CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.

Effect of an intensive nutrition intervention of a high protein and low glycemic load diet on weight of kidney transplant recipients: a randomized clinical trial.

PURPOSE: The purpose of this study is to evaluate the effect of a high protein and low glycemic load diet in preventing weight gain after kidney transplantation. METHODS: We designed a prospective, single-center, open-label, randomized controlled study to compare the efficacy of a high protein (1.3-1.4 g/kg/day) and low glycemic load diet versus a conventional diet (0.8-1.0 g/kg/day of protein and no recommendations on glycemic load) in preventing weight gain (ClinicalTrials.gov identifier: NCT02883777). A total of 120 patients were evaluated. Patients were followed for 12 months, and the primary outcome was weight maintenance or weight gain lower than 5%. RESULTS: There were no differences in total energy intake, carbohydrates, and total fats between groups. Intervention group (IG) increased protein intake to 1.38 ± 0.56 g/kg/day and decreased the glycemic load to 87.27 ± 4.54 g/day, while control group (CG) had a dietary protein intake of 1.19 ± 0.43 g/kg/day and a glycemic load of 115.60 ± 7.01 g/day. Total fiber intake was greater and trans-fat was lower in IG. Dietetic cholesterol increased in IG over time and was significantly different between groups. Overall, patients had an increase in body weight over time, with a mean increment of 4.1 ± 5.5 kg (5.75%). The percentage of patients who achieved the primary outcome was 50% of sample size, without differences between groups. The glomerular filtration rate improved over time in both groups. Considering 24-h proteinuria and albuminuria, a similar rise was observed in both groups. CONCLUSION: The present dietary intervention was safe, but had no effect on weight gain in kidney transplant subjects. Our findings suggest that other strategies, including alternative dietary and/or pharmacological and psychological interventions might be tested in randomized control trials in order to improve patients' body weight outcomes after transplant.

Metaviromic reveals the dynamics and diversity of the virosphere in wastewater samples from Natal, Brazil.

The COVID-19 pandemic underscored the significance of omics technology and Wastewater-Based Epidemiology for epidemic preparedness. This study investigates the virosphere in wastewater samples from Natal (Brazil), aiming to understand its structure, relationships, and potential. Metaviromic analysis was used on DNA and RNA from weekly samples collected over a year (June/2021 to May/2022) from three wastewater treatment plants. The virosphere showed stability, particularly in viruses infecting microorganisms and plants. However, an alternation of representatives of viruses that infect animals has been observed. Among the most abundant viruses infecting microorganisms are genera associated with the bacterial genera Escherichia, Pseudomonas, and Caulobacte. Regarding the viruses infecting plants, Sobemovirus and Tobamovirus are the most abundant genera. Odontoglossum ringspot virus was identified as a possible RNA virus biomarker. Among DNA viruses infecting animals, genera Bocaparvovirus and Mastadenovirus are the most prevalent. Intriguingly, some Poxviridae family members were observed in the samples. Co-occurrence network analysis identified potential biomarkers like Volepox virus, Anatid herpesvirus 1, and Caviid herpesvirus 2. Among RNA viruses affecting animals, Mamastrovirus, Rotavirus, and Norovirus genera were the most abundant pathogens. Furthermore, members of the Coronaviridae family exhibited a high degree of centrality values in the co-occurrence network, even connecting with unclassified viruses. The study emphasizes the importance of research in understanding the roles of unclassified viruses. In addition, we observed an association between Coronaviridae reads, rainfall, and the number of reported COVID-19 cases. Our study highlights the diversity and complexity of the viral community in wastewater and the need for research to understand better the ecological roles unclassified viruses play. Such advances will significantly contribute to our preparedness and response to future viral threats. Furthermore, our study contributes to knowledge of virosphere dynamics, offering insights that can contribute to the direction of future public health policies and interventions.

Causes and risk factors for early death in adult patients with acute promyelocytic leukemia: a real-life experience.

