Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function.

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation.

The extent of postpartum cardiac reverse remodeling is reflected in urine proteome.

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.

Equipe de enfermagem das unidades básicas de saúde na fronteira franco brasileira / Nursing team from basic health units on the Franco-Brazilian border

Objetivo: O estudo teve como objetivo traçar o perfil da equipe de enfermagem que atuam nas unidades básicas de saúde no município de Oiapoque, identificando as variáveis socioeconômica e demográfica, nível de formação profissional e o seu aperfeiçoamento no processo de trabalho. Métodos: Tratou-se de uma pesquisa descritiva transversal, com abordagem quantitativa, composta pelos técnicos e enfermeiros que trabalham nas cinco unidades básicas de saúde em funcionamento no município de Oiapoque, feita através de um questionário aplicado individualmente. Resultados: Os resultados obtidos constataram que a maioria dos pesquisados; encontra-se numa faixa etária entre 31 a 35 anos (30%); são do sexo feminino (86%); técnicos de enfermagem (57%), seguido de enfermeiros (43%); possuem ensino superior (29%), pós-graduação (14%), atuação na profissão de 1 a 5 anos (42%), com vínculo contratual temporário (86%); e a principal dificuldade encontrada pelos profissionais é a falta de recursos matérias e equipamentos (56%). Conclusão: Espera-se que os resultados apresentados possam contribuir para melhores investimentos na formação e inserção do profissional da enfermagem nos cuidados primários de áreas transfronteiriças, visto que ainda há carência de profissionais qualificados, principalmente para prestar assistência em tais regiões com saúde singular.(AU)

Objective: The study aimed to outline the profile of the nursing team working in basic health units in the municipality of Oiapoque, identifying the socioeconomic and demographic variables, level of professional training and their improvement in the work process. Methods: This was a cross-sectional descriptive study, with a quantitative approach, composed of technicians and nurses working in the five basic health units operating in the municipality of Oiapoque, carried out through a questionnaire applied individually. Results: The results obtained found that the majority of those surveyed; is in an age range between 31 to 35 years (30%); are female (86%); nursing technicians (57%), followed by nurses (43%); have higher education (29%), postgraduate (14%), work in the profession from 1 to 5 years (42%), with temporary contractual relationship (86%); and the main difficulty encountered by professionals is the lack of material resources and equipment (56%). Conclusion: It is hoped that the results presented can contribute to better investments in the training and insertion of nursing professionals in primary care in cross-border areas, since there is still a shortage of qualified professionals, mainly to provide assistance in such regions with unique health.(AU)

El estudio tuvo como objetivo determinar el perfil del equipo de enfermería que trabaja en unidades básicas de salud en el municipio de Oiapoque, identificando como variables socioeconómicas y demográficas, el nivel de capacitación profesional y su mejora en el proceso de trabajo. Métodos: Esta es una investigación descriptiva transversal, con un enfoque cuantitativo, compuesta por técnicos y enfermeras que utilizan las cinco unidades básicas de salud que operan en el municipio de Oiapoque, realizadas mediante un cuestionario utilizado. Resultados: Los resultados obtenidos encontraron que la mayoría de los encuestados; tiene un rango de edad entre 31 y 35 años (30%); son mujeres (86%); técnicos de enfermería (57%), seguidos por enfermeras (43%); tener educación superior (29%), posgrado (14%), trabajar en la profesión de 1 a 5 años (42%), con relación contractual temporal (86%); La principal dificultad encontrada por los profesionales es la falta de recursos materiales y de equipo (56%). Conclusión: Se espera que los resultados mostrados puedan contribuir a mejores inversiones y capacitación de enfermería profesional en atención primaria en áreas transfronterizas, ya que todavía hay una escasez de profesionales calificados, principalmente para brindar asistencia en tales situaciones con una salud única.(AU)

Mudanças na rotina de instituições delonga permanência para idosos em função da pandemia da COVID-19 / Changes in the routine of long-stay institutions for the elderly due to the COVID-19 pandemic

