Epigenetic Mechanisms Histone Deacetylase-Dependent Regulate the Glioblastoma Angiogenic Matrisome and Disrupt Endothelial Cell Behavior In Vitro.

Glioblastoma (GBM) is the most aggressive brain tumor and different efforts have been employed in the search for new drugs and therapeutic protocols for GBM. Epitranscriptomics has shed light on new druggable Epigenetic therapies specifically designed to modulate GBM biology and behavior such as Histone Deacetylase inhibitors (iHDAC). Although the effects of iHDAC on GBM have been largely explored, there is a lack of information on the underlaying mechanisms HDAC-dependent that modulate the repertoire of GBM secreted molecules focusing on the set of Extracellular Matrix (ECM) associated proteins, the Matrisome, that may impact the surrounding tumor microenvironment. To acquire a better comprehension of the impacts of HDAC activity on the GBM Matrisome, we studied the alterations on the Matrisome-associated ECM regulators, Core Matrisome ECM glycoproteins, ECM-affiliated proteins and Proteoglycans upon HDAC inhibition in vitro as well as their relationship with glioma pathophysiological/clinical features and angiogenesis. For this, U87MG GBM cells were treated for with iHDAC or vehicle (control) and the whole secretome was processed by Mass Spectrometry NANOLC-MS/MS. In silico analyses revealed that proteins associated to the Angiogenic Matrisome (AngioMatrix), including Decorin, ADAM10, ADAM12 and ADAM15 were differentially regulated in iHDAC versus control secretome. Interestingly, genes coding for the Matrisome proteins differentially regulated were found mutated in patients and were correlated to glioma pathophysiological/clinical features. In vitro functional assays, using HBMEC endothelial cells exposed to the secretome of control or iHDAC treated GBM cells, coupled to 2D and 3D GBM cell culture system, showed impaired migratory capacity of endothelial cells and disrupted tubulogenesis in a Fibronectin and VEGF independent fashion. Collectively, our study provides understanding of epigenetic mechanisms HDAC-dependent to key Matrisomal proteins that may contribute to identify new druggable Epigenetic therapies or gliomagenesis biomarkers with relevant implications to improve therapeutic protocols for this malignancy.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).

Exploring the Chagas disease-Stroke 'Connection': Findings from a Large Multicenter Study.

INTRODUCTION: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. METHODS: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. RESULTS: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific EKG abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR:0.98, CI 0.970 - 0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR:0.221 |CI 0.104 - 0.472), highlighting the importance of accurate etiological classification. Conversely, female gender(OR:1.83 CI 1.039 - 3.249) emerged as a significant risk factor for stroke recurrence. CONCLUSION: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.

Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8+ T-Cell Pathogenic Responses and Recognition of Type 1 Collagen in Rheumatic Heart Valve Disease.

BACKGROUND: Rheumatic heart valve disease (RHVD) is a leading cause of cardiovascular death in low- and middle-income countries and affects predominantly women. The underlying mechanisms of chronic valvular damage remain unexplored and regulators of sex predisposition are unknown. METHODS: Proteomics analysis of human heart valves (nondiseased aortic valves, nondiseased mitral valves [NDMVs], valves from patients with rheumatic aortic valve disease, and valves from patients with rheumatic mitral valve disease; n=30) followed by system biology analysis identified ProTα (prothymosin alpha) as a protein associated with RHVD. Histology, multiparameter flow cytometry, and enzyme-linked immunosorbent assay confirmed the expression of ProTα. In vitro experiments using peripheral mononuclear cells and valvular interstitial cells were performed using multiparameter flow cytometry and quantitative polymerase chain reaction. In silico analysis of the RHVD and Streptococcuspyogenes proteomes were used to identify mimic epitopes. RESULTS: A comparison of NDMV and nondiseased aortic valve proteomes established the baseline differences between nondiseased aortic and mitral valves. Thirteen unique proteins were enriched in NDMVs. Comparison of NDMVs versus valves from patients with rheumatic mitral valve disease and nondiseased aortic valves versus valves from patients with rheumatic aortic valve disease identified 213 proteins enriched in rheumatic valves. The expression of the 13 NDMV-enriched proteins was evaluated across the 213 proteins enriched in diseased valves, resulting in the discovery of ProTα common to valves from patients with rheumatic mitral valve disease and valves from patients with rheumatic aortic valve disease. ProTα plasma levels were significantly higher in patients with RHVD than in healthy individuals. Immunoreactive ProTα colocalized with CD8+ T cells in RHVD. Expression of ProTα and estrogen receptor alpha correlated strongly in circulating CD8+ T cells from patients with RHVD. Recombinant ProTα induced expression of the lytic proteins perforin and granzyme B by CD8+ T cells as well as higher estrogen receptor alpha expression. In addition, recombinant ProTα increased human leukocyte antigen class I levels in valvular interstitial cells. Treatment of CD8+ T cells with specific estrogen receptor alpha antagonist reduced the cytotoxic potential promoted by ProTα. In silico analysis of RHVD and Spyogenes proteomes revealed molecular mimicry between human type 1 collagen epitope and bacterial collagen-like protein, which induced CD8+ T-cell activation in vitro. CONCLUSIONS: ProTα-dependent CD8+ T-cell cytotoxicity was associated with estrogen receptor alpha activity, implicating ProTα as a potential regulator of sex predisposition in RHVD. ProTα facilitated recognition of type 1 collagen mimic epitopes by CD8+ T cells, suggesting mechanisms provoking autoimmunity.

Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort.

BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center. METHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. RESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ß = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (ß = -0.37, 99.5% CI -0.48 to -0.26), and stress (ß = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. CONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.

Predictors and management of post-banding ulcer bleeding in cirrhosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Post-banding ulcer bleeding (PBUB) is an understudied complication of oesophageal varices endoscopic band ligation (EBL). This systematic review with meta-analysis aimed at: (a) evaluating the incidence of PBUB in patients with cirrhosis treated with EBL in primary or secondary prophylaxis or urgent treatment for acute variceal bleeding and (b) identifying predictors of PBUB. METHODS: We conducted a systematic review of articles in English published in 2006-2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were made in eight databases including Embase, PubMed and Cochrane Library. Random-effects meta-analysis was used to determine the incidence, mean interval and predictors of PBUB. RESULTS: Eighteen studies (9034 patients) were included. The incidence of PBUB was 5.5% (95% CI 4.3-7.1). The mean time for it to occur was 11 days (95% CI 9.94-11.97). Model for End-stage Liver Disease (MELD) score (OR 1.162, 95% CI 1.047-1.291) and EBL done in emergency setting (OR 4.902, 95% CI 2.99-8.05) independently predicted post-ligation ulcer bleeding. Treatment included drugs, endoscopic procedures and transjugular intrahepatic portosystemic shunt. Refractory bleeding was treated with self-expandable metallic stents or balloon tamponade. Mortality was on average 22.3% (95% CI 14.1-33.6). CONCLUSIONS: Patients with high MELD score and receiving EBL in an emergency setting are more prone to develop PBUB. Prognosis is still poor and the best therapeutic strategy to address remains to be ascertained.

Spatial orientation: A relationship with inferential memory.

Two branches of the scientific literature have dominated our understanding of hippocampal function. One focuses on the support this structure offers to declarative memory, while the other views the hippocampus as a part of a system dedicated to spatial navigation. These two different visions can be reconciled in relational theory, which suggests that the hippocampus processes all kinds of associations and sequences of events. According to this, processing would be similar to a route calculation based on associations of spatial information acquired during navigation and the associative relationship established between memories without spatial content. In this paper, we present a behavioral study of healthy individuals to explore the performance of inferential memory tasks and spatial orientation tasks in a virtual environment. Inferential memory and spatial orientation task performances were positively correlated. However, after controlling for a non-inferential memory task, only the correlation between allocentric spatial orientation and inferential memory remained significant. These results provide support for the similarity between the two cognitive functions, lending credence to the relational theory of the hippocampus. Additionally, our behavioral findings are in line with the cognitive map theory, which suggests a potential association between the hippocampus and allocentric spatial representations.

Treatment of salt from hides curing stage by electrocoagulation for use in the pickling stage of the tanning industry.

The raw materials for the tanning industry, namely hides and skins, are preserved (curing stage) and carried with common salt, i.e., sodium chloride (NaCl). Proceeding to conversion into leather, pickling is a key stage of the tannery process, which entails high demand of water and salt. In this work, the salt-derived brine (SdB) generated from the curing of hides was treated by iron-driven electrocoagulation (EC), aiming at its later application in the pickling stage of the tanning industry, promoting a transition to zero waste emission policy. Focusing on reducing the brine's total organic carbon (TOC), central composite rotational design and response surface methodology were adopted to study the effect of electrolysis time (6.2-14.2 min) and current density (74-431 A·m-2) on the treatment of the SdB (≅ 7.5 % wt. NaCl). The quality of the treated brines was then assessed in pickling trials and compared with virgin brine. 68-83 % removal of TOC from the SdB were achieved under electrolysis time ranging 6.2-14.2 min and current density ranging 126-252 A·m-2. Under these operating ranges the quality of the wet-blue leathers was guaranteed. Lowest power consumption (0.44 kWh·m-3) was achieved under electrolysis time of 6 min and current density of 126 A·m-2, yielding 68 % removal of TOC. Moreover, the shrinkage temperature of the hides was improved with treated brine (103.5 °C-110.5 °C) compared to virgin brine (103.0 °C). The present study provides strong evidence that contaminated salt from the curing stage can be valorised within the tanning industry through electrocoagulation treatment and then used in another production stage, instead of being landfilled.

