Ultra-Processed Food Consumption, Poorer Nutritional Quality, and Lower Muscle Mass in Immediate and Late Postkidney Transplant Periods.

OBJECTIVE: To assess the consumption of ultra-processed foods (UPFs) in the immediate (2 months after transplantation) and late post-transplant (14 months after transplantation) periods among kidney transplant patients and to examine its correlation with nutritional quality and body composition. DESIGN AND METHODS: A cross-sectional analysis of 96 kidney transplant recipients divided into 2 groups: immediate post-transplant (n = 71) and late post-transplant (n = 25). Sociodemographic, anthropometric, and laboratory data were collected and grouped in a database. Food intake was evaluated by a validated food frequency questionnaire and foods were divided according to the NOVA classification system. The consumption of UPFs was calculated and statistical analyses were performed to evaluate its correlation with nutritional components and body composition. RESULTS: The consumption of UPFs was 649.4 [420.0-1061.72] kcal/day, accounting for 33.3 ± 11.9% of the total daily energy intake. The immediate post-transplant group showed higher total daily energy and UPFs intake compared to the late post-transplant group (P = .002 and P = .046, respectively), although the energy contribution of UPFs was similar between both groups. UPFs intake was positively correlated with higher percentages of total fat, trans fat, saturated, monounsaturated fat, polyunsaturated fat, starch, and sodium (P < .05 for all analyses). An inverse correlation was observed between UPFs consumption and the percentage of protein and carbohydrates in the food intake (P = .025 and P = .008, respectively). In the immediate post-transplant group, a higher intake of UPFs was correlated with lower muscle mass (r = -0.250, P = .037). CONCLUSIONS: The findings of this study reveal a pattern of increased consumption of UPFs among kidney transplant patients in comparison to the national average. This higher intake of UPFs was correlated with lower nutritional quality during both periods. Moreover, a significant correlation was observed between UPFs consumption and adverse body composition parameters, specifically in the immediate post-transplant period.

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19.

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Impact of the COVID-19 pandemic on cancer screenings in Portugal.

OBJECTIVES: This study aimed to evaluate the impact of the COVID-19 pandemic on cancer screening in Portugal, and its consequences on cancer morbidity and mortality. METHODS: The pre-pandemic and pandemic periods were compared using publicly available data on performance and health outcomes indicators of the Portuguese NHS, namely the numbers and proportions of eligible individuals who underwent cancer screening (breast, cervical or colorectal). Pre-pandemic data were modelled to project hypothetical scenarios without a pandemic using an exponential smoothing algorithm, and then compared with data collected during the COVID-19 pandemic. A Markov model was developed to estimate years of life lost (YLL) due the reduction in the number of cancer screenings during the pandemic. The MS Excel and the PRISM symbolic model checker software were used. RESULTS: There was a decrease in the number of breast (13 %), cervical (15 %) and colorectal (9-11 %) cancers screenings during the first two years of the pandemic. The model projections are 506, 41, and 148 additional deaths, losses of 11, 6, and 4 months of life per patient, and 12.8 thousand, 576, and 4 thousand YLL by the population due to breast, cervical, and colorectal cancer, respectively, over a 25-year time horizon in Portugal. CONCLUSIONS: The disruption in cancer screening may contribute to increase cancer morbidity and mortality, with significant YLL. The long-term implications of the impaired cancer screening should be assessed, and proactive measures put in place to mitigate the increase in cancer morbidity, and mortality associated with the COVID-19 pandemic.

Protocolo de avaliação para apraxia de fala adquirida / Assessment protocol for acquired apraxia of speech

