NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning.

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken Germline depletion of Salsa and splice site mutations within gurken first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a gurken construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.

Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia.

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1-xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.

Oral health issues in children and adolescents with vision impairment: A systematic review and meta-analysis.

BACKGROUND: Children and adolescents with vision impairment (VI) may be at increased risk of oral health issues, such as periodontal inflammation, poor oral hygiene, dental caries, and dental trauma, but this is inconclusive in the literature. AIM: To systematically review the literature to determine the main oral health issues of children and adolescents with VI compared to those without VI. DESIGN: Electronic and manual searches were performed to identify observational studies involving children and adolescents with and without VI, to determine and compare their oral health issues. The methodological quality was assessed using the Joanna Briggs Institute critical appraisal tool. Studies that had homogeneity of methods were incorporated into meta-analyses. RESULTS: Fifteen cross-sectional studies were included. Overall, most studies presented methodological flaws and high risk of bias. The meta-analysis showed that children and adolescents with VI were 3.86 times as likely to exhibit dental trauma (OR = 3.86, 95% CI = 2.63-5.68, I2  = 0%) and had higher/poorer values for plaque (MD = 0.80, 95% CI = 0.58-1.02, I2  = 96%), gingivitis (MD = 0.69, 95% CI = 0.02-1.37, I2  = 100%), calculus (MD = 0.04, 95% CI = 0.03-0.06, I2  = 0%), and oral hygiene indices (MD = 0.71, 95% CI = 0.24-1.18, I2  = 97%), as well as DMFS (MD = 0.90, 95% CI = 0.68-1.13, I2  = 26%). CONCLUSION: Across a wide array of assessments, children and adolescents with vision impairment had worse oral health outcomes than those without VI.

The T-box transcription factor brachyury behaves as a tumor suppressor in gliomas.

The oncogene brachyury (TBXT) is a T-box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not been investigated previously in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples. Our glioma samples were analyzed for copy number (n = 372), promoter methylation status (n = 170), and mutation status (n = 1569 tissues and n = 52 cell lines) of the brachyury gene. The prognostic impact of brachyury expression was studied in 1524 glioma patient tumors. The functional impact of brachyury on glioma proliferation, viability, and cell death was evaluated both in vitro and in vivo. Brachyury was expressed in the normal brain, and significantly downregulated in glioma tissues. Loss of brachyury was associated with tumor aggressiveness and poor survival in glioma patients. Downregulation of brachyury was not associated with gene deletion, promoter methylation, or inactivating point mutations. Brachyury re-expression in glioma cells was found to decrease glioma tumorigenesis by induction of autophagy. These data strongly suggest that brachyury behaves as a tumor suppressor gene in gliomas by modulating autophagy. It is important to note that brachyury constitutes an independent positive biomarker of patient prognosis. Our findings indicate that the role of brachyury in tumorigenesis may be tissue-dependent and demands additional investigation to guide rational interventions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Strengthening Self-Care and Child Care of Adolescent Mothers Through an Event History Calendar.

PURPOSE: To identify events and experiences of adolescent mothers relevant to their own care and the care of their children so as to support the elaboration of a future Event History Calendar (EHC) tool. DESIGN AND METHODS: Qualitative study was conducted based on the Grounded Theory, from the constructivist perspective. Data were collected through in-depth interviews with 11 Brazilian adolescent mothers. Initial and focused coding was applied in the data analysis. RESULTS: The results present events that demarcate the adolescent mothers' perspectives of child care. Self-care and child care are related to everyday learning, ways of coping, strengthening of various support sources, mastery of gaps in health care, and sensory events. CONCLUSIONS: The different events for adolescents are related to the transience of life, strategies of the moment, and the process of support for pregnancy-motherhood, which is dependent on a network of people and institutions that provide cooperation and participation in the reengagement of the adolescents while encouraging quality of life and development. The events identified can contribute to a list of relevant elements to structure a tool using EHC to guide the clinical practice of nurses so as to strengthen the adolescent's self-care and child care. PRACTICE IMPLICATIONS: In the context of fragility in the communicative process between adolescent mothers and nurses, the strategy of an EHC can contribute to the expansion of nursing care, aid in developing new coping strategies addressing vulnerabilities, recognize multidimensional needs, strengthen the potentialities and confidence of mothers, and encourage involvement, advocacy and empowerment.

StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs. It is based on careful selection, standardized processing and stringent quality control of relevant transcriptomics datasets to minimize artefacts, and includes currently over 960 transcriptomes covering a broad range of SC types. Each of the integrated datasets was individually inspected and manually curated. StemMapper's user-friendly interface enables fast querying, comparison, and interactive visualization of quality-controlled SC gene expression data in a comprehensive manner. A proof-of-principle analysis discovering novel putative astrocyte/neural SC lineage markers exemplifies the utility of the integrated data resource. We believe that StemMapper can open the way for new insights and advances in SC research by greatly simplifying the access and analysis of SC transcriptomic data. StemMapper is freely accessible at http://stemmapper.sysbiolab.eu.

Do family functioning and mothers' and children's stress increase the odds of probable sleep bruxism among schoolchildren? A case control study.

OBJECTIVE: To investigate the association between probable sleep bruxism (PSB) and associated factors in schoolchildren. MATERIALS AND METHODS: A case-control study was conducted with a representative sample of 320 schoolchildren aged 8 to 10 years. The case group (160 children with PSB) and the control group (160 children without PSB) were matched for sex and age at a proportion of 1:1. Information on audible characteristics of PSB, harmful oral habits, and socio-demographic characteristics as collected through questionnaires answered by the parents/caregivers. The family functioning of children was measured through The Family Adaptability and Cohesion Evaluation Scales (FACES III). Mothers self-administered the Lipp Stress Symptoms Inventory (LSSI) for adults to measure mothers' stress and the children filled out the Child Stress Scale (CSS) to measure the children stress. Data analysis used descriptive and logistic regression analyses (p < 0.05). RESULTS: Among the children with stress, 67.3% had PSB. Children with stress (OR = 2.22, 95% CI 1.18-4.19), those with a history of nail biting (OR = 2.22, 95% CI 1.39-3.55), and biting objects (OR = 1.77, 95% CI 1.09-2.87) were more likely to have PSB. CONCLUSION: Childhood stress and a history of nail biting or biting objects are important signs to be considered in schoolchildren with PBS. CLINICAL RELEVANCE: These results alert that the PBS might be a sign of stress and other psychological problems such as tension and anxiety related to the presence of harmful oral habits. Furthermore, the results could help in the targeting of anamnesis, improved prevention and treatment strategies for sleep bruxism which should involve an interdisciplinary approach.

Shape Anisotropic Iron Oxide-Based Magnetic Nanoparticles: Synthesis and Biomedical Applications.

Research on iron oxide-based magnetic nanoparticles and their clinical use has been, so far, mainly focused on the spherical shape. However, efforts have been made to develop synthetic routes that produce different anisotropic shapes not only in magnetite nanoparticles, but also in other ferrites, as their magnetic behavior and biological activity can be improved by controlling the shape. Ferrite nanoparticles show several properties that arise from finite-size and surface effects, like high magnetization and superparamagnetism, which make them interesting for use in nanomedicine. Herein, we show recent developments on the synthesis of anisotropic ferrite nanoparticles and the importance of shape-dependent properties for biomedical applications, such as magnetic drug delivery, magnetic hyperthermia and magnetic resonance imaging. A brief discussion on toxicity of iron oxide nanoparticles is also included.

Do Patients with Extrinsic Black Tooth Stains Have a Lower Dental Caries Experience? A Systematic Review and Meta-Analysis.

Studies have suggested that individuals affected by extrinsic black tooth stains have less dental caries experience in comparison to those without this condition. The aim of the present study was to perform a systematic review and meta-analysis to determine whether there is scientific evidence demonstrating that extrinsic black stains are a protective factor for the occurrence of dental caries. This systematic review was developed in accordance with the PRISMA statement and the research question was determined using the PECO strategy. Electronic searches were conducted in the PubMed, Science Direct, Virtual Health Library, Cochrane, Web of Science, and Google Scholar databases for relevant articles published up to September 2018. All articles included were submitted to an appraisal of methodological quality using the Newcastle-Ottawa Scale and the data were extracted for meta-analysis. The search strategy resulted in the retrieval of 9,108 publications. After the application of the eligibility criteria, 18 articles were selected for analysis, 13 of which were included in the meta-analysis. The meta-analysis demonstrated that individuals with extrinsic black stains involving primary (median, MD: -0.78 [-1.09; -0.48]; I2 = 44%) and permanent (MD: -0.50 [-0.93; -0.08]; I2 = 86%) teeth have a lower dental caries experience in comparison to those without this condition. Patients with extrinsic black tooth stains have a lower dental caries experience in cross-sectional studies.

