Growth of teeth and bones in adult subjects with congenital untreated isolated growth hormone deficiency.

OBJECTIVE: To understand the growth of teeth and mandibular and maxillary bones in subjects with isolated growth hormone deficiency (IGHD). MATERIAL AND METHODS: Mesiodistal tooth width of 28 maxillary and mandibular dental models of 14 adult IGHD subjects (9 men) were digitalized and compared to 40 models of 20 normal-statured controls (11 men). The mean SDS of the maxillary and mandibular teeth were compared with height, cephalic perimeter, total anterior facial height, total maxillary and mandibular length, and maxillary and mandibular arches. RESULTS: All average mesiodistal dimensions in absolute values of the 14 dental pairs were reduced in the IGHD group. Eight of 28 (28.6%) mesiodistal dimensions in IGHD subjects of both sexes had an average SDS below -2, thirteen of them (46.4%) had mean SDS between -1 and - 2, and seven of them (25.0%) had SDS above -1. The highest SDS values were the upper lateral incisor (-0.32 in women), and the upper canine (-0.91 in men). The lowest SDS values were the 2nd upper molar (-3.51 in men), and the 2nd upper premolar (-2.64 in women). The ascending order of the mean SDS was height, total maxillary length, total mandibular length, total anterior height of the face, cephalic perimeter, the maxillary arches width, the mesiodistal width of the mandibular teeth, the mesiodistal width of the maxillary teeth and the mandibular arches width. CONCLUSIONS: Reduction in mesiodistal width is present in untreated IGHD adults with magnitude of tooth size reduction being lower than height, cephalic perimeter, total anterior facial height, and most jaw measurements. IGHD abolishes the sexual dimorphism in mesiodistal dental measures.

Dental arches in inherited severe isolated growth hormone deficiency.

OBJECTIVES: The growth of the dental arches depends on GH and insulin-like growth factor type 1 (IGF1), but the consequences of GH deficiency (GHD) on their growth are still unclear, probably due to the acquired etiology of GHD in most described series, often associated with additional pituitary deficits (thyrotrophic, corticotrophic and gonadotrophic hormones), and imperfections of related replacement therapies, which may affect the dental arch growth. To avoid these limitations, we took advantage of a unique cohort of subjects with isolated GH deficiency (IGHD) due the same mutation in the GH releasing hormone receptor gene, living with very low serum GH and low to undetectable circulating IGF1 levels. Our purpose was to analyze the dimensions of maxillary and mandibular dental arches. METHODS: 22 adult IGHD (15 untreated and 7 previously partially treated with GH) and 33 controls were enrolled in a cross-sectional study using the Ortho Insight 3D and MeshMixer software, RESULTS: In untreated IGHD subjects all maxillary arch measures were smaller than controls, while among mandibular arches, only the mandibular canine width and the mandibular arch length were reduced. In partially GH treated subjects only the palate depth, the maxillary canine width, the maxillary and mandibular arch lengths remained smaller than controls. CONCLUSIONS: IGHD reduces the growth of maxillary arch to a greater degree than the mandibular arch, suggesting different control of superior and inferior dental arches. GH treatment increases some of these measures.

Spatio-temporal sublittoral macrobenthic distribution and dominant species in Guanabara Bay, Rio de Janeiro, Brazil / Distribuição espaço-temporal do macrobentos de infralitoral e espécies dominantes na Baía de Guanabara, Rio de Janeiro, Brasil

Abstract Soft-bottom macrobenthic invertebrates are sensitive to natural or anthropogenic changes in aquatic ecosystems. The distribution patterns of sublittoral macrobenthic species in Guanabara Bay were studied from 2005 to 2007. Samples were collected at ten stations during six surveys throughout the rainfall regime (dry, early and late rainy). Ten replicates were collected at each station by Gravity corer or skin diving. Van Dorn bottles (bottom water) and by Ekman sediment sampler (granulometry) provided material for abiotic data. Stations were grouped into sectors (Entrance, Intermediary and Inner) based on abiotic data and location. The Redundancy Analysis (RDA) and Parsimonious RDA for all years and each annual cycle showed indicator taxa with high dominance in each sector. PERMANOVA indicated a regular seasonality between the surveys for the first annual cycle (p <0.05), and an atypical pattern for the second (p> 0.05), possibly due the low rainfall observed during this period. The mosaic of soft-bottom substrates infers structural variables, and patterns of temporal distribution were basically influenced by parameters those indicating pollution and the SACW (South Atlantic Central Water) intrusion, as well as ecological attributes among species, such as: predation, competition. The Ervilia concentrica and Cypridinidae could be used as indicators for anthropic and natural impacts in the Guanabara Bay for the Entrance sector, while Cyprideis salebrosa and Cyprideis sp. for the Intermediary sector and Heleobia australis for the Inner sector.