Early triage echocardiography to predict outcomes in patients admitted with COVID-19: a multicenter study.

INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, especially in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside triage echocardiography (echo), in patients admitted to emergency departments (ED) in the US with COVID-19. We also assessed the feasibility of using cloud imaging for sharing and interpreting echocardiograms. METHODS: Patients admitted to three reference EDs with confirmed COVID-19 underwent triage echo within 72 h of symptom onset with remote interpretation. Clinical and laboratory data, as well as COVID-19 symptoms, were collected. The association between echo variables, demographics and clinical data with all-cause hospital mortality and intensive care unit (ICU) admission was assessed using logistic regression. RESULTS: Three hundred ninety-nine patients were enrolled, 41% women, with a mean age of 62±16 years. Mean oxygen saturation on presentation was 92.3± 9.2%. Compared to in-hospital survivors, non-survivors were older, had lower oxygen saturation on presentation, were more likely to have a chronic condition and had lower LV ejection fraction (50.3±19.7% vs. 58.0±13.6%) (P < .05). In the cohort, 101 (25%) patients had moderate/severe LV dysfunction, 131 (33%) had moderate/severe RV dysfunction. Advanced age and lower oxygen saturation were independently associated with death and ICU admission. LV and RV function, or other echo variables, were not independent predictors of outcomes. CONCLUSION: In patients admitted with COVID-19 undergoing early echo triage, the independent predictors of death and ICU admission were age and oxygen saturation. The inclusion of echo variables did not improve prediction of unfavorable outcomes.

Comparative Chemical Profiling and Antimicrobial/Anticancer Evaluation of Extracts from Farmed versus Wild Agelas oroides and Sarcotragus foetidus Sponges.

Marine sponges are highly efficient in removing organic pollutants and their cultivation, adjacent to fish farms, is increasingly considered as a strategy for improving seawater quality. Moreover, these invertebrates produce a plethora of bioactive metabolites, which could translate into an extra profit for the aquaculture sector. Here, we investigated the chemical profile and bioactivity of two Mediterranean species (i.e., Agelas oroides and Sarcotragus foetidus) and we assessed whether cultivated sponges differed substantially from their wild counterparts. Metabolomic analysis of crude sponge extracts revealed species-specific chemical patterns, with A. oroides and S. foetidus dominated by alkaloids and lipids, respectively. More importantly, farmed and wild explants of each species demonstrated similar chemical fingerprints, with the majority of the metabolites showing modest differences on a sponge mass-normalized basis. Furthermore, farmed sponge extracts presented similar or slightly lower antibacterial activity against methicillin-resistant Staphylococcus aureus, compared to the extracts resulting from wild sponges. Anticancer assays against human colorectal carcinoma cells (HCT-116) revealed marginally active extracts from both wild and farmed S. foetidus populations. Our study highlights that, besides mitigating organic pollution in fish aquaculture, sponge farming can serve as a valuable resource of biomolecules, with promising potential in pharmaceutical and biomedical applications.

Healthy Lifestyle Beliefs Scale: Psychometric properties in Portuguese pregnant women.

Healthy lifestyle during pregnancy influences the pregnant woman's and child's physical and mental health, impacting perinatal outcomes. Healthy lifestyle beliefs are predictors of lifestyle behaviors, requiring a valid and reliable instrument to assess them during prenatal care. The 16-item Healthy Lifestyle Belief Scale (HLBS) measures a person's beliefs about their ability to live a healthy lifestyle. This study aimed to examine the psychometric properties of a Portuguese version of the HLBS among pregnant women. A methodological study was developed in two phases: cross-cultural adaptation and evaluation of the psychometric properties of the Portuguese version in a nonprobability sample of 192 Portuguese pregnant women. The exploratory factor analysis suggested three subscales, which explained 53.8% of the total variance. Cronbach's α was 0.83 for the overall scale and for the subscales ranged between 0.71 and 0.81. The HLBS is a reliable and valid instrument to assist health professionals in assessing the ability of Portuguese pregnant women to adopt a healthy lifestyle. Assessing healthy lifestyle beliefs potentially contributes to the development of health behavior interventions in pregnant women and consequently improves perinatal outcomes through evidence-based practices.

