Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Potent Anthelmintic Activity of Chalcones Synthesized by an Effective Green Approach.

There is currently an urgent need for new anthelmintic agents due to increasing resistance to the limited available drugs. The chalcone scaffold is a privileged structure for developing new drugs and has been shown to exhibit potential antiparasitic properties. We synthesized a series of chalcones via Claisen-Schmidt condensation, introducing a novel recoverable catalyst derived from biochar obtained from the pyrolysis of tree pruning waste. Employing microwave irradiation and a green solvent, this approach demonstrated significantly reduced reaction times and excellent compatibility with various functional groups. The result was the generation of a library of functionalized chalcones, exhibiting exclusive (E)-selectivity and high to excellent yields. The chalcone derivatives were evaluated on the free-living nematode Caenorhabditis elegans. The chalcone scaffold, along with two derivatives incorporating a methoxy substituent in either ring, caused a concentration-dependent decrease of worm motility, revealing potent anthelmintic activity and spastic paralysis not mediated by the nematode levamisole-sensitive nicotinic receptor. The combination of both methoxy groups in the chalcone scaffold resulted in a less potent compound causing worm hypermotility at the short term, indicating a distinct molecular mechanism. Through the identification of promising drug candidates, this work addresses the demand for new anthelmintic drugs while promoting sustainable chemistry.

Ag-NP-Decorated Carbon Nanostructures: Synthesis, Characterization, and Antimicrobial Properties.

As the global urgency for effective antimicrobial agents intensifies, this work harnesses the widely demonstrated antimicrobial activity of silver nanoparticles (Ag-NPs) and proposes alternative synthesis approaches to metal-organic hybrid systems with antimicrobial activity. In this study, the proposed synthesis route involves decorating metallic nanoparticles into organic substrates without previous doping. The synthesis simultaneously uses polyethylene glycol for three crucial purposes: (1) acting as a mild reducing agent to generate Ag-NPs with a spherical shape and diameters ranging from 10 to just over 20 nm, (2) functioning as a dispersing agent for flakes of commercial nanostructured carbon supports, including reduced graphene oxide (rGO, ID-nano), and commercial carbon nanoplatelets from Sigma-Aldrich (GNPs, Sigma-Aldrich), and (3) serving as a promoter for the homogeneous anchoring of Ag-NPs in the carbon lattice without altering the conformation of the carbon lattice. This intricate interaction involves the π-orbitals from the sp2 hybridization honeycomb and the d-orbitals from the Ag-NPs, leading to the constructive rehybridization of rGO and GNPs. In our study, Ag-NPs/rGO are compared with a support lacking oxygenated groups in the lattice, such as commercial GNPs (Sigma-Aldrich), to produce Ag-NPs/GNPs. This comparison maintains constructive sp2 rehybridization, preserving the characteristic properties of rGO (ID-nano) and graphene nanoplatelets, including commercial GNPs (Sigma-Aldrich). Notably, oxygenated groups from rGO exhibit greater availability for exchanging oxo and hydroxy defects for Ag-NPs compared with GNPs (Sigma-Aldrich). The resulting Ag-NPs/rGO and Ag-NPs/GNP systems are thoroughly physicochemically characterized, employing techniques such as Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, and scanning transmission electron microscopy, revealing the successful integration of Ag-NPs with minimal alteration to the carbon lattice. Subsequent antimicrobial evaluation against Escherichia coli (E. coli) demonstrates significant activity, with Ag-NPs/rGO and Ag-NPs/GNPs registering similar minimum inhibitory concentrations of 50 µg mL-1. This study underscores the potential of our metal-organic hybrid systems as antimicrobial agents and provides insights into the constructive rehybridization process, paving the way for diverse applications in the biomedical and environmental fields.

Effects of parity, seasonal heat stress, and colostrum collection time postpartum on colostrum quality of Holstein cattle in an arid region.