Resumo Os invertebrados macrobentônicos são sensíveis as alterações naturais e antrópicas nos ecossistemas aquáticos. O padrão de distribuição das espécies macrobentônicas do infralitoral da Baía de Guanabara foram estudados de 2005 até 2007. Amostras foram coletadas em dez estações durante seis campanhas em todo o regime pluviométrico (seco, pré e pós chuvoso). Dez réplicas foram coletadas em cada estação por meio do amostrador Gravity corer ou por mergulho livre. Os dados abióticos foram coletados por meio de garrafa oceanográfica do tipo van Dorn (água de fundo) e por busca fundo do tipo Ekman (granulometria). As estações foram agrupadas em setores (Entrada, Intermediária e Interna) baseada nos dados abióticos e localização. A Análise de Redundância (RDA) e RDA Parcimoniosa para todos os anos e em cada ano evidenciou taxa indicadores como elevada dominância em cada setor. A PERMANOVA indicou sazonalidade regular entre as campanhas para o primeiro ciclo anual (p<0.05), padrão atípico para o segundo ano (p> 0.05), possivelmente por causa da baixa pluviosidade observada durante esse período. O mosaico do substrato não consolidado infere que as variáveis estruturais, e os padrões de distribuição temporal foram basicamente influenciadas por parâmetros que indicam poluição e intrusão de ACAS (Água Central do Atlântico Sul), bem como atributos ecológicos entre espécies, tais como: predação, competição, entre outros. Ervilia concentrica e Cypridinidae podem ser utilizados como indicadores de alterações naturais e antrópicos no setor da Entrada da Baía de Guanabara, enquanto Cyprideis salebrosa e Cyprideis sp. para o setor Intermediário e Heleobia australis para o setor Interno.

Spatio-temporal sublittoral macrobenthic distribution and dominant species in Guanabara Bay, Rio de Janeiro, Brazil.

Soft-bottom macrobenthic invertebrates are sensitive to natural or anthropogenic changes in aquatic ecosystems. The distribution patterns of sublittoral macrobenthic species in Guanabara Bay were studied from 2005 to 2007. Samples were collected at ten stations during six surveys throughout the rainfall regime (dry, early and late rainy). Ten replicates were collected at each station by Gravity corer or skin diving. Van Dorn bottles (bottom water) and by Ekman sediment sampler (granulometry) provided material for abiotic data. Stations were grouped into sectors (Entrance, Intermediary and Inner) based on abiotic data and location. The Redundancy Analysis (RDA) and Parsimonious RDA for all years and each annual cycle showed indicator taxa with high dominance in each sector. PERMANOVA indicated a regular seasonality between the surveys for the first annual cycle (p <0.05), and an atypical pattern for the second (p> 0.05), possibly due the low rainfall observed during this period. The mosaic of soft-bottom substrates infers structural variables, and patterns of temporal distribution were basically influenced by parameters those indicating pollution and the SACW (South Atlantic Central Water) intrusion, as well as ecological attributes among species, such as: predation, competition. The Ervilia concentrica and Cypridinidae could be used as indicators for anthropic and natural impacts in the Guanabara Bay for the Entrance sector, while Cyprideis salebrosa and Cyprideis sp. for the Intermediary sector and Heleobia australis for the Inner sector.

