Economic, Psychological, and Emotional Well-Being of Pregnant Women During the COVID-19 Pandemic.

INTRODUCTION: The intersection between perinatal mental health and the coronavirus disease 2019 (COVID-19) pandemic remains of significant public health importance. The current study examined the emotional and financial well-being and predictors of elevated depressive symptoms among pregnant women during the COVID-19 pandemic. METHODS: This online survey was conducted with 2118 women ≥18 years old who were pregnant at the time of the survey and living in the United States or Puerto Rico. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale, with scores ≥10 indicative of elevated depressive symptoms. The final logistic regression model included housing insecurity, financial distress, COVID-19 diagnosis, exposure to COVID-19, and demographic covariates. RESULTS: More than half the sample (53.8%) had elevated depressive symptoms. In logistic regression analyses, the odds of having elevated depressive symptoms were significantly higher for participants reporting housing insecurity (adjusted odds ratio [aOR], 1.56; 95% CI, 1.22-2.01), financial distress (aOR, 1.57; 95% CI, 1.17-2.12), COVID-19 diagnosis (aOR, 2.53; 95% CI, 1.53-4.17), and COVID-19 exposure (aOR, 1.41; 95% CI, 1.07-1.86), after adjusting for covariates. The association of elevated depressive symptoms with housing insecurity was especially strong among those who experienced COVID-19 (aOR, 6.04; 95% CI, 2.15-17.0). DISCUSSION: Our findings are consistent with previous literature revealing that diagnosis, exposure, concerns about family, and effects on financial stability were related to depressive symptoms during the pandemic. The relationships between financial and housing concerns with elevated depressive symptoms, independent of concerns about infection in family members, suggest that there may be direct and indirect effects of the pandemic on mental health.

Procedural sedation by advanced practice providers in the emergency medical service in the Netherlands: a retrospective study.

BACKGROUND: Procedural sedation and analgesia (PSA) is a technique of administering sedatives to induce a state that allows the patient to tolerate painful procedures while maintaining cardiorespiratory function, a condition that is frequently desired prehospital. Non-physician prehospital clinicians often have a limited scope of practice when it comes to providing analgesia and sedation; sometimes resulting in a crew request for back-up from physician-staffed prehospital services.". This is also the case if sedation is desirable. Advanced practice providers (APPs), who are legally authorized and trained to carry out this procedure, may be a solution when the physician-staffed service is not available or will not be available in time. METHODS: The aim of this study is to gain insight in the circumstances in which an APP, working at the Dutch ambulance service "RAV Brabant MWN" from January 2019 to December 2022, uses propofol for PSA or to provide sedation. With this a retrospective observational document study we describe the characteristics of patients and ambulance runs and evaluates the interventions in terms of safety. RESULTS: During the study period, the APPs administered propofol 157 times for 135 PSA and in 22 cases for providing sedation. The most common indication was musculoskeletal trauma such as fracture care or the reduction of joint dislocation. In 91% of the situations where propofol was used, the predetermined goal e.g. alignment of fractured extremity, repositioning of luxated joint or providing sedation the goal was achieved. There were 12 cases in which one or more adverse events were documented and all were successfully resolved by the APP. There were no cases of laryngospam, airway obstruction, nor anaphylaxis. None of the adverse events led to unexpected hospitalization or death. CONCLUSION: During the study period, the APPs performed 135 PSAs and provided 22 sedations. The success rate of predetermined goals was higher than that stated in the literature. Although there were a number of side effects, their incidences were lower than those reported in the literature, and these were resolved by the APP during the episode of care. Applying a PSA by an APP at the EMS "RAV Brabant MWN" appears to be safe with a high success rate.

State legislation and policies to improve perinatal mental health: a policy review and analysis of the state of Illinois.