The aim of this study was to determine effects of parity (primiparous vs. multiparous), seasonal heat stress at calving (summer vs. winter), and time postpartum on some parameters associated with colostrum quality in Holstein cows reared in the Sonoran Desert ecosystem. Forty-seven cows (11 primiparous and 36 multiparous) expected to calve during summer, and 46 cows during winter (14 primiparous and 32 multiparous) were randomly selected. Management and feeding before and after parturition were similar for cows in both seasons. After parturition, colostrum from all cows was evaluated for volume, weight, temperature, density, and content of fat, protein, solids non-fat (SNF), and immunoglobulins (IGG). Data were analyzed with a model that included effects of parity status, calving season, and time postpartum, as well as all interactions. Colostrum produced in summer was warmer (P < 0.01) by almost 6 °C than winter colostrum, while colostrum from multiparous was warmer (P = 0.02) by 1.2 °C than that produced by primiparous cows. Colostrum volume and weight were not impacted by parity, calving season or time postpartum. Density, protein, and SNF content in colostrum were higher (P < 0.01) in multiparous vs. primiparous cows, as well as at parturition (0 h postpartum) than at 12 h postpartum (P < 0.01). At calving (0 h), spring colostrum had higher fat content (P < 0.01) and lower (P < 0.01) IGG concentration than that collected in summer, and no difference (P > 0.05) between seasons was observed for these components at 12 h postpartum. Multiparous cows produced colostrum with higher (P < 0.01) IGG concentrations than primiparous cows. In conclusion, only 0-h colostrum and that from multiparous cows was categorized as "Excellent," meanwhile the colostrum produced under summer heat stress was characterized as "Good" with reduced fat content. While the lacteal secretion collected at 12 post-partum still classified as colostrum, substantially lower contents of IGG, protein, fat, and SNF decreased its classification to "Poor" from the classification of "Excellent" at 0 h postpartum.

A new FRAX model for Brazil.

Fracture probabilities derived from the original FRAX model for Brazil were compared to those from an updated model based on more recent regional estimates of the incidence of hip fracture. Fracture probabilities were consistently lower in the updated FRAX model. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. OBJECTIVE: Recent epidemiological data indicate that the risk of hip fracture in Brazil is lower than that used to create the original FRAX model. This paper describes the epidemiology of hip fracture in Brazil and the synthesis of an updated FRAX model with the aim of comparing this new model with the original model. METHODS: Hip fracture rates from three cities in three regions were combined, weighted by the population of each region. For other major fractures, incidence rates for Brazil were estimated using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm or clinical vertebral fractures). Mortality estimates were taken from the UN. RESULTS: Compared to the original FRAX model, the updated model gave lower 10-year fracture probabilities in men and women at all ages. Notwithstanding, there was a very close correlation in fracture probabilities between the original and updated models (r > 0.99) so that the revisions had little impact on the rank order of risk. CONCLUSION: The disparities between the original and updated FRAX models indicate the importance of updating country-specific FRAX models with the advent of significant changes in fracture epidemiology.

Expression of enzymes involved in the urea cycle and muscle and mammary gland development of Holstein × Gyr heifers in a rotational grazing system supplemented with increasing protein levels.

