Fibroelastoma, an Incidentaloma Disease? - Image Cases of Fibroelastomas as Incidental Findings in Four Patients, Four Different Valves. / Fibroelastoma, uma Doença Incidentaloma? ­ Imagem de Casos de Fibroelastomas como Achados Incidentais em Quatro Pacientes, Quatro Valvas Diferentes.

Fibroelastomas are the second most common benign cardiac tumor1. They are small avascular structures with a mean size of 9mm, ranging up to 70mm, usually attached to the heart valves' surface (aortic and mitral are the most affected, followed by tricuspid and pulmonary valves). Their etiology is unclear, but the hypothesis of coalescence of microthrombus at the coaptation margins of valves is the most widely accepted theory. On echocardiography, they are pedicled, mobile, with a filamentous surface, and usually have a speckled appearance with echolucencies and a stippled pattern near the edges. Clinically, they may be associated with embolic phenomena; however, in most cases, the diagnosis is incidental. We present a series of four clinical cases with an incidental diagnosis of fibroelastomas across the four cardiac valves as assessed by transthoracic echocardiography (Video 1; Figure 1). Video 1 From left to right and top to bottom: fibroelastomas of the anterior leaflet of the tricuspid valve, anterior leaflet of the mitral valve, left cusp of the pulmonary valve and left cuspid of the aortic valve, each corresponding to a different patient. Link: http://abccardiol.org/supplementary-material/2024/12102/2023-0222_IM_video01.mp4 Figure 1 From left to right and top to bottom: fibroelastomas of the anterior leaflet of the tricuspid valve, anterior leaflet of the mitral valve, left cusp of the pulmonary valve and left cuspid of the aortic valve, each corresponding to a different patient.

Os fibroelastomas são o segundo tumor cardíaco benigno mais comum. São estruturas pequenas, avasculares, com uma dimensão média de 9mm, podendo atingir até 70mm, habitualmente aderentes à superfície das válvulas cardíacas (válvulas aórtica e mitral são as mais comumente afetadas, seguidas das válvulas tricúspide e pulmonar). A etiologia não é clara, sendo a hipótese de formação de microtrombos nas margens de coaptação das válvulas a mais aceite. Na ecocardiografia apresentam aspeto pediculado, móvel, com superfície filamentosa, tipicamente com uma aparência pontilhada nas margens e ecolucente. Do ponto de vista clínico, podem estar associados a fenómenos embólicos, no entanto, na maioria dos casos o diagnóstico é incidental. Apresentamos de seguida quatro casos de diagnóstico incidental de fibroelastomas nas quatro válvulas cardíacas, diagnosticados por ecocardiograma transtorácico (ETT) (Vídeo 1; Figura 1). Vídeo 1Da esquerda para a direita, de cima para baixo: fibroelastomas no folheto anterior da válvula tricúspide, folheto anterior da válvula mitral, cúspide esquerda da válvula pulmonar e cúspide esquerda da válvula aórtica, cada um correspondendo a um doente diferente. Em: http://abccardiol.org/supplementary-material/2024/12102/2023-0222_IM_video01.mp4 Figura 1Da esquerda para a direita, de cima para baixo: fibroelastomas no folheto anterior da válvula tricúspide, folheto anterior da válvula mitral, cúspide esquerda da válvula pulmonar e cúspide esquerda da válvula aórtica, cada um correspondendo a um doente diferente.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

AIMS: Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). METHODS AND RESULTS: In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Our study highlights the impact of including coronary artery calcium score (CACS) and genetic risk score (GRS) alongside Systematic Coronary Risk Evaluation 2 (SCORE2) for enhancing cardiovascular (CV) risk assessment in primary prevention. In our population, adding CACS to SCORE2 exhibited a superior discriminative capacity for CV events compared with GRS alone in terms of risk prediction, discrimination, and reclassification. Our results emphasize the potential clinical relevance of using all three scores to identify high-risk individuals who would benefit from earlier and more stringent cardiovascular risk management strategies to prevent future cardiovascular events.