Objetivo: Identificar as mudanças surgidas como resultado das medidas implementadas em Instituições de Longa Permanecia para Idosos para a prevenção do contágio pelo novo coronavírus SARS-CoV-2 no município de Teresina no Estado do Piauí. Método: Trata-se de um estudo transversal de natureza quantitativa com os gestores de quatro instituições na cidade de Teresina no Piauí, realizada por meio de um formulário, estruturado e eletrônico, na plataforma Google Forms. Resultados: Foram implementados protocolos preventivos em todas as instituições, com foco em medidas de segurança para os idosos e focando em condutas de higiene, de forma unanime a obrigatoriedade do uso de máscara e suspensão de visitas. Conclusões: Foram analisadas quatro Instituições de Longa Permanência para Idosos e de acordo com os dados coletados as instituições passaram por processo de adaptação as necessidades que surgem para melhorar a qualidade de vida dos idosos institucionalizados.(AU)

Objective: To identify the changes that have arisen as a result of measures implemented in Long Stay Institutions for the Elderly for the prevention of contagion by the new SARS-CoV-2 coronavirus in the municipality of Teresina, State of Piauí. Method: This is a cross-sectional study of a quantitative nature with managers of four institutions in the city of Teresina, Piauí, carried out through a structured and electronic form, on the Google Forms platform. Results: Preventive protocols were implemented in all institutions, focusing on safety measures for the elderly and focusing on hygiene behaviors, unanimously the mandatory use of masks and suspension of visits. Conclusions: Four long-stay institutions for the elderly were analyzed and, according to the data collected as institutions, they underwent an adaptation process as needed to improve the quality of life of institutionalized elderly.(AU)

Objetivos: Identificar los cambios que han surgido como resultado de las medidas implementadas en Instituciones de Larga Estancia para Personas Mayores para la prevención del contagio por el nuevo coronavirus SARS-CoV-2 en el municipio de Teresina, Estado de Piauí. Método: Se trata de un estudio transversal de carácter cuantitativo con responsables de cuatro instituciones de la ciudad de Teresina, Piauí, realizado a través de un formulario estructurado y electrónico, en la plataforma Google Forms. Resultados: Se implementaron protocolos preventivos en todas las instituciones, enfocándose en las medidas de seguridad para los adultos mayores y enfocados en las conductas higiénicas, por unanimidad el uso obligatorio de mascarillas y suspensión de visitas. Conclusiones: Se analizaron cuatro instituciones de larga estancia para ancianos que, de acuerdo con los datos recolectados como instituciones, se sometieron a un proceso de adaptación según fue necesario para mejorar la calidad de vida de los ancianos institucionalizados.(AU)

Acute and chronic effects of levosimendan in the ZSF1 obese rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by impaired cardiovascular reserve in which therapeutic options are scarce. Our aim was to evaluate the inodilator levosimendan in the ZSF1 obese rat model of HFpEF. Twenty-week-old male Wistar-Kyoto (WKY), ZSF1 lean (ZSF1 Ln) and ZSF1 obese rats chronically treated for 6-weeks with either levosimendan (1 mg/kg/day, ZSF1 Ob + Levo) or vehicle (ZSF1 Ob + Veh) underwent peak-effort testing, pressure-volume (PV) haemodynamic evaluation and echocardiography (n = 7 each). Samples were collected for histology and western blotting. In obese rats, skinned and intact left ventricular (LV) cardiomyocytes underwent in vitro functional evaluation. Seven additional ZSF1 obese rats underwent PV evaluation to assess acute levosimendan effects (10 µg/kg + 0.1 µg/kg/min). ZSF1 Ob + Veh presented all hallmarks of HFpEF, namely effort intolerance, elevated end-diastolic pressures and reduced diastolic compliance as well as increased LV mass and left atrial area, cardiomyocyte hypertrophy and increased interstitial fibrosis. Levosimendan decreased systemic arterial pressures, raised cardiac index, and enhanced LV relaxation and diastolic compliance in both acute and chronic experiments. ZSF1 Ob + Levo showed pronounced attenuation of hypertrophy and interstitial fibrosis alongside increased effort tolerance (endured workload raised 38 %) and maximum O2 consumption. Skinned cardiomyocytes from ZSF 1 Ob + Levo showed a downward shift in sarcomere length-passive tension relationship and intact cardiomyocytes showed decreased diastolic Ca2+ levels and enhanced Ca2+ sensitivity. On molecular grounds, levosimendan enhanced phosphorylation of phospholamban and mammalian target of rapamycin. The observed effects encourage future clinical trials with levosimendan in a broad population of HFpEF patients.

