Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

Effect of modified citrus pectin on galectin-3 inhibition in cisplatin-induced cardiac and renal toxicity.

This study evaluated the effect of pharmacological inhibition of galectin 3 (Gal-3) with modified citrus pectin (MCP) on the heart and kidney in a model of cisplatin-induced acute toxicity. Male Wistar rats were divided into four groups (n = 6/group): SHAM, which received sterile saline intraperitoneally (i.p.) for three days; CIS, which received cisplatin i.p. (10 mg/kg/day) for three days; MCP, which received MCP orally (100 mg/kg/day) for seven days, followed by sterile saline i.p. for three days; MCP+CIS, which received MCP orally for seven days followed by cisplatin i.p. for three days. The blood, heart, and kidneys were collected six hours after the last treatment. MCP treatment did not change Gal-3 protein levels in the blood and heart, but it did reduce them in the kidneys of the MCP groups compared to the SHAM group. While no morphological changes were evident in the cardiac tissue, increased malondialdehyde (MDA) levels and deregulation of the mitochondrial oxidative phosphorylation system were observed in the heart homogenates of the MCP+CIS group. Cisplatin administration caused acute tubular degeneration in the kidneys; the MCP+CIS group also showed increased MDA levels. In conclusion, MCP therapy in the acute model of cisplatin-induced toxicity increases oxidative stress in cardiac and renal tissues. Further investigations are needed to determine the beneficial and harmful roles of Gal-3 in the cardiorenal system since it can act differently in acute and chronic diseases/conditions.

[Screen time, quality of the adolescent diet, and profile of the school environment]. / Tempo de tela, qualidade da dieta de adolescentes e características do entorno escolar.

Adolescents from 30 state schools in Curitiba, State of Paraná, reported total screen time, namely television, video games and laptops. Diet quality was assessed by the frequency of food consumption. The income of the school environment was taken from the Census. The built environment for physical activity was investigated by systematic observation of the school surroundings. Multilevel Poisson Regression was used to estimate associations with the exposure variables. Among 1,200 adolescents, 50.9% being male, and 74.4% were found to be exposed to excessive screen time. Excessive TV screen time (56.5%) was associated with poor diet quality. Excessive video game time (22.0%) was lower among females (PR 0.25; 95%CI 0.18;0.36), associated with poor diet quality, lower school environment income, and the worst classification of the built environment for physical activity. Excessive use of portable screens (53.2%) tended to increase with the income of the school environment. Excessive use of TV and laptops was widespread among adolescents, with different demographic and contextual variables associated according to the type of device used.

Objetivou-se investigar a associação entre o tempo de uso excessivo de diferentes telas, a qualidade da dieta em adolescentes e características do entorno escolar. Adolescentes de 30 escolas estaduais de Curitiba/PR relataram tempo de tela: televisão, videogame e portáteis. A qualidade da dieta foi avaliada pela frequência de consumo de alimentos. A renda do entorno escolar foi obtida do Censo. O ambiente construído para atividade física investigado por observação sistemática do entorno escolar. A regressão de Poisson multinível foi empregada para estimar associações com as variáveis de exposição. Entre 1.200 adolescentes, 50,9% do sexo masculino, 74,4% tiveram tempo excessivo de tela. O tempo excessivo de TV (56,5%) esteve associado à pior qualidade da alimentação. O tempo excessivo de videogame (22,0%) foi menor no sexo feminino (RP 0,25; IC95% 0,18;0,36), associado à pior qualidade da alimentação, à menor renda do entorno escolar, e à pior classificação do ambiente construído para atividade física. O tempo excessivo de telas portáteis (53,2%) apresentou tendência de aumento com a renda do entorno escolar. O uso excessivo de TV e telas portáteis foi amplamente praticado por adolescentes, com diferentes variáveis demográficas e contextuais associadas de acordo com o tipo de dispositivo utilizado.

The Huntington's Disease Gene Discovery.

