliar os estudos relacionados à avaliação da inteligência de crianças com Transtorno do Espectro Autista (TEA) este estudo investigou a relação entre os testes não verbais de inteligência R-2 e Raven, avaliando 30 crianças com TEA, grau leve e moderado, de idade entre 5 e 11 anos e 9 meses. Os dados foram analisados de forma padronizada e os escores da amostra evidenciaram níveis intelectuais dentro da média no Raven e médio superior no R-2. Com alta correlação e convergência (coeficiente r = 0,897) estes resultados creditam o R-2 como um instrumento psicométrico potencial na avaliação da inteligência no TEA.

Aiming to expand the studies related to the assessment of the intelligence of children with Autistic Spectrum Disorder (ASD) this study investigated the relationship between the non-verbal tests of intelligence R-2 and Raven, evaluating 30 children with ASD, mild and moderate, of age between 5 and 11 years and 9 months. The data were analyzed in a standardized, way and the sample scores showed intellectual levels within the mean in Raven and upper mean in R-2. With high correlation and convergence (coefficient r = 0.897) these results credit R-2 as a potential psychometric instrument in the assessment of intelligence in ASD.

Con el objetivo de ampliar los estudios relacionados con la evaluación de la inteligencia de los niños con trastorno del espectro autista (TEA), este estudio investigó la relación entre las pruebas no verbales de inteligencia R-2 y Raven, evaluando a 30 niños con TEA, leve y moderada, de edad Entre 5 y 11 años y 9 meses. Los datos se analizaron de manera estandarizada y las puntuaciones de la muestra mostraron niveles intelectuales dentro de la media en Raven y la media superior en R-2. Con alta correlación y convergencia (coeficiente r = 0,897) estos resultados acreditan a R-2 como un instrumento psicométrico potencial en la evaluación de la inteligencia en TEA.

Evaluación del SAME-TT2R2 score en la calidad de la anticoagulación con warfarina / Evaluation of SAME-TT2R2 score on the quality of anticoagulation with warfarin

Resumen Introducción: la fibrilación auricular (FA) es la arritmia cardiaca más frecuente y está relacionada con eventos embólicos. La eficacia y seguridad de la warfarina en prevención del ictus depende del tiempo en rango terapéutico (TTR). Se han diseñado escalas para predecir el comportamiento del TTR al inicio de la terapia. El objetivo de este trabajo fue evaluar la capacidad predictiva y discriminativa del SAMeTT2R2 score en una población no caucásica. Material y métodos: estudio analítico de cohorte retrospectiva en pacientes con FA no valvu lar tratados con warfarina entre 2013 y 2016 en una clínica de anticoagulación. Se caracterizó la muestra sociodemográfica y clínicamente. Se definió mal control de la anticoagulación como (TTR/ PINNR<65%). Se comparó el TTR/PINNR <65% y SAMeTT2R2 <=2 versus >2 con la prueba U de Mann-Whitney y chi cuadrado. Se construyeron curvas ROC para determinar discriminación de la escala. Se evaluó cada uno de sus elementos a través de regresión logística. Resultados: se incluyeron 646 pacientes (edad media 77 años ± 8,8 años, 51,4% hombres). El TTR promedio fue 67.7% y el PINNR 63.6%. Al comparar la frecuencia de pobre control entre SAMeTT2R2 score ≤2 versus >2 con una prueba chi cuadrado, el PINNR fue significativo (p=0.004). La capacidad discriminativa de la escala para el TTR/PINNR fue baja (AUC: 0.52 y 0.54 respectivamente). No se encontró relación entre cada una de las variables que integran el SAMeTT2R2 score y el TTR/PINNR. Conclusiones: la puntuación SAMeTT2R2 no mostró buena capacidad predictiva y discriminativa en la población estudiada. La calidad de la anticoagulación es el resultado de un proceso dinámico en relación con el cumplimiento, estado de salud o enfermedad intercurrente. (Acta Med Colomb 2019; 44: 75-81).