Accuracy of computer-assisted image analysis in the diagnosis of maxillofacial radiolucent lesions: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing maxillofacial radiolucent lesions. METHODS: A systematic review was conducted according to the statements of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols and considering 10 databases, including the gray literature. Protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018089945). The population, intervention, comparison and outcome strategy was used to define the eligibility criteria and only diagnostic test studies were included. Their risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal tool. Random-effects model meta-analysis was performed and heterogeneity among the included studies was estimated using the I2 statistic. The grade of recommendation, assessment, development, and evaluation (GRADE) tool assessed the quality of evidence and strength of recommendation across included studies. RESULTS: Out of 715 identified citations, four papers, published between 2009 and 2017, fulfilled the criteria and were included in this systematic review. A total of 191 lesions, classified as periapical granuloma and cyst, dentigerous cyst or keratocystic odontogenic tumor, were analyzed. All selected articles scored low risk of bias. The pooled accuracy estimation, regardless of the classification method used, was 88.75% (95% CI = 85.19-92.30). Heterogeneity test reached moderate values (I2 = 57.89%). According to the GRADE tool, the analyzed outcome was classified as having low level of certainty. CONCLUSIONS: The overall evaluation showed all studies presented high accuracy rates of computer-aided diagnosis systems in classifying radiolucent maxillofacial lesions compared to histopathological biopsy. However, due to the moderate heterogeneity found among the studies included in this meta-analysis, a pragmatic recommendation about the use of computer-assisted analysis is not possible.

Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

The regulatory effect of Tau protein on polymerization of MCF7 microtubules in vitro.

Growing evidence continues to point toward the critical role of beta tubulin isotypes in regulating some intracellular functions. Changes that were observed in the microtubules' intrinsic dynamics, the way they interact with some chemotherapeutic agents, or differences on translocation specifications of some molecular motors along microtubules, were associated to their structural uniqueness in terms of beta tubulin isotype distributions. These findings suggest that the effects of microtubule associated proteins (MAPs) may also vary on structurally different microtubules. Among different microtubule associated proteins, Tau proteins, which are known as neuronal MAPs, bind to beta tubulin, stabilize microtubules, and consequently promote their polymerizations. In this study, in a set of well controlled experiments, the direct effect of Tau proteins on the polymerization of two structurally different microtubules, porcine brain and breast cancer (MCF7), were tested and compared. Remarkably, we found that in contrast with the promoted effect of Tau proteins on brain microtubules' polymerization, MCF7 expressed a demoted polymerization while interacting with Tau proteins. This finding can potentially be a novel insight into the mechanism of drug resistance in some breast cancer cells. It has been reported that microtubules show destabilizing behavior in some MCF7 cells with overexpression of Tau protein when treated with a microtubules' stabilizing agent, Taxol. This behavior has been classified by others as drug resistance, but it may instead be potentially caused by a competition between the destabilizing effect of the Tau protein and the stabilizing effect of the drug on MCF7 microtubules. Also, we quantified the polarization coefficient of MCF7 microtubules in the presence and absence of Tau proteins by the electro-orientation method and compared the values. The two significantly different values obtained can possibly be one factor considered to explain the effect of Tau proteins on the polymerization of MCF7 microtubules.

In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba

Abstract Five coumarins (5,7,8-trimethoxycoumarin (1), sabandin (2), cubreuva lactone (3), 5,7-dimethoxycoumarin (5) and braylin (6)), seven furoquinoline alkaloids (isopimpinelin (4), pteleine (7), maculine (8), skimianine (10), robustine (11), y-fagarine (12) and dictamine (13) and the furofuran type lignin syringaresinol (9)) have been identified for the first time in the roots of Zanthoxylum tingoassuiba A. St.-Hil., Rutaceae. Pure compounds 1, 6, 9, 12 were tested against Leishmania amazonensis parasites and epimastigotes forms of Trypanosoma cruzi. All the tested products displayed an antiparasitic activity similar to that of the positive controls (benznidazole and amphotericin B). Compound 9 was the most active against both parasites with IC50 values of 11.98 µM and 7.55 µM against L. amazonensis and T. cruzi, respectively.

Electrostatic differences: A possible source for the functional differences between MCF7 and brain microtubules.