RESUMO Objetivo Elaborar um protocolo de avaliação do planejamento motor da fala com estímulos fonologicamente balanceados para o português brasileiro e que contemple todas as variáveis necessárias para este diagnóstico. Método Foram realizadas três etapas: Na primeira, construíram-se listas de palavras cujo critério principal foram os padrões silábicos e acentuais. Do levantamento realizado na Etapa 1, procedeu-se à seleção dos vocábulos que compuseram a primeira versão do protocolo na Etapa 2, reunidas em duas tarefas: de repetição e de Leitura em Voz Alta (LVA). Em seguida, investigou-se a ocorrência das palavras usando a base de dados do Corpus Brasileiro (PUC-SP) - Linguateca. Na etapa 3 realizou-se a análise estatística para verificar se as listas de repetição e de LVA estavam equilibradas quanto à ocorrência das palavras. Assim, as listas foram distribuídas em quartis e foram analisadas de forma descritiva e bivariada. O nível de significância utilizado foi de 5%. Resultados Após a realização de todas as etapas, foi possível obter as palavras que compuseram as listas das tarefas de repetição e de LVA. Finalmente, foram então acrescidas ao protocolo as demais tarefas consideradas essenciais para a avaliação da apraxia como as taxas diadococinéticas e a prancha para a emissão oral espontânea. Conclusão O protocolo desenvolvido contém as tarefas consideradas padrão para a avaliação da apraxia de fala pela literatura internacional, o que torna esse instrumento importante para o diagnóstico desse distúrbio em falantes do português brasileiro.

ABSTRACT Purpose To develop an assessment protocol for speech motor planning with phonologically balanced stimuli for Brazilian Portuguese, including all necessary variables for this diagnosis. Methods Three stages were carried out: In the first, word lists were built with the main criterion being syllabic and accentual patterns. From the survey conducted in Stage 1, the words that composed the first version of the protocol lists in Stage 2 were selected, and grouped into two fundamental tasks for diagnosing acquired apraxia of speech (AOS): repetition and Reading Aloud (RA). In Stage 3, the occurrence of words was investigated using the Brazilian Corpus (PUC-SP) - Linguateca database, and a statistical analysis was performed to verify if the repetition and RA lists were balanced in terms of the occurrences. Thus, the lists were distributed in quartiles and submitted to both descriptive and bivariate analyses. A significance level of 5% (p<0.05) was adopted. Results After completion of all stages, the words that composed the lists of the repetition and RA tasks were obtained. Finally, other tasks considered essential for the assessment of AOS, such as diadochokinetic rates and the board for spontaneous oral emission, were then added to the protocol. Conclusion The developed protocol contains the tasks considered standard for the assessment of AOS according to the international literature, which makes this instrument important for diagnosing this disorder in speakers of Brazilian Portuguese.

Protocolos gerenciados por enfermeiros para identificação precoce da sepse: revisão de escopo / Nurse-managed protocols for early identification of sepsis: a scoping review / Protocolos administrados por enfermeros para la identificación temprana de la sepsis: revisión del alcance

Objetivo: mapear os protocolos assistenciais utilizados por enfermeiros para identificação precoce da sepse no ambiente hospitalar. Método: trata-se de uma revisão de escopo ancorada nas recomendações do Joanna Briggs Institute, desenvolvida em sete bases de dados. A busca e seleção ocorreu em 17 de julho de 2021, utilizando os descritores: sepse, protocolos de enfermagem, avaliação de enfermagem e cuidados de enfermagem. Resultados: a amostra foi composta de seis estudos, destacaram-se os protocolos implementados por projetos de melhoria de qualidade e utilização sistemas eletrônicos de alerta para deterioração clínica. Conclusão: protocolos assistenciais impulsionam a aderência dos profissionais às recomendações oficiais para o manejo da sepse no ambiente hospitalar e o desenvolvimento de cuidados de enfermagem baseados em evidências, contribuindo para melhorar os indicadores de qualidade e reduzir a mortalidade entre pacientes com sepse.

Objective: to map the care protocols used by nurses for the early identification of sepsis in the hospital environment. Method: this is a scope review anchored in the recommendations of the Joanna Briggs Institute, developed in seven databases. The search and selection took place on July 17, 2021, using the descriptors: sepsis, nursing protocols, nursing assessment and nursing care. Results: the sample consisted of six studies, highlighting the protocols implemented by quality improvement projects and the use of electronic warning systems for clinical deterioration. Conclusion: care protocols boost professionals' adherence to official recommendations for the management of sepsis in the hospital environment and the development of evidence-based nursing care, contributing to improve quality indicators and reduce mortality among patients with sepsis.