INTRODUCTION: Early Death (ED) remains challenging in newly diagnosed acute promyelocytic leukemia (APL), especially in developing countries. The clinical and laboratory profile at diagnosis were evaluated and causes and risk factors were investigated in adult APL patients. METHOD: A retrospective real-life analysis of 141 medical records was performed of patients diagnosed with APL between 2007 and 2018, whether they were treated with the IC-APL 2006 protocol or not. Risk factors were assessed by univariate and multivariate analysis. MAIN RESULTS: Overall, 112 patients were included in the study. ED occurred in 22.3% of cases, surpassing clinical trial reports, with non-protocol-eligible patients presenting notably higher rates (60%), potentially due to their clinical status. Hemorrhage (60%) and infection (33.3%) were the leading causes of ED. Univariate analysis associated ED to the ECOG score; white blood cell (WBC) count; body mass index; levels of hemoglobin, albumin, uric acid, and creatinine, aPTT and INR and FLT3 mutations. Multivariate analysis identified ECOG score ≥2 and elevated WBC count as independent risk factors. CONCLUSION: ED remains a substantial challenge in APL, especially in real-world settings with hemorrhage and infection being the leading causes. ECOG status and WBC count emerged as independent risk factors, while age and platelet count lacked a 30-day prognostic correlation. Evaluating prognostic enhancement tools in controlled trials and real-life settings is pivotal to improving APL outcomes.

A network analysis of early trauma and impulsive behavior in individuals with mono- and poly-dependence of alcohol and crack cocaine.

OBJECTIVE: To investigate the relationship between impulsivity and early trauma through a network analysis in individuals diagnosed with different substance use disorders (SUD). METHODS: This cross-sectional study includes a sample of 556 men with SUD (195 with alcohol use, 157 with crack cocaine use and 214 with multiple substance use). The Childhood Trauma Questionnaire was applied to investigate early trauma and the Barratt Impulsiveness Scale to assess impulsive behavior. The connection between trauma and impulsivity was assessed using network analysis through Fused Graphical Lasso algorithm. RESULTS: No connection was observed between impulsivity and trauma networks in individuals with alcohol use. In cocaine users, networks were linked through the motor domain and sexual abuse nodes. Inversely connections were observed between emotional neglect node and perseverance and not planning nodes. In poly-use, the connection between impulsivity and trauma networks was weak, with cognitive complexity being the node that connects to the trauma network through physical abuse. There were inversely proportional connections between motor domain and emotional neglect nodes, and cognitive instability and physical neglect. CONCLUSIONS: Our results suggest that the relationship between the type of early (childhood) trauma and the expression of impulsivity could lead to a different substance use profile.

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity.

During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus-host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g., S100A9, LY96, and RAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, including TP53, IL2RB, and NCL Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.

Respiratory sarcopenia screening in dialysis patients: cross-sectional and multicentre study protocol.

BACKGROUND: Respiratory sarcopenia is characterized by the weakness of respiratory muscles associated with sarcopenia due to aging or systemic diseases such as chronic kidney disease (CKD). Patients with CKD undergoing dialysis are particularly susceptible to respiratory muscle weakness caused by factors such as fluid overload and electrolyte imbalance. This weakness not only affects ventilation but also impairs oxygen uptake and delivery to muscle tissue, potentially leading to severe sarcopenia. Thus, the objective of this study is to conduct a respiratory sarcopenia screening in patients with CKD undergoing haemodialysis (HD) and peritoneal dialysis (PD). METHODS: This is an observational, cross-sectional and multicentre study conducted between March 2023 and March 2025. The study was approved by the Research Ethics Committee at two centres. Sarcopenia diagnosis is determined based on low handgrip strength and amount of appendicular skeletal muscle mass, assessed through bioelectrical impedance analysis. Respiratory sarcopenia is diagnosed in patients with sarcopenia who have low inspiratory muscle strength, evaluated through a manovacuometry test. The severity of sarcopenia and respiratory sarcopenia is defined, respectively, by low physical performance (measured using the Short Physical Performance Battery and Timed-Up and Go test) and pulmonary performance (measured through spirometry). Thus, this study will include 81 patients undergoing dialysis (41 on HD and 40 on PD) from three participating centres. DISCUSSION: The literature has been focused on respiratory function in CKD; however, the relationship with sarcopenia remains understudied. We believe that, similar to appendicular skeleton muscles, the axial skeleton muscles are also likely to weaken with the presence of chronic disease, such as CKD.

Surface properties and flexural fatigue strength of an advanced lithium disilicate.