The gene for Huntington's disease (HD) was discovered in 1993, after an international collaborative initiative that led researchers to remote regions of South America. It was the most remarkable milestone, since George Huntington's initial description. Through the phenomenological discussions led by Jean-Martin Charcot and Willian Osler, and finally Americo Negrette's reports, which served as the inspiration for the Venezuela Project led by Nancy Wexler, the journey toward discovering the Huntington's disease (HD) gene was marked by substantial efforts. This monumental achievement involved the analysis of more than 18,000 blood samples and gathered dozens of researchers in an integrated effort, enabling the mapping of the gene on chromosome 4 in 1983 and leading, a decade later, to the precise localization and identification of the HTT gene. The discovery of the HD mutation represented a pivotal moment in the field of genetics and neurology, significantly enhancing our understanding of the disease and creating opportunities for future treatments. The progress made and the knowledge gained during this journey catalyzed the development of many innovative molecular techniques that have advanced research in other medical conditions. In this article, the authors celebrate three decades of this memorable event, revisiting the historical aspects, providing insights into the techniques developed, and delving into the paths that ultimately led to the discovery of the HD gene. © 2024 International Parkinson and Movement Disorder Society.

Nipple shield use in the maternity ward increases risk of exclusive breastfeeding interruption in the first six months of infant's life.

OBJECTIVE: The objective of this study was to investigate the association between use of silicone nipple shields in the maternity ward and exclusive breastfeeding interruption in the first 6 months of the infant's life. DESIGN: Cohort study. SETTING: Interviews were conducted personally at the mother's home at 1 and 6 months postpartum and by telephone at 2 and 4 months. PARTICIPANTS: 287 mother-infant dyads. METHODS: Lactating mothers were randomly selected at two maternity wards (one public, one private) in Porto Alegre, Brazil. Data were analyzed using Kaplan-Meier survival curves and Cox multivariate regression. The outcome of interest was exclusive breastfeeding interruption before 6 months of the infant's life. FINDINGS: Nipple shields were used by 6.2 % of the women in the public maternity ward and by 25.8 % of those in the private setting. Median duration of exclusive breastfeeding was 11 days (95 %CI 0.0-36.9) among women who used the accessory vs. 89 days (95 %CI 60.8-117.2) among those who did not. Nipple shield use in the maternity ward was associated with exclusive breastfeeding interruption before 6 months of infant's life (adjusted risk ratio = 1.47; 95 %CI 1.01-2.15). The risk was higher in the first months of breastfeeding, ranging from 2.0 to 1.47 in the first and sixth months, respectively. CONCLUSIONS: The use of silicone nipple shields in the maternity ward increased the risk of exclusive breastfeeding interruption before 6 months of the infant's life, especially in the first months. These findings suggest caution in recommending this accessory to new mothers.

Tempo de tela, qualidade da dieta de adolescentes e características do entorno escolar / Screen time, quality of the adolescent diet, and profile of the school environment

Resumo Objetivou-se investigar a associação entre o tempo de uso excessivo de diferentes telas, a qualidade da dieta em adolescentes e características do entorno escolar. Adolescentes de 30 escolas estaduais de Curitiba/PR relataram tempo de tela: televisão, videogame e portáteis. A qualidade da dieta foi avaliada pela frequência de consumo de alimentos. A renda do entorno escolar foi obtida do Censo. O ambiente construído para atividade física investigado por observação sistemática do entorno escolar. A regressão de Poisson multinível foi empregada para estimar associações com as variáveis de exposição. Entre 1.200 adolescentes, 50,9% do sexo masculino, 74,4% tiveram tempo excessivo de tela. O tempo excessivo de TV (56,5%) esteve associado à pior qualidade da alimentação. O tempo excessivo de videogame (22,0%) foi menor no sexo feminino (RP 0,25; IC95% 0,18;0,36), associado à pior qualidade da alimentação, à menor renda do entorno escolar, e à pior classificação do ambiente construído para atividade física. O tempo excessivo de telas portáteis (53,2%) apresentou tendência de aumento com a renda do entorno escolar. O uso excessivo de TV e telas portáteis foi amplamente praticado por adolescentes, com diferentes variáveis demográficas e contextuais associadas de acordo com o tipo de dispositivo utilizado.