Introduction: Maternal mental health problems, such as perinatal depression, are a major public health issue. In the U.S., several states have policies related to mental health during pregnancy and postpartum. The extent of these laws at the state level needs to be further explored and described. Methods: We systematically searched the Illinois General Assembly to determine all existing legislation on the topic of perinatal mental health. Results: This search uncovered two major Acts that 1) require universal perinatal depression screening and 2) raise awareness of the symptoms and treatment options related to maternal mental health. We also discovered provisions in the law that allow for untreated or undiagnosed postpartum depression or psychosis to be considered as a mitigating factor for women who commit forcible felonies. Discussion: Through legislation, states can lead change at the systems-level to improve perinatal mental health outcomes.

Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort.

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Machine Learning Nucleation Collective Variables with Graph Neural Networks.

The efficient calculation of nucleation collective variables (CVs) is one of the main limitations to the application of enhanced sampling methods to the investigation of nucleation processes in realistic environments. Here we discuss the development of a graph-based model for the approximation of nucleation CVs that enables orders-of-magnitude gains in computational efficiency in the on-the-fly evaluation of nucleation CVs. By performing simulations on a nucleating colloidal system mimicking a multistep nucleation process from solution, we assess the model's efficiency in both postprocessing and on-the-fly biasing of nucleation trajectories with pulling, umbrella sampling, and metadynamics simulations. Moreover, we probe and discuss the transferability of graph-based models of nucleation CVs across systems using the model of a CV based on sixth-order Steinhardt parameters trained on a colloidal system to drive the nucleation of crystalline copper from its melt. Our approach is general and potentially transferable to more complex systems as well as to different CVs.

Determination of loyalty among high school students to retain in the same university for higher education: An integration of Self-Determination Theory and Extended Theory of Planned Behavior.

Student loyalty generally refers to the formed bond between the student and a university. This relationship between a university and its students proves essential in a university's success in the competitive field of higher education institutions. The aim of this study was to determine the factors affecting students' loyalty among high school students to pursue their college or higher education in their current universities by utilizing Self-Determination Theory and Extended Theory of Planned Behavior. A total of 1224 high school students voluntarily participated and answered an online questionnaire that consist of 80 questions. Structural Equation Modeling (SEM) showed that competency had the highest direct significant effect on perceived behavioral control which subsequently led to student satisfaction, followed by relatedness and empathy. In addition, student satisfaction had the highest direct effect significant effect on student loyalty, followed by university image and effectiveness. Interestingly, university ranking, programs offered, and kinship patronage also had significant indirect effects on student loyalty. This new framework may be a theoretical foundation for universities to enhance student loyalty and student recruitment. Considering students as customers, the satisfaction of students would result in an increase in the application which would present an increase in population, sales, marketability, and profitability of the university.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry.

BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Tailoring evidence into action: using a codesign approach for biodiversity information in the Tropical Andes / Toma de decisiones basadas en la evidencia: un enfoque de codiseño para la información sobre biodiversidad en los Andes tropicales / Tomada de decisão baseada em evidências: uma abordagem de co-design para informações sobre biodiversidade nos Andes tropicais

Biodiversity conservation is a complex and transdisciplinary problem that requires engagement and cooperation among scientific, societal, economic, and political institutions. However, historical approaches have often failed to bring together and address the needs of all relevant stakeholders in decision­making processes. The Tropical Andes, a biodiversity hotspot where conservation efforts often conflict with socioeconomic issues and policies that prioritize economic development, provides an ideal model to develop and implement more effective approaches. In this study, we present a co­design approach that mainstreams and improves the flow of biodiversity information in the Tropical Andes, while creating tailored outputs that meet the needs of economic and societal stakeholders. We employed a consultative process that brought together biodiversity information users and producers at the local, national, and regional levels through a combination of surveys and workshops. This approach identified priority needs and limitations of the flow of biodiversity information in the region, which led to the co­design of user­relevant biodiversity indicators. By leveraging the existing capacities of biodiversity information users and producers, we were able to co­design multiple biodiversity indicators and prioritize two for full implementation ensuring that the data was findable, accessible, interoperable, and reusable based on the FAIR principles. This approach helped address limitations that were identified in the stakeholder engagement process, including gaps in data availability and the need for more accessible biodiversity information. Additionally, capacity­building workshops were incorporated for all producers of biodiversity information involved, which aimed to not only improve the current flow of biodiversity information in the region but also facilitate its future sustainability. Our approach can serve as a valuable blueprint for mainstreaming biodiversity information and making it more inclusive in the future, especially considering the diverse worldviews, values, and knowledge systems between science, policy, and practice.