The aim of this study was to evaluate the surface properties and fatigue mechanical behavior of an advanced lithium disilicate ceramic in comparison to lithium disilicate and zirconia. First, discs (n = 15, diameter = 13.5 mm and thickness = 1.2 mm) were made from the following materials: 4Y-PSZ - 4% mol yttria-stabilized zirconia (IPS e.max ZirCAD A2); LD - lithium disilicate (IPS e.max CAD); ALD - advanced lithium disilicate (CEREC Tessera). The specimens were crystalized/sintered and subsequently analyzed by a rugosimeter (Mitutoyo SJ-410) to determine surface roughness (parameters Ra and Rz). Specimens were subjected to biaxial flexural fatigue testing using the step-test method (20 Hz; 10,000 cycles per step; initial stress of 200 MPa; and step size of 25 MPa) until specimen fracture. Statistical analyses included Shapiro-Wilk, Kruskal-Wallis, and post-hoc tests for roughness data, while survival analysis (Kaplan-Meier and Mantel-Cox) and reliability analysis (Weibull modulus) were applied to flexural fatigue strength data. Hardness (Vickers) results were submitted to analysis of variance (1-way ANOVA) and Tukey's test. Zirconia (4Y-PSZ) showed higher FFS, CFF (467 MPa and 115216 cycles) and survival compared to the other materials. ALD had the lowest FFS, CFF (215 MPa and 11,908 cycles) and survival. ALD showed lower Weibull modulus (m = 6.63 for FFS; m = 1.27 for CFF) than LD for FFS (m = 17.33), and lower than LD (m = 4.64) and 4Y-PSZ (m = 6.69) for CFF. ALD showed the lowest Ra (0.07 µm) and Rz (1.05 µm) values, while 4Y-PSZ (Ra = 0.22 µm; Rz = 1.91 µm) and LD (Ra = 0.21 µm; Rz = 2.17 µm) showed higher and similar values. Zirconia (4-YPSZ) was the hardest material, while lithia-based ceramics (LD and ALD) presented the lowest and similar hardness values. Fractures originated in surface defects in the tensile stress concentration region. ALD has lower flexural fatigue strength compared to the other tested materials, along with higher variability (lower structural reliability).

Advanced lithium disilicate: A comparative evaluation of translucency and fatigue failure load to other ceramics for monolithic restorations.

The aim of this in vitro study was to evaluate the surface roughness, translucency, fatigue failure load (FFL), and number of cycles for fatigue failure (CFF) of a recently released lithia-based material called advanced lithium disilicate and three other ceramics indicated for monolithic restorations. First, ALD (advanced lithium disilicate, CEREC Tessera, Dentsply Sirona), LD (lithium disilicate, IPS e. max CAD, Ivoclar), LS (lithium silicate-disilicate, Suprinity, Vita Zahnfabrik), and 4Y-PSZ (Yttria-stabilized zirconia, IPS e.max ZirCAD MT, Ivoclar) discs (n = 15, Ø = 10 mm and thickness = 1.0 mm) were fabricated from CAD/CAM blocks/discs, A2 shade. The discs were sintered/crystallized and subsequently analyzed by a rugosimeter (Mitutoyo SJ-410) to determine Ra and Rz surface roughness parameters. Next, they were evaluated to determine the translucency parameter (TP) using a bench-top spectrophotometer (SP60, EX-Rite). The discs were subsequently cemented to glass fiber epoxy resin discs, and the specimens were tested under cyclic loading (Step-test), immersed in distilled water at a frequency of 20 Hz, with an initial cyclic load of 200 N for 5,000 cycles and increments of 50 N every 10,000 cycles until failure. Fatigue failure load (FFL) and number of cycles for fatigue failure (CFF) were recorded for subsequent Kaplan Meier analysis, with post-hoc Mantel-Cox and Weibull analysis (α = 0.05). Complementary fractographic, topographic and energy dispersive spectroscopy analyses (EDS) were performed. 4Y-PSZ showed higher survival (p < 0.05), with higher FFL and CFF (1077 N; 180,333 cycles), followed by LD (980 N; 161,000 cycles), LS (937 N; 152,333 cycles) and ALD (910 N; 147,000 cycles). No differences were observed between the tested groups regarding Weibull modulus. ALD presented TP (28.14) equal to DL (28.27) and higher than LS (25.51). All lithia-based materials had higher translucency than 4Y-PSZ (TP = 8.62) (p < 0.05). ALD appears to have a similar elemental composition to LD and LSD for oxygen and silicon. ALD and LSD have a similar zirconium content. Fractures originated on the cemented surface of the ceramic discs. Lithia-based ceramics showed lower surface roughness, with ALD (Ra = 0.04 µm; Rz = 0.66 µm) showing the lowest values (p < 0.05). Despite showing lower FFL when compared to LD and 4Y-PSZ, ALD has compatible translucency and mechanical fatigue performance with its indication for fabricating monolithic, anterior and posterior adhesively cemented single-unit restorations. However, further studies are needed to substantiate its clinical performance.