Fibroelastoma, uma Doença Incidentaloma? - Imagem de Casos de Fibroelastomas como Achados Incidentais em Quatro Pacientes, Quatro Valvas Diferentes / Fibroelastoma, an Incidentaloma Disease? - Image Cases of Fibroelastomas as Incidental Findings in Four Patients, Four Different Valves

Resumo Os fibroelastomas são o segundo tumor cardíaco benigno mais comum. São estruturas pequenas, avasculares, com uma dimensão média de 9mm, podendo atingir até 70mm, habitualmente aderentes à superfície das válvulas cardíacas (válvulas aórtica e mitral são as mais comumente afetadas, seguidas das válvulas tricúspide e pulmonar). A etiologia não é clara, sendo a hipótese de formação de microtrombos nas margens de coaptação das válvulas a mais aceite. Na ecocardiografia apresentam aspeto pediculado, móvel, com superfície filamentosa, tipicamente com uma aparência pontilhada nas margens e ecolucente. Do ponto de vista clínico, podem estar associados a fenómenos embólicos, no entanto, na maioria dos casos o diagnóstico é incidental. Apresentamos de seguida quatro casos de diagnóstico incidental de fibroelastomas nas quatro válvulas cardíacas, diagnosticados por ecocardiograma transtorácico (ETT) (Vídeo 1; Figura 1). Vídeo 1 Da esquerda para a direita, de cima para baixo: fibroelastomas no folheto anterior da válvula tricúspide, folheto anterior da válvula mitral, cúspide esquerda da válvula pulmonar e cúspide esquerda da válvula aórtica, cada um correspondendo a um doente diferente. Em: http://abccardiol.org/supplementary-material/2024/12102/2023-0222_IM_video01.mp4 Figura 1 Da esquerda para a direita, de cima para baixo: fibroelastomas no folheto anterior da válvula tricúspide, folheto anterior da válvula mitral, cúspide esquerda da válvula pulmonar e cúspide esquerda da válvula aórtica, cada um correspondendo a um doente diferente.

Abstract Fibroelastomas are the second most common benign cardiac tumor1. They are small avascular structures with a mean size of 9mm, ranging up to 70mm, usually attached to the heart valves' surface (aortic and mitral are the most affected, followed by tricuspid and pulmonary valves). Their etiology is unclear, but the hypothesis of coalescence of microthrombus at the coaptation margins of valves is the most widely accepted theory. On echocardiography, they are pedicled, mobile, with a filamentous surface, and usually have a speckled appearance with echolucencies and a stippled pattern near the edges. Clinically, they may be associated with embolic phenomena; however, in most cases, the diagnosis is incidental. We present a series of four clinical cases with an incidental diagnosis of fibroelastomas across the four cardiac valves as assessed by transthoracic echocardiography (Video 1; Figure 1). Video 1 From left to right and top to bottom: fibroelastomas of the anterior leaflet of the tricuspid valve, anterior leaflet of the mitral valve, left cusp of the pulmonary valve and left cuspid of the aortic valve, each corresponding to a different patient. Link: http://abccardiol.org/supplementary-material/2024/12102/2023-0222_IM_video01.mp4 Figure 1 From left to right and top to bottom: fibroelastomas of the anterior leaflet of the tricuspid valve, anterior leaflet of the mitral valve, left cusp of the pulmonary valve and left cuspid of the aortic valve, each corresponding to a different patient.

RNA Vaccines: Yeast as a Novel Antigen Vehicle.

In the last decades, technological advances for RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle. Among the systems, yeasts emerge as a new approach, already employed to deliver protein antigens, with efficacy demonstrated through preclinical and clinical trials. ß-glucans and mannans in their walls are responsible for the adjuvant property of this system. Yeast ß-glucan capsules, microparticles, and nanoparticles can modulate immune responses and have a high capacity to carry nucleic acids, with bioavailability upon oral immunization and targeting to receptors present in antigen-presenting cells (APCs). In addition, yeasts are suitable vehicles for the protection and specific delivery of therapeutic vaccines based on RNAi. Compared to protein antigens, the use of yeast for DNA or RNA vaccine delivery is less established and has fewer studies, most of them in the preclinical phase. Here, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing the current challenges and prospects of this promising strategy.

Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment.

The understanding of the relationship between immunological responses and cancers, especially those related to HPV, has allowed for the study and development of therapeutic vaccines against these neoplasias. There is a growing number of studies about the composition and influence of the tumor microenvironment (TME) in the progression or establishment of the most varied types of cancer. Hence, it has been possible to structure immunotherapy approaches based on therapeutic vaccines that are even more specific and directed to components of TME and the immune response associated with tumors. Among these components are dendritic cells (DCs), which are the main professional antigen-presenting cells (APCs) already studied in therapy strategies for HPV-related cancers. On the other hand, tumor-associated macrophages are also potential targets since the profile present in tumor infiltrates, M1 or M2, influences the prognosis of some types of cancer. These two cell types can be targets for therapy or immunomodulation. In this context, our review aims to provide an overview of immunotherapy strategies for HPV-positive tumors, such as cervical and head and neck cancers, pointing to TME immune cells as promising targets for these approaches. This review also explores the potential of immunotherapy in cancer treatment, including checkpoint inhibitors, cytokine immunotherapies, immunotherapy vaccines, and cell therapies. Furthermore, it highlights the importance of understanding the TME and its effect on the design and achievement of immunotherapeutic methods.

