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The largely binary nature of biological sex and its conflation with the socially constructed concept of gender has created much strife in the last few years. The notion of gender identity and its differences and similarities with sex have fostered much scientific and legal confusion and disagreement. Settling the debate can have significant repercussions for science, medicine, legislation, and people's lives. The present review addresses this debate though different levels of analysis (i.e., genetic, anatomical, physiological, behavioral, and sociocultural), and their implications and interactions. We propose a rationale where both perspectives coexist, where diversity is the default, establishing a delimitation to the conflation between sex and gender, while acknowledging their interaction. Whereas sex in humans and other mammals is a biological reality that is largely binary and based on genes, chromosomes, anatomy, and physiology, gender is a sociocultural construct that is often, but not always, concordant with a person' sex, and can span a multitude of expressions.
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Identidade de Gênero , Humanos , Masculino , Feminino , Comportamento Sexual/psicologia , Caracteres SexuaisRESUMO
The UPPS-P Impulsive Behavior Model and the various psychometric instruments developed and validated based on this model are well established in clinical and research settings. However, evidence regarding the psychometric validity, reliability, and equivalence across multiple countries of residence, languages, or gender identities, including gender-diverse individuals, is lacking to date. Using data from the International Sex Survey (N = 82,243), confirmatory factor analyses and measurement invariance analyses were performed on the preestablished five-factor structure of the 20-item short version of the UPPS-P Impulsive Behavior Scale to examine whether (a) psychometric validity and reliability and (b) psychometric equivalence hold across 34 country-of-residence-related, 22 language-related, and three gender-identity-related groups. The results of the present study extend the latter psychometric instrument's well-established relevance to 26 countries, 13 languages, and three gender identities. Most notably, psychometric validity and reliability were evidenced across nine novel translations included in the present study (i.e., Croatian, English, German, Hebrew, Korean, Macedonian, Polish, Portuguese-Portugal, and Spanish-Latin American) and psychometric equivalence was evidenced across all three gender identities included in the present study (i.e., women, men, and gender-diverse individuals).
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Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries (N = 75,117; Mage = 32.07; SDage = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.
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Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples. Electrochemical methods, including microfluidic devices and biosensors, can obtain robust results that reduce time, cost, and assay complexity. This comprehensive review will explore specific studies, methodologies, and detection limits and contribute to the depth of the discussion, making it a valuable resource for researchers and clinicians interested in lung cancer diagnosis.
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Background: The three-item Sexual Distress Scale (SDS-3) has been frequently used to assess distress related to sexuality in public health surveys and research on sexual wellbeing. However, its psychometric properties and measurement invariance across cultural, gender and sexual subgroups have not yet been examined. This multinational study aimed to validate the SDS-3 and test its psychometric properties, including measurement invariance across language, country, gender identity, and sexual orientation groups. Methods: We used global survey data from 82,243 individuals (Mean age=32.39 years; 40.3â¯% men, 57.0â¯% women, 2.8â¯% non-binary, and 0.6â¯% other genders) participating in the International Sexual Survey (ISS; https://internationalsexsurvey.org/) across 42 countries and 26 languages. Participants completed the SDS-3, as well as questions regarding sociodemographic characteristics, including gender identity and sexual orientation. Results: Confirmatory factor analysis (CFA) supported a unidimensional factor structure for the SDS-3, and multi-group CFA (MGCFA) suggested that this factor structure was invariant across countries, languages, gender identities, and sexual orientations. Cronbach's α for the unidimensional score was 0.83 (range between 0.76 and 0.89), and McDonald's ω was 0.84 (range between 0.76 and 0.90). Participants who did not experience sexual problems had significantly lower SDS-3 total scores (M = 2.99; SD=2.54) compared to those who reported sexual problems (M = 5.60; SD=3.00), with a large effect size (Cohen's d = 1.01 [95â¯% CI=-1.03, -0.98]; p < 0.001). Conclusion: The SDS-3 has a unidimensional factor structure and appears to be valid and reliable for measuring sexual distress among individuals from different countries, gender identities, and sexual orientations.