Getting a handle on embryo limb development: Molecular interactions driving limb outgrowth and patterning.

Development of the vertebrate embryo involves multiple segmentation processes to generate a functional, articulated organism. Cell proliferation, differentiation and patterning involve spatially and temporally regulated gene expression and signal transduction mechanisms. The developing vertebrate limb is an excellent model to study such fine-tuned regulations, whereby cells proliferate and are differentially sculptured along the proximal-distal, anterior-posterior and dorsal-ventral axes to form a functional limb. Complementary experimental approaches in different organisms have enhanced our knowledge on the molecular events underlying limb development. Herein, we summarize the current knowledge of the main signaling mechanisms governing vertebrate limb initiation, outgrowth, specification of limb segments and termination.

Mechanisms of vertebrate embryo segmentation: Common themes in trunk and limb development.

Various ultradian rhythms ensure proper temporal regulations during embryo development. The embryo molecular clock, which was first identified in the presomitic mesoderm (PSM) underlying periodic somite formation, is one among them. Somites are the earliest manifestation of the segmented vertebrate body and they are formed with strict temporal precision. The tetrapod limb is also a segmented structure and the formation of limb bone elements have also been associated with a molecular clock, operating in the distal limb mesenchyme. In both the PSM and the distal limb mesenchyme, the molecular clock (MC) is influenced by FGF, SHH and RA, which are also the key regulators of the development of these tissues. While somitogenesis has been continuously scrutinized to understand the mechanisms of the MC, the limb bud has served as an outstanding paradigm to study how a cohort of undifferentiated cells is organized into functional 3D structures. The fact that both the trunk and limb development are shaped by the MC and by common signaling molecules has prompted the exciting possibility of establishing parallelisms between somitogenesis and limb development. Systematically correlating various parameters during trunk and limb development will help us to appreciate the common principles underlying segmented structure formation and allow the rise of new questions in order to fill the gaps in our present understanding. In this review we have established the parallelisms between somitogenesis and limb development at the level of gene expression patterns and their regulation. Finally, we have also discussed the most evident new avenues this exercise could open to the scientific community.

Prevalence of probable sleep bruxism and associated factors in Brazilian schoolchildren.

AIM: To determine the prevalence of probable sleep bruxism (PSB) and associated factors among schoolchildren. DESIGN: This cross-sectional study was carried out with a representative sample of 440 schoolchildren. The children were submitted to a clinical oral examination for the evaluation of tooth wear and/or muscle discomfort. Parents/caregivers filled out a questionnaire with information related to characteristic sounds of sleep bruxism, sociodemographic factors, and the presence of harmful oral habits of children. The stress of the mothers was measured through the Lipp's Stress Symptoms Inventory for Adults (LSSI) instrument. The child's stress was measured through the Child Stress Scale (CSS). Data analysis included descriptive analysis and hierarchical Poisson regression (95% CI, P < 0.05). RESULTS: The prevalence of PSB was 40.0% (n = 176). The final Poisson regression model showed that PSB was significantly more prevalent in children with a history of nail biting (PR: 1.50; 95% CI: 1.19-1.90; P = 0.001) and biting objects (PR: 1.30; 95% CI: 1.03-1.63; P = 0.025) and less prevalent among girls (PR: 0.78; 95% CI: 0.63-0.98; P = 0.033). CONCLUSIONS: The prevalence of PSB in schoolchildren was high. Schoolchildren with a history of nail biting and biting objects had a higher prevalence of PSB.

The embryonic Brachyury transcription factor is a novel biomarker of GIST aggressiveness and poor survival.

BACKGROUND: The T-box transcription factor Brachyury was recently reported to be upregulated and associated with prognosis in solid tumors. Here, we proposed to evaluate the potential use of Brachyury protein expression as a new prognostic biomarker in gastrointestinal stromal tumors (GIST). METHODS: Brachyury protein expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST patients. Brachyury expression profiles were correlated with patients' clinicopathological features and prognostic impact. Additionally, an in silico analysis was performed using the Oncomine database to assess Brachyury alterations at DNA and mRNA levels in GISTs. RESULTS: We found that Brachyury was overexpressed in the majority (81.0 %) of primary GISTs. We observed Brachyury staining in the nucleus alone in 4.8 % of cases, 23.8 % depicted only cytoplasm staining, and 52.4 % of cases exhibited both nucleus and cytoplasm immunostaining. The presence of Brachyury was associated with aggressive GIST clinicopathological features. Particularly, Brachyury nuclear (with or without cytoplasm) staining was associated with the presence of metastasis, while cytoplasm sublocalization alone was correlated with poor patient survival. CONCLUSIONS: Herein, we demonstrate that Brachyury is overexpressed in GISTs and is associated with worse outcome, constituting a novel prognostic biomarker and a putative target for GIST treatment.