E7 Oncogene HPV58 Variants Detected in Northeast Brazil: Genetic and Functional Analysis.

Cervical cancer is associated with persistent infections by high-risk Human Papillomavirus (HPV) types that may have nucleotide polymorphisms and, consequently, different oncogenic potentials. Therefore, this study aimed to evaluate the genetic variability and structural effects of the E7 oncogene of HPV58 in cervical scraping samples from Brazilian women. The study was developed with patients from hospitals in the metropolitan area of Recife, PE, Brazil. The most frequent HPV types were, in descending order of abundance, HPV16, 31, and 58. Phylogenetic analysis demonstrated that the isolates were classified into sublineages A2, C1, and D2. Two positively selected mutations were found in E7: 63G and 64T. The mutations G41R, G63D, and T64A in the E7 protein reduced the stability of the protein structure. Utilizing an NF-kB reporter assay, we observed a decrease in the NK-kB pathway activity with the HPV58-E7 variant 54S compared to the WT E7. The other detected E7 HPV58 variants presented similar NF-kB pathway activity compared to the WT E7. In this study, it was possible to identify mutations that may interfere with the molecular interaction between the viral oncoproteins and host proteins.

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.

Immunoinformatics applications in the development of therapeutic vaccines against human papillomavirus-related infections and cervical cancer.

The human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. HPV penetrates the epithelium through microlesions and establishes an infectious focus that can lead to the development of cervical cancer. Prophylactic HPV vaccines are available, but do not affect already-established infections. Using in silico prediction tools is a promising strategy for identifying and selecting vaccine candidate T cell epitopes. An advantage of this strategy is that epitopes can be selected according to the degree of conservation within a group of antigenic proteins. This makes achieving comprehensive genotypic coverage possible with a small set of epitopes. Therefore, this paper revises the general characteristics of HPV biology and the current knowledge on developing therapeutic peptide vaccines against HPV-related infections and cervical cancer.

Physical exercise alleviates oxidative stress in brown adipose tissue and causes changes in body composition and nutritional behavior in rats with polycystic ovary syndrome.

AIM: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS. METHODS: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT). KEY FINDINGS: In PCOS we observed an increase (P < 0.05) in body weight vs. the Control group. But, the PCOS + Exercise group prevent this weight gain (P < 0.05). The temperature in BAT, decrease (P < 0.05) in the PCOS group vs. Control group. PCOS + Exercise prevented this reduction (P < 0.05) in BAT temperature vs. PCOS groups. We observed decreases (P < 0.05) in Lee Index and BMI in POS + Exercise vs. PCOS group. In PCOS rats, we observed an increase (P < 0.05) in murinometric (SRWG, EI, and FE) and body composition parameters (TWB, ECF, ICF, and FFM) vs. the Control group. The PCOS + Exercise prevents (P < 0.05) these changes in all groups, compared with PCOS. Regarding the BAT, we observe an increase (P < 0.05) in MPO and MDA levels in the PCOS vs. Control group. PCOS + Exercise prevents (P < 0.05) these increases vs. the PCOS group. SIGNIFICANCE: PCOS modifies body composition, and nutritional parameters, and induces changes in oxidative stress in BAT. Physical exercise prevented these alterations.

Healthcare workers exposed to COVID-19 patients present an inflammatory status and Th2/Th17/Th22 immune profile: findings from before vaccine application in Brazil.

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.

Communicating Extremity: Fitness Efficacy and Standards Relate to Using Extreme Imagery and Messaging to Create Fitness-Related Media.

Health-related social media increasingly competes with other forms of health communication for public attention. To advance understanding of the genesis of health-related social media communicating extreme fitness standards, we investigated women's creation of fitspiration, social-media content combining fitness images with effortful messages. In a pre-registered study, we hypothesized that creating extreme fitspiration content would relate positively to fitness fantasizing and to exercise self-efficacy, fitness perfectionism, physical activity, thin- and muscular-ideal internalizations, and self-objectification. Undergraduate women (N = 277) created their own fitspiration content by selecting from fitness images and messages that varied in extremity. Fitness fantasizing related positively to creating more extreme fitspiration. When controlling statistically for all other individual-difference variables, exercise self-efficacy and perfectionistic strivings emerged as key variables associated with creating extreme fitspiration content. Results suggest that women who are confident and strive toward challenging goals may create fitspiration content that communicates extreme standards. This work has implications for understanding a potential disconnect between fitspiration creators and consumers, which may illuminate ways to promote healthy fitness communications online.