Studies evaluating the crude protein (CP) supplementation strategies across the year for grazing cattle and its association with the enzymes involved in the urea cycle and muscle and mammary gland developments are scarce. Thus, we aimed to evaluate the effect of supplementation with different levels of CP on the expression of genes involved in the urea cycle and muscle and mammary gland development of Holstein × Gyr crossbreed heifers grazing intensively managed Brachiaria decumbens throughout the year. Thirty-eight heifers with average initial BW of 172.5 ± 11.15 kg (mean ± SE) and 8.2 ± 0.54 mo of age were randomly assigned to 1 of 4 treatments: 3 protein supplements (SUP) fed at 5g/kg of body weight, plus a control group (CON, non-supplemented animals). The supplement CP levels evaluated were: 12, 24, and 36%. The study was divided into 4 seasons: rainy, dry, rainy-dry transition (RDT), and dry-rainy transition (DRT). On the penultimate day of each season, ultrasound images of the carcass and mammary gland were taken. Five animals from each treatment were randomly chosen on the last day of each season, and liver and muscle tissue biopsies were performed. The target genes were the mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) in the muscle samples. Carbamoyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), arginosuccinate lyase (ASL), and arginase (ARG) were evaluated in the liver samples. Data were analyzed using PROC GLIMMIX of the SAS with repeated measures. We observed a greater rib eye area (cm2) and fat thickness (mm) in SUP animals than in non-supplemented animals. However, we did not observe differences among SUP levels for both variables. No effects of supplementation were detected on mammary gland development. Nevertheless, seasonal effects were observed, where the RDT and dry season had the most and least accumulated fat in the mammary gland. In muscle, we observed greater expression of AMPK in non-supplemented animals than SUP animals. On the other hand, no differences were observed in gene expression between SUP and non-supplemented animals and among SUP animals for mTOR. Season affected both AMPK and mTOR; heifers had a greater AMPK gene expression on rainy than RDT. For mTOR, we observed greater gene expression in RDT and DRT than in rainy. No differences were observed among RDT, dry, and DRT, and between dry and rainy seasons for mTOR. We observed greater CPS, ASL, and ARG gene expression in SUP animals than in non-supplemented animals. Among SUP animals, supplement CP linearly affected CPS. In conclusion, the supplementation strategy did not affect mammary gland development and mTOR expression in muscle tissue. However, we observed a seasonal effect on mammary gland development and AMPK and mTOR expression. The CP supplementation increased the rib eye area and fat thickness, directly affecting AMPK expression in the muscle. Moreover, the CP supplementation increased urea cycle enzyme expression, indicating greater urea production in the liver.

A case of natural infection with Dirofilaria immitis in a coati (Nasua narica) from Mexico.

This paper aims to describe the natural infection with Dirofilaria immitis in Nasua narica (white-nosed coati) from Yucatán, Mexico. Two carcasses of N. narica were collected on a highway that crosses through a dense forest with patches used for agriculture and livestock activities. We performed necropsies, and two female adult nematode parasites from the heart of one specimen were collected and preserved for their molecular identification using a conventional PCR directed at a fragment of the small subunit (18S) ribosomal RNA (18S-rRNA) gene. Bioinformatic analysis showed a similarity of 99 % with three sequences from D. immitis (two from Japan). Additionally, we performed a phylogenetic tree with the recovered sequence. All these analyses showed that D. immitis is present in N. narica from Mexico. The transmission of D. immitis toward populations of Nasua sp. may be due to indirect and accidental contact with domestic dogs or wild canids that share the same environment.

Interpopulation characterization of quinoa (Chenopodium quinoa Willd.) from different agroecological environments of Colombia.

Chenopodium quinoa Willd. it is an Andean cereal of great importance for human consumption due to its high nutritional value. In Colombia there is a high phenotypic and genotypic variability within quinoa crops, which has not been studied and has been maintained by the same farmers cycle after production cycle. The objective of this study was to carry out an interpopulation characterization of quinoa cultivated in different producing municipalities of the department of Boyacá, in Colombia, for which 19 morphological descriptors were used, which were evaluated in situ in nine municipalities and analyzed through descriptive statistics, principal component analysis, correlation and conglomerates. In the evaluation of the quantitative traits for all the populations, it was observed that the most variable descriptors were Number of teeth lower leaf (DHI), Lower leaf length (LHI), Width upper leaf (AHI) and Number of teeth upper leaf (DHS). Great segregation between and within individuals of Blanca de Jericó and Piartal was observed for panicle and leaf color and shape, stem color, presence of teeth, and axils on upper and lower leaves. A classification key is proposed that allows in the field to be able to morphologically differentiate the genotypes of Piartal and Blanca de Jericó. This research shows that among the most cultivated genotypes in the department of Boyacá, there is still an important phenotypic diversity given at the inter and intra-individual level, due to the phenological state and the agroclimatological conditions of the different producing regions.

