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El libro de texto es una herramienta muy utilizada por docentes y alumnos en el ámbito escolar. Todas estas colecciones cuentan con un manual didáctico, disponible para acceso sólo a los maestros. Así, la presente investigación buscó develar el conocimiento especializado del manual didáctico chileno para la enseñanza de Probabilidad y Estadística en el primer y segundo año de la primaria, en el que se matriculan regularmente alumnos de seis y siete años. La comprensión de estos conocimientos, así como sus influencias, permite al educador identificar las posibles dificultades que los estudiantes pueden adquirir en el aprendizaje de esta área temática. En consecuencia, será más fácil establecer estrategias que minimicen estos impactos. El estudio se realizó en forma de investigación documental, centrándose en la colección Sumo Primero (2022). El referencial se basó en el modelo teórico del Mathematics Teacher’s Specialized Knowledge, que categorizó el conocimiento especializado del profesor de matemáticas en seis subdominios principales. Mediante el estudio y análisis del mencionado manual, se buscó identificar los conocimientos que más se destacaban, según la clasificación de las partes indicadas según las normas del mencionado modelo. Como resultado, el subdominio más evidente fue el Conocimiento de los Parámetros de Aprendizaje de las Matemáticas y el que menos prevaleció fue el Conocimiento de la Estructura de las Matemáticas. Se espera que esta investigación contribuya a la formación de docentes, a fin de constituirse también para el pensamiento de nuevas investigaciones.

O presente artigo tem como objetivo geral investigar se a atual condução das relações Brasil-China no governo Lula contribui para que o Brasil ascenda a uma posição mais próxima ao centro na Economia Mundo Capitalista (E-MC). Para tanto, os objetivos específicos são: 1) Analisar as relações Brasil-China nos últimos vinte anos, sob aspectos políticos e econômicos, em termos dos principais acontecimentos da política externa sino-brasileira; 2) Comparar os acordos firmados entre Brasil e China na última viagem do presidente Lula com os acordos nas demais gestões dos mandatários brasileiros entre 2003 e 2023. Metodologicamente, o artigo parte da perspectiva histórica da Teoria dos Sistemas-Mundo para realizar um estudo de caso sobre os acordos firmados entre Brasil e China, de 2003 a 2023. Como conclusões, ressalta-se que apesar do foco dos acordos em Ciência, Tecnologia e Inovação e desenvolvimento industrial, as relações sino-brasileiras ainda reforçam um padrão centro-periferia com foco na exportação de commodities.

On 6 November 2023, the Italian Prime Minister Giorgia Meloni and the Prime Minister of Albania Edi Rama announced the signing of the Agreement for Strengthening of Collaboration in the Field of Migration. The agreement proposes a relocation of asylum seekers who are rescued at sea by Italian vessels to two centres that would be built in Albania and could host up to 3’000 people. This is part of a broader trend whereby European governments seek to move asylum procedures outside of their territory. At the same time, the agreement contains some innovations compared to previous proposals. Indeed, this move has been hailed as a “model and example for other collaboration agreements of this kind” by the Italian Prime Minister. This article contends that this is unlikely to be the case: the legality and feasibility of offshoring asylum procedures remain dubious at best.