Memory persistence induced by environmental enrichment is dependent on different brain structures.

Environmental enrichment (EE) has been demonstrated to have a beneficial effect on different functions of the central nervous system in several mammal species, being used to improve behavior and cell damage in various neurological and psychiatric diseases. However, little has been investigated on the effect of EE in healthy animals, particularly regarding its impact on memory persistence and the brain structures involved. Therefore, here we verified in male Wistar rats that contextual fear conditioning (CFC) memory persistence, tested 28 days after the CFC training session, was facilitated by 5 weeks of exposure to EE, with no effect in groups tested 7 or 14 days after CFC training. However, a two-week exposure to EE did not affect memory persistence. Moreover, we investigated the role of specific brain regions in mediating the effect of EE on memory persistence. We conducted inactivation experiments using the GABAergic agonist Muscimol to target the basolateral amygdala (BLA), medial prefrontal cortex (mPFC), and CA1 region of the hippocampus (CA1). Inactivation of the BLA immediately and 12 h after CFC training impaired the effect of EE on memory persistence. Similarly, inactivation of the CA1 region and mPFC 12 h after training, but not immediately, also impaired the effect of EE on memory persistence. These results have important scientific implications as they shed new light on the effect of an enriched environment on memory persistence and the brain structures involved, thereby helping elucidate how an environment rich in experiences can modify the persistence of learned information.

The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.

BACKGROUND: Soluble oligomeric forms of alpha-synuclein (aSyn-O) are believed to be one of the main toxic species in Parkinson's disease (PD) leading to degeneration. aSyn-O can induce Ca2+ influx, over activating downstream pathways leading to PD phenotype. Calcineurin (CN), a phosphatase regulated by Ca2+ levels, activates NFAT transcription factors that are involved in the regulation of neuronal plasticity, growth, and survival. METHODS: Here, using a combination of cell toxicity and gene regulation assays performed in the presence of classical inhibitors of the NFAT/CN pathway, we investigate NFAT's role in neuronal degeneration induced by aSyn-O. RESULTS: aSyn-O are toxic to neurons leading to cell death, loss of neuron ramification and reduction of synaptic proteins which are reversed by CN inhibition with ciclosporin-A or VIVIT, a NFAT specific inhibitor. aSyn-O induce NFAT nuclear translocation and transactivation. We found that aSyn-O modulates the gene involved in the maintenance of synapses, synapsin 1 (Syn 1). Syn1 mRNA and protein and synaptic puncta are drastically reduced in cells treated with aSyn-O which are reversed by NFAT inhibition. CONCLUSIONS: For the first time a direct role of NFAT in aSyn-O-induced toxicity and Syn1 gene regulation was demonstrated, enlarging our understanding of the pathways underpinnings synucleinopathies.

Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.

Representing the most attractive and successful druggable receptors of the proteome, GPCRs regulate a myriad of physiological and pathophysiological functions. Although over half of present pharmaceuticals target GPCRs, the advancement of drug discovery is hampered by a lack of adequate screening tools, the majority of which are limited to probing agonist-induced G-protein and ß-arrestin-2-mediated events as a measure of receptor activation. Here, we develop Tango-Trio, a comprehensive cell-based high-throughput platform comprising cumate-inducible expression of transducers, capable of the parallelized profiling of both basal and agonist-dependent GPCR activities. We capture the functional diversity of GPCRs, reporting ß-arrestin-1/2 couplings, selectivities, and receptor internalization signatures across the GPCRome. Moreover, we present the construction of cumate-induced basal activation curves at approximately 200 receptors, including over 50 orphans. Overall, Tango-Trio's robustness is well-suited for the functional characterization and screening of GPCRs, especially for parallel interrogation, and is a valuable addition to the pharmacological toolbox.