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Interpopulation characterization of quinoa (Chenopodium quinoa Willd) from different agroecological environments of Colombia / Caracterização interpopulacional de quinoa (Chenopodium quinoa Willd) de diferentes ambientes agroecológicos da Colômbia

Chenopodium quinoa Willd. it is an Andean cereal of great importance for human consumption due to its high nutritional value. In Colombia there is a high phenotypic and genotypic variability within quinoa crops, which has not been studied and has been maintained by the same farmers cycle after production cycle. The objective of this study was to carry out an interpopulation characterization of quinoa cultivated in different producing municipalities of the department of Boyacá, in Colombia, for which 19 morphological descriptors were used, which were evaluated in situ in nine municipalities and analyzed through descriptive statistics, principal component analysis, correlation and conglomerates. In the evaluation of the quantitative traits for all the populations, it was observed that the most variable descriptors were Number of teeth lower leaf (DHI), Lower leaf length (LHI), Width upper leaf (AHI) and Number of teeth upper leaf (DHS). Great segregation between and within individuals of Blanca de Jericó and Piartal was observed for panicle and leaf color and shape, stem color, presence of teeth, and axils on upper and lower leaves. A classification key is proposed that allows in the field to be able to morphologically differentiate the genotypes of Piartal and Blanca de Jericó. This research shows that among the most cultivated genotypes in the department of Boyacá, there is still an important phenotypic diversity given at the inter and intra-individual level, due to the phenological state and the agroclimatological conditions of the different producing regions.

Chenopodium quinoa Willd. é um cereal andino de grande importância para a alimentação humana por causa do seu alto valor nutricional. Na Colômbia, existe uma alta variabilidade fenotípica e genotípica nos cultivos de quinoa, que não foi estudada e tem sido mantida pelo mesmo produtor ciclo após ciclo de produção. O objetivo deste estudo foi realizar uma caracterização interpopulacional da quinoa cultivada em diferentes municípios produtores do departamento de Boyacá, na Colômbia. Para tanto, foram utilizados 19 descritores morfológicos, avaliados in situ em nove municípios e analisados por meio de estatísticas descritivas, análise de componentes principais, correlação e conglomerados. Na avaliação dos caracteres quantitativos para todas as populações, observou-se que os descritores mais variáveis foram: número de dentes da folha inferior (DHI), comprimento da folha inferior (LHI), largura da folha superior (AHI) e número de dentes da folha superior (DHS). Entre os indivíduos de Blanca de Jericó e Piartal e dentro deles, observou-se grande segregação quanto à cor, formato da panícula e folha, cor do caule, presença de dentes e axilas nas folhas superiores e inferiores. É proposta uma chave de classificação que permite no campo poder diferenciar morfologicamente os genótipos de Piartal e Blanca de Jericó. Esta pesquisa mostra que, entre os genótipos mais cultivados no departamento de Boyacá, ainda existe uma importante diversidade fenotípica em nível inter e intraindividual, em razão do estado fenológico e das condições agroclimatológicas das diferentes regiões produtoras.

Natural Growth Promoters Replacing Traditional Growth Promoters in Diets for Light Replacement Pullets: A Systematic Approach

The effect of using natural growth promoters (NGP) to replace traditional antimicrobials on performance, biometry of digestive and reproductive organs, sexual maturity and bone characteristics of replacement pullets was evaluated; and the relationship between these variables according to the diets was verified. Eight-week-old birds were randomly assigned to a completely randomized design and fed different diets: negative control (without growth promoters); positive control - conventional growth promoter; organic acids (OA); symbiotic (S); essential oil (EO); OA + S; and EO + S. The performance, relative weight of digestive and reproductive organs and length intestines, height and crest length, sternum length, bone quality and sexual maturity of birds were similar (p>0.05) between treatments. The heat map combined with cluster analysis showed a uniform static pattern with the formation of three horizontal groups formed by the treatments: 1) negative control, S and OA + S; 2) positive control and OE and 3) OA and OE + S. A null relationship between the treatments and the variables under study was observed. The principal components analysis revealed an association of variables in three components with 60.55% of variation. NGP can replace traditional promoters, as they do not interfere with performance, biometrics or sexual maturity. Height and length are predictive variables for the development of reproductive organs, especially the oviduct. A similarity was identified through multivariate techniques between symbiotic and organic + symbiotic acids; positive control and essential oils; and organic and symbiotic acids + essential oils.(AU)

Factores de riesgo, etapificación y pronóstico en carcinoma escamoso de cavidad oral / Risk factors, staging and prognosis in oral cavity squamous cell carcinoma