Abstract Adolescents from 30 state schools in Curitiba, State of Paraná, reported total screen time, namely television, video games and laptops. Diet quality was assessed by the frequency of food consumption. The income of the school environment was taken from the Census. The built environment for physical activity was investigated by systematic observation of the school surroundings. Multilevel Poisson Regression was used to estimate associations with the exposure variables. Among 1,200 adolescents, 50.9% being male, and 74.4% were found to be exposed to excessive screen time. Excessive TV screen time (56.5%) was associated with poor diet quality. Excessive video game time (22.0%) was lower among females (PR 0.25; 95%CI 0.18;0.36), associated with poor diet quality, lower school environment income, and the worst classification of the built environment for physical activity. Excessive use of portable screens (53.2%) tended to increase with the income of the school environment. Excessive use of TV and laptops was widespread among adolescents, with different demographic and contextual variables associated according to the type of device used.

Cell type dependent stability and virulence of a recombinant SARS-CoV-2, and engineering of a propagation deficient RNA replicon to analyze virus RNA synthesis.

Engineering of reverse genetics systems for newly emerged viruses allows viral genome manipulation, being an essential tool for the study of virus life cycle, virus-host interactions and pathogenesis, as well as for the development of effective antiviral strategies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent human coronavirus that has caused the coronavirus disease (COVID-19) pandemic. The engineering of a full-length infectious cDNA clone and a fluorescent replicon of SARS-CoV-2 Wuhan-Hu-1, using a bacterial artificial chromosome, is reported. Viral growth and genetic stability in eleven cell lines were analyzed, showing that both VeroE6 cells overexpressing transmembrane serin protease 2 (TMPRSS2) and human lung derived cells resulted in the optimization of a cell system to preserve SARS-CoV-2 genetic stability. The recombinant SARS-CoV-2 virus and a point mutant expressing the D614G spike protein variant were virulent in a mouse model. The RNA replicon was propagation-defective, allowing its use in BSL-2 conditions to analyze viral RNA synthesis. The SARS-CoV-2 reverse genetics systems developed constitute a useful tool for studying the molecular biology of the virus, the development of genetically defined vaccines and to establish systems for antiviral compounds screening.

The problem of conserving an ecosystem that has not been completely delineated and mapped: the case of the Cocais Palm Forest.

Land cover changes threaten biodiversity and alter the geographic distribution of forests worldwide. Studies on this topic are important to establish conservation strategies and public policies. However, different studies may propose different spatial representations due to differences when identifying, classifying, and/or mapping the same vegetation formation, as observed for the Cocais Forest region. This palm-dominated ecosystem predominates the Brazilian mid-north region in an ecotone region with 3 of the 6 Brazilian biomes. In this study, we conducted a literature review of studies that delineated and mapped the Cocais Forest, aiming to compare different mapped regions and to establish a new distribution map integrating these spatial data. We found seven sources that revealed spatial divergences in identifying the spatial distribution of Cocais Forest, including its characteristics in terms of size and shape, which could affect the conservation, socioeconomic, and cultural policies and studies carried out on this emblematic vegetation formation and influence area. The delineation proposed by de Sousa Nascimento and Lima (Revista de Políticas Públicas 189-192, 2016) encompassed the largest area. In addition, there was a lack of consensus regarding the nomenclature for this ecosystem, and few works offered a detailed description of the mapping process. Despite the different spatial distributions found for the Cocais Forest, we succeeded in establishing a common area by overlapping individual maps, resulting in the identification of a core region exclusive located in the State of Maranhão.

Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response.

Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-ß1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-ß1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.

Unraveling surface-enhanced Raman spectroscopy results through chemometrics and machine learning: principles, progress, and trends.

