As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the ...same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAF
and
promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAF
(52.9%) and
(13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The
rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the
and/or
genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAF
and
; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the
and/or
genes may explain their increased expression in the tumor milieu.
Understanding the relationships between trait diversity, species diversity and ecosystem functioning is essential for sustainable management. For functions comprising two trophic levels, trait ...matching between interacting partners should also drive functioning. However, the predictive ability of trait diversity and matching is unclear for most functions, particularly for crop pollination, where interacting partners did not necessarily co‐evolve. World‐wide, we collected data on traits of flower visitors and crops, visitation rates to crop flowers per insect species and fruit set in 469 fields of 33 crop systems. Through hierarchical mixed‐effects models, we tested whether flower visitor trait diversity and/or trait matching between flower visitors and crops improve the prediction of crop fruit set (functioning) beyond flower visitor species diversity and abundance. Flower visitor trait diversity was positively related to fruit set, but surprisingly did not explain more variation than flower visitor species diversity. The best prediction of fruit set was obtained by matching traits of flower visitors (body size and mouthpart length) and crops (nectar accessibility of flowers) in addition to flower visitor abundance, species richness and species evenness. Fruit set increased with species richness, and more so in assemblages with high evenness, indicating that additional species of flower visitors contribute more to crop pollination when species abundances are similar. Synthesis and applications. Despite contrasting floral traits for crops world‐wide, only the abundance of a few pollinator species is commonly managed for greater yield. Our results suggest that the identification and enhancement of pollinator species with traits matching those of the focal crop, as well as the enhancement of pollinator richness and evenness, will increase crop yield beyond current practices. Furthermore, we show that field practitioners can predict and manage agroecosystems for pollination services based on knowledge of just a few traits that are known for a wide range of flower visitor species.
Changes in protein levels in different components of the apical junctional complex occur in colorectal cancer (CRC).Claudin-3 is one of the main constituents of tight junctions, and its ...overexpression can increase the paracellular flux of macromolecules, as well as the malignant potential of CRC cells. The aim of this study was to investigate the molecular mechanisms involved in the regulation of claudin-3 and its prognostic value in CRC. In silico evaluation in each of the CRC consensus molecular subtypes (CMSs) revealed that high expression levels of CLDN3 (gene encoding claudin-3) in CMS2 and CMS3 worsened the patients' long-term survival, whereas a decrease in claudin-3 levels concomitant with a reduction in phosphorylation levels of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R)could be achieved by inhibiting N-glycan biosynthesis in CRC cells. We also observed that specific inactivation of these receptor tyrosine kinases (RTKs) led to a decrease in claudin-3 levels, and this regulation seems to be mediated by phospholipase C (PLC) and signal transducer and activator of transcription 3 (STAT3) in CRC cells. RTKs are modulated bytheir N-linked glycans, and inhibition of N-glycan biosynthesis decreased the claudin-3 levels; therefore, we evaluated the correlation between N-glycogenes and CLDN3 expression levels in each of the CRC molecular subtypes. The CMS1 (MSIimmune) subtype concomitantly exhibited low expression levels of CLDN3 and N-glycogenes (MGAT5, ST6GAL1, and B3GNT8), whereas CMS2 (canonical) exhibited high gene expression levels of CLDN3 and N-glycogenes (ST6GAL1 and B3GNT8). A robust positive correlation was also observed between CLDN3 and B3GNT8 expression levels in all CMSs. Theseresults support the hypothesis of a mechanism integrating RTK signaling and N-glycosylation for the regulation of claudin-3 levels in CRC, and they suggest that CLDN3 expression can be used to predict the prognosis of patients identified as CMS2 or CMS3.
The interaction between galactomannans, guar gum (GG) with sodium lauryl ether sulphate (SLES) was demonstrated using conductometric, tensiometric, pyrene probe and 1H NMR analyses. SLES and GG ...formed aggregates and reduced the surface tension at a critical aggregation concentration. The interaction was attributed to the presence of surfactant ethoxyl (EO) groups, since in conductometric, tensiometry and pyrene probe analyses using the non-ethoxylated form, sodium lauryl sulphate – SLS, no aggregation was observed. The aggregates formed between SLES and GG presented a negative zeta potential indicating that the polymer is surrounded by SLES and according to the dynamic light scattering analysis (DLS), presented a size of approximately 26 nm. The determination of the thermodynamic parameters showed that the aggregation occurs spontaneously and is a driven-enthalpy and entropy process. SLES and GG interaction could be explored to produce formulations with lower concentrations of surfactants, using commonly used thickeners as GG.
•Galactomannans and SLES interaction were demonstrated using different techniques.•Galactomannans and SLES interacts forming aggregated structures.•The GG and SLES aggregates presented interfacial properties.•The aggregates are stable and presented a size of approximately 26 nm.•The interaction is non-ionic and may involve SLES EO groups.
We describe herein a synthetic strategy for the synthesis of new fluorescent imidazole and phenazine derivatives synthesized from lapachol, a naturally occurring naphthoquinone isolated from Tabebuia ...species (ipê tree). The photophysical properties and computational details of these compounds have been studied, aiming at gaining a complete understanding of the potential of these derivatives as probes capable of staining mitochondria selectively. Cell imaging experiments proved the capacity of the imidazole derivatives as selective fluorescent mitochondrial imaging probes. These heterocycles present the same staining patterns as MitoTracker Red, corroborating the potential of these compounds as new mitochondria markers permeable to the cell membrane.