Objetivo: mapear los protocolos de atención utilizados por las enfermeras para identificar de forma temprana la sepsis en el ambiente hospitalario. Método: se trata de una revisión de alcance anclada en las recomendaciones del Instituto Joanna Briggs, desarrollada en siete bases de datos. La búsqueda y selección se realizó el 17 de julio de 2021, utilizando los descriptores: sepsis, protocolos de enfermería, evaluación de enfermería y cuidados de enfermería. Resultados: la muestra estuvo compuesta por seis estudios, se destacaron los protocolos implementados por los proyectos de mejora de la calidad y utilización de sistemas electrónicos de alerta con respecto al deterioro clínico. Conclusión: los protocolos asistenciales impulsan la adherencia de los profesionales a las recomendaciones oficiales para el manejo de la sepsis en el ámbito hospitalario y el desarrollo de cuidados de enfermería basados en evidencias, contribuyendo a mejorar los indicadores de calidad y reducir la mortalidad entre los pacientes con sepsis.

Sequential Process of Subcritical Water Hydrolysis and Hydrothermal Liquefaction of Butia Capitata Endocarp to Obtain Fermentable Sugars, Platform Chemicals, Bio-oil, and Biochar.

Butia capitata endocarp (BCE) is a biomass residue with the potential to produce a wide variety of bio-products. The processing of BCE in a sequential process of subcritical water hydrolysis (SWH) and hydrothermal liquefaction (HTL) was investigated to obtain fermentable sugars, platform chemicals, bio-oil, and biochar. The SWH was evaluated at 230 and 260 °C and solvent: feed mass ratios (R) of 10 and 20 for the production of fermentable sugars and platform chemicals. The solid residue from SWH was sequentially submitted to the HTL at 330 and 360 °C for bio-oil and biochar production. The results were analyzed by comparing the sequential (SWH/HTL) and individual (HTL only) processes. The highest yields of fermentable sugars (5.26 g/ 100 g BCE) were obtained for SWH at 260 °C and R-20 with higher contents of xylose (2.64 g/100 g BCE) and cellobiose (1.75 g/100 g BCE). The highest yields of platform chemicals (2.44 g/100 g BCE) were obtained for SWH at 260 °C and R-10 with higher contents of acetic acid (1.78 g/100 g BCE) and furfural (0.54 g/100 g BCE). The highest yield of bio-oil (25.30 g/100 g BCE) occurred in HTL individual process at 360 °C and R-20. Sequential process SWH/HTL showed a decrease in bio-oil yield but maintained a similar biochar yield compared to HTL, in addition to the production of fermentable sugars and platform chemicals.

Carbetocin Inhibits Behavioral Sensitization to Ethanol in Male and Female Mice, Independent of Corticosterone Levels.

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT's properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT's impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

Assessment protocol for acquired apraxia of speech. / Protocolo de avaliação para apraxia de fala adquirida.

PURPOSE: To develop an assessment protocol for speech motor planning with phonologically balanced stimuli for Brazilian Portuguese, including all necessary variables for this diagnosis. METHODS: Three stages were carried out: In the first, word lists were built with the main criterion being syllabic and accentual patterns. From the survey conducted in Stage 1, the words that composed the first version of the protocol lists in Stage 2 were selected, and grouped into two fundamental tasks for diagnosing acquired apraxia of speech (AOS): repetition and Reading Aloud (RA). In Stage 3, the occurrence of words was investigated using the Brazilian Corpus (PUC-SP) - Linguateca database, and a statistical analysis was performed to verify if the repetition and RA lists were balanced in terms of the occurrences. Thus, the lists were distributed in quartiles and submitted to both descriptive and bivariate analyses. A significance level of 5% (p<0.05) was adopted. RESULTS: After completion of all stages, the words that composed the lists of the repetition and RA tasks were obtained. Finally, other tasks considered essential for the assessment of AOS, such as diadochokinetic rates and the board for spontaneous oral emission, were then added to the protocol. CONCLUSION: The developed protocol contains the tasks considered standard for the assessment of AOS according to the international literature, which makes this instrument important for diagnosing this disorder in speakers of Brazilian Portuguese.