Abstract Introduction: atrial fibrillation (AF) is the most common cardiac arrhythmia and is related to embolic events. The efficacy and safety of warfarin in stroke prevention depends on the time in therapeutic range (TTR). Scales have been designed to predict the behavior of TTR at the start of therapy. The objective of this work was to evaluate the predictive and discriminative capacity of the SAMeTT2R2 score in a non-Caucasian population. Material and methods: retrospective cohort analytical study in patients with non-valvular AF treated with warfarin between 2013 and 2016 in an anticoagulation clinic. The sample was demodemographically and clinically characterized. Poor control of anticoagulation was defined as (TTR / PINNR <65%). The TTR / PINNR <65% and SAMeTT2R2 <= 2 versus> 2 were compared with the Mann-Whitney U test and chi square. ROC curves were constructed to determine scale discrimination. Each of its elements was evaluated through logistic regression. Results: 646 patients were included (mean age 77 years ± 8.8 years, 51.4% men). The average TTR was 67.7% and the PINNR 63.6%. When comparing the frequency of poor control between C. L. Sandoval-Riveros y cols. SAMeTT2R2 score ≤2 versus> 2 with a chi square test, the PINNR was significant (p = 0.004). The discriminative capacity of the scale for the TTR / PINNR was low (AUC: 0.52 and 0.54 respec tively). No relationship was found between each of the variables that constitute the SAMeTT2R2 score and the TTR / PINNR. Conclusions: the SAMeTT2R2 score did not show good predictive and discriminative capac ity in the studied population. The quality of anticoagulation is the result of a dynamic process in relation to compliance, health status or intercurrent disease. Acta Med Colomb 2019; 44: 75-81).

The Antimicrobial Activity of Annona emarginata (Schltdl.) H. Rainer and Most Active Isolated Compounds against Clinically Important Bacteria.

Annona emarginata (Schltdl.) H. Rainer, commonly known as "arachichú", "araticú", "aratigú", and "yerba mora", is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (-) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250⁻1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16⁻125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250⁻500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound-(R)-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl (E)-3-(4-hydroxyphenyl)acrylate (1). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12⁻6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.

Genetic Variations in Sweet Taste Receptor Gene Are Related to Chocolate Powder and Dietary Fiber Intake in Obese Children and Adolescents.

Childhood obesity is a major public health problem. It has a direct impact on the quality of life of children and adolescents, as well as on their future risk of developing chronic diseases. Dietary patterns rich in fats and sugars and lacking dietary fibers, vitamins, and minerals, as well as lack of physical exercise have been associated with the rise of obesity prevalence. However, factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in taste-related genes may explain the variability of taste preference and food intake. The aim of this research is to evaluate the influence of polymorphisms of the sweet taste receptor gene TAS1R2 on diet and metabolic profile in obese children and adolescents. A cross-sectional study with 513 obese children and adolescents and 135 normal-weight children was carried out. A molecular study was performed for the single nucleotide polymorphisms (SNPs) rs9701796 and rs35874116 of TAS1R2, and dietary intake, anthropometric parameters (weight, height, waist circumference, waist-to-height ratio (WHtR)), and metabolic profile (including fasting glucose, insulin, triglyceride, high-density lipoprotein (HDL)-cholesterol, and leptin levels) were analyzed. The variant rs9701796 was associated with increased waist-height ratio, as well as with a higher chocolate powder intake in obese children. The variant rs35874116 was associated with a lower dietary fiber intake. In conclusion, there was no relationship between genotypes and risk of obesity. Obese adolescents carrying the serine allele of SNP rs9701796 in TAS1R2 showed higher waist-to-height ratio and chocolate powder intake, whereas those carrying the valine allele of SNP rs35874116 in TAS1R2 were characterized by lower dietary fiber intake.

Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children

Abstract Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.