Surface-enhanced Raman spectroscopy (SERS) has gained increasing attention because it provides rich chemical information and high sensitivity, being applicable in many scientific fields including medical diagnosis, forensic analysis, food control, and microbiology. Although SERS is often limited by the lack of selectivity in the analysis of samples with complex matrices, the use of multivariate statistics and mathematical tools has been demonstrated to be an efficient strategy to circumvent this issue. Importantly, since the rapid development of artificial intelligence has been promoting the implementation of a wide variety of advanced multivariate methods in SERS, a discussion about the extent of their synergy and possible standardization becomes necessary. This critical review comprises the principles, advantages, and limitations of coupling SERS with chemometrics and machine learning for both qualitative and quantitative analytical applications. Recent advances and trends in combining SERS with uncommonly used but powerful data analysis tools are also discussed. Finally, a section on benchmarking and tips for selecting the suitable chemometric/machine learning method is included. We believe this will help to move SERS from an alternative detection strategy to a general analytical technique for real-life applications.

Galectin-3 is a key hepatoprotective molecule against the deleterious effect of cisplatin.

AIMS: Evaluate the role of galectin-3 in the liver using an acute model of cisplatin-induced toxicity. MATERIAL AND METHODS: Modified citrus pectin (MCP) treatment was used to inhibit galectin-3. Rats were distributed into four groups: SHAM, CIS, MCP and MCP + CIS. On days 1-7, animals were treated by oral gavage with 100 mg/kg/day of MCP (MCP and MCP + CIS groups). On days 8, 9 and 10, animals received intraperitoneal injection of 10 mg/kg/day of cisplatin (CIS and MCP + CIS groups) or saline (SHAM and MCP groups). KEY FINDINGS: Cisplatin administration caused a marked increase in hepatic leukocyte influx and liver degeneration, and promoted reactive oxygen species production and STAT3 activation in hepatocytes. Plasma levels of cytokines (IL-6, IL-10), and hepatic toxicity biomarkers (hepatic arginase 1, α-glutathione S-transferase, sorbitol dehydrogenase) were also elevated. Decreased galectin-3 levels in the livers of animals in the MCP + CIS group were also associated with increased hepatic levels of malondialdehyde and mitochondrial respiratory complex I. Animals in the MCP + CIS group also exhibited increased plasma levels of IL-1ß, TNF-α, and aspartate transaminase 1. Furthermore, MCP therapy efficiently antagonized hepatic galectin-9 in liver, but not galectin-1, the latter of which was increased. SIGNIFICANCE: Reduction of the endogenous levels of galectin-3 in hepatocytes favors the process of cell death and increases oxidative stress in the acute model of cisplatin-induced toxicity.

The Guadalajara Declaration on sepsis: emergency physicians' constructive comments on the Surviving Sepsis Campaign's 2021 updated guidelines. / Declaración de Guadalajara: una visión constructiva desde el servicio de urgencias a partir de la Surviving Sepsis Campaign 2021.

TEXT: The Surviving Sepsis Campaign (SSC) published a 2021 update of its 2016 recommendations. The update was awaited with great anticipation the world over, especially by emergency physicians. Under the framework of the CIMU 2022 (33rd World Emergency Medicine Conference) in Guadalajara, Mexico in March, emergency physiciansreviewed and analyzed the 2021 SSC guidelines from our specialty's point of view. In this article, the expert reviewers present their consensus on certain key points of most interest in emergency settings at this time. The main aims of the review are to present constructive comments on 10 key points and/or recommendations in the SSC 2021 update and to offer emergency physicians' experience- and evidence-based proposals. Secondarily, the review's recommendations are a starting point for guidelines to detect severe sepsis in emergency department patients and prevent progression, which is ultimate goal of what has become known as the Guadalajara Declaration on sepsis.