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems.

Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used-due to its impact on the immune response and desired final effect.

Standardization and Key Aspects of the Development of Whole Yeast Cell Vaccines.

In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is the use of yeast cells as vehicles for the delivery of recombinant antigens. These vaccines, named whole yeast vaccines (WYVs), can induce humoral and cellular immune responses, with the additional advantage of dispensing with the use of adjuvants due to the immunostimulatory properties of their cell wall components. However, there are some gaps in the methodologies for obtaining and validating recombinant strains and vaccine formulations. The standardization of these parameters is an important factor for WYVs approval by regulatory agencies and, consequently, their licensing. This review aimed to provide an overview of the main parameters to consider when developing a yeast-based vaccine, addressing some available tools, and highlighting the main variables that can influence the vaccine production process.

Third-Generation Vaccines: Features of Nucleic Acid Vaccines and Strategies to Improve Their Efficiency.

Gene immunization comprises mRNA and DNA vaccines, which stand out due to their simple design, maintenance, and high efficacy. Several studies indicate promising results in preclinical and clinical trials regarding immunization against ebola, human immunodeficiency virus (HIV), influenza, and human papillomavirus (HPV). The efficiency of nucleic acid vaccines has been highlighted in the fight against COVID-19 with unprecedented approval of their use in humans. However, their low intrinsic immunogenicity points to the need to use strategies capable of overcoming this characteristic and increasing the efficiency of vaccine campaigns. These strategies include the improvement of the epitopes' presentation to the system via MHC, the evaluation of immunodominant epitopes with high coverage against emerging viral subtypes, the use of adjuvants that enhance immunogenicity, and the increase in the efficiency of vaccine transfection. In this review, we provide updates regarding some characteristics, construction, and improvement of such vaccines, especially about the production of synthetic multi-epitope genes, widely employed in the current gene-based vaccines.

Memory elicitation, T-cell response and antibody production: an independent study of an inactivated entire virus vaccine (Coronavac).

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.

Estimation of Radial Basis Function Network Centers via Information Forces.

The determination of The Radial Basis Function Network centers is an open problem. This work determines the cluster centers by a proposed gradient algorithm, using the information forces acting on each data point. These centers are applied to a Radial Basis Function Network for data classification. A threshold is established based on Information Potential to classify the outliers. The proposed algorithms are analysed based on databases considering the number of clusters, overlap of clusters, noise, and unbalance of cluster sizes. Combined, the threshold, and the centers determined by information forces, show good results in comparison to a similar Network with a k-means clustering algorithm.

Assessment of black liquor hydrothermal treatment under sub- and supercritical conditions: Products distribution and economic perspectives.

This study reports an alternative method for black liquor treatment with potential for energy and process savings in the paper and pulp industry. Gasification of black liquor was carried out under sub- and supercritical conditions, varying the black liquor feed composition (0.10, 2.55 and 5.00 wb%) and temperature (350, 425 and 500 °C). Liquid products were identified by high resolution mass spectrometry (FT-Orbitrap MS) and compounds belonging to classes O3 and O4 were found to be the most representative in the products of reactions performed at 500 °C. The mass spectra results also revealed the overall selectivity of reactions, where decarboxylation and demethoxylation reactions were favored under subcritical and supercritical conditions, respectively. Among the gaseous products, hydrogen and methane were produced with maximum of 69.04 and 28.75 mol%, respectively, at 2.55 wb% and 425 °C. The proposed thermodynamic modelling of the reaction system satisfactorily predicted the gas phase behavior of the system. In the economic analysis, the simulated conditions indicated that the main energy requirements for a scaled-up black liquor gasification process are related to the necessary heat exchangers and pressurizing of the black liquor solution. Furthermore, the cost of the black liquor gasification is around 0.06 US$ per kg of feed stream. Liquid and gaseous products from gasification could be obtained at a cost of 56.64 US$ and 3.35 US$ per tonne of stream, respectively. Therefore, black liquor gasification is an interesting route for obtaining combustible gases and value-added bioproducts.