Dental caries, but not malocclusion or developmental defects, negatively impacts preschoolers' quality of life.

BACKGROUND: Oral diseases can negatively influence the quality of life causing harm in the development of routine activities, child development and their well-being. AIM: To investigate the impact of dental caries, malocclusion and developmental defects of enamel (DDE) on the oral health-related quality of life of preschool children and their parents. DESIGN: A cross-sectional study was carried out with 646 children aged 2-6 years in Diamantina, Brazil. Calibrated dental examiners performed the oral examinations. Parents answered the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS) and a questionnaire on socio-economic indicators. Statistical analyses involved the chi-square test and Poisson regression. RESULTS: Malocclusion and DDE did not cause a negative impact on the children's quality of life. Children with dental caries (PR: 1.92; 95%CI: 1.56-2.35) and those aged 5 (PR: 1.51; 95%CI: 1.13-2.02) and 6 years (PR: 1.51; 95%CI: 1.02-2.23) were more likely to have a negative quality of life impact on the total B-ECOHIS. CONCLUSIONS: Dental caries was associated with a negative impact on the quality of life of children. Malocclusion and DDE did not cause a negative impact on the children's quality of life. Older children had higher frequency of negative impact on OHRQoL.

Impact of traumatic dental injury on the quality of life of young children: a case-control study.

There are no longitudinal studies that assess the impact of traumatic dental injury (TDI) on the oral health-related quality of life (OHRQoL) of preschool children. To investigate the impact of TDI on OHRQoL among preschool children, a population-based case-control study was carried out with a representative sample of 335 children, 3-5 years of age, enrolled at public and private preschools in the city of Campina Grande, Brazil. The case group and the control group were matched for age, gender, type of preschool and monthly household income at a ratio of 1:4 (67 cases and 286 controls). Impact on the OHRQoL of children was assessed through administration of the Early Childhood Oral Health Impact Scale (ECOHIS). The occurrence of TDI was determined through clinical examinations performed by three calibrated dentists. Data analysis involved descriptive statistics, McNemar's test, the chi-square test with linear trend and conditional logistic regression analysis [P≤0.05; 95% confidence interval (95% CI)]. The most frequent responses were 'felt pain' (19.4%) and 'difficulty eating' (16.4%). The prevalence of TDI was 37.3% in the case group and 33.9% in the control group. No statistically significant differences were found between case and control groups regarding the presence of TDI (odds ratio=1.16; 95% CI: 0.66-2.02). TDI had no impact on the quality of life of preschool children.

Impact of oral mucosal conditions on oral health-related quality of life in preschool children: a hierarchical approach.

OBJECTIVE: To determine the impact of oral mucosal conditions on OHRQoL in preschool children. METHODS: A cross-sectional study was carried out with a selected representative sample of 724 children aged 2-5 years and their parents/caregivers. Data were collected through interviews with parents/caregivers, who also answered the B-ECOHIS. A clinical oral examination was performed to determine oral mucosal conditions, dental caries, dental trauma, and malocclusion. Data analysis involved descriptive statistics, the Kolmogorov-Smirnov normality test, the Mann-Whitney U-test and hierarchically adjusted Poisson regression models (P < 0.05, 95% CI). RESULTS: The prevalence of oral mucosal conditions was 50.7%, the most prevalent of which were melanotic macules (17.8%), oral ulcers (11.0%), Fordyce's spots (9.4%), geographic tongue (5.2%), fissured tongue (1.9%), median rhomboid glossitis (1.8%), and fistula (1.4%). In the final multivariate model, child with 5 years of age (RR = 1.60; 95% CI: 1.08-2.38; P = 0.020), with presence of fistula (RR = 1.94; 95% CI: 1.27-2.95; P = 0.002), and with dental caries (RR = 2.58; 95% CI: 2.00-3.35; P < 0.001) had a negative impact on children's OHRQoL. CONCLUSION: Child with 5 years of age, presence of fistula, and dental caries were associated with a negative impact on the quality of life of preschool children.