TEXTO: En noviembre del año 2021, la Surviving Sepsis Campaign (SSC) publicó una actualización de sus recomendaciones y directrices de 2016. Estas fueron recibidas con una enorme expectativa en todo el mundo, especialmente entre los médicos de urgencias y emergencias (MUE). Recientemente, en el marco del CIMU 2022 (33 Congreso Mundial de Medicina de Urgencias celebrado en marzo de 2022 en Guadalajara ­ México) se ha revisado y analizado, desde la perspectiva del MUE, la Guía SSC de 2021. Los expertos que realizaron esa tarea y también consensuaron algunos de los puntos clave que más interesan y preocupan a los MUE en la actualidad han elaborado este documento. Su objetivo principal es analizar de forma constructiva diez de los puntos clave y recomendaciones de la SSC 2021 para complementarlas con argumentos y propuestas desde la experiencia, evidencia y perspectiva del urgenciólogo. Además, de forma secundaria, pretende ser el punto de partida de la elaboración de las guías para detectar, prevenir la progresión y atender a los pacientes con infección grave y sepsis en urgencias, que supone la meta final de lo que desde la MUE ya se conoce como "la Declaración de Guadalajara".

Pactolo Bar: An Approach to Mitigate the Midas Touch Problem in Non-Conventional Interaction.

New ways of interacting with computers is driving research, which is motivated mainly by the different types of user profiles. Referred to as non-conventional interactions, these are found with the use of hands, voice, head, mouth, and feet, etc. and these interactions occur in scenarios where the use of mouse and keyboard would be difficult. A constant challenge in the adoption of new forms of interaction, based on the movement of pointers and the selection of interface components, is the Midas Touch (MT) problem, defined as the involuntary action of selection by the user when interacting with the computer system, causing unwanted actions and harming the user experience during the usage process. Thus, this article aims to mitigate the TM problem in interaction with web pages using a solution centered on the Head Tracking (HT) technique. For this purpose, a component in the form of a Bar was developed and inserted on the left side of the web page, called the Pactolo Bar (PB), in order to enable or disable the clicking event during the interaction process. As a way of analyzing the effectiveness of PB in relation to TM, two stages of tests were carried out based on the collaboration of voluntary participants. The first step aims to find the data that would lead to the best configuration of the BP, while the second step aims to carry out a comparative analysis between the PB solution and the eViacam software, whose use is also focused on the HT technique. The results obtained from the use of PB were considered promising, since the analysis of quantitative data points to a significant prevention of involuntary clicks in the iteration interface and the analysis of qualitative data showed the development of a better user experience due to the ease of use, which can be noticed in elements such as the PB size, the triggering mechanism, and its positioning in the graphical interface. This study benefits in the context of the user experience, because, when using non-conventional interactions, basic items such as aspects of the graphic elements, and interaction events raise new studies that seek to mitigate the problem of the Midas Touch.

Declaración de Guadalajara: una visión constructiva desde el servicio de urgencias a partir de la Surviving Sepsis Campaign 2021 / The Guadalajara Declaration on sepsis: emergency physicians’ constructive comments on the Surviving Sepsis Campaign’s 2021 updated guidelines

En noviembre del año 2021, la Surviving Sepsis Campaign (SSC) publicó una actualización de sus recomendaciones y directrices de 2016. Estas fueron recibidas con una enorme expectativa en todo el mundo, especialmente entre los médicos de urgencias y emergencias (MUE). Recientemente, en el marco del CIMU 2022 (33 Congreso Mundial de Medicina de Urgencias celebrado en marzo de 2022 en Guadalajara – México) se ha revisado y analizado, desde la perspectiva del MUE, la Guía SSC de 2021. Los expertos que realizaron esa tarea y también consensuaron algunos de los puntos clave que más interesan y preocupan a los MUE en la actualidad han elaborado este documento. Su objetivo principal es analizar de forma constructiva diez de los puntos clave y recomendaciones de la SSC 2021 para complementarlas con argumentos y propuestas desde la experiencia, evidencia y perspectiva del urgenciólogo. Además, de forma secundaria, pretende ser el punto de partida de la elaboración de las guías para detectar, prevenir la progresión y atender a los pacientes con infección grave y sepsis en urgencias, que supone la meta final de lo que desde la MUE ya se conoce como “la Declaración de Guadalajara”. (AU)