OBJETIVO: Elaborar um protocolo de avaliação do planejamento motor da fala com estímulos fonologicamente balanceados para o português brasileiro e que contemple todas as variáveis necessárias para este diagnóstico. MÉTODO: Foram realizadas três etapas: Na primeira, construíram-se listas de palavras cujo critério principal foram os padrões silábicos e acentuais. Do levantamento realizado na Etapa 1, procedeu-se à seleção dos vocábulos que compuseram a primeira versão do protocolo na Etapa 2, reunidas em duas tarefas: de repetição e de Leitura em Voz Alta (LVA). Em seguida, investigou-se a ocorrência das palavras usando a base de dados do Corpus Brasileiro (PUC-SP) - Linguateca. Na etapa 3 realizou-se a análise estatística para verificar se as listas de repetição e de LVA estavam equilibradas quanto à ocorrência das palavras. Assim, as listas foram distribuídas em quartis e foram analisadas de forma descritiva e bivariada. O nível de significância utilizado foi de 5%. RESULTADOS: Após a realização de todas as etapas, foi possível obter as palavras que compuseram as listas das tarefas de repetição e de LVA. Finalmente, foram então acrescidas ao protocolo as demais tarefas consideradas essenciais para a avaliação da apraxia como as taxas diadococinéticas e a prancha para a emissão oral espontânea. CONCLUSÃO: O protocolo desenvolvido contém as tarefas consideradas padrão para a avaliação da apraxia de fala pela literatura internacional, o que torna esse instrumento importante para o diagnóstico desse distúrbio em falantes do português brasileiro.

Extraction of collagenolytic proteases from Aspergillus heteromorphus URM 0269 in an aqueous two-phase system for application in collagen hydrolysis.

Collagenolytic proteases produced by Aspergillus heteromorphus URM0269 were extracted using a PEG/sulfate aqueous two-phase system (ATPS). A 23 factorial design was performed to analyze the independent variables: PEG molar mass (MPEG), PEG concentration (CPEG), and sulfate concentration (Csulf). The extracted proteases were also evaluated for their optimum pH and stability at different pH levels (4.0 - 11.0) after 20 h of incubation. Collagen was extracted from mutton snapper (Lutjanus analis) skin using acetic acid (0.5 mol L-1). The enzyme was preferentially partitioned to the PEG-rich phase (K > 1), whose highest purification factor and recovery (PF = 6.256 and Y = 404.432%) were obtained under specific conditions: MPEG 8000 g.mol-1, CPEG 30%, Csulf 10%. The ATPS extraction provided an enzymatic activity range of pH 7.0 - 11.0, exhibiting greater stability compared to the crude extract. Approximately 80% of protease activity was maintained after 20 hours of incubation at all analyzed pH levels, except pH 11.0. Collagen extraction from L. analis skin yielded 8.056%, and both crude extract samples and ATPS-derived samples successfully hydrolyzed the extracted collagen, reaching peak hydrolysis after 36 hours of treatment. These findings demonstrate the feasibility of extracting highly purified and active proteases capable of hydrolyzing L. analis collagen.

Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models.

Osteosarcoma (OS) is a frequent bone cancer, affecting largely children and young adults. Cisplatin (CDDP) has been efficacious in the treatment of different cancer such us OS but the development of chemoresistance and important side effects leading to therapeutic failure. Novel therapies including copper compounds have shown to be potentially effective as anticancer drugs and one alternative to usually employed platinum compounds. The goal of this work is the evaluation of the in vitro and in vivo antitumoral activity and dilucidate the molecular target of a Cu(II) cationic complex containing a tridentate hydrazone ligand, CuHL for short, H2L=N'-'-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide, against human OS MG-63 cells. Anticancer activity on MG-63 cell line was evaluated in OS monolayer and spheroids. CuHL significantly impaired cell viability in both models (IC50 2D: 2.1 ± 0.3 µM; 3D: 9.1 ± 1.0 µM) (p < 0.001). Additional cell studies demonstrated the copper compound inhibits cell proliferation and conveys cells to apoptosis, determined by flow cytometry. CuHL showed a great genotoxicity, evaluated by comet assay. Proteomic analysis by Orbitrap Mass Spectometry identified 27 differentially expressed proteins: 17 proteins were found overexpressed and 10 underexpressed in MG-63 cells after the CuHL treatment. The response to unfolded protein was the most affected biological process. In addition, in vivo antitumor effects of the compound were evaluated on human OS tumors xenografted in nude mice. CuHL treatment, at a dose of 2 mg/kg i.p., given three times/week for one month, significantly inhibited the progression of OS xenografts and was associated to a reduction in mitotic index and to an increment of tumor necrosis (p < 0.01). Administration of standard-of-care cytotoxic agent CDDP, following the same treatment schedule as CuHL, failed to impair OS growth and progression.