Comprehensive characterization of protein modifications using mass spectrometry and dry blood spots.

PURPOSE: The main objective of this study is to characterize and analyze modified peptides in DBS samples. This includes deciphering their specific PTMs and understanding their potential impact on the population or disease cohort under study. EXPERIMENTAL DESIGN: Using mass spectrometry-based proteomic approaches, we performed a comprehensive analysis of DBS samples. Our focus was on the identification and quantification of modified peptides. We also took advantage of recent advances in DBS mass spectrometry to ensure accurate detection and quantification. RESULTS: A comprehensive analysis identified 972 modified peptides in DBS samples. Of these, a subset of 211 peptides was consistently present in all samples, highlighting their potential biological importance and relevance. This indicates a diverse spectrum of PTMs in the proteome of DBS samples. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of mass spectrometry and proteomics has revealed a broad spectrum of modified peptides in DBS samples and highlighted their importance in biological processes and disease progression. Accurate detection of these PTMs may be critical for risk stratification and disease management. This study improves the understanding of molecular mechanisms underlying biological processes and disease development, providing important insights for clinical applications.

Desafios e perspectivas na atuação de estomaterapeutas durante a pandemia de COVID-19 / Challenges and perspectives in the work of stomatherapists during the COVID-19 pandemic

Objetivo: Analisar os desafios e perspectivas na atuação de estomaterapeutas durante a pandemia de COVID-19.Métodos: Pesquisa descritiva de abordagem qualitativa, por meio de entrevista semiestruturada com oito estomaterapeutas, selecionadas pela técnica snowball. Utilizou-se a Análise de Conteúdo, da qual emergiram três categorias: Desafios na atuação de estomaterapeutas durantea pandemia da COVID-19; Estratégias para viabilizar a assistência remota e presencial na estomaterapia; e Impacto da pandemia no cuidado de estomaterapia. Resultados: Os principais desafios citados foram: fechamento de ambulatórios e agravamento do quadro de saúde dos pacientes. As estratégias incluíram: adaptação da metodologia dos atendimentos, utilização de precauções-padrão e comunicação remota. Dentre as perspectivas futuras, destacam-se o crescimento da especialidade e valorização por outros profissionais da saúde. Conclusão: Houve diversos desafios na atuação de estomaterapeutas na pandemia, contornados, sobretudo, com a diversificação de estratégias assistenciais e modificações nos atendimentos. No entanto, destaca-se como perspectiva futura o aumento da visibilidade da especialidade. Descritores: Enfermagem; Estomaterapia; COVID-19

Objective: To analyze the challenges and perspectives in the work of stomatherapists during the COVID-19 pandemic. Methods: Descriptive research with a qualitative approach, through semi-structured interviews with eight stomatherapists, selected by the snowball technique. Content Analysis was used, emerging three categories: Challenges in the work of stomatherapists during the COVID-19 pandemic; Strategies to enable remote and face-to-face assistance in stomatherapy; and Impact of the pandemic on stomatherapy care. Results: The main challenges mentioned were: closure of outpatient clinics and worsening of the patients' health situation. The strategies included: adaptation of the care methodology, use of standard precautions and remote communication. Among the future perspectives, the growth of the specialty and appreciation by other health professionals stand out. Conclusion: There were several challenges in the work of stomatherapists in the pandemic, circumvented, above all, with the diversification of care strategies and modifications in care. However, the increased visibility of the specialty stands out as a future perspective. Descriptors:Nursing; Enterostomal Therapy; COVID-19.

Multiomics tools for improved atherosclerotic cardiovascular disease management.

Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using artificial intelligence (AI) and machine learning (ML) approaches, it is possible to integrate multiple 'omics and clinical data sets into tools that can be utilized for the development of personalized diagnostic and therapeutic approaches. However, currently multiple challenges in data quality, integration, and privacy still need to be addressed. In this opinion, we emphasize that joined efforts, exemplified by the AtheroNET COST Action, have a pivotal role in overcoming the challenges to advance multiomics approaches in ASCVD research, with the aim to foster more precise and effective patient care.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

The PERInatal MYocardial Remodeling (PERIMYR) cohort study protocol: A prospective study of cardiac remodeling and "recovery" in pregnancy as a model to understand the impact of comorbidities in cardiac remodeling and reverse remodeling.