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Abstract Background Ultraviolet-B radiation (UV-B, 280-315 nm) is a natural component of sunlight, which has numerous regulatory effects on plant physiology. The nature of the response to UV-B is dependent on fluence rate, dose, duration and wavelength of the UV-B treatment. Some reports have analyzed the changes in gene expression caused by UV-B light on several plant species using microarray technology. However, there is no information on the transcriptome response triggered by UV-B in grapevine. In this paper we investigate the gene expression responses of leaves from in vitro cultured Vitis vinifera cv. Malbec plants subjected to the same dose of biologically effective UV-B radiation (4.75 kJ m-2 d-1) administered at two different fluence rates (16 h at ≅ 8.25 μW cm-2, 4 h at ≅ 33 μW cm-2) using a new custom made GrapeGen Affymetrix GeneChip®. Results The number of genes modulated by high fluence rate UV-B doubled the number of genes modulated by low fluence UV-B. Their functional analyses revealed several functional categories commonly regulated by both UV-B treatments as well as categories more specifically modulated depending on UV-B fluence rate. General protective responses, namely the induction of pathways regulating synthesis of UV-B absorbing compounds such as the Phenylpropanoid pathway, the induction of different antioxidant defense systems and the activation of pathways commonly associated with pathogen defense and abiotic stress responses seem to play critical roles in grapevine responses against UV-B radiation. Furthermore, high fluence rate UV-B seemed to specifically modulate additional pathways and processes in order to protect grapevine plantlets against UV-B-induced oxidative stress, stop the cell cycle progression, and control protein degradation. On the other hand, low fluence rate UV-B regulated the expression of specific responses in the metabolism of auxin and abscisic acid as well as in the modification of cell walls that could be involved in UV-B acclimation-like processes. Conclusion Our results show the UV-B radiation effects on the leaf transcriptome of grapevine (Vitis vinifera cv. Malbec) plantlets. Functional categories commonly modulated under both UV-B treatments as well as transcripts specifically regulated in an UV-B-intensity dependent way were identified. While high fluence rate UV-B had regulatory effects mainly on defense or general multiple-stress responses pathways, low fluence rate UV-B promoted the expression of genes that could be involved in UV-B protection or the amelioration of the UV-B-induced damage. This study also provides an extensive list of genes regulating multiple metabolic pathways involved in the response of grapevine to UV-B that can be used for future researches.

Although scholars started investigating self-objectification more than twenty years ago, only a few studies focused on men and even fewer have taken into account the cross-cultural dimension. Our study focused on the antecedents of self-objectification paying attention to the role of biological and sociodemographic variables (gender, BMI), psychological characteristics (self-esteem, perfectionism) together with social and cultural factors (internalization of media standards, influence of family and friends). Self-objectification was operationalized as Body Shame and Body Surveillance. A self-reported questionnaire was administered to 2165 adults living in four European countries (UK, Italy, Poland and Romania) and Iran. Ten regression models were performed (2 per country) to analyse the correlates of self-objectification. Overall, self-objectification emerged as a process affected by factors entrenched in psychological, biological, social and cultural domains, partially different for Body Shame and Body Surveillance. Findings showed the key role of self-esteem as a protective factor against Body Shame across countries. On the other hand, the internalization of media standards emerged as risk factor for both Body Shame and Body Surveillance in the five countries. Taken together, these results underline the complexity of self-objectification and the need to deepen research on this topic among non-Western countries.

Abstract Background Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. Methods One hundred seventy-two BC survivor women, aged 30–70 years, non-metastatic, stage 0–III, non-physically active, 6–12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40–70% of heart rate reserve) and duration (20–60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). Discussion This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. Trial registration ClinicalTrials.gov NCT04818359 . Retrospectively registered on March 26, 2021

Abstract The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy.

Mechanistic modeling constitutes a powerful tool to unravel complex biological phenomena. This study describes the construction of a mechanistic, dynamic model for grapevine plant growth and canopy biomass (vigor). To parametrize and validate the model, the progeny from a cross of Ramsey (Vitis champinii) × Riparia Gloire (V. riparia) was evaluated. Plants with different vigor were grown in a greenhouse during the summer of 2014 and 2015. One set of plants was grafted with Cabernet Sauvignon. Shoot growth rate (b), leaf area (LA), dry biomass, whole plant and root specific hydraulic conductance (kH and Lpr), stomatal conductance (gs), and water potential (Ψ) were measured. Partitioning indices and specific leaf area (SLA) were calculated. The model includes an empirical fit of a purported seasonal pattern of bioactive GAs based on published seasonal evolutionary levels and reference values. The model provided a good fit of the experimental data, with R = 0.85. Simulation of single trait variations defined the individual effect of each variable on vigor determination. The model predicts, with acceptable accuracy, the vigor of a young plant through the measurement of Lpr and SLA. The model also permits further understanding of the functional traits that govern vigor, and, ultimately, could be considered useful for growers, breeders and those studying climate change.

ObjectivesTo identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere.Study designThe Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected.ResultsWe enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P = .09), or in experiencing portal hypertension (28% vs 21%; P = .16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P = .04. Development of portal hypertension was associated with a reduced height Z-score.ConclusionsPortal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A history of neonatal cholestasis is a weak predictor of severe disease.