Role of Hippocampal Wnt Signaling Pathways on Contextual Fear Memory Reconsolidation.

Memories already consolidated when reactivated return to a labile state and can be modified, this process is known as reconsolidation. It is known the Wnt signaling pathways can modulate hippocampal synaptic plasticity as well as learning and memory. Yet, Wnt signaling pathways interact with NMDA (N-methyl-D-aspartate) receptors. However, whether canonical Wnt/ß-catenin and non-canonical Wnt/Ca2 + signaling pathways are required in the CA1 region of hippocampus for contextual fear memory reconsolidation remains unclear. So, here we verified that the inhibition of canonical Wnt/ß-catenin pathway with DKK1 (Dickkopf-1) into CA1 impaired the reconsolidation of contextual fear conditioning (CFC) memory when administered immediately and 2 h after reactivation session but not 6 h later, while the inhibition of non-canonical Wnt/Ca2+ signaling pathway with SFRP1 (Secreted frizzled-related protein-1) into CA1 immediately after reactivation session had no effect. Moreover, the impairment induced by DKK1 was blocked by the administration of the agonist of the NMDA receptors glycine site, D-Serine, immediately and 2 h after reactivation session. We found that hippocampal canonical Wnt/ß-catenin is necessary to the reconsolidation of CFC memory at least two hours after reactivation, while non-canonical Wnt/Ca2+ signaling pathway is not involved in this process and, that there is a link between Wnt/ß-catenin signaling pathway and NMDA receptors. In view of this, this study provides new evidence regarding the neural mechanisms underlying contextual fear memory reconsolidation and contributes to provide a new possible target for the treatment of fear related disorders.

Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: An integrative review.

INTRODUCTION: Checkpoint inhibitors (PCI) have reached an important place in the pharmaceutical market in the treatment of various types of cancer. However, due to immune-related adverse events (IRAE) to the treatment, patients with preexisting autoimmune diseases (PAD) are excluded from clinical studies, leading to a large gap in knowledge on this topic. This study aims to discuss the use of PCI in the patients with cancer and PAD by an integrative review. METHODS: For this integrative review we carried out research from 2013 to 2022 using database platforms for observational studies reporting data from safety and efficacy of PCI in patients with cancer and PAD. RESULTS: The search resulted in 161 articles and after applying the exclusion criteria, 15 clinical studies that adopted a retrospective observational design were selected and analyzed. The age range of patients was 54-71 years, with 19-68% male. The proportion of patients clinically active or receiving immunosuppressants who were initiated on PCI ranged from 0% to 57% and 14% to 73%, respectively. The mean reported follow-up time ranged from 8.0 to 16.8 months. The occurrence of an outbreak or the new IRAE had an average of 32.6%. CONCLUSION: IRAE are frequent in patients who use PCI and have cancer and PAD, carrying discontinuation of therapy. However, the multidisciplinary team needs to be aligned to manage these situations in the best way.

Influence of two caries detection strategies on the quality of life of preschool children: An analysis of secondary outcomes of a 2-Year randomized clinical trial.

OBJECTIVE: This randomized clinical trial aimed to evaluate the influence of two caries diagnosis strategies, and subsequent management, on oral health-related quality of life (OHRQoL) of preschoolers. Additionally, the association of the OHRQoL outcomes with the clinician-centred primary outcome used in the main study was also explored. MATERIALS AND METHODS: This study refers to the OHRQoL secondary outcomes analyses of the so-called RCT 'CARDEC-1'. Three- to 6-year-old children were randomly allocated in two caries detection strategies in primary molars: visual inspection (VIS) or visual + radiographic (RAD) assessment. Participants were diagnosed and treated according to the allocated group and followed up for 2 years. Caregivers answered the Early Childhood Oral Health Impact Scale (ECOHIS) at baseline and after 2 years. Intention-to-treat analysis was performed. ECOHIS scores at baseline and 2 years later were compared using the Mann-Whitney test. Effect sizes, change scores and the minimally important difference (MID) were also compared between groups. Additional analysis was performed to assess if OHRQoL variables could reflect the primary clinical outcome (number of new operative interventions during the follow-up), observing if these met the Prentice criteria. RESULTS: Two hundred and five children had the ECOHIS answered in both period times (18.7% attrition rate). There was a decrease in total ECOHIS scores, as well as for different domains for both trial groups, with effect sizes varying from 0.43 to 0.77. Comparisons between groups, however, did not show significant differences. In the additional analysis, the OHRQoL variables met the Prentice criteria and presented the same trends observed with the clinician-centred primary endpoint. CONCLUSION: Caries detection performed by visual inspection alone or associated with radiographic method does not influence the long-term impact on OHRQoL. Furthermore, OHRQoL variables reflect clinical outcomes in this type of clinical trial. CLINICALTRIALS: gov NCT02078453.