La conservación de la biodiversidad es un problema complejo y transdisciplinario que requiere el compromiso y la cooperación entre instituciones científicas, sociales, económicas y políticas. Sin embargo, los enfoques tradicionales/convencionales  a menudo no logran  reunir y abordar las necesidades de todos los actores relevantes en los procesos de toma de decisiones. Los Andes tropicales, un área clave  de biodiversidad donde los esfuerzos de conservación a menudo entran en conflicto con cuestiones socioeconómicas y políticas que priorizan el desarrollo económico, proporcionan un modelo ideal para desarrollar e implementar enfoques más efectivos. En este estudio, presentamos un enfoque co-diseño que integra y mejora el flujo de información sobre biodiversidad en los Andes tropicales, creando resultados personalizados que satisfacen las necesidades, tanto económicas como sociales, de las partes interesadas. Empleamos un proceso de consulta que reunió a usuarios y productores de información sobre biodiversidad a nivel local, nacional y regional, a través de encuestas y talleres. Este enfoque ha permitido identificar necesidades prioritarias y limitaciones del flujo de información sobre biodiversidad en la región; lo cual llevó al codiseño de indicadores de biodiversidad relevantes para los usuarios. Aprovechando las capacidades existentes de los usuarios y productores de información sobre biodiversidad, pudimos co-diseñar múltiples indicadores de biodiversidad y priorizar dos de estos para su implementación completa, asegurando que los datos sean localizables, accesibles, interoperables y reutilizables, según los principios FAIR. Este enfoque ayudó a abordar las limitaciones que se identificaron en el proceso de participación de las partes interesadas; incluidas las brechas en la disponibilidad de datos y la necesidad de información sobre biodiversidad más accesible. Además, se incorporaron talleres de desarrollo de capacidades para todos los productores de información sobre biodiversidad involucrados, los cuales apuntaron no sólo a mejorar el flujo actual de información sobre biodiversidad en la región, sino también facilitar su sostenibilidad futura. Nuestro enfoque puede servir como un modelo valioso para incorporar la información sobre biodiversidad y hacerla más inclusiva en el futuro; especialmente si consideramos las diversas perspectivas globales, valores y sistemas de conocimiento implicados en las interacciones entre  la ciencia, la política y su aplicación práctica.

A conservação da biodiversidade é um problema complexo e transdisciplinar que requer compromisso e cooperação entre instituições científicas, sociais, económicas e políticas. No entanto, as abordagens tradicionais/convencionais muitas vezes não conseguem reunir e responder às necessidades de todos os intervenientes relevantes nos processos de tomada de decisão. Os Andes tropicais, uma área chave para a biodiversidade onde os esforços de conservação entram frequentemente em conflito com questões socioeconómicas e políticas que dão prioridade ao desenvolvimento económico, fornecem um modelo ideal para desenvolver e implementar abordagens mais eficazes. Neste estudo, apresentamos uma abordagem de co-design que integra e melhora o fluxo de informações sobre biodiversidade nos Andes tropicais, criando resultados personalizados que atendem às necessidades, tanto econômicas quanto sociais, das partes interessadas. Empregamos um processo de consulta que reuniu usuários e produtores de informações sobre biodiversidade nos níveis local, nacional e regional, por meio de pesquisas e workshops. Esta abordagem permitiu identificar necessidades prioritárias e limitações do fluxo de informação sobre a biodiversidade na região; o que levou à concepção conjunta de indicadores de biodiversidade relevantes para os utilizadores. Aproveitando as capacidades existentes dos utilizadores e produtores de informação sobre biodiversidade, fomos capazes de conceber em conjunto vários indicadores de biodiversidade e priorizar dois deles para implementação total, garantindo que os dados sejam localizáveis, acessíveis, interoperáveis ​​e reutilizáveis, de acordo com os princípios FAIR. Esta abordagem ajudou a resolver as limitações identificadas no processo de envolvimento das partes interessadas; incluindo lacunas na disponibilidade de dados e a necessidade de informações mais acessíveis sobre biodiversidade. Além disso, foram incorporados workshops de capacitação para todos os produtores de informação sobre biodiversidade envolvidos, que visaram não só melhorar o fluxo actual de informação sobre biodiversidade na região, mas também facilitar a sua sustentabilidade futura. A nossa abordagem pode servir como um modelo valioso para incorporar informações sobre biodiversidade e torná-las mais inclusivas no futuro; especialmente se considerarmos as diversas perspectivas globais, valores e sistemas de conhecimento envolvidos nas interações entre ciência, política e sua aplicação prática.