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia–reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis. While pericytes have an essential physiological function in erythropoietin production, a lesser-known role of HIF stabilization during IRI is that pericytes’ HIF expression could influence vascular remodeling, cell loss and organ fibrosis. Better knowledge of mechanisms that control functions and consequences of HIF stabilization in pericytes beyond erythropoietin production is advisable for the development of therapeutic strategies to influence disease progression and improve treatments. Thus, in this review, we discuss the dual roles—for good or bad—of HIF stabilization during IRI, focusing on pericytes, and consequences in particular for the kidneys.

Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, thus reaching final products by cross-contamination. With the growing demand for clean-label products, the search for natural antimicrobials as biopreservants, such as bacteriocins, has shown promising potential. In this context, this study aimed to evaluate the anti-listerial action of bacteriocins produced by Enterococcus lactis LBM BT2 in an alternative medium containing sugarcane molasses (SCM). Molecular analyses were carried out to characterize the strain, including the presence of bacteriocin-related genes. In the kinetic study on SCM medium E. lactis, LBM BT2 showed biomass and bacteriocin productions similar to those observed on a sucrose-based medium (control), highlighting the potential of the sugarcane molasses as a low-cost substrate. Stability tests revealed that the molecule remained active in wide ranges of pH (4–10) and temperature (60–100 °C). Furthermore, the proteolytic treatment reduced the biomolecule’s antimicrobial activity, highlighting its proteinaceous nature. After primary purification by salting out and tangential flow filtration, the bacteriocin-like inhibitory substance (BLIS) showed bacteriostatic activity on suspended L. monocytogenes cells and against biofilm formation at a concentration of 0.625 mg/mL. These results demonstrate the potential of the produced BLIS as a biopreservative in the food industry.

Alzheimer’s disease (AD) is the most common form of dementia, characterized by the accumulation of β-amyloid plaques, tau tangles, neuroinflammation, and synaptic/neuronal loss, the latter being the strongest correlating factor with memory and cognitive impairment. Through an in vitro study on a neurons–astrocytes–microglia (NAM) co-culture system, we analyzed the effects of cerebrospinal fluid (CSF) samples from AD and non-AD patients (other neurodegenerative pathologies). Treatment with CSF from AD patients showed a loss of neurofilaments and spheroids, suggesting the presence of elements including CX3CL1 (soluble form), destabilizing the neurofilaments, cellular adhesion processes, and intercellular contacts. The NAM co-cultures were analyzed in immunofluorescence assays for several markers related to AD, such as through zymography, where the expression of proteolytic enzymes was quantified both in cell extracts and the co-cultures’ conditioned medium (CM). Through qRT-PCR assays, several genes involved in the formation of β-amyloid plaque, in phosphorylation of tau, and in inflammation pathways and MMP expression were investigated.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antiradical capacity (AC), anthocyanins and non-anthocyanin PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits received the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to incorporate components like PCs and dietary fiber into traditional consumers’ diets.

The presence and coexistence of deagrarianization and reagrarianization movements within Italian Inner Areas implies the adoption of keys to understanding their evolution that take into account both processes that generate the so-called "voids" (e.g. demographic decline, erosion of territorial capital, etc.) and processes of territorial resistance and renaissance. Accordingly, the paper explores the nature and peculiarities of both movements in Central Sardinia, specifically in the territories of Barbagia, Mandrolisai and Ogliastra. Empirically, it focuses on the mechanisms that characterize a young farmers’ back-to-the-land process by individuating the motivational aspects that determine the choices for starting an agricultural business for the first time or taking over an existing farm, and identifying the elements that place the action of the farm beyond its perimeter, in an articulated system in which the new agrarization is a pivotal element of a broad process of territorial regeneration and reconnection with urban areas.