El carcinoma escamoso de cavidad oral corresponde a una de las neoplasias malignas más frecuentes en cabeza y cuello, teniendo una incidencia mundial según GLOBOCAN para el año 2020 de 377.713 casos nuevos. Este cáncer tiene la ventaja potencial de su diagnóstico precoz por su accesibilidad al examen físico, por lo que es importante tener un alto índice de sospecha en pacientes con los factores de riesgo como tabaquismo crónico, consumo de alcohol, consumo de nuez de betel, inmunodeficiencias, entre otros, teniendo una conducta activa con el fin de lograr un diagnóstico precoz. Por otro lado, la etapificación actual incorpora nuevos factores pronósticos, como la profundidad de invasión, con el fin de asignar de mejor forma una clasificación adecuada y con ello, guiar el tratamiento de estos pacientes. Finalmente, se debe procurar un diagnóstico y tratamiento precoz con el fin de lograr los mejores resultados oncológicos.

Squamous cell carcinoma of the oral cavity represents one of the most frequent malignant neoplasms in the head and neck, having an incidence according to GLOBOCAN for the year 2020 of 377,713 new cases. This cancer has the potential advantage of early diagnosis due to its accessibility to physical examination, so it is important to have a high index of suspicion in patients with risk factors such as chronic smoking, alcohol consumption, betel nut consumption, immunodeficiencies, among others, having an active behavior in order to achieve an early diagnosis. On the other hand, the current staging incorporates new prognostic factors, such as depth of invasion, in order to better assign an adequate classification and thus guide the treatment of these patients. Finally, early diagnosis and treatment should be sought in order to achieve the best oncological outcomes.

Trichoderma: biological control efficiency and perspectives for the Brazilian Midwest states and Tocantins.

Brazil is one of the world leaders in the agribusiness sector tending to directly influence a growing dependence on imported inputs, specifically synthetic agrochemicals. At the state level, in 2013, Tocantins stood out in first place in the ranking of agrochemical consumers, however, these products can cause several problems, such as poisoning to humans, environmental contamination, and increased resistance to phytopathogens. Biological control is an alternative to the use of agrochemicals towards eliminating pests naturally by using living organisms called Biological Control Agents (BCA). Currently, fungi of the Trichoderma genus are some of the most used organisms in biological pest control for their relevant characteristics that favor them in terms of survival in the environment, such as high capacity to adapt to ecological conditions, potential to colonize the rhizosphere of plants, mycoparasitism, production of volatile and non-volatile metabolites. In addition, it works on plant growth and productivity. In general, the use of Trichoderma favors the control of soil pathogens, such as Rhizoctonia, Pythium, Sclerotinia, and nematodes. Thus, this review aims to demonstrate the importance of using Trichoderma in biological control, as well as to present an overview and perspectives of research developed by respondents in the Brazilian Midwest region and Tocantins state.

Mutual synchronization of spin-torque oscillators within a ring array.

An array of spin torque nano-oscillators (STNOs), coupled by dipolar interaction and arranged on a ring, has been studied numerically and analytically. The phase patterns and locking ranges are extracted as a function of the number N, their separation, and the current density mismatch between selected subgroups of STNOs. If [Formula: see text] for identical current densities through all STNOs, two degenerated modes are identified an in-phase mode (all STNOs have the same phase) and a splay mode (the phase makes a 2[Formula: see text] turn along the ring). When inducing a current density mismatch between two subgroups, additional phase shifts occur. The locking range (maximum current density mismatch) of the in-phase mode is larger than the one for the splay mode and depends on the number N of STNOs on the ring as well as on the separation. These results can be used for the development of magnetic devices that are based on STNO arrays.

Clinician Agreement on the Classification of Thyroid Nodules Ultrasound Features: A Survey of 2 Endocrine Societies.