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High-molecular-weight anionic polyacrylamide was used to analyze the effect of kaolin on the structure of particle aggregates formed in freshwater and seawater. Batch flocculation experiments were performed to determine the size of the flocculated aggregates over time by using focused beam reflectance measurements. Sedimentation tests were performed to analyze the settling rate of the solid-liquid interface and the turbidity of the supernatant. Subsequently, a model that relates the hindered settling rate to the aggregate size was used to determine the mass fractal dimension (Df). Flocculation kinetics revealed that greater amounts of kaolin generated larger aggregates because of its lamellar morphology. The maximum size was between 10 and 20 s of flocculation under all conditions. However, the presence of kaolin reduced the settling rate. The fractal dimension decreased with the increase in the kaolin content, resulting in the formation of irregular and porous aggregates. By contrast, factors such as the flocculation time, water quality, and quartz size had limited influences on the fractal dimension. Seawater produced a clearer supernatant because of its higher ionic strength and precoagulation of particles. Notably, the harmful effect of clays in seawater was reduced.
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Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.
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Spodumene flotation stands as the most commonly used method to concentrate lithium minerals. However, it faces significant challenges related to low collector recoveries and similarity in the surface characteristics of the minerals, which make the effective separation of this valuable mineral difficult. For this reason, numerous researchers have conducted studies to address and confront this problem. In this work, an exhaustive bibliographic search was carried out using keywords and search queries, and the results were structured in three sections according to temporal, methodological, and thematic criteria. The first section covers the period from 1950 to 2004, focusing on experimental tests. The second section covers from 2004 to the present and focuses on flotation tests and measurement analysis. Simultaneously, the third section spans from 2011 to the present and is based on molecular dynamics simulations. Topics covered include spodumene surface properties, the influence of metal ions, pre-treatment techniques, and the use of collectors. Ultimately, molecular dynamics simulations are positioned as a tool that accurately represents experimental phenomena. In this context, specialized software such as Materials Studio or Gromacs prove to be reliable instruments that allow a detailed study of mineral surfaces and other elements to be carried out, which justifies their consideration for future research in this scientific field.
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Metais , Minerais , Lítio , ÍonsRESUMO
Hypergraph neural networks (HyperGNNs) are a family of deep neural networks designed to perform inference on hypergraphs. HyperGNNs follow either a spectral or a spatial approach, in which a convolution or message-passing operation is conducted based on a hypergraph algebraic descriptor. While many HyperGNNs have been proposed and achieved state-of-the-art performance on broad applications, there have been limited attempts at exploring high-dimensional hypergraph descriptors (tensors) and joint node interactions carried by hyperedges. In this article, we depart from hypergraph matrix representations and present a new tensor-HyperGNN (T-HyperGNN) framework with cross-node interactions (CNIs). The T-HyperGNN framework consists of T-spectral convolution, T-spatial convolution, and T-message-passing HyperGNNs (T-MPHN). The T-spectral convolution HyperGNN is defined under the t-product algebra that closely connects to the spectral space. To improve computational efficiency for large hypergraphs, we localize the T-spectral convolution approach to formulate the T-spatial convolution and further devise a novel tensor-message-passing algorithm for practical implementation by studying a compressed adjacency tensor representation. Compared to the state-of-the-art approaches, our T-HyperGNNs preserve intrinsic high-order network structures without any hypergraph reduction and model the joint effects of nodes through a CNI layer. These advantages of our T-HyperGNNs are demonstrated in a wide range of real-world hypergraph datasets. The implementation code is available at https://github.com/wangfuli/T-HyperGNNs.git.