Introdução: Algumas proteínas do coronavírus desempenham um papel importante na modulação da imunidade inata do hospedeiro, mas poucos estudos foram conduzidos sobre SARS-CoV-2. Neste estudo, examinamos a proteína viral ORF8, que é capaz de mimetizar a IL-17A causando a tempestade de citocinas e, ainda, é potencial inibidora da via de sinalização do interferon tipo I (IFN-1), um componente chave para a resposta antiviral da imunidade inata do hospedeiro. A Orf8 é uma região genômica hipervariável e pouco conservada entre os coronavírus, os quais podem persistir sem uma Orf8 funcional. As mutações na Orf8 do SARS-CoV-2 podem ser preditoras do prognóstico da COVID-19. Assim, o paciente pode apresentar diferentes estágios clínicos da COVID-19. Objetivos: Analisar retrospectivamente as mutações na Orf8 do SARS-CoV-2 circulante na região central do Rio Grande do Sul, Brasil. Métodos: Foram sequenciadas 1449 amostras positivas para SARS-CoV-2 de laboratórios públicos e privados da 4ª Coordenadoria Regional de Saúde do estado do Rio Grande do Sul das semanas epidemiológicas 26/2021 a 17/2023. O sequenciamento foi realizado pela tecnologia MinION ou Illumina iSeq 100 no LABIOMIC. As sequências consenso foram montadas utilizando o protocolo de bioinformática ARTIC nCoV-2019 ou Dragen COVID. Os clados e linhagens foram determinados pelo Nextclade e Pangolim, respectivamente. As mutações na região da Orf8 foram analisadas na plataforma Nextclade. Resultados: Das amostras sequenciadas, 75 foram classificadas como Gamma, 293 Delta, 982 Ômicron e 105 recombinantes, destas 67 eram XBB. A mutação E92K foi observada em 97% das sequências Gamma. Todas as Delta possuíam as deleções D119- e D120-. Na Ômicron, 7% das Orf8 possuíam alguma mutação. Foram encontradas as mutações P36L, V62L, E64D, L95F (Delta), V62L, A65S, S67F, F120V, I121L, I121F, T11I (Ômicron) e A65V (XBB). Na literatura, T11I está associada a maior severidade da doença. Já as demais, a uma atenuação dos sintomas da COVID-19. A mutação G8*, que interromperia o processo de transcrição gerando uma proteína truncada, foi observada em 85,6% das XBB. As mutações encontradas aqui, possivelmente abrandaram ou suprimiram os efeitos causados pela ORF8. Conclusão: Foram encontradas mutações que, hipoteticamente, podem alterar o fenótipo viral e interferir na resposta do hospedeiro. Estudos posteriores são necessários para demonstrar correlação clínica das diferentes evoluções dos casos de covid-19 com essas mutações.

Introdução: A linhagem recombinante XBB, em circulação no Brasil, evade a imunidade mediada por anticorpos adquiridos pela vacinação ou infecções prévias por SARS-CoV-2 devido a múltiplas mutações no gene S. Indivíduos com esquema vacinal completo permanecem protegidos contra a forma grave, hospitalização e morte por COVID-19. No entanto, aqueles com doses insuficientes ou passados mais de seis meses podem ter proteção reduzida contra o vírus. Objetivo: Realizar a genotipagem de amostras positivas para SARS-CoV-2 e investigar o esquema vacinal de indivíduos infectados com a linhagem XBB na região central do RS, Brasil. Métodos: Foram sequenciadas amostras positivas para SARS-CoV-2 de laboratórios públicos e privados da 4ª Coordenadoria Regional de Saúde do RS, das semanas epidemiológicas 47/2022 a 17/2023. As tecnologias MinION ou Illumina iSeq 100 foram empregadas para realizar o sequenciamento no LABIOMIC. Utilizou-se o protocolo de bioinformática ARTIC nCoV-2019 ou Dragen COVID para montar as sequências consenso. Os clados e linhagens foram determinados pelo Nextclade e Pangolin, respectivamente. Os dados epidemiológicos e clínicos dos pacientes infectados com a variante XBB foram obtidos do DATASUS, e-SUS e SIVEP GRIPE. Resultados e discussão: Das 340 amostras sequenciadas, 89 foram identificadas como XBB ou suas sublinhagens. Em relação à faixa etária, 41,6% com 40-59 anos; 33,7% com +60 anos e se recuperaram da infecção por XBB (97,7%). Apenas três pacientes foram hospitalizados (dois na UTI e um na enfermaria), resultando em dois óbitos. Ambos os pacientes tinham idade ≥80 anos, sendo um com esquema vacinal incompleto. Em relação ao esquema vacinal, 41,6% dos indivíduos receberam duas doses da vacina e um reforço, enquanto 27% receberam dois reforços. No entanto, 55% dos indivíduos receberam sua última dose há mais de um ano. Cinco indivíduos não foram vacinados. A capacidade de neutralização da dose de reforço (Pfizer-BioNTech BNT162b2) é 66 vezes menos eficaz contra a cepa XBB.1.5 em comparação com a cepa WA.1. Conclusão: A maioria dos pacientes infectados com XBB se recuperou, porém, receberam sua última dose de vacina ou reforço há mais de um ano, indicando possível declínio ou ausência de anticorpos contra o vírus. Portanto, é importante enfatizar a importância de completar o esquema vacinal.