"Studying cognitive reappraisal as an antidote to the effect of negative emotions on medical residents' learning: a randomized experiment".

BACKGROUND: Medical trainees often encounter situations that trigger emotional reactions which may hinder learning. Evidence of this effect on medical trainees is scarce and whether it could be counteracted is unclear. This study investigated the effect of negative emotions on medical residents' learning and whether cognitive reappraisal counteracts it. METHODS: Ninety-nine medical residents participated in a three-phase experiment consisting of: (1) watching a video, either a neutral or an emotion-induction version, the latter either followed by cognitive reappraisal or not (2) learning: all participants studied the same medical text; study-time and cognitive engagement were measured; (3) test: a recall-test measured learning. Data was analysed using Chi-square test and one-way ANOVA. RESULTS: Study time significantly varied between conditions (p = 0.002). The two emotional conditions spent similar time, both significantly less than the neutral condition. The difference in test scores failed to reach significance level (p = 0.053). While the emotional conditions performed similarly, their scores tended to be lower than those of the neutral condition. CONCLUSION: Negative emotions can adversely affect medical residents' learning. The effect of emotions was not counteracted by cognitive reappraisal, which has been successfully employed to regulate emotions in other domains. Further research to examine emotion regulation strategies appropriate for medical education is much needed.

Is Modified Early Warning Score associated with clinical outcomes of patients admitted to a university internal medicine ward?

OBJECTIVE: To assess the MEWS association with the clinical outcomes (CO) of patients admitted to an internal medicine ward (IMW) at a Brazilian university hospital (UH). INTRODUCTION: It is important to quickly identify patients with clinical deterioration, especially in wards. The health team must recognize and act before the situation becomes an adverse event. In Brazil, nurses' work to overcome performance myths and the application of standardized predictive scales for patients in wards is still limited. DESIGN: An observational cohort study designed and developed by a registered nurse that followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. METHODS: Data were collected from the IMW of a UH located in the city of São Paulo, Brazil (2017). An ROC curve was calculated to strengthen the use of a MEWS of < or ≥ 4 as a cutoff. CO of the two subgroups were compared. RESULTS: Three hundred patients completed the study; their vital signs were recorded consecutively throughout hospitalization in the IMW. The highest MEWS value each day was considered for analysis. Scores < 4 were significantly associated with a higher probability of hospital discharge, a lower chance of transfer to the ICU, a lower total number of days of hospitalization, and a lower risk of death. Score ≥ 4 had worse CO (orotracheal intubation and cardiac monitoring), transfer to the ICU, and increased risk of death. CONCLUSION: Scores < 4 were associated with positive outcomes, while scores ≥ 4 were associated with negative outcomes. MEWS can help prioritize interventions, increase certainty in decision-making, and improve patient safety, especially in a teaching IMW with medical teams undergoing professional development, thereby ensuring the central role of the nursing team in Brazil. RELEVANCE FOR CLINICAL PRACTICE: MEWS aid nurses in identifying and managing patients, prioritizing interventions through assertive decision-making.

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

The Experimental Development of Emulsions Enriched and Stabilized by Recovering Matter from Spirulina Biomass: Valorization of Residue into a Sustainable Protein Source.

Spirulina consists of a cluster of green-colored cyanobacteria; it is commonly consumed as a food or food supplement rich in bioactive compounds with antioxidant activity, predominantly C-phycocyanin (C-PC), which is related to anti-inflammatory action and anticancer potential when consumed frequently. After C-PC extraction, the Spirulina residual biomass (RB) is rich in proteins and fatty acids with the potential for developing food products, which is interesting from the circular economy perspective. The present work aimed to develop a vegan oil-in-water emulsion containing different contents of Spirulina RB, obtaining a product aligned with current food trends. Emulsions with 3.0% (w/w) of proteins were prepared with different chickpea and Spirulina RB ratios. Emulsifying properties were evaluated regarding texture and rheological properties, color, antioxidant activity, and droplet size distribution. The results showed that it was possible to formulate stable protein-rich emulsions using recovering matter rich in protein from Spirulina as an innovative food ingredient. All the concentrations used of the RB promoted the formulation of emulsions presenting interesting rheological parameters compared with a more traditional protein source such as chickpea. The emulsions were also a source of antioxidant compounds and maintained the color for at least 30 days after production.

Characterization of Chia Seeds, Cold-Pressed Oil, and Defatted Cake: An Ancient Grain for Modern Food Production.