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Chlorpyrifos (CP) is a globally used pesticide with acute toxicity. This work studied the photocatalytic degradation of CP using TiO2, ZnO nanoparticles, and nanocomposites of TiO2 and ZnO supported on SPIONs (SPION@SiO2@TiO2 and SPION@SiO2@ZnO). The nanocomposites were synthesized by multi-step incipient wetness impregnation. The effects of the initial pH, catalyst type, and dose were evaluated. The nanocomposites of SPION@SiO2@TiO2 and SPION@SiO2@ZnO showed higher CP photodegradation levels than free nanoparticles, reaching 95.6% and 82.3%, respectively, at pH 7. The findings indicate that iron oxide, as a support material for TiO2 and ZnO, extended absorption edges and delayed the electron-hole recombination of the nanocomposites, improving their photocatalytic efficiency. At the same time, these nanocomposites, especially SPION@SiO2@TiO2, showed efficient degradation of 3,5,6-trichloropyridinol (TCP), one of the final metabolites of CP. The stability and reuse of this nanocomposite were also evaluated, with 74.6% efficiency found after six cycles. Therefore, this nanomaterial represents an eco-friendly, reusable, and effective alternative for the degradation of chlorpyrifos in wastewater treatment.
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Nanotechnology has emerged as a cornerstone in contemporary research, marked by the advent of advanced technologies aimed at nanoengineering materials with diverse applications, particularly to address challenges in human health. Among these challenges, antimicrobial resistance (AMR) has risen as a significant and pressing threat to public health, creating obstacles in preventing and treating persistent diseases. Despite efforts in recent decades to combat AMR, global trends indicate an ongoing and concerning increase in AMR. The primary contributors to the escalation of AMR are the misuse and overuse of various antimicrobial agents in healthcare settings. This has led to severe consequences not only in terms of compromised treatment outcomes but also in terms of substantial financial burdens. The economic impact of AMR is reflected in skyrocketing healthcare costs attributed to heightened hospital admissions and increased drug usage. To address this critical issue, it is imperative to implement effective strategies for antimicrobial therapies. This comprehensive review will explore the latest scientific breakthroughs within the metal-organic frameworks and the use of mesoporous metallic oxide derivates as antimicrobial agents. We will explore their biomedical applications in human health, shedding light on promising avenues for combating AMR. Finally, we will conclude the current state of research and offer perspectives on the future development of these nanomaterials in the ongoing battle against AMR.
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OBJECTIVE: We analyzed adult ADHD symptoms in a cross-cultural context, including investigating the occurrence and potential correlates of adult ADHD and psychometric examination of the Adult ADHD Self-Report Scale (ASRS) Screener. METHOD: Our analysis is based on a large-scale research project involving 42 countries (International Sex Survey, N=72,627, 57% women, Mage=32.84; SDage=12.57). RESULTS: The ASRS Screener demonstrated good reliability and validity, along with partial invariance across different languages, countries, and genders. The occurrence of being at risk for adult ADHD was relatively high (21.4% for women, 18.1% for men). The highest scores were obtained in the US, Canada, and other English-speaking Western countries, with significantly lower scores among East Asian and non-English-speaking European countries. Moreover, ADHD symptom severity and occurrence were especially high among gender-diverse individuals. Significant associations between adult ADHD symptoms and age, mental and sexual health, and socioeconomic status were observed. CONCLUSIONS: Present results show significant cross-cultural variability in adult ADHD occurrence as well as highlight important factors related to adult ADHD. Moreover, the importance of further research on adult ADHD in previously understudied populations (non-Western countries) and minority groups (gender-diverse individuals) is stressed. Lastly, the present analysis is consistent with previous evidence showing low specificity of adult ADHD screening instruments and contributes to the current discussion on accurate adult ADHD screening and diagnosis.