Introdução: O SARS-CoV-2 é capaz de infectar as células do sistema nervoso central (SNC), promovendo estresse oxidativo e inflamação. Múltiplas manifestações neurológicas como cefaléia, confusão mental, fadiga, anosmia e ageusia tem sido descritas. O mecanismo pelo qual o SARS-CoV-2 causa estas manifestações, ainda não está estabelecido. Neste sentido, o transcriptoma de indivíduos com COVID-19 pode indicar modulação transcricional que, no futuro, pode ser utilizada como biomarcador de alterações clínicas. Objetivos: Investigar a modulação transcricional de genes associados ao sistema antioxidante endógeno (KEGG N00243) no córtex pré-frontal de pacientes com COVID-19. Métodos: Utilizamos dois bioprojetos (PRJNA755712 e PRJNA755713), disponíveis no NCBI, de autópsias de córtex pré-frontal de indivíduos infectados e não infectados, totalizando 10 transcriptomas. Após, foram baixadas as sequências de mRNA e as sequências codificadoras foram utilizadas para o mapeamento das leituras dos transcriptomas. O mapeamento e a análise de expressão diferencial foram realizados no CLC Genomics Workbench 23.0.4. Foram considerados diferencialmente expressos, os genes que apresentaram p < 0,05. Resultados e discussão: A infecção pelo SARS-CoV-2 induziu um aumento na transcrição da Gpx4 (FC = 7,71) e da Nqo1 (FC = 5,83) indicando uma adaptação do organismo no combate ao estresse oxidativo. Em contrapartida, houve uma diminuição na transcrição da GstA4 (FC = -19,33), GstM2 (FC = -2,21), GstM4 (FC = -16,6), GstT1 (FC = -10,52). A glutationa S-transferase (GST) é uma enzima de fase 2 de detoxificação, que conjuga a glutationa com moléculas xenobióticas (substâncias estranhas ao organismo humano). A redução na transcrição de GSTs pode resultar em uma detoxificação ineficaz. Polimorfismos neste gene são considerados fatores de risco para esquizofrenia, transtorno bipolar e ansiedade. Além disso, estudos in vitro indicam que a perda da GSTA4 prejudica a diferenciação, remielinização e sobrevivência de oligodendrócitos, o que pode contribuir para a neurodegeneração. Conclusão: O SARS-CoV-2 pode provocar uma modulação transcricional comparável àquela observada em patologias que comprometem o SNC. As implicações de longo prazo da COVID-19 parecem incluir uma gama de distúrbios, sobretudo no SNC. Estudos complementares são necessários para aprofundar estes achados e os correlacionar com as manifestações neurológicas dos pacientes acometidos por COVID-19.

Adhesive bonding presents many advantages, such as efficient manufacturing and improved structural performance [1]. However, in structures subjected to fatigue, cracks might initiate and propagate in joints, leading to in-service failure [2]. Most adhesively bonded joints are subjected to combination of peel and shear loads, so mixed I+II mode loading conditions are present [3]. In this work, Cracked Lap Shear specimens, which feature mixed I+II mode loading conditions, were tested under fatigue loading. During tests, crack growth was monitored using Visual Testing and Digital Image Correlation. With Digital Image Correlation, opening and sliding displacements in the bondline were extracted from the substrates’ displacement fields and compared against a Finite Element Model, revealing a highly strained process zone ahead of the crack tip. Results highlight the usefulness of DIC in capturing the deformation behaviour of adhesive joints under mixed mode loading conditions.

A great number of bioceramic sealers commercially available nowadays show a great diversity in their biological, chemical, and physical properties. Such differences can also significantly affect clinical performance, and consequently, new commercially available products must be carefully investigated to assess quality and check differences with existing products. The current in vitro study investigated five physicochemical properties (setting time, solubility, pH analysis, radiopacity, and film thickness) of two commercially available bioceramic sealers. The null hypothesis was that the composition of the two products was the same, the manufacturing site was the same and consequently, they should exhibit the same properties when subjected to in vitro tests. Tests were conducted based on the International Standard Organization (ISO) 6876/2012 recommendations. For each test 10 samples for each product were evaluated. All data were recorded and analyzed statistically by ANOVA and Tukey’s test at the 5% significance level. For all tests, no statistically significant differences were found between the two groups. Based on the findings of this study, we may conclude that there is a great similarity in chemical composition and manufacturing or, more likely, the two products, which are made by the same manufacturers, are identical.