SARS-CoV-2 Infection in Cities from the Southern Region of Bahia State, Brazil: Analysis of Variables Associated in Both Individual and Community Level.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), challenged public health systems worldwide. Individuals in low-income countries/regions are still at individual and community risk concerning inequality, sanitation, and economic conditions. Besides, during the pandemic, the transmission in municipalities and communities in the countryside and less developed regions kept viral spread and required structured and strengthened clinical and laboratory surveillance. Here, we present an observational, analytic, cross-sectional study conducted using secondary data from the Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM)-Universidade Estadual de Santa Cruz (UESC), to evaluate individual and community factors associated to SARS-CoV-2 infection in outpatients from different cities from Southern Region of Bahia State, in Brazil. The data were collected between June 2021 and May 2022. The SARS-CoV-2 positivity by RT-qPCR was correlated with low socio-economic indicators, including the Human development index (HDIc) and Average worker salary (AWSc). Besides, in general, females were less likely to test positive for SARS-CoV-2 (OR = 0.752; CI 95% 0.663-0.853; p < 0.0001), while brown individuals had more positivity for infection (p < 0.0001). In addition, those who had clinical symptoms were more likely to test positive for SARS-CoV-2 (OR = 6.000; CI 95% 4.932-7.299; p < 0.0001). Although dry cough, headache, and fever were the most frequent, loss of taste (OR = 5.574; CI 95% 4.334-7.186) and loss of smell (OR = 6.327; CI 95% 4.899-8.144) presented higher odds ratio to be positive to SARS-CoV-2 by RT-qPCR. Nonetheless, the distribution of these characteristics was not homogenous among the different cities, especially for age and gender. The dynamic of SARS-CoV-2 positivity differed between cities and the total population and reinforces the hypothesis that control strategies for prevention needed to be developed based on both individual and community risk levels to mitigate harm to individuals and the health system.

Combining the amplification refractory mutation system and high-resolution melting analysis for KRAS mutation detection in clinical samples.

The success of personalized medicine depends on the discovery of biomarkers that allow oncologists to identify patients that will benefit from a particular targeted drug. Molecular tests are mostly performed using tumor samples, which may not be representative of the tumor's temporal and spatial heterogeneity. Liquid biopsies, and particularly the analysis of circulating tumor DNA, are emerging as an interesting means for diagnosis, prognosis, and predictive biomarker discovery. In this study, the amplification refractory mutation system (ARMS) coupled with high-resolution melting analysis (HRMA) was developed for detecting two of the most relevant KRAS mutations in codon 12. After optimization with commercial cancer cell lines, KRAS mutation screening was validated in tumor and plasma samples collected from patients with pancreatic ductal adenocarcinoma (PDAC), and the results were compared to those obtained by Sanger sequencing (SS) and droplet digital polymerase chain reaction (ddPCR). The developed ARMS-HRMA methodology stands out for its simplicity and reduced time to result when compared to both SS and ddPCR but showing high sensitivity and specificity for the detection of mutations in tumor and plasma samples. In fact, ARMS-HRMA scored 3 more mutations compared to SS (tumor samples T6, T7, and T12) and one more compared to ddPCR (tumor sample T7) in DNA extracted from tumors. For ctDNA from plasma samples, insufficient genetic material prevented the screening of all samples. Still, ARMS-HRMA allowed for scoring more mutations in comparison to SS and 1 more mutation in comparison to ddPCR (plasma sample P7). We propose that ARMS-HRMA might be used as a sensitive, specific, and simple method for the screening of low-level mutations in liquid biopsies, suitable for improving diagnosis and prognosis schemes.

Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics.

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-of-function-mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.

Customized Tray for Impression Taking in Children With Cleft Lip and Palate.

The assessment of rehabilitation outcomes requires a patient documentation protocol, including records obtained at standardized ages, to compare different types of surgeries, their effects, as well as between different rehabilitation centers. The aim of this paper was to present proper trays for babies with different types of cleft lip and palate, which are used in the outpatient routine at Hospital of Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP). The customized trays are made with self-curing acrylic resin. The tray must have suitable depth to copy the buccal sulcus, and wax is usually applied to contour the tray edge, and the adjustment of the tray to the fornix, making the tray specific for each child. The impression precludes the utilization of dental casts for diagnosis, treatment plan, and research measurements. In the clinical practice at HRAC-USP, it was observed that customized trays increased the quality of impression, accurately reproducing anatomical features of dental arches of babies with oral clefts.

A relação entre o contexto familiar e o envolvimento com bullying escolar: uma revisão sistemática / The relationship between family context and involvement with school bullying: a systematic review / La relación entre el contexto familiar y la participación en el acoso escolar: una revisión sistemática

O envolvimento com o bullying escolar pode relacionar-se ao amplo contexto desenvolvimental do indivíduo, incluindo a família. Esta revisão sistemática objetivou identificar a produção científica nacional e internacional entre 2015 e 2019 sobre a relação entre bullying escolar e família. Os artigos foram coletados nas bases de dados LILACS, PubMed, PsycInfo e ERIC, a partir dos descritores "bullying AND família", nos idiomas português, inglês e espanhol. Foram analisados 48 artigos empíricos. Eles foram apresentados quanto à forma de relação entre família e bullying e situados como fatores de proteção ou risco aos escolares. Os resultados foram submetidos à análise temática, embasada na teoria sistêmica bioecológica. Identificou-se que o contexto familiar tem sido associado ao envolvimento em situações de bullying escolar, enquanto fator de proteção, mas principalmente de risco para a prática ou vitimização por bullying. Esta revisão auxilia na interpretação desta relação, indicando lacunas e possibilidades para pesquisas futuras

Involvement with school bullying can be related to the broad developmental context of the individual, including the family. This systematic review aimed to identify the national and international scientific production between 2015 and 2019 on the relationship between family context and involvement with school bullying. The articles were collected in the LILACS, PubMed, PsycINFO and ERIC databases using the descriptors "bullying AND family" in Portuguese, English and Spanish. 48 empirical articles were selected for analysis. They were presented focusing on the relationship between family and bullying and classifi ed as protective or risk factors for students. The results were subjected to thematic analysis, based on bioecological systemic theory. It was identifi ed that the family context has been associated with involvement in situations of school bullying, as a protective factor, but mainly as a risk for the practice or victimization by bullying. This review helps in the interpretation of this relationship, indicating gaps and possibilities for future research

La participación en el acoso escolar puede estar relacionada con el contexto de desarrollo amplio del individuo, incluida la familia. Esta revisión sistemática tuvo como objetivo identificar la producción científica nacional e internacional entre 2015 y 2019 sobre la relación entre el contexto familiar y la participación en acoso escolar. Los artículos fueron recopilados en las bases de datos LILACS, PubMed, PsycINFO y ERIC de los descriptores "acoso escolar AND familia" en portugués, inglés y español. Se seleccionaron 48 artículos empíricos para su análisis. Ellos fueron presentados en cuanto a la forma de relación entre la familia y la intimidación y colocados como factores protectores o de riesgo para los estudiantes. Los resultados fueron sometidos a análisis temático, basado en la teoría sistémica bioecologica. Se identificó que el contexto familiar se ha asociado con la participación en situaciones de acoso escolar, como un factor protector, pero principalmente un riesgo para la práctica o la victimización por acoso escolar. Esta revisión ayuda en la interpretación de esta relación, indicando brechas y posibilidades para futuras investigaciones

Revisão de escopo sobre teoria da mente e bullying: uma atualização crítica / Scoping review on theory of mind and bullying: a critical update / Revisión del alcance sobre teoría de la mente y bullying: una actualización crítica