INTRODUCTION: Heart failure (HF) is among the leading causes of morbidity and mortality worldwide. Several conditions trigger left ventricular chronic pressure or volume overload, hypertrophy, systolic and diastolic dysfunction, leading to cardiac remodeling and a rapid progression toward HF. Therapeutic interventions elicit reverse remodeling (RR), a highly variable myocardial response that ranges from none to total ventricular structural/functional recovery. However, HF patients present several comorbidities and medications that mask a comprehensive molecular knowledge of RR and hinder the identification of potential biomarkers of its progression or prognosis. Therefore, instead of using this heterogeneous population or even animal models to understand myocardial remodeling, we propose studying pregnancy-induced cardiovascular remodeling and postpartum-induced RR. OBJECTIVES: To assess cardiovascular functional and structural adaptations during pregnancy and in postpartum, characterizing the associated molecular changes; as well as to explore the impact of hypertension, obesity and diabetes on these processes. METHODS: We will perform echocardiography and assess endothelial function and arterial stiffness (EndoPAT® and pulse wave velocity, respectively) and assess potential markers of remodeling and RR using plasma and urine samples from pregnant women. To translate to a HF context, we will determine the impact of risk factors (hypertension, obesity and diabetes) by studying subgroups of pregnant women with these comorbidities. RESULTS: Not applicable. CONCLUSION: We are convinced that understanding the impact of these comorbidities in such a homogeneous population, such as pregnant women, provides a valuable model to unveil the most relevant pathologic and often masked signaling pathways underlying cardiac remodeling and incomplete RR in a heterogeneous population, such as HF patients. Moreover, we expect to identify potential novel biomarkers of RR progression/prognosis more easily.

Coronary Artery Disease and Aortic Valve Stenosis: A Urine Proteomics Study.

Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).

Optimization of a Protocol for Protein Extraction from Calcified Aortic Valves for Proteomics Applications: Development of a Standard Operating Procedure.

The comprehension of the pathophysiological mechanisms, the identification of druggable targets, and putative biomarkers for aortic valve stenosis can be pursued through holistic approaches such as proteomics. However, tissue homogenization and protein extraction are made difficult by tissue calcification. The reproducibility of proteome studies is key in clinical translation of the findings. Thus, we aimed to optimize a protocol for aortic valve homogenization and protein extraction and to develop a standard operating procedure (SOP), which researchers can use to maximize protein yield while reducing inter-laboratory variability. We have compared the protein yield between conventional tissue grinding in nitrogen followed by homogenization with a Potter apparatus with a more advanced bead-beating system. Once we confirmed the superiority of the latter, we further optimized it by testing the effect of beads size, the number of homogenization cycles, tube capacity, lysis buffer/tissue mass ratio, and two different lysis buffers. Optimal protein extraction was achieved with 2.8 mm zirconium dioxide beads, in two homogenization cycles, in the presence of 20 µL RIPA buffer/mg tissue, using 2 mL O-ring cryotubes. As a proof of concept of the usefulness of this SOP for proteomics, the AV proteome of men and women with aortic stenosis was characterized, resulting in the quantification of proteins across six orders of magnitude and uncovering some putative proteins dysregulated by sex.

Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study.

Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and a well-established risk factor for the development of cardiovascular disease (CVD). Gut dysbiosis may contribute to CVD and inflammation in CKD patients. Nonetheless, the role of gut and blood microbiomes in CKD-associated VC remains unknown. Therefore, this pilot study aimed to explore the link between gut and blood microbiomes and VC in CKD patients on peritoneal dialysis (CKD-PD). Our results showed relative changes in specific taxa between CKD-PD patients with and without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and Eubacterium eligens group in the gut, and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. An association between VC and all-cause mortality risk in CKD-PD patients was also observed, and patients with higher mortality risk corroborate the changes of Eubacterium eligens in the gut and Devosia genus in the blood. Although we did not find differences in uremic toxins, intestinal translocation markers, and inflammatory parameters among CKD-PD patients with and without VC, soluble CD14 (sCD14), a nonspecific marker of monocyte activation, positively correlated with VC severity. Therefore, gut Eubacterium eligens group, blood Devosia, and circulating sCD14 should be further explored as biomarkers for VC, CVD, and mortality risk in CKD.

Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study.

To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer.

Pericardial Fluid Annexin A1 Is a Marker of Atrial Fibrillation in Aortic Stenosis: A Proteomics Analysis.

Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC-MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated ≥2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein-protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis.

Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart.

Heart failure (HF) is growing in prevalence, due to an increase in aging and comorbidities. Heart failure with reduced ejection fraction (HFrEF) is more common in men, whereas heart failure with preserved ejection fraction (HFpEF) has a higher prevalence in women. However, the reasons for these epidemiological trends are not clear yet. Since HFpEF affects mostly postmenopausal women, sex hormones should play a pivotal role in HFpEF development. Furthermore, for HFpEF, contrary to HFrEF, effective therapeutic approaches are missing. Interestingly, studies evidenced that some therapies can have better results in women than in HFpEF men, emphasizing the necessity of understanding these observations at a molecular level. Thus, herein, we review the molecular mechanisms of estrogen and androgen actions in the heart in physiological conditions and explain how its dysregulation can lead to disease development. This clarification is essential in the road for an effective personalized management of HF, particularly HFpEF, towards the development of sex-specific therapeutic approaches.

Mining the Biomarker Potential of the Urine Peptidome: From Amino Acids Properties to Proteases.

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.

The potential impact of salivary peptides in periodontitis.

Periodontitis is a complex immune-inflammatory condition characterized by the disruption of the periodontal ligament and subsequent formation of periodontal pockets, and by alveolar bone loss, often resulting in tooth loss. A myriad of factors, namely, genetic, metabolic, immunological, and inflammatory, is associated with progression of periodontitis. Periodontitis is also associated with systemic conditions such as neoplastic disorders, obesity, and diabetes. The current diagnosis of this disease relies on clinical measurements such as clinical attachment loss and probing depth, which have poor precision due to patient, operator and probe-related factors. Thus, there is a need to develop reliable, objective, and reproducible biomarkers for early diagnosis of periodontitis. In this regard, saliva, with contributions from the gingival crevicular fluid, holds great potential. However, most of the information on biomarkers of periodontium-related salivary proteins has come from studies on the molecular pathogenesis of periodontitis. In periodontitis, a more holistic approach, such as the use of -omics technologies, for biomarker discovery, is needed. Herein, we review the biomarkers proposed to date for the assessment of periodontitis, with emphasis on the role of salivary peptides in periodontitis and their assessment by high-throughput saliva proteomics. We also discuss the challenges pertaining to the identification of new periodontitis biomarkers in saliva.

Automatic text-mining as an unbiased approach to uncover molecular associations between periodontitis and coronary artery disease.

The increasing prevalence of periodontal and cardiovascular diseases is the result of a sedentary lifestyle associated with poor diet, obesity, hypercholesterolaemia, smoking habits, alcohol consumption and stress. The present study aims to uncover molecular associations between periodontitis and coronary heart disease using an unbiased strategy of automatic text mining traditionally applied to bibliometric studies. A total of 1590 articles on these diseases were retrieved from the Web of knowledge database and searched using the VOS viewer to create a network of keywords associated with both diseases. These data were supplemented with data from DisGeNET, which stores known associations to either periodontitis or coronary heart disease. Overall, the automated text mining approach presented here highlighted inflammatory molecules as common associations between periodontitis and coronary heart disease. Specifically, this study showed that molecules such as C-reactive protein, interleukins 6 and 1-ß, myeloperoxidase, and matrix metalloproteinase 9 are simultaneously associated with periodontitis and coronary artery disease by both text mining and DisGeNET analyses. This association validates the multiplex assessment of salivary inflammatory markers as a tool to assess cardiovascular disease risk and could become an important tool to identify common molecular targets to monitor both diseases simultaneously. In addition, the text mining protocol and subsequent data processing and methods using bioinformatics tools could be useful to uncover links between other diseases.