Characterisation of the novel HLA-B*35:593 allele using short and long-read sequencing technologies.

The novel HLA-B*35:593 allele, first described in a potential bone marrow donor from Brazil.

Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

Characterisation of the novel HLA-A*30:218 allele using two different sequencing technologies.

The novel HLA-A*30:218 allele, first described in a potential bone marrow donor from Brazil.

First- and second-generation integrated process for bioethanol production: Fermentation of molasses diluted with hemicellulose hydrolysate by recombinant Saccharomyces cerevisiae.

The integration of first- (1G) and second-generation (2G) ethanol production by adding sugarcane juice or molasses to lignocellulosic hydrolysates offers the possibility to overcome the problem of inhibitors (acetic acid, furfural, hydroxymethylfurfural and phenolic compounds), and add nutrients (such as salts, sugars and nitrogen sources) to the fermentation medium, allowing the production of higher ethanol titers. In this work, an 1G2G production process was developed with hemicellulosic hydrolysate (HH) from a diluted sulfuric acid pretreatment of sugarcane bagasse and sugarcane molasses. The industrial Saccharomyces cerevisiae CAT-1 was genetically modified for xylose consumption and used for co-fermentation of sucrose, fructose, glucose, and xylose. The fed-batch fermentation with high cell density that mimics an industrial fermentation was performed at bench scale fermenter, achieved high volumetric ethanol productivity of 1.59 g L-1 h-1, 0.39 g g-1 of ethanol yield, and 44.5 g L-1 ethanol titer, and shown that the yeast was able to consume all the sugars present in must simultaneously. With the results, it was possible to establish a mass balance for the global process: from pretreatment to the co-fermentation of molasses and HH, and it was possible to establish an effective integrated process (1G2G) with sugarcane molasses and HH co-fermentation employing a recombinant yeast.

Upper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema.

Breast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.

Left ventricular structural abnormalities in the assessment of diastolic function in the elderly: source of discrepancies between the 2009 and 2016 criteria.

Diastolic dysfunction (DD) is routinely evaluated in echocardiography to support diagnosis, prognostication, and management of heart failure, a condition highly prevalent in elderly patients. Clinical guidelines were published in 2009, and updated in 2016, pursuing to standardize and improve DD categorization. We aimed to assess the concordance of DD between these two documents in an elderly population and to investigate how left ventricular structural abnormalities (LVSA) impact the reclassification. To evaluate this we analyzed the 308 consecutive transthoracic echocardiograms in patients older than 60 years (70.4 ± 7.7 years-old, 59% women) that fulfilled the inclusion criteria out of the 1438 echocardiograms performed in a tertiary hospital. We found that the prevalence of DD was lower according to the 2016 criteria (64% vs. 91%; p < 0.001), with 207 (67.2%) patients changing category, indicating poor agreement between the guidelines (kappa = 0.21). There were 188 (61%) patients with LVSA, which drove most of the reclassifications in 2016 Grade I DD cases. The prevalence of elevated filling pressures by Doppler halved in this elderly population using the updated recommendations (20.9% vs. 39.2%; p < 0.001). In conclusion the prevalence of DD was lower applying the 2016 guidelines, with a poor agreement with 2009 guidelines in all DD grades. The role of LVSA in reclassifications was particularly evident in Grade I DD, while Doppler parameters drove reclassifications among the more severe grades. If not properly addressed, these discrepancies may undermine the reliance on DD as a diagnostic and prognostic tool, particularly in an elderly population at a higher risk of heart failure.

Associations Between Coronary Artery Calcification and Left Ventricular Global Longitudinal Strain and Diastolic Parameters: the ELSA-Brasil Study.