Key Clinical Message Fibromyalgia is a rare disease, difficult to diagnose and to treat. We think that hyperbaric oxygen therapy could improve its signs and symptoms although more evidences have to be accumulated.

BackgroundBreast cancer (BC) is the second-leading cause of cancer-related death worldwide. This study aimed to investigate the effects of a 12-week home-based lifestyle intervention (based on nutrition and exercise) on gut microbial composition in twenty BC survivors of the MoviS clinical trial (protocol: NCT 04818359).MethodsGut microbiota analysis through 16S rRNA gene sequencing, anthropometrics, Mediterranean Diet (MD) adherence, and cardiometabolic parameters were evaluated before (Pre) and after (Post) the lifestyle intervention (LI).ResultsBeneficial effects of the LI were observed on MD adherence, and cardiometabolic parameters (pre vs post). A robust reduction of Proteobacteria was observed after LI, which is able to reshape the gut microbiota by modulating microorganisms capable of decreasing inflammation and others involved in improving the lipid and glycemic assets of the host. A significant negative correlation between fasting glucose and Clostridia_vadinBB60 (r = -0.62), insulin and homeostatic model assessment (HOMA) index and Butyricicoccus genera (r = -0.72 and -0.66, respectively), and HDL cholesterol and Escherichia/Shigella (r = -0.59) have been reported. Moreover, positive correlations were found between MD adherence and Lachnospiraceae_ND3007 (r = 0.50), Faecalibacterium (r = 0.38) and Butyricimonas (r = 0.39).ConclusionThese data suggest that adopting a healthy lifestyle, may contribute to ameliorate several biological parameters that could be involved in the prevention of cancer relapses through the modulation of gut microbiota.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1–17, interquartile range (IQR) 8–15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42–64, IQR 18–81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3–9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

Objetivo: avaliar a intensidade e o desconforto provocados pela sede em pacientes em pós-operatório imediato. Método: estudo exploratório-descritivo, desenvolvido com pacientes internados na sala de recuperação pós-anestésica de um hospital público paranaense. Avaliaram-se indivíduos maiores de 18 anos, de ambos os sexos, com cognitivo preservado, internados de junho de 2021 a janeiro de 2022. A intensidade e o desconforto da sede foram mensurados por escalas específicas. Resultados: avaliaram-se 150 pacientes, com média de 43,9 anos. A maioria era do sexo masculino (65,3%), sem comorbidades (68,7%), submetida à raquianestesia (58%) e cirurgia ortopédica (59,3%), com soroterapia em curso (92,7%). O tempo médio de cirurgia foi 1,5 hora e 14,6 horas de jejum; 72,7% da amostra verbalizou sede, sendo que 37,6% queixaram-se de forma espontânea. Conclusão: os participantes de pesquisa apresentaram intensidade (6,6) e desconforto (7,6) moderados de sede no pós-operatório, tornando-se necessário discutir protocolos institucionais de intervenção para diminuir tal evento.

Bio-based plastics are gaining attention as environmentally friendly alternatives to traditional petroleum-based plastics in food packaging. Biodegradable films made from biocompatible macromolecules like polysaccharides and proteins offer promising solutions. This study investigated the effects of incorporating dihydroeugenol and glycoside into whey protein isolate (WPI) films to enhance their antimicrobial and antioxidant properties for food packaging. The findings showed that the glycoside film surpassed the dihydroeugenol film in inhibiting bacterial growth, forming larger inhibition halos against Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella Enteritidis (inhibition halos ≥15 mm). The glycoside film exhibited superior effectiveness against Gram-positive bacteria, indicating enhanced penetration through their cell membranes. Additionally, the synthesized compounds significantly boosted the antioxidant activity of the films compared to the control film without dihydroeugenol and glycoside. With a relatively low solubility (23% ± 2.87% and 24% ± 3.92% for dihydroeugenol and glycoside, respectively), these films are suitable for packaging and safeguarding food products with medium to high humidity. This study concluded that incorporating dihydroeugenol and its glycoside into WPI films holds great promise for developing active packaging solutions in the food industry. These films offer both antibacterial and antioxidant properties, particularly advantageous for food products with medium to high humidity.