Genome sequence of bacteriophage Aoka, a cluster FO phage isolated using Arthrobacter globiformis.

We report the discovery and genome sequence of bacteriophage Aoka, an actinobacteriophage isolated from a soil sample in Pueblo, Colorado using Arthrobacter globiformis, B2880-SEA. Its genome length is 36,744 base pairs with 54 protein-coding genes. Based on gene content similarity to other actinobacteriophages, Aoka is assigned to cluster FO.

The Role of Swelling in the Regulation of OPA1-Mediated Mitochondrial Function in the Heart In Vitro.

Optic atrophy-1 (OPA1) plays a crucial role in the regulation of mitochondria fusion and participates in maintaining the structural integrity of mitochondrial cristae. Here we elucidate the role of OPA1 cleavage induced by calcium swelling in the presence of Myls22 (an OPA1 GTPase activity inhibitor) and TPEN (an OMA1 inhibitor). The rate of ADP-stimulated respiration was found diminished by both inhibitors, and they did not prevent Ca2+-induced mitochondrial respiratory dysfunction, membrane depolarization, or swelling. L-OPA1 cleavage was stimulated at state 3 respiration; therefore, our data suggest that L-OPA1 cleavage produces S-OPA1 to maintain mitochondrial bioenergetics in response to stress.

Mitochondrial Volume Regulation and Swelling Mechanisms in Cardiomyocytes.

Mitochondrion, known as the "powerhouse" of the cell, regulates ion homeostasis, redox state, cell proliferation and differentiation, and lipid synthesis. The inner mitochondrial membrane (IMM) controls mitochondrial metabolism and function. It possesses high levels of proteins that account for ~70% of the membrane mass and are involved in the electron transport chain, oxidative phosphorylation, energy transfer, and ion transport, among others. The mitochondrial matrix volume plays a crucial role in IMM remodeling. Several ion transport mechanisms, particularly K+ and Ca2+, regulate matrix volume. Small increases in matrix volume through IMM alterations can activate mitochondrial respiration, whereas excessive swelling can impair the IMM topology and initiates mitochondria-mediated cell death. The opening of mitochondrial permeability transition pores, the well-characterized phenomenon with unknown molecular identity, in low- and high-conductance modes are involved in physiological and pathological increases of matrix volume. Despite extensive studies, the precise mechanisms underlying changes in matrix volume and IMM structural remodeling in response to energy and oxidative stressors remain unknown. This review summarizes and discusses previous studies on the mechanisms involved in regulating mitochondrial matrix volume, IMM remodeling, and the crosstalk between these processes.

Crosstalk between adenine nucleotide transporter and mitochondrial swelling: experimental and computational approaches.