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Transtorno do Deficit de Atenção com Hiperatividade , Adulto , Humanos , Masculino , Feminino , Autorrelato , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Reprodutibilidade dos Testes , Comparação Transcultural , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Depression and anxiety are among the most prevalent mental health issues experienced worldwide. However, whereas cross-cultural studies utilize psychometrically valid and reliable scales, fewer can meaningfully compare these conditions across different groups. To address this gap, the current study aimed to psychometrically assess the Brief Symptomatology Index (BSI) in 42 countries. METHODS: Using data from the International Sex Survey (N = 82,243; Mage = 32.39; SDage = 12.52; women: n = 46,874; 57 %), we examined the reliability of depression and anxiety symptom scores of the BSI-18, as well as evaluated evidence of construct, invariance, and criterion-related validity in predicting clinically relevant variables across countries, languages, genders, and sexual orientations. RESULTS: Results corroborated an invariant, two-factor structure across all groups tested, exhibiting excellent reliability estimates for both subscales. The 'caseness' criterion effectively discriminated among those at low and high risk of depression and anxiety, yielding differential effects on the clinical criteria examined. LIMITATIONS: The predictive validation was not made against a clinical diagnosis, and the full BSI-18 scale was not examined (excluding the somatization sub-dimension), limiting the validation scope of the BSI-18. Finally, the study was conducted online, mainly by advertisements through social media, ultimately skewing our sample towards women, younger, and highly educated populations. CONCLUSIONS: The results support that the BSI-12 is a valid and reliable assessment tool for assessing depression and anxiety symptoms across countries, languages, genders, and sexual orientations. Further, its caseness criterion can discriminate well between participants at high and low risk of depression and anxiety.
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Comparação Transcultural , Depressão , Humanos , Feminino , Masculino , Adulto , Criança , Depressão/diagnóstico , Reprodutibilidade dos Testes , Psicometria , Ansiedade/diagnóstico , Inquéritos e QuestionáriosRESUMO
To enable large in silico trials and personalized model predictions on clinical timescales, it is imperative that models can be constructed quickly and reproducibly. First, we aimed to overcome the challenges of constructing cardiac models at scale through developing a robust, open-source pipeline for bilayer and volumetric atrial models. Second, we aimed to investigate the effects of fibres, fibrosis and model representation on fibrillatory dynamics. To construct bilayer and volumetric models, we extended our previously developed coordinate system to incorporate transmurality, atrial regions and fibres (rule-based or data driven diffusion tensor magnetic resonance imaging (MRI)). We created a cohort of 1000 biatrial bilayer and volumetric models derived from computed tomography (CT) data, as well as models from MRI, and electroanatomical mapping. Fibrillatory dynamics diverged between bilayer and volumetric simulations across the CT cohort (correlation coefficient for phase singularity maps: left atrial (LA) 0.27 ± 0.19, right atrial (RA) 0.41 ± 0.14). Adding fibrotic remodelling stabilized re-entries and reduced the impact of model type (LA: 0.52 ± 0.20, RA: 0.36 ± 0.18). The choice of fibre field has a small effect on paced activation data (less than 12 ms), but a larger effect on fibrillatory dynamics. Overall, we developed an open-source user-friendly pipeline for generating atrial models from imaging or electroanatomical mapping data enabling in silico clinical trials at scale (https://github.com/pcmlab/atrialmtk).
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INTRODUCTION: Demonstration of nociceptive fiber abnormality is important for diagnosing neuropathic pain and small fiber neuropathies. This is usually assessed by brief heat pulses using lasers, contact heat, or special electrodes. We hypothesized that pain-related evoked potentials to conventional surface electrical stimulation (PREPse) can index Aδ afferences despite tactile Aß fibers coactivation. PREPse may be more readily used clinically than contact heat evoked potentials (CHEPS). METHODS: Twenty-eight healthy subjects. Vertex (Cz-A1/A2) recordings. Electrical stimulation of middle finger and second toe with conventional ring, and forearm/leg skin with cup, electrodes. Contact heat stimulation to forearm and leg. Compression ischemic nerve blockade. RESULTS: PREPse peripheral velocities were within the midrange of Aδ fibers. N1-P1 amplitude increased with pain numerical rating scale graded (0-10) electrical stimulation (n = 25) and decreased with increasing stimulation frequency. Amplitudes were unchanged by different presentation orders of four stimulation intensities. PREPse N1 (â¼130 milliseconds) and N2 (â¼345 milliseconds) peaks were approximately 40 milliseconds earlier than that with CHEPS. PREPse and CHEPS N1-N2 interpeak latency (â¼207 milliseconds) were similar. PREPse became unrecordable with nerve blockade of Aδ fibers. CONCLUSIONS: PREPse earlier N1 and N2 peaks, and similar interpeak N1-N2 latencies and central conduction velocities, or synaptic delays, to CHEPS are consistent with direct stimulation of Aδ fibers. The relation of vertex PREPse amplitude and pain, or the differential effects of frequency stimulation, is similar to pain-related evoked potential to laser, special electrodes, or contact heat stimulation. The relationship to Aδ was validated by conduction velocity and nerve block. Clinical utility of PREPse compared with CHEPS needs validation in somatosensory pathways lesions.