Imaginários Morais no Discurso Midiático Sobre o Uso da Inseminação Caseira por Mulheres Lésbicas / Moral Imaginaries on the Media Discourse on the Use of Homemade Insemination by Lesbian Women / Imaginarios Morales en el Discurso Mediático Sobre Uso de la Inseminación Domiciliaria por Mujeres Lesbianas

O presente artigo objetiva refletir sobre o discurso moral midiático produzido em torno da Inseminação Caseira e seu uso como tecnologia reprodutiva por casais de mulheres lésbicas. Esta é uma modalidade reprodutiva autônoma, que consiste em uma autoinseminação de baixo custo, feita com o uso de material biológico de doador não anônimo. Para esta reflexão, utilizou-se cinco obras midiáticas produzidas por canais de comunicação de grande alcance no cenário nacional, analisadas sob a ótica da análise do discurso. Foram traçadas cinco categorias analíticas: apresentação textual-imagética das obras; narrativa das mulheres tentantes; discursos promovidos pelos ditos especialistas; e representação da figura do doador. Conclui-se pela necessidade de estímulo ao debate acerca da inseminação caseira realizada por mulheres lésbicas, de modo que tanto profissionais da área da saúde como a sociedade de uma forma geral não se baseiem apenas em discursos morais condenatórios ditos científicos, como aqueles propagados pela grande mídia em relação à Inseminação Caseira. Soma-se a isso a importância em garantir visibilidade para os relatos das mulheres que estão se submetendo à inseminação caseira, compreendendo-as enquanto protagonistas da produção de sua saúde sexual e reprodutiva e projetos parentais e que, por isso, devem ter seus discursos e experiências legitimados.

The present article aims to reflect on the media moral discourse produced around Homemade Insemination and its use as a reproductive technology by lesbian couples. This is an autonomous reproductive modality, which consists in a low-cost self-insemination performed with the use of biological material from a non-anonymous donor. This reflection was made using five media works produced by communication channels of great reach in the Brazilian scenario, analyzed from the point of view of discourse analysis. Five analytical categories were drawn: textual-imagetic presentation of the works; narrative of women trying to conceive; speeches promoted by the so-called experts; and representation of the donor figure. We conclude that it is necessary to stimulate the debate about homemade insemination performed by lesbian women, so that both health professionals and society in general do not rely only on condemning moral speeches called scientific, such as those propagated by the media in relation to Homemade Insemination. Added to that it is important to ensure visibility of the reports of women who are submitting themselves to homemade insemination, understanding them as protagonists of the production of their sexual and reproductive health and parental projects and that, therefore, they must have their speeches and experiences legitimated.

Este artículo pretende reflexionar sobre el discurso moral mediático producido sobre la Inseminación Domiciliaria y su uso como tecnología reproductiva por parejas lesbianas. Se trata de una modalidad reproductiva autónoma, que consiste en una autoinseminación de bajo coste realizada con el uso de material biológico de donante no anónimo. Para esta reflexión, se utilizaron cinco obras mediáticas producidas por canales de comunicación de gran alcance en Brasil analizadas desde la perspectiva del análisis del discurso. Se trazaron cinco categorías analíticas: presentación textual-imagen de las obras; narración de las mujeres que intentan; discursos promovidos por los llamados especialistas; y representación de la figura del donante. Se concluye por la necesidad de estimular el debate sobre la Inseminación Domiciliaria realizada por mujeres lesbianas, de manera que tanto los profesionales de salud como la sociedad en general no se basen apenas en los discursos morales condenatorios de los científicos, como los propagados por la gran prensa sobre Inseminación Domiciliaria. A esto se suma la importancia de garantizar la visibilidad de los relatos de las mujeres que hacen la Inseminación Domiciliaria, entendiéndolas como protagonistas de la producción de su salud sexual y reproductiva y de sus proyectos parentales y debe tener sus discursos y experiencias legitimados.