Mitochondrial metabolism and function are modulated by changes in matrix Ca2+. Small increases in the matrix Ca2+ stimulate mitochondrial bioenergetics, whereas excessive Ca2+ leads to cell death by causing massive matrix swelling and impairing the structural and functional integrity of mitochondria. Sustained opening of the non-selective mitochondrial permeability transition pores (PTP) is the main mechanism responsible for mitochondrial Ca2+ overload that leads to mitochondrial dysfunction and cell death. Recent studies suggest the existence of two or more types of PTP, and adenine nucleotide translocator (ANT) and FOF1-ATP synthase were proposed to form the PTP independent of each other. Here, we elucidated the role of ANT in PTP opening by applying both experimental and computational approaches. We first developed and corroborated a detailed model of the ANT transport mechanism including the matrix (ANTM), cytosolic (ANTC), and pore (ANTP) states of the transporter. Then, the ANT model was incorporated into a simple, yet effective, empirical model of mitochondrial bioenergetics to ascertain the point when Ca2+ overload initiates PTP opening via an ANT switch-like mechanism activated by matrix Ca2+ and is inhibited by extra-mitochondrial ADP. We found that encoding a heterogeneous Ca2+ response of at least three types of PTPs, weakly, moderately, and strongly sensitive to Ca2+, enabled the model to simulate Ca2+ release dynamics observed after large boluses were administered to a population of energized cardiac mitochondria. Thus, this study demonstrates the potential role of ANT in PTP gating and proposes a novel mechanism governing the cryptic nature of the PTP phenomenon.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry

Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Effects of Ferroptosis on the Metabolome in Cardiac Cells: The Role of Glutaminolysis.

Ferroptosis is a novel iron-dependent regulated cell death mechanism that affects cell metabolism; however, a detailed metabolomic analysis of ferroptotic cells is not yet available. Here, we elucidated the metabolome of H9c2 cardioblasts by gas chromatography-mass spectrometry during ferroptosis induced by RSL3, a GPX4 inhibitor, in the presence of ferrostatin-1 (a ferroptosis inhibitor), XJB-5-131 (a mitochondrial-targeted ROS scavenger), or TSM-1005-44 (a newly developed cellular ROS scavenger). Results demonstrated that RSL3 decreased the levels of amino acids involved in glutathione synthesis more than two-fold. In contrast, saturated fatty acids levels were markedly increased in RSL3-challenged cells, with no effects on unsaturated fatty acids. RSL3 significantly altered the levels of mitochondrial tricarboxylic acid cycle intermediates; isocitrate and 2-oxoglutarate were found to increase, whereas succinate was significantly decreased in RSL3-challenged cells. Ferrostatin-1, XJB-5-131, and TSM-1005-44 prevented RSL3-induced cell death and conserved the metabolomic profile of the cells. Since 2-oxoglutarate is involved in the regulation of ferroptosis, particularly through glutamine metabolism, we further assessed the role of glutaminolysis in ferroptosis in H9c2 cardioblasts. Genetic silencing of GLS1, which encodes the K-type mitochondrial glutaminase (glutaminase C), protected against ferroptosis in the early stage. In conclusion, our study demonstrates that RSL3-induced ferroptosis impairs the metabolome of H9c2 cardioblasts.

Beta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells.

Alzheimer's disease (AD) includes the formation of extracellular deposits comprising aggregated ß-amyloid (Aß) fibers associated with oxidative stress, inflammation, mitochondrial abnormalities, and neuronal loss. There is an associative link between AD and cardiac diseases; however, the mechanisms underlying the potential role of AD, particularly Aß in cardiac cells, remain unknown. Here, we investigated the role of mitochondria in mediating the effects of Aß1-40 and Aß1-42 in cultured cardiomyocytes and primary coronary endothelial cells. Our results demonstrated that Aß1-40 and Aß1-42 are differently accumulated in cardiomyocytes and coronary endothelial cells. Aß1-42 had more adverse effects than Aß1-40 on cell viability and mitochondrial function in both types of cells. Mitochondrial and cellular ROS were significantly increased, whereas mitochondrial membrane potential and calcium retention capacity decreased in both types of cells in response to Aß1-42. Mitochondrial dysfunction induced by Aß was associated with apoptosis of the cells. The effects of Aß1-42 on mitochondria and cell death were more evident in coronary endothelial cells. In addition, Aß1-40 and Aß1-42 significantly increased Ca2+ -induced swelling in mitochondria isolated from the intact rat hearts. In conclusion, this study demonstrates the toxic effects of Aß on cell survival and mitochondria function in cardiac cells.