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Temperatura Alta , Neuralgia , Humanos , Potenciais Somatossensoriais Evocados/fisiologia , Potenciais Evocados , Pele/inervação , Pele/patologia , Estimulação ElétricaRESUMO
INTRODUCTION AND OBJECTIVES: There is limited evidence regarding the use of subcutaneous implantable cardioverter-defibrillators (S-ICD) in pediatric patients. The aim of this study was to determine the incidence of complications in these patients at our center, according to the type of ICD and patient size. METHODS: We included all patients aged<18 years who received an S-ICD since 2016 at our center. As a control group, we also included contemporary patients (since 2014) who received a transvenous ICD (TV-ICD). The primary endpoint was a composite of complications and inappropriate shocks. RESULTS: A total of 26 patients received an S-ICD (median age, 14 [5-17] years; body mass index [BMI], 20.2 kg/m2). Implantation was intermuscular in 23 patients (88%) and subserratus in the remainder. Two incisions were used in 24 patients (92%). In all patients, 2 zones were programmed: a conditional zone set at 230 (220-230) bpm, and a shock zone set at 250 bpm. Nineteen patients received a TV-ICD (median age, 11 [range, 5-16] years; BMI, 19.2 kg/m2, 79% single-chamber). Survival free from the primary endpoint at 5 years was 80% in the S-ICD group and 63% in the TV-ICD group (P=.54). Survival free from inappropriate shocks was similar (85% vs 89%, P=.86), while survival free from complications was higher in the S-ICD group (96% vs 57%, cloglog P=.016). There were no therapy failures in the S-ICD group, and no increased complication rates were observed in patients with BMI ≤20 kg/m2. CONCLUSIONS: With contemporary implantation techniques and programming, S-ICD is a safe and effective therapy in pediatric patients. The number of inappropriate shocks is similar to TV-ICD, with fewer short- and mid-term complications.
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INTRODUCTION: Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; Mage: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.
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Alcoolismo , Humanos , Masculino , Feminino , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Comparação Transcultural , Psicometria , Estudos Transversais , Comportamento Sexual , Inquéritos e Questionários , Análise Fatorial , Reprodutibilidade dos TestesRESUMO
This study investigated the interaction of monovalent cations with different sizes on quartz surfaces and the rheological impact that this causes in concentrated suspensions when subjected to the action of a rheological modifier, in this case, sodium polyacrylate (NaPA). Yield stress was determined using a rheometer with a vane-in-cup configuration to establish the relationship between shear stress and strain. Experiments were carried out in LiCl, NaCl, KCl, and CsCl solutions. The results show that the yield stress increases following the order Li < Na < K < Cs in the absence of PAA. However, the addition of NaPA significantly reduced the yield stress in all cases. This reduction was more noticeable in the LiCl and NaCl solutions than in the KCl and CsCl solutions, suggesting a more pronounced effect of PA in maker salts. We conducted molecular dynamics simulations to understand how PA interacts with dissolved salts on the quartz surface. Our results showed that Li had the highest adsorption, followed by Na, K, and Cs. As the salt concentration increased, so did the adsorption. We validated these simulation results with rheological experiments, which helped us understand the observed differences. The molecular interactions indicate that, in the lithium system, cationic bridges and the synergy between hydrogen bridges and hydrophobic bridges predominate mainly. This tendency decreases as the type of cation is changed due to the decrease in the electrical density of the cation in the following order: Li < Na < K < Cs. This reduces bridging with the quartz surface and, therefore, directly impacts the system's rheological properties.