The increasing demand for superfoods has resulted in an increase in chia seeds consumption. The reintroduction of this ancient crop in agriculture is useful to ensure food security since it can grow in high-stress conditions. The current study aimed to characterize chia seeds, cold-pressed oil, and defatted cake (the oil extraction by-product) to improve their value and to meet consumer's expectations (low-fat products). Chia seeds presented a significantly higher energy value than cake (444 vs. 284 kcal/100 g, respectively) due to fat removal (33 vs. 7%). The cake showed higher contents of total minerals (6 vs. 5%), protein (27 vs. 18%), and fiber (48 vs. 38%) in comparison to the seeds, and was hence considered a promising food ingredient. The major fatty acid in oil, seeds, and cake was α-linolenic acid (62-66%), and the vitamin E content was 409, 200, and 44 mg/kg, respectively. The major amino acid in the seeds and cake was glutamic acid (49 vs. 36 mg/g). The oil had a low oxidative stability (1 h), and the total phenolics content was 1.3 mg gallic acid equivalents/100 g. Chia cake incorporation in food formulations will follow consumer's interests, and the obtained oil can be used to improve the oil supply for different applications. This approach adds value to the concept of "one health" since it includes the culture, the environment, and the consumers.

Effect of Different Time/Temperature Binomials on the Chemical Features, Antioxidant Activity, and Natural Microbial Load of Olive Pomace Paste.

Olive pomace is a by-product from olive oil production that can be further processed to obtain olive pomace paste. In this work, the influence of different time/temperature binomials (65 °C/30 min; 77 °C/1 min; 88 °C/15 s; and 120 °C/20 min) on the nutritional quality, chemical composition, and efficiency on control/elimination of natural microbial load of olive pomace paste was ascertained. The treatments significantly impacted the contents of ash, fat, vitamin E, phenolics (including hydroxytyrosol), flavonoids, and antioxidant activity, but not the fatty acids profile. The binomial 88 °C/15 s showed the greatest potential since it better preserved the phytochemical and antioxidant properties as well as the protein and fiber contents. This binomial is also faster and easy to be implemented at an industrial level, allowing the obtention of a safe functional ingredient to satisfy consumers' demands for novel sustainable products, simultaneously, responding to food safety and food security concerns.

Nutritional Improvement of Fresh Cheese with Microalga Chlorella vulgaris: Impact on Composition, Structure and Sensory Acceptance.

Research background: The production of foods fortified with bioactive ingredients has been recognized by food companies as a way to position their products in health food markets. The fortification of cheese represents a major challenge, due to the chemical and structural complexity of the cheese matrix, as well as the complexity of the biochemical reactions occurring during the fermentation and maturation processes. Microalgae are nutritious and sustainable food sources with important bioactive compounds such as proteins, polyunsaturated fatty acids, polysaccharides, chlorophylls, carotenoids, vitamins and minerals. Experimental approach: This work aims to study the impact of the 2 and 4 % microalga Chlorella vulgaris addition on the nutritional composition, bioactivity, structure and sensory profile of quark and cream cheese, both probiotic fermented products. Texture profile analysis and fundamental rheology measurements (oscillatory and stationary) were performed to evaluate the impact of C. vulgaris on the mechanical properties of the fresh cheese. The nutritional composition was evaluated using standard methods and bioactivity through the determination of total phenolic compounds and antioxidant capacity.1. Results and conclusions: C. vulgaris had an impact on the firmness of both cheeses. In general, the cheese with added C. vulgaris had a better nutritional profile, with an increase in protein content, content of Mg, P, S, Cu, Zn, Fe and Mn, and better bioactivity with an increase in the antioxidant activity. Sensory testing results were promising, especially for cream cheese. Novelty and scientific contribution: The enrichment of traditional foods such as fresh cheese with microalgae represents an interesting strategy to develop hybrid products (with protein from animal and vegetable sources), obtain innovative and more sustainable products, and improve their nutritional profile in terms of protein and mineral content and bioactivity.

Ising Ladder with Four-Spin Plaquette Interaction in a Transverse Magnetic Field.

The spin-1/2 quantum transverse Ising model, defined on a ladder structure, with nearest-neighbor and four-spin interaction on a plaquette, was studied by using exact diagonalization on finite ladders together with finite-size-scaling procedures. The quantum phase transition between the ferromagnetic and paramagnetic phases has then been obtained by extrapolating the data to the thermodynamic limit. The critical transverse field decreases as the antiferromagnetic four-spin interaction increases and reaches a multicritical point. However, the exact diagonalization approach was not able to capture the essence of the dimer phase beyond the multicritical transition.