A water-soluble manganese(II) octanediaoate/phenanthroline complex acts as an antioxidant and attenuates alpha-synuclein toxicity.

The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn2+-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn2+-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn2+-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn2+-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.

Efficacy of a calcium-phosphate/fluoride varnish and ionomeric sealant on cervical dentin hypersensitivity: A randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Dentin hypersensitivity (DH) is a common problem in the population that can have a significant impact on the quality of life of those who suffer from the condition. OBJECTIVES: Compare the efficacy of two treatments for DH: Ca/PO4 - /F- varnish (Clinpro White Varnish) and ionomeric sealant (IS) (Clinpro XT Varnish) with a placebo. METHODS: Participants (121) with at least one tooth with visual analogue scale (VAS) score of 4 and above were randomly and blindly allocated to the groups. Treatments were performed by a trained researcher. DH was evaluated by another blind researcher after the treatment and after 1 week, 4 weeks, 3 months and 6 months. After 4 weeks, placebo received the DH treatment with IS; thus, the participants were not assessed after 3 and 6 months. Primary outcome was DH reduction after 4 weeks. Differences in VAS scores in the other time intervals and entire values of VAS were considered secondary outcomes. Comparisons were made among the groups (α = 0.05). RESULTS: IS showed the highest VAS value difference between baseline and 4 weeks (mean ± SD: 3.7 ± 2.2), differing significantly from placebo (2.3 ± 1.7) and Ca/PO4/F- varnish (2.6 ± 2.0). Ca/PO4- /F- varnish did not differ from placebo. In all time intervals, VAS values of all groups were significantly lower than the baseline value, without differences among groups. For the long-term differences in VAS values (3 and 6 months), the IS exhibited significantly higher values than Ca/PO4- /F- varnish. CONCLUSIONS: The IS was the most efficacious product for reducing DH, whereas Ca/PO4- /F- varnish did not differ from placebo. Registered in ClinicalTrials.gov (NCT04591444).

Negligible therapeutic impact, false-positives, overdiagnosis and lead-time are the reasons why radiographs bring more harm than benefits in the caries diagnosis of preschool children.

BACKGROUND: To evaluate the clinical course and interventions required during two years of follow-up of dental surfaces of deciduous molars diagnosed, and consequently treated, by two different strategies: diagnosis made by clinical examination alone or associated with radiographs. METHODS: This is a secondary analysis of a two-arm randomized clinical trial with parallel groups related to the diagnostic strategy for caries detection in preschool children. 216 children (3-6 years old) were followed-up for two years. All dental surfaces were diagnosed by visual inspection and later, through radiographic assessment. Baseline treatment was made in accordance with the results obtained by visual inspection performed alone or combined with radiographic method, considering the allocated group. Dental surfaces with no restoration needs, or those restored at the beginning of the study were followed-up for two years. The treatment decision was made according to the allocated group. The outcome was the occurrence of failure (a new caries lesion or a restoration replacement) during the follow-up. RESULTS: 4383 proximal and occlusal surfaces of deciduous molars in 216 preschool children were diagnosed and treated according to the abovementioned diagnostic strategies and followed-up for 24 months. The assessment of radiographs made change the initial decision reached by visual inspection in about 30% of the surfaces when all types of interventions were considered. However, most disagreements occurred for initial lesions, where radiographs tended to underestimate them. Discordances between methods occurred in less than 5% of all surfaces when considered lesions requiring operative treatment. For discrepancy cases, the placed interventions guided by following the radiographic results did not present less failures against those made following only visual inspection. As a matter of fact, the use of radiographs in the diagnostic strategy for caries detection in children brought more harms than benefits due to the occurrence of false-positives, overdiagnosis and lead-time bias. CONCLUSIONS: Simultaneous association of visual inspection and radiographic assessment for caries detection in preschool children causes more harms than benefits, and therefore, visual inspection should be conducted alone in the regular clinical practice. Trial registration Clinicaltrials.gov platform: NCT02078453, registered on 5th March 2014.