Atherosclerosis burden can be evaluated in asymptomatic patients by measuring coronary artery calcification (CAC), whereas the global longitudinal strain (GLS) and diastolic function parameters (mitral E/e' ratio, septal e', and lateral e') are used to evaluate subclinical left ventricular (LV) dysfunction. We investigated whether subjects with CAC (CAC >0 Agatston units) would present with an impairment in LV functional parameters. Among the participants of the ELSA-Brasil cohort free of clinically prevalent cardiovascular disease who performed cardiac computed tomography and echocardiography within the study protocol, we tested whether those with CAC >0 presented with worse GLS and diastolic function parameters. CAC >0 was present in 203 of the 612 included participants (33.17%; age 51.4 ± 8.6 years, 52.1% women). Absolute CAC values did not correlate with GLS (ro = 0.07, p = 0.105) but did so with E/e' (ro = 0.19, p <0.001), septal e' (ro = 0.28, p <0.001), and lateral e' (ro = 0.30, p <0.001), with stronger correlations in men. Those with CAC >0 had worse mitral E/e' ratios (7.75 ± 0.13 vs 7.01 ± 0.09; p ≤0.001), septal e' (8.25 ± 0.15 vs 9.59 ± 0.11 cm/s; p <0.001), and lateral e' (10.13 ± 0.20 vs 11.99 ± 0.14 cm/s; p ≤0.001), respectively. However, these associations were not independent of diabetes, obesity, hypertension, smoking, and low-density lipoprotein cholesterol, persisting only as significant associations of CAC >0 with mitral E/e' ratio and septal e' in men. There is an association between subclinical coronary atherosclerosis and impaired LV functional parameters. These associations are more likely attributed to the presence of common cardiovascular risk factors in the general population. However, in men, it seems to exist as an independent association.

Biochemical and Biotechnological Insights into Fungus-Plant Interactions for Enhanced Sustainable Agricultural and Industrial Processes.

The literature is full of studies reporting environmental and health issues related to using traditional pesticides in food production and storage. Fortunately, alternatives have arisen in the last few decades, showing that organic agriculture is possible and economically feasible. And in this scenario, fungi may be helpful. In the natural environment, when associated with plants, these microorganisms offer plant-growth-promoting molecules, facilitate plant nutrient uptake, and antagonize phytopathogens. It is true that fungi can also be phytopathogenic, but even they can benefit agriculture in some way-since pathogenicity is species-specific, these fungi are shown to be useful against weeds (as bioherbicides). Finally, plant-associated yeasts and molds are natural biofactories, and the metabolites they produce while dwelling in leaves, flowers, roots, or the rhizosphere have the potential to be employed in different industrial activities. By addressing all these subjects, this manuscript comprehensively reviews the biotechnological uses of plant-associated fungi and, in addition, aims to sensitize academics, researchers, and investors to new alternatives for healthier and more environmentally friendly production processes.

Reproducibility of right ventricular function by longitudinal strain and other echocardiographic parameters in the ELSA-Brasil study.

Right ventricular (RV) free wall longitudinal strain (RVFWLS), and four-chamber longitudinal strain (RV4CLS) using speckle tracking echocardiography have demonstrated increased accuracy and discrimination to measure right ventricular function in different clinical conditions. Reproducibility data of these measures are scarce and mainly tested in small or reference populations. The main objective of this study was to investigate their reproducibility, and of other traditional RV parameters, from unselected participants of a large cohort study. RV strain reproducibility was analyzed using echocardiographic images of 50 participants from a randomly selected sample from The ELSA-Brasil Cohort. Images were acquired and analyzed following the study protocols. The mean RVFWLS was - 26.9 ± 2.6% and the mean RV4CLS was - 24.4 ± 1.9%. The intra-observer reproducibility parameters of RVFWLS demonstrated a coefficient of variation (CV) of 5.1% and an intraclass correlation coefficient (ICC [95%CI] 0.78[0.67-0.89]), and for RV4CLS were CV = 5.1% and ICC = 0.78[0.67-0.89]. Reproducibility for RV fractional area change was CV = 12.1%; ICC = 0.66 [0.50-0.81] and for RV basal diameter was CV = 6.3%; ICC = 0.82 [0.73-0.91]. The inter-observer reproducibility for RVFWLS was CV = 8.3%; ICC 0.54[0.34-0.74] and for RV4CLS, CV = 6.3%; ICC = 0.53[0.34-0.73], following the same pattern among conventional RV parameters. We found adequate reproducibility of RV longitudinal strain parameters. This information is relevant for the long-term follow-up of cohort participants and reinforces the utility of RV longitudinal strain as a tool to monitor subclinical changes in RV systolic function.