O presente estudo teve por objetivo realizar uma revisão de escopo sobre pesquisas que investigam a re-lação entre a Teoria da Mente (ToM) e o bullying escolar em sete bases de dados nas áreas da saúde/psico-logia (PubMed, PsycInfo e Lilacs), da educação (Eric) e interdisciplinares (SciELO, Web of Science e Scopus). Dos 270 arquivos identificados inicialmente, 14 foram elegíveis para a revisão e analisados a respeito dos seus principais resultados, das medidas em ToM utilizadas e das variáveis relacionadas à classificação de bullying. Verificou-se que a maioria dos estudos reportou uma relação direta (relações que tendem a ser estatisticamente significativas) e/ou indireta (mediada por outras variáveis) entre papéis dos envolvidos e tipos de bullying e o desempenho em tarefas de ToM. Contudo, uma discussão crítica em relação às medi-das de avaliação em ToM foi realizada e apontou a necessidade de esclarecimento no tipo de avaliação e de atualização das tarefas.

The present study aimed to conduct a scoping review on researches which investigated the relationship between Theory of Mind (ToM) and school bullying in seven databases in the areas of health/psychology (PubMed, PsycInfo, and Lilacs), education (Eric), and interdisciplinary (SciELO, Web of Science, and Scopus). Of the 270 results initially identified, 14 were eligible for review and analyzed regarding their main results, the measures in ToM used, and variables related to the classification of bullying. It was found that most studies reported a direct (relationships that tend to be statistically significant) and/or indirect (mediated by other variables) relationship between the roles of the students involved and types of bullying and the performance in tasks of ToM. However, a critical discussion regarding the assessment measures in ToM was carried out pointing to the need for clarification in the type of assessment and updating of tasks.

El presente estudio tuvo como objetivo llevar a cabo una revisión del alcance de estudios que investigan la relación entre Teoría de la Mente (ToM) y el bullying en siete bases de datos de las áreas de salud/psicología (PubMed, PsycInfo y Lilacs), educación (Eric) e interdisciplinares (SciELO, Web of Science y Scopus). De los 270 estudios identificados inicialmente, 14 fueron revisados y analizados con respecto a sus principales resultados, a las medidas utilizadas en ToM y a las variables relacionadas con la clasificación del bullying. Se encontró que la mayoría de los estudios reportaron una relación directa (relaciones que tienden a ser estadísticamente significativas) y/o indirecta (mediada por otras variables) entre los roles de los involu-crados y los tipos de bullying y el desempeño en las tareas de ToM. Sin embargo, se realizó un debate crítico sobre las medidas de evaluación en ToM, señalando la necesidad de aclaración en el tipo de evaluación y actualización de las tareas.

Prenatal diagnosis study using array comparative genomic hybridization for genotype-phenotype correlation in 772 fetuses.

OBJECTIVE: The aim was to evaluate the main indications for prenatal diagnosis, the prevalence of abnormal copy number variations (CNVs), correlate them with clinical findings, analyze the prevalence of VUS, report the rare variants found and additionally highlight the clinical importance of microarray-based comparative genomic hybridization (aCGH) in prenatal diagnosis. STUDY DESIGN: We retrospectively analyzed a cohort of 772 fetuses with indication for genetic study in two tertiary hospitals, in a 9-years-period, using aCGH. RESULTS: Our results demonstrated 8.3 % (6.4-10.5 %, 95 % CI) detection rate of pathogenic CNVs. Within this group, the main indication was structural malformations (57 %) mainly involving central nervous system, skeletal and cardiac systems. Pathogenic results in cases with multiple malformations were higher than in cases with isolated anatomical system malformations showing statistical significant differences (p < 0.001). The second indication where we found more pathogenic CNVs was increased nuchal translucency (5-6.4 mm). In fact, the rate of pathogenic CNVs did not show significant differences between structural and non-structural malformations (p > 0.001), highlighting the relevance of genetic study by aCGH also in cases with no structural malformations. A total of 217 fetuses with CNVs classified as VUS were identified, mainly involving chromosomes X, 1 and 16. CONCLUSION: Our findings demonstrate 4.9 % (4.2-5.6 %, 95 % CI) increased in the diagnostic yield using aCGH compared to the use of conventional karyotype alone, confirming that the aCGH can improve the accuracy of prenatal diagnosis. Our survey provides a full genotype-phenotype analysis that can be clinically useful for the classification of variants in the context of prenatal setting, helping to provide a better reproductive genetic counselling.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Is There a Difference in Fear-Avoidance, Beliefs, Anxiety and Depression Between Post-Surgery and Non-Surgical Persistent Spinal Pain Syndrome Patients?