Background & aimsGut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.MethodsWe collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n = 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.ResultsIn the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P = .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P = .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.ConclusionsIn an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.

Objective. Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3–4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear.

The SI4CARE project is a transnational project which aims to develop both strategy and action plans to improve health and social care in the Adriatic–Ionian region. Starting from a survey of the status quo, each partner has developed some pilots to support the development and monitoring of the policy actions. In particular, partner number three, the Municipality of Miglierina, designed and developed a pilot related to the use of wearable devices for monitoring elderly patients in rural areas. With the collaboration of the complex unity of primary care (UCCP) of the Reventino area, the pilot is based on the use of smart wearable devices to monitor some parameters of older adults after their vaccinations for flu and covid. This paper focused on the design and implementation of the system. It describes its application in the Municipality of Miglierina. Presentation of the results and a discussion of the strengths and weaknesses will be presented, in detail, in future work. Finally, the possibility of extending the experiment to other Adriatic–Ionian regions is addressed.

Abstract. Objectives. To test hypothesized associations between the ABO blood group (ABO-bg) system and the pathological features of prostate cancer (PCa). Material and methods. Between January 2013 and September 2019, 1173 patients underwent radical prostatectomy. Associations between ABO-bg levels and pathological features were evaluated using statistical methods. Results. Overall, 1149 consecutive patients were evaluated using the ABO-bg system, which was represented by O-bg (42.8%) and A-bg (41.3%), followed by B-bg (11.1%) and AB-bg (4.8%). Only positive surgical margins (PSMs) was correlated with ABO-bg (Pearson correlation coefficient, r = 0.071; p = 0.017), and the risk was increased in group-O (odds ratio [OR], 1.497; 95% confidence interval, 1.149–1.950; p = 0.003) versus non–O-bg. In clinical and pathological models, O-bg was at increased risk of PSM after the adjustment for prostate-specific antigen, percentage of biopsy-positive cores, and high surgical volume (adjusted OR, 1.546; 95% confidence interval, 1.180–2.026; p = 0.002); however, the adjusted OR did not change after the adjustment for tumor load and stage as well as high surgical volume. Conclusions. In clinical PCa, the risk of PSM was higher in O-bg versus non–O-bg patients after the adjustment for standard predictors. Confirmatory studies are needed to confirm the association between ABO-bg and unfavorable PCa features.

Abstract Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p

Abstract The rice husk, agro-industrial residue, stands out for having silica, the main oxide former of the bioactive glass. To avoid contamination in this biomaterial, substances with bactericidal properties, like silver can be incorporated. Thus, the objective of this work is the synthesis of silver nanoparticles to functionalize a bioactive glass synthesized from rice husk ash (BRHA). The bioglass was prepared by the sol-gel method from the rice husk ash as a silica source. Silver nanoparticles were synthesized from thyme extract with AgNO3 and their formation was verified by UV-vis spectroscopy. The glass powder was added to this solution and its structure was evaluated by SEM-EDS, ATR-FTIR, and microbiology. The bioglass powder appeared in the form of porous agglomerates and the addition of silver altered its superficial roughness by deposition. The chemical bonds of the glass network related to bioactivity were maintained after the incorporation of the nanoparticles. Microbiological analysis by the agar diffusion test confirmed the inhibitory action of the nanoparticles for P. aeruginosa and S. aureus. Therefore, the developed material presented great potential for biomedical applications.

The differential diagnosis between new occurrence or revelation of chronic kidney diseases in pregnancy and hypertensive disorders of pregnancy is not easy, and the presence of a hypertensive disorder superimposed on a glomerular disease is even more challenging, as this case exemplifies. A 29-year-old woman was referred with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome at the end of her pregnancy. Immediately after cesarean delivery, she developed anuria, unexplained by blood loss or hypotension, and in the absence of known nephrotoxic drugs. While the laboratory features of HELLP rapidly resolved, AKI persisted, and the finding of high-level proteinuria was the hint leading to diagnosis of a glomerular disease (focal segmental glomerulosclerosis, FSGS), later proven by kidney biopsy. This case, reporting on the rare association between HELLP and FSGS, offers the opportunity to discuss the role of proteinuria, hypertension, and in the differential diagnosis of pregnancy-related acute kidney injury (pAKI).