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Resumen El síndrome de Hamman, o neumomediastino es pontáneo, es la presencia de aire en mediastino en pacientes sin antecedentes de enfermedad pulmonar previa, trauma torácico o iatrogenia. Se ha descrito como una complicación rara en pacientes con neumo nía por COVID-19. Se postula que un aumento en la presión de la vía aérea asociado a daño alveolar difuso generado por el virus, producen una fuga de aire hacia el mediastino. El dolor torácico y disnea, asociado a enfisema subcutáneo, deben hacer sospechar al médico tratante. Presentamos un paciente de 79 años que du rante su internación por neumonía secundaria al virus SARS-CoV-2 evolucionó súbitamente con disnea, dolor torácico, accesos de tos y broncoespasmo con hallaz go de neumomediastino espontáneo en la tomografía de tórax. Evolucionó favorablemente con tratamiento broncodilatador y oxigenoterapia. El síndrome de Ham man es una causa poco frecuente de progresión de insuficiencia respiratoria en pacientes con neumonía por COVID-19. Su identificación es crucial para imple mentar el tratamiento adecuado.
Abstract Hamman's syndrome, or spontaneous pneumome diastinum, is the presence of air in the mediastinum without a history of previous pulmonary pathology, chest trauma or iatrogenesis. It has been described as a rare complication in patients with COVID-19 pneu monia. It is postulated that an increase in airway pres sure associated with diffuse alveolar damage caused by the virus produces an air leak into the mediastinum. Chest pain and dyspnea associated with subcutaneous emphysema should make the treating physician suspi cious. We introduce a 79-year-old patient who, during hospitalization for pneumonia secondary to COVID-19, suddenly developed dyspnea, chest pain, coughing spells and bronchospasm with the discovery of spontaneous pneumomediastinum on chest tomography. He evolved favorably with bronchodilator treatment and temporary oxygen therapy. Hamman's syndrome is a rare cause of respiratory failure progression in patients with COVID-19 pneumonia. Its recognition is crucial to implement the appropriate treatment.
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In botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women. Previous work has demonstrated that RCE reduces estrogen detoxification pathways in breast cancer cells (MCF-7) and, thus, may serve to negatively affect estrogen metabolism-induced chemical carcinogenesis. Clinical RCE contains ca. 30% of biochanin A and formononetin, which potentially mask activities of less abundant compounds. These two isoflavonoids are aryl hydrocarbon receptor (AhR) agonists that activate P450 1A1, responsible for estrogen detoxification, and P450 1B1, producing genotoxic estrogen metabolites in female breast cells. Clinical RCE also contains the potent phytoestrogen, genistein, that downregulates P450 1A1, thereby reducing estrogen detoxification. To identify less abundant bioactive constituents, countercurrent separation (CCS) of a clinical RCE yielded selective lipophilic to hydrophilic metabolites in six enriched DESIGNER fractions (DFs 01-06). Unlike solid-phase chromatography, CCS prevented any potential loss of minor constituents or residual complexity (RC) and enabled the polarity-based enrichment of certain constituents. Systematic analysis of estrogen detoxification pathways (ERα-degradation, AhR activation, CYP1A1/CYP1B1 induction and activity) of the DFs uncovered masked bioactivity of minor/less abundant constituents including irilone. These data will allow the optimization of RCE with respect to estrogen detoxification properties. The DFs revealed distinct biological activities between less abundant bioactives. The present results can inspire future carefully designed extracts with phytochemical profiles that are optimized to increase in estrogen detoxification pathways and, thereby, promote resilience in women with high-risk for breast cancer. The DESIGNER approach helps to establish links between complex chemical makeup, botanical safety and possible efficacy parameters, yields candidate DFs for (pre)clinical studies, and reveals the contribution of minor phytoconstituents to the overall safety and bioactivity of botanicals, such as resilience promoting activities relevant to women's health.