The Surviving Sepsis Campaign (SSC) published a 2021 update of its 2016 recommendations. The update was awaited with great anticipation the world over, especially by emergency physicians. Under the framework of the CIMU 2022 (33rd World Emergency Medicine Conference) in Guadalajara, Mexico in March, emergency physicians reviewed and analyzed the 2021 SSC guidelines from our specialty’s point of view. In this article, the expert reviewers present their consensus on certain key points of most interest in emergency settings at this time. The main aims of the review are to present constructive comments on 10 key points and/or recommendations in the SSC 2021 update and to offer emergency physicians’ experience- and evidence-based proposals. Secondarily, the review’s recommendations are a starting point for guidelines to detect severe sepsis in emergency department patients and prevent progression, which is ultimate goal of what has become known as the Guadalajara Declaration on sepsis. (AU)

Few-Shot User-Adaptable Radar-Based Breath Signal Sensing.

Vital signs estimation provides valuable information about an individual's overall health status. Gathering such information usually requires wearable devices or privacy-invasive settings. In this work, we propose a radar-based user-adaptable solution for respiratory signal prediction while sitting at an office desk. Such an approach leads to a contact-free, privacy-friendly, and easily adaptable system with little reference training data. Data from 24 subjects are preprocessed to extract respiration information using a 60 GHz frequency-modulated continuous wave radar. With few training examples, episodic optimization-based learning allows for generalization to new individuals. Episodically, a convolutional variational autoencoder learns how to map the processed radar data to a reference signal, generating a constrained latent space to the central respiration frequency. Moreover, autocorrelation over recorded radar data time assesses the information corruption due to subject motions. The model learning procedure and breathing prediction are adjusted by exploiting the motion corruption level. Thanks to the episodic acquired knowledge, the model requires an adaptation time of less than one and two seconds for one to five training examples, respectively. The suggested approach represents a novel, quickly adaptable, non-contact alternative for office settings with little user motion.

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Coronaviruses (CoVs) of genera α, ß, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Silica extraction from rice hull ash through the sol-gel process under ultrasound.

Rice is among the main foods produced in the world and is part of the daily diet of most families. The main waste from rice processing is rice husk (RH), which has been used as biomass for energy generation through combustion. In this process, rice husk ash (RHA) is generated as a residue, and its silica (SiO2) content varies from 85 to 98%. The present work describes the study of the extraction of silica from RHA by the ultrasound-assisted sol-gel method. An experimental design based on the response surface methodology (RSM) with the symmetrical, second-order rotational central composite design (RCCD) was applied to determine the best extraction conditions considering extraction time and molar ratio (n) as variables = nNaOH/nSilica). These optimal conditions were then applied to three ash samples, two obtained by the combustion process in a boiler furnace, with a mobile grate system (RHAC1 and RHAC2), and one obtained by the pyrolysis process (RHAP) carried out in a fixed bed reactor. Results showed that a molar ratio of 4.4, and an extraction time of 107 min were the best extraction conditions, leading to a yield of 73.3% for RHAP, 43.9% for RHAC1, and 31.1% for RHAC2. It was found that the extraction yield and textural properties of the silica obtained depend on the characteristics of the ash used. The silica extracted from RHAC1 presented a surface area of 465 m2.g-1, mesopores of 4.69 nm, purity greater than 95%, and an ultra-fine granulometric distribution, reaching nanoparticle dimensions, characteristics comparable to commercially available silicas.

IMPACT OF COVID-19 ON MORTALITY AND HOSPITALIZATION IN OLDER ADULTS WITH HIP FRACTURE.