CONTEXT: Thyroid nodule risk stratification allows clinicians to standardize the evaluation of thyroid cancer risk according to ultrasound features. OBJECTIVE: To evaluate interrater agreement among clinicians assessing thyroid nodules ultrasound features and thyroid cancer risk categories. DESIGN, SETTING, AND PARTICIPANTS: We surveyed Endocrine Society and Latin American Thyroid Society members to assess their interpretation of composition, echogenicity, shape, margins, and presence of echogenic foci of 10 thyroid nodule cases. The risk category for thyroid cancer was calculated following the American College of Radiology-Thyroid Imaging Reporting & Data System (ACR-TIRADS) framework from individual responses. MAIN OUTCOMES AND MEASURES: We used descriptive statistics and Gwet's agreement coefficient (AC1) to assess the primary outcome of interrater agreement for ACR-TIRADS risk category. As secondary outcomes, the interrater agreement for individual features and a subgroup analysis of interrater agreement for the ACR-TIRADS category were performed (ultrasound reporting system, type of practice, and number of monthly appraisals). RESULTS: A total of 144 participants were included, mostly endocrinologists. There was moderate level of agreement for the absence of echogenic foci (AC1 0.53, 95% CI 0.24-0.81) and composition (AC1 0.54, 95% CI 0.36-0.71). The agreement for margins (AC1 0.24, 95% CI 0.15-0.33), echogenicity (AC1 0.34, 95% CI 0.22-0.46), and shape assessment (AC1 0.42, 95% CI 0.13-0.70) was lower. The overall agreement for ACR-TIRADS assessment was AC1 0.29, (95% CI 0.13-0.45). The AC1 of ACR-TIRADS among subgroups was similar. CONCLUSIONS: This study found high variation of judgments about ACR-TIRADS risk category and individual features, which poses a potential challenge for the widescale implementation of thyroid nodule risk stratification.

Regionalización en la atención de cáncer de cabeza y cuello: Concepto y consideraciones / Regionalization of care in head and neck cancer: Concept and considerations

Resumen El cáncer de cabeza y cuello es una enfermedad infrecuente, con un manejo tanto médico como quirúrgico complejo. La regionalización o centralización de la atención, definida como la concentración de pacientes con enfermedades complejas, en instituciones que presenten equipos multidisciplinarios con mayor experiencia y altamente funcionales, puede ser una alternativa viable para lograr mejores resultados oncológicos. Actual-mente existe evidencia que avala esta estrategia, dando cuenta de mejores resultados oncológicos en centros con un mayor volumen; que tengan una mayor adherencia a guías clínicas basadas en la evidencia y a indicadores de calidad; y que presenten un equipo multidisciplinario a cargo de la toma de decisiones en estos pacientes. La población de Ontario, Canadá, se enmarca como uno de los ejemplos de esta estrategia, consiguiendo mejorar sus resultados manteniendo un alto nivel de calidad en su manejo. El objetivo del presente artículo de revisión es sistematizar el conocimiento actual en relación con la centralización de la atención en oncología de cabeza y cuello y sus consecuencias en la práctica de la otorrinolaringología-cirugía de cabeza y cuello.

Abstract Head and neck cancer is an infrequent disease, with complex medical and surgical management. The regionalization of care, defined as the concentration of patients with complex diseases, in institutions that present highly experienced and highly functional multidiscipli-nary teams, may be an efficient alternative to achieve better oncological outcomes. Currently, there is evidence that supports this strategy, accounting for better oncological outcomes in institutions with higher volume; that have greater compliance to evidence-based guidelines and quality indicators; and that present a multidisciplinary team in charge of the decision-making process in these patients. The population of Ontario, Canada, is framed as one of the examples of this strategy, managing to improve its results while maintaining a high level of quality in its management. The aim of this review paper is to systematize the current knowledge regarding head and neck regionalization of cancer care and its impact in the practice of otolaryngology-head and neck surgery.

PI3K inhibition by BKM120 results in anti-proliferative effects on corticotroph tumor cells.