Introduction: Patients with post-surgery persistent spinal pain syndrome (PSPS) or non-surgical PSPS might be affected by sustained fear-avoidance beliefs (FAB), anxiety and depression. In this scenario, this study aimed to describe those aspects in patients with post-surgery PSPS and non-surgical PSPS. Methods: This study included patients with PSPS, and non-surgical PSPS, over 18 years, with quarterly evaluations at the Chronic Pain Clinic. After evaluation, demographic and clinical characteristics were obtained. The Beck Depression Inventory-II, Beck Anxiety Inventory, Douleur neuropathique 4 questions, Visual Analog Pain Scale, and Fear-Avoidance Beliefs Questionnaire-Brazilian Version (FABQ-Brazil) were used to evaluate psychological aspects. Results: Forty-six patients were included, 23 patients with post-surgery PSPS and 23 with non-surgical PSPS. Both groups had high scores in the physical and work domains of the FABQ, high rates of absenteeism and most patients in these groups had moderate-to-severe neuropathic pain and some degree of anxiety and/or depression. The groups showed no statistically significant difference (p > 0.05) when comparing all questionnaires. Discussion: This is one of the first studies to evaluate FAB and other associated psychological factors, such as anxiety and depression, in patients with post-surgery PSPS in a follow-up several years after surgery and compare with patients diagnosed with non-surgical PSPS. In this study, most patients in both groups had high scores in the FABQ domains, not having statistically relevant difference between groups. Conclusion: Even though there was no statistically relevant difference between the PSPS patient with or without surgical history in terms of the assessed outcome measures, the described scores for fear-avoidance beliefs, pain, anxiety and depression were high, showing an interference in the daily life activities of those patients.

Cellular Interaction of Bone Marrow Mesenchymal Stem Cells with Polymer and Hydrogel 3D Microscaffold Templates.

Biomimicking biological niches of healthy tissues or tumors can be achieved by means of artificial microenvironments, where structural and mechanical properties are crucial parameters to promote tissue formation and recreate natural conditions. In this work, three-dimensional (3D) scaffolds based on woodpile structures were fabricated by two-photon polymerization (2PP) of different photosensitive polymers (IP-S and SZ2080) and hydrogels (PEGDA 700) using two different 2PP setups, a commercial one and a customized one. The structures' properties were tuned to study the effect of scaffold dimensions (gap size) and their mechanical properties on the adhesion and proliferation of bone marrow mesenchymal stem cells (BM-MSCs), which can serve as a model for leukemic diseases, among other hematological applications. The woodpile structures feature gap sizes of 25, 50, and 100 µm and a fixed beam diameter of 25 µm, to systematically study the optimal cell colonization that promotes healthy cell growth and potential tissue formation. The characterization of the scaffolds involved scanning electron microscopy and mechanical nanoindenting, while their suitability for supporting cell growth was evaluated with live/dead cell assays and multistaining 3D confocal imaging. In the mechanical assays of the hydrogel material, we observed two different stiffness ranges depending on the indentation depth. Larger gap woodpile structures coated with fibronectin were identified as the most promising scaffolds for 3D BM-MSC cellular models, showing higher proliferation rates. The results indicate that both the design and the employed materials are suitable for further assays, where retaining the BM-MSC stemness and original features is crucial, including studies focused on BM disorders such as leukemia and others. Moreover, the combination of 3D scaffold geometry and materials holds great potential for the investigation of cellular behaviors in a co-culture setting, for example, mesenchymal and hematopoietic stem cells, to be further applied in medical research and pharmacological studies.