[Child care and health rights: perspectives of adolescent mothers]. / O cuidado da criança e o direito à saúde: perspectivas de mães adolescents.

OBJECTIVE: To analyze child health care and the defense of their rights from the perspective of adolescent mothers. METHODS: An exploratory study with qualitative thematic analysis of data, based on conceptual aspects of care and the right to health, from semi-structured interviews with 20 adolescent mothers ascribed by Family Health teams. RESULTS: Maternal reports indicate that child health care requires responsibility and protection, with health practices that promote child advocacy. Gaps in assistance which preclude the full guarantee of the right to child health care were also highlighted. CONCLUSION: The right to health care assumed different meanings, and the forms to guarantee them were linked to individual behavior in detriment to broader actions that consider health as a social product, connected to the guarantee of other fundamental rights.

Plasmodium vivax malaria elimination: should innovative ideas from the past be revisited?

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.

Quality Standards in Upper Gastrointestinal Endoscopy: Can Deep Sedation Influence It?

Introduction: According to the guideline published by ESGE/UEG, a high-quality esophagogastroduodenoscopy (EGD) implies the application of some criteria that enable better healthcare outcomes. Although intra-procedural performance measures are dependent on patient factors, there is no reference to sedation practices in the guideline mentioned above. Objective: This study aimed to evaluate whether deep sedation influences EGD performance measures established by ESGE/UEG. Methods: This was a cross-sectional study, with a prospective enrollment, that considered for inclusion consecutive patients referred for EGD. Two questionnaires were used to assess performance measures and patient satisfaction after EGD. Results: Sedation had a statistically significant impact on most quality indicators, including complete examination (77.2% without sedation vs. 97.8% with sedation), inspection time (6.17 ± 3.45 vs. 8.39 ± 2.67 min), photodocumentation (78% vs. 97.8%), biopsies (39.3% vs. 60.7%), and patient satisfaction (5.42 ± 2.93 vs. 9.1 ± 1.19). The main reason for an incomplete procedure was patient intolerance (82.6%). Discussion: Deep sedation of patients submitted to EGD proved to be a determinant in the applicability of the ESGE/UEG quality indicators. Patient intolerance was eliminated in the group with sedation, enhancing procedure completeness, adequate pathology identification, management, and consequently, the effectiveness of the exam. Conclusion: Sedation administration should be considered in patients undergoing EGD since it ensures a high-quality procedure.

Introdução: Uma endoscopia digestiva alta (EDA) de qualidade proporciona melhores resultados em termos de saúde e implica a aplicação dos critérios descritos pelas recomendações da ESGE/UEG. Embora os critérios perprocedimento sejam dependentes da colaboração e tolerância do doente, não está explicito o papel da anestesia. Objetivos: Este estudo pretende avaliar se o recurso a anestesia influencia o cumprimento dos critérios de qualidade para a EDA publicados pela ESGE/UEG. Materiais e métodos: Estudo transversal, com recrutamento prospetivo, que incluiu pacientes consecutivamente encaminhados para realização de EDA. Foram utilizados 2 questionários para avaliar medidas de desempenho e satisfação dos pacientes após realização de EDA. Resultados: A anestesia teve um impacto estatisticamente significativo na maioria dos indicadores de qualidade: exame completo (77,2% sem anestesia vs. 97,8% com anestesia); tempo de inspeção (6,17 ± 3,45 vs. 8,39 ± 2,67 minutos); fotodocumentação (78% vs. 97,8%); biópsias (39,3% vs. 60,7%); satisfação do paciente (5,42 ± 2,93 vs. 9,1 ± 1,19). O principal motivo para um procedimento incompleto foi a intolerância do paciente (82,6%). Discussão: A sedação profunda dos doentes submetidos a EDA provou ser determinante na aplicabilidade dos critérios de qualidade da ESGE/UEG. Eliminando por completo a intolerância por parte do doente, proporcionou a realização de exames completos, com correta identificação e gestão de patologias, potenciando assim a efetividade do exame. Conclusão: A administração de anestesia deve ser ponderada, sempre que possível, nos doentes submetidos a EDA, visto que permite garantir a alta qualidade do procedimento.