PURPOSE: Cushing's disease is associated with significant morbidity; thus, additional tumor-directed drugs with the potential to exert antineoplastic effects on corticotroph adenoma cells are desired. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway, which plays regulatory role in cell survival and proliferation, is activated in pituitary adenomas. The present study evaluated the effects of BKM120 (Buparlisib), an oral PI3K inhibitor, on cell viability, apoptosis, cell cycle phase distribution, and ACTH production in mouse corticotroph tumor cells. METHODS: AtT-20/D16v-F2 mouse pituitary corticotroph tumor cells were treated with increasing concentrations of BKM120 or vehicle. Cell viability was measured using an MTS-based assay. Apoptosis was evaluated by Annexin V staining. Cell cycle analysis was performed by propidium iodide DNA staining and flow cytometry. Gene expression of cell cycle regulators (Cdkn1b, Ccnd1, Ccne1, Cdk2, Cdk4, Myc, and Rb1) was assessed by qPCR. Protein expression of p27, total and phosphorylated Akt was assessed by Western blot. ACTH levels were measured in the culture supernatants by chemiluminescent immunometric assay. RESULTS: Treatment with BKM120 decreased AtT-20/D16v-F2 cell viability, induced a G0/G1 cell cycle arrest, reduced the phosphorylation of Akt at Serine 473, and increased p27 expression. Furthermore, BKM120 treatment diminished ACTH levels in the cell culture supernatants. CONCLUSION: In vitro inhibition of PI3K/AKT pathway by BKM120 resulted in anti-proliferative effects on corticotroph tumor cells, decreasing cell viability and ACTH production. These encouraging findings shape the path for further experiments with the inhibition of PI3K/AKT pathway in Cushing's disease.

Trichoderma: biological control efficiency and perspectives for the Brazilian Midwest states and Tocantins / Trichoderma: eficiência no controle biológico e perspectivas para os estados do Centro-Oeste brasileiro e Tocantins

Brazil is one of the world leaders in the agribusiness sector tending to directly influence a growing dependence on imported inputs, specifically synthetic agrochemicals. At the state level, in 2013, Tocantins stood out in first place in the ranking of agrochemical consumers, however, these products can cause several problems, such as poisoning to humans, environmental contamination, and increased resistance to phytopathogens. Biological control is an alternative to the use of agrochemicals towards eliminating pests naturally by using living organisms called Biological Control Agents (BCA). Currently, fungi of the Trichoderma genus are some of the most used organisms in biological pest control for their relevant characteristics that favor them in terms of survival in the environment, such as high capacity to adapt to ecological conditions, potential to colonize the rhizosphere of plants, mycoparasitism, production of volatile and non-volatile metabolites. In addition, it works on plant growth and productivity. In general, the use of Trichoderma favors the control of soil pathogens, such as Rhizoctonia, Pythium, Sclerotinia, and nematodes. Thus, this review aims to demonstrate the importance of using Trichoderma in biological control, as well as to present an overview and perspectives of research developed by respondents in the Brazilian Midwest region and Tocantins state.

O Brasil é um dos líderes mundiais no setor do agronegócio e essa liderança tende a impactar diretamente numa dependência crescente de insumos importados, especificamente, agroquímicos sintéticos. A nível de estado, em 2013, o Tocantins se destacava em primeiro lugar no ranking de consumidores de agroquímicos, contudo, esses produtos podem causar diversos problemas, como intoxicação ao homem, contaminação do ambiente e aumento da resistência de fitopatógenos. Um método alternativo ao uso de agroquímicos é o controle biológico, o qual busca a eliminação de pragas de forma natural, utilizando-se de organismos vivos chamados de Agentes de Controle Biológico (ACB). Atualmente, entre os organismos mais usados no controle biológico de pragas estão os fungos do gênero Trichoderma, isto, por possuir algumas características relevantes que os favorecem em termos de sobrevivência no ambiente, tais como: a alta capacidade de adaptação às condições ecológicas, potencial em colonizar a rizosfera das plantas, micoparasitismo, produção de metabólitos voláteis e não voláteis. Além disso, atua no crescimento e produtividade das plantas. Geralmente, o uso de Trichoderma favorece o controle de patógenos do solo, como: Rhizoctonia, Pythium, Sclerotinia e nematoides. Assim, a presente revisão visa demostrar a importância da utilização do Trichoderma no controle biológico, assim como apresentar um panorama e perspectivas das pesquisas desenvolvidas por pesquisados da região Centro-Oeste brasileiro e no estado do Tocantins.