A synthetic strategy for the synthesis of new fluorescent imidazole and phenazine derivatives prepared from naturally occurring naphthoquinones as selective fluorescent mitochondrial imaging probes is reported. These heterocycles present the same staining patterns as MitoTracker Red, corroborating the potential of these compounds as new mitochondria markers permeable to the cell membrane.
IMPORTANCE: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain ...uncertain. OBJECTIVE: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. INTERVENTIONS: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. RESULTS: A total of 1010 patients (37.5% female; mean SD age, 50.9 17.4 years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio HR, 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. CONCLUSIONS AND RELEVANCE: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01374022
Com o passar dos tempos novos estudos sobre materiais didáticos vem sendo desenvolvidos, com a intenção de aumentar a interação na sala de aula, proporcionando maior conforto e capacidade de ...assimilação dos alunos além de desenvolver as capacidades cognitivas. Neste sentido, este trabalho tem por objetivo analisar a eficácia de um instrumento didático a partir de uma pesquisa desenvolvida com a utilização de questionários aplicados antes e depois da construção e utilização de uma coleção de abelhas, tendo como público de pesquisa as turmas deprimeiro ano do curso Técnico em Apicultura. A partir disso, os resultados mostraram a eficiência de uma coleção de abelhas como ferramenta mediadora no processo de ensino e aprendizagem. Quando avaliado o aumento dos percentuais estatísticos conclui-se que a montagem e utilização da coleção de abelhas auxiliou na aprendizagem e desenvolvimento dos alunos, demonstrando que a criação de novas ferramentas didáticas são essenciais para a educação técnica.
This manuscript reports the synthesis and characterization of the first organic-inorganic hybrid material exhibiting efficient multimodal spectral converting properties. The nanocomposite, made of ...Er3+, Yb3+ codoped zirconia nanoparticles (NPs) entrapped in a di-ureasil d-U(600) hybrid matrix, is prepared by an easy two-step sol-gel synthesis leading to homogeneous and transparent materials that can be very easily processed as monolith or film. Extensive structural characterization reveals that zirconia nanocrystals of 10-20 nm in size are efficiently dispersed into the hybrid matrix and that the local structure of the di-ureasil is not affected by the presence of the NPs. A significant enhancement in the refractive index of the di-ureasil matrix with the incorporation of the ZrO2 nanocrystals is observed. The optical study demonstrates that luminescent properties of both constituents are perfectly preserved in the final hybrid. Thus, the material displays a white-light photoluminescence from the di-ureasil component upon excitation at UV visible radiation and also intense green and red emissions from the Er3+- and Yb3+-doped NPs after NIR excitation. The dynamics of the optical processes were also studied as a function of the lanthanide content and the thickness of the films. Our results indicate that these luminescent hybrids represent a low-cost, environmentally friendly, size-controlled, easily processed and chemically stable alternative material to be used in light harvesting devices such as luminescent solar concentrators, optical fibres and sensors. Furthermore, this synthetic approach can be extended to a wide variety of luminescent NPs entrapped in hybrid matrices, thus leading to multifunctional and versatile materials for efficient tuneable nonlinear optical nanodevices.
Objectives: To investigate the quality of life (QOL) of and to characterize patients with atopic dermatitis (AD) in Portugal. Methods: This was a cross-sectional study of patients with AD and other ...eczemas. Skindex-29, Skindex-teen, and the Childhood Atopic Dermatitis Impact Scale (CADIS) were the instruments used to assess QOL in adults, teenagers, and children, respectively. The SF-12 was also used, and disease severity was evaluated using the Patient-Oriented SCORAD (PO-SCORAD) instrument. Associations with QOL were assessed based on the odds ratio (OR). P values <.05 and 95%CIs were considered statistically significant. Results: The study population comprised 162 participants aged 0.5-74 years. We found that 37.3% of AD patients consider their disease disabling and that more than half of the patients feel stigmatized by society. The mean Skindex score for AD was 39.68, and the impact on QOL was severe in 44%. “Symptoms” was the most affected category in adults. AD was moderate to severe in 87% of the sample. One of the factors that most influenced poorer QOL in AD was age: with increasing age, the Skindex is likely to increase (OR, 1.03; 95%CI, 1.00-1.06). “Considering the disease a disability” was also associated (OR, 6.72; 95%CI, 2.56-17.63). QOL worsens with increasingly affected body area (OR, 1.07; 95%CI, 1.03-1.11) and the presence of edema (OR, 2.0; 95%CI, 1.23-3.40). Conclusions: This is the first study to provide data on QOL in patients with AD in Portugal. Our data show an expected negative impact. More awareness-raising activities are needed to increase knowledge, decrease stigmatization, and, consequently, address the factors involved in the QOL of patients with AD.
The present study aimed to perform an epidemiological survey on the prevalence rate of oral lesions diagnosed in a referral center in Brazil and to establish association between the lesions and the ...age and gender of the affected patients. This analytical observational study analyzed 3521 medical records of anatomopathological exams of the Pathological Anatomy and Cytopathology Laboratory of the Cancer Hospital of the state of Mato Grosso (Brazil), from December 2011 to September 2015. A total of 1550 relevant medical records was detected. Patients aging between 41 and 60 consisted of 42.84% of the sample. Males were more affected than females (60.13%). Inflammatory processess consisted of the most prevalent diagnosis (43.29%), followed by squamous cell carcinoma (6.06%), and periapical granuloma (5.23%). Oral health public policies must give major attention to Brazilian males aged between the fourth and sixth decades of life in order to improve their quality of life.