Objective: To evaluate the impact of the COVID-19 pandemic on hospital admission and mortality indicators in older adults with fractures of the proximal femur. Methods: Observational and retrospective study that took place from June 2016 to 2020. Patients of both genders who underwent surgical treatment for fractures of the proximal end of the femur, aged over 60 years, were included. Results: The population consisted of 379 patients, treated before (group 1; N = 278; 73.35%) and during the pandemic (group 2; N = 101; 26.65%). Higher mortality was observed in group 2 (N = 24; 23.8%) versus group 1 (N = 10; 3.6%), p < 0.001. The highest proportion of deaths in group 2 was maintained in patients aged 70-79 years (p = 0.011), 80-89 years (p ≤ 0.001) and > 90 years (p ≤ 0.001). In addition, the preoperative time and hospital stay were longer in group 2 compared to group 1 (p ≤ 0.001). Conclusion: The present study demonstrated that the pandemic period increased the mortality rate and the preoperative and hospitalization time in older patients with femur fractures. Thus, the pandemic has affected the care of fractures of the proximal femur in older adults, which reinforces the need to adopt measures to reduce complications and mortality. Level of Evidence II, Retrospective Study.

Objetivo: Avaliar o impacto da pandemia de COVID-19 nos indicadores de internação e mortalidade hospitalar em idosos com fraturas do fêmur proximal. Métodos: Estudo observacional e retrospectivo, que ocorreu de junho de 2016 a 2020. Foram incluídos pacientes de ambos os sexos submetidos ao tratamento cirúrgico para fratura da extremidade proximal do fêmur, com idade acima de 60 anos. Resultados: A população foi composta por 379 pacientes, atendidos antes (grupo 1; N = 278; 73,35%) e durante a pandemia (grupo 2; N = 101; 26,65%). Foi verificada maior mortalidade no grupo 2 (N = 24; 23,8%) versus o grupo 1 (N = 10; 3,6%), p < 0,001. A maior proporção de óbitos no grupo 2 se manteve nos pacientes com 70-79 anos (p = 0,011), 80-89 anos (p ≤ 0,001) e > 90 anos (p ≤ 0,001). Os períodos pré-operatório e de permanência hospitalar foram maiores no grupo 2 em comparação ao grupo 1 (p ≤ 0,001). Conclusão: Este estudo demonstrou que o período pandêmico aumentou a taxa de mortalidade e o tempo pré-operatório e de internação em pacientes idosos com fratura do fêmur. Dessa forma, a pandemia tem afetado o atendimento das fraturas do fêmur proximal em idosos, o que reforça a necessidade da adoção de medidas de redução de complicações e mortalidade. Nível de Evidência II, Estudo Retrospectivo.

Surface-enhanced Raman spectroscopy of one and a few molecules of acid 4-mercaptobenzoic in AgNP enabled by hot spots generated by hydrogen bonding.

The present study reports a direct approach to generate efficient hot spots using a nonresonant molecule bound to the inner part or hot spots that can increase the SERS sensitivity to obtain spectra of one and a few molecules. The 4-Mercaptobenzoic acid (4-MBA) adsorbate, connected to the Ag surface by a thiolate-Ag bonding, was able to trigger a self-assembly process of AgNP, which occurred by cooperative hydrogen bonds between the carboxylic groups of 4-MBA located in different nanoparticles when the pH was adjusted to 4. The self-assembly structure was characterized by UV-Vis spectroscopy and SERS (Surface Enhancement Raman Scattering), and DFT-based calculation of the model complex [AgNP-(4-MBA)2-AgNP] was employed to improve the understanding of the self-assembled complex formation through the comparison of calculated and experimental SERS spectra. The SERS signal of 4-MBA on AgNP above the pKa of the carboxyl group was not observed below 1 × 10-6 mol L-1 in any condition. Additionally, the SERS spectra of 4-bromobezenothiol (4-BrBT) at 5.0 × 10-7 mol L-1 had no bands assignable to 4-BrBT, reinforcing the hypothesis that the SERS intensification for 4-MBA in low concentrations (below 1 × 10-6 mol L-1) is due to the hydrogen bonding triggered self-assembly of AgNP below 4-MBA pKa. The average SERS of the 4-MBA in low surface coverage shows a mixture of structures, such as protonated and deprotonated 4-MBA, as well as a small amount of benzenethiol coming from decarboxylation of part of 4-MBA molecules. The few molecules SERS detection of 4-MBA was demonstrated experimentally and the experimental results were associated with a greater number of hot spots formed, being befitting with the generalized Mie theory simulations.