Recent studies suggested a link between diversity of beta tubulin isotypes in microtubule structures and the regulatory roles that they play not only on microtubules' intrinsic dynamic, but also on the translocation characteristics of some of the molecular motors along microtubules. Remarkably, unlike porcine brain microtubules, MCF7 microtubules are structured from a different beta tubulin distribution. These types of cancer microtubules show a relatively stable and slow dynamic. In addition, the translocation parameters of some molecular motors are distinctly different along MCF7 as compared to those parameters on brain microtubules. It is known that the diversity of beta tubulin isotypes differ predominantly in the specifications and the electric charge of their carboxy-terminal tails. A key question is to identify whether the negative electrostatic charge of tubulin isotypes and, consequently, microtubules, can potentially be considered as one of the sources of functional differences in MCF7 vs. brain microtubules. We tested this possibility experimentally by monitoring the electro-orientation of these two types of microtubules inside a uniform electric field. Through this evaluation, we quantified and compared the average normalized polarization coefficient of MCF7 vs. Porcine brain microtubules. The higher value obtained for the polarization of MCF7 microtubules, which is associated to the higher negative charge of these types of microtubules, is significant as it can further explain the slow intrinsic dynamic that has been recently reported for single MCF7 microtubules in vitro. Furthermore, it can be potentially considered as a factor that can directly impact the translocation parameters of some molecular motors along MCF7 microtubules, by altering the mutual electrostatic interactions between microtubules and molecular motors.

Spatio-temporal sublittoral macrobenthic distribution and dominant species in Guanabara Bay, Rio de Janeiro, Brazil

Abstract Soft-bottom macrobenthic invertebrates are sensitive to natural or anthropogenic changes in aquatic ecosystems. The distribution patterns of sublittoral macrobenthic species in Guanabara Bay were studied from 2005 to 2007. Samples were collected at ten stations during six surveys throughout the rainfall regime (dry, early and late rainy). Ten replicates were collected at each station by Gravity corer or skin diving. Van Dorn bottles (bottom water) and by Ekman sediment sampler (granulometry) provided material for abiotic data. Stations were grouped into sectors (Entrance, Intermediary and Inner) based on abiotic data and location. The Redundancy Analysis (RDA) and Parsimonious RDA for all years and each annual cycle showed indicator taxa with high dominance in each sector. PERMANOVA indicated a regular seasonality between the surveys for the first annual cycle (p 0.05), and an atypical pattern for the second (p> 0.05), possibly due the low rainfall observed during this period. The mosaic of soft-bottom substrates infers structural variables, and patterns of temporal distribution were basically influenced by parameters those indicating pollution and the SACW (South Atlantic Central Water) intrusion, as well as ecological attributes among species, such as: predation, competition. The Ervilia concentrica and Cypridinidae could be used as indicators for anthropic and natural impacts in the Guanabara Bay for the Entrance sector, while Cyprideis salebrosa and Cyprideis sp. for the Intermediary sector and Heleobia australis for the Inner sector.

Resumo Os invertebrados macrobentônicos são sensíveis as alterações naturais e antrópicas nos ecossistemas aquáticos. O padrão de distribuição das espécies macrobentônicas do infralitoral da Baía de Guanabara foram estudados de 2005 até 2007. Amostras foram coletadas em dez estações durante seis campanhas em todo o regime pluviométrico (seco, pré e pós chuvoso). Dez réplicas foram coletadas em cada estação por meio do amostrador Gravity corer ou por mergulho livre. Os dados abióticos foram coletados por meio de garrafa oceanográfica do tipo van Dorn (água de fundo) e por busca fundo do tipo Ekman (granulometria). As estações foram agrupadas em setores (Entrada, Intermediária e Interna) baseada nos dados abióticos e localização. A Análise de Redundância (RDA) e RDA Parcimoniosa para todos os anos e em cada ano evidenciou taxa indicadores como elevada dominância em cada setor. A PERMANOVA indicou sazonalidade regular entre as campanhas para o primeiro ciclo anual (p 0.05), padrão atípico para o segundo ano (p> 0.05), possivelmente por causa da baixa pluviosidade observada durante esse período. O mosaico do substrato não consolidado infere que as variáveis estruturais, e os padrões de distribuição temporal foram basicamente influenciadas por parâmetros que indicam poluição e intrusão de ACAS (Água Central do Atlântico Sul), bem como atributos ecológicos entre espécies, tais como: predação, competição, entre outros. Ervilia concentrica e Cypridinidae podem ser utilizados como indicadores de alterações naturais e antrópicos no setor da Entrada da Baía de Guanabara, enquanto Cyprideis salebrosa e Cyprideis sp. para o setor Intermediário e Heleobia australis para o setor Interno.