Effects of Antihypertensive Treatment on Left and Right Ventricular Global Longitudinal Strain and Diastolic Parameters in Patients with Hypertension and Obstructive Sleep Apnea: Randomized Clinical Trial of Chlorthalidone plus Amiloride vs. Amlodipine.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

Monocyte-to-lymphocyte ratio as predictor of cancer therapy-related cardiotoxicity in patients with breast cancer: a pilot cohort study.

BACKGROUND: Elevated pre-treatment baseline inflammation has been associated with cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer. Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index (NLR × platelets) have emerged in clinical context as markers of disease-related inflammation. OBJECTIVES: To evaluate development of CTRCD according to pre-treatment blood inflammatory biomarkers in patients with breast cancer. METHODS: Pilot cohort study including consecutive female patients ≥ 18 years with HER2-positive early breast cancer who consulted at the institution's breast oncology outpatient clinic between march/2019 and march/2022. CTRCD: absolute reduction in LVEF > 10% to below 53% (2D-echocardiogram). Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test, and discrimination ability was evaluated through AUC-ROC. RESULTS: Forty-nine patients (53.3 ± 13.3 y) were included and followed-up for a median of 13.2 months. CTRCD was observed in 6 (12.2%) patients. Patients with high blood inflammatory biomarkers had lower CTRCD-free survival (P < 0.050 for all). MLR showed statistically significant AUC (0.802; P = 0.017). CTRCD was observed in 27.8% of patients with high MLR versus 3.2% with low MLR (P = 0.020); negative predictive value was 96.8% (95%CI 83.3-99.4%). CONCLUSION: In patients with breast cancer, elevated pre-treatment inflammatory markers were associated with increased risk of cardiotoxicity. Among these markers, MLR had good discriminatory performance and high negative predictive value. The incorporation of MLR might improve risk evaluation and selection of patients for follow-up during cancer therapy.

Development of a Nutraceutical Product Derived from By-Products of the Lipid Extraction of the Brazil Nut (Bertolletia excelsa H.B.K).

The objective of this investigation was to develop a nutraceutical product, in bars, using defatted Brazil nut by-products. The methodological bases of analyses followed the guidelines of the Association of Official Analytical Chemists international and experimental tests of formulations. The bars presented with high protein content with high nutraceutical potential expressed as high levels of magnesium, sodium, calcium and potassium, with emphasis on selenium, supplying around 50% of the daily recommendations. The sulfur amino acids reach approximately the recommended chemical score (97%), the aromatic amino acids with a proportion close to 50% and those of the branched chain supplying the established recommendations for adults. In the sensory tests, the formulation that presented the best attributes and the greatest acceptance (91.78% for the flavor and 97.89% for the general impression) by the tasters was the bar formulation made with a 75:25 ratio of defatted Brazil nuts flour and isolated soy protein.

Responses Triggered by the Immune System in Hypertensive Conditions and Repercussions on Target Organ Damage: A Review.

BACKGROUND: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature. OBJECTIVE: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage. METHODS: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement. RESULTS: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal. CONCLUSION: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage.

Prognostic value of right ventricular strain and peak oxygen consumption in heart failure with reduced ejection fraction.

Our purpose is to evaluate the combined predictive value of cardiopulmonary exercise testing (CPET) and echocardiographic evidence of left ventricular (LV) and right ventricular (RV) strain in predicting mortality and heart transplant (HTx) in a series of outpatients with heart failure with reduced ejection fraction (HFrEF). A retrospective cohort study of 66 patients with HFrEF (median age, 57 years; 51% women) who underwent CPET and echocardiography (up to 90 days apart) to assess prognosis. The primary outcome was a composite of death and need for HTx. At a median follow-up of 27 [20-39] months, 19 patients (29%) experienced the primary outcome. In unadjusted analysis, most echocardiographic and CPET parameters were associated with the primary outcome, including percentage of predicted peak oxygen consumption (ppVO2), VE/VCO2 slope, LV ejection fraction, and LV and RV longitudinal strain. After adjusting for other clinical, echocardiographic and CPET variables, RV free wall longitudinal strain and ppVO2 remained significantly associated with the primary outcome. Kaplan-Meier survival curves for death and HTx, based on the best cutoff values, showed lower survival rates in patients with impairment in both ppVO2 and RV FW-LS than in those with one or neither parameter impaired (p < 0.001). RV dysfunction and low cardiorespiratory fitness were independent markers of death and need for HTx. Impairment of both ppVO2 and RV FW-LS had a strong additive impact on prognostic assessment in this cohort of patients with HFrEF.

Description of the HLA-DQB1*03:491 allele, first identified in a Brazilian individual.

The novel HLA-DQB1*03:491 allele, first described in a potential bone marrow donor from Brazil.

Description of the HLA-C*04:01:145 allele, first identified in a Brazilian individual.

The novel HLA-C*04:01:145 allele, first described in a potential bone marrow donor from Brazil.

Description of the HLA-B*41:01:08 allele: First identified in a Brazilian individual.

The novel HLA-B*41:01:08 allele, first described in a potential bone marrow donor from Brazil.

Description of the HLA-DRB1*03:196 allele, first identified in a Brazilian individual.

The novel HLA-DRB1*03:196 allele, first described in a potential bone marrow donor from Brazil.

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by the Microgramma vacciniifolia Frond Lectin (MvFL).

Most anti-inflammatory drugs used nowadays have an excessive cost and their prolonged use has been connected with several injurious effects. Thus, the search for new anti-inflammatory agents is increasing. Lectins are carbohydrate-interacting proteins that can modulate immune response and the release of inflammation mediators. The Microgramma vacciniifolia frond lectin (MvFL) was previously reported to be an immunomodulatory agent in vitro. This work aimed to evaluate the effects of MvFL on the in vivo inflammatory status in the carrageenan-induced peritonitis and paw edema, using female Swiss mice. The animals were pretreated intraperitoneally with MvFL (5 and 10 mg/kg). In the peritonitis assay, the total and differential migration of white blood cells was evaluated, as well as the levels of cytokines, nitric oxide (NO), and total proteins in the peritoneal fluid. In the paw edema evaluation, the paw volume was measured in the early (from 30 min-2 h) and late (3-4 h) phases of edema formation. MvFL (5 and 10 mg/kg) was efficient in reducing neutrophil infiltration, pro-inflammatory cytokines (IL-6, IL-17, and TNF-α), NO, and protein content in the peritoneal fluid. It also repressed the edema formation in the late phase of the assay. In conclusion, MvFL showed inhibitory effects in in vivo acute inflammation, which encouraged future studies exploiting its immunomodulatory ability.

Strategies for Efficient Expression of Heterologous Monosaccharide Transporters in Saccharomyces cerevisiae.

In previous work, we developed a Saccharomyces cerevisiae strain (DLG-K1) lacking the main monosaccharide transporters (hxt-null) and displaying high xylose reductase, xylitol dehydrogenase and xylulokinase activities. This strain proved to be a useful chassis strain to study new glucose/xylose transporters, as SsXUT1 from Scheffersomyces stipitis. Proteins with high amino acid sequence similarity (78-80%) to SsXUT1 were identified from Spathaspora passalidarum and Spathaspora arborariae genomes. The characterization of these putative transporter genes (SpXUT1 and SaXUT1, respectively) was performed in the same chassis strain. Surprisingly, the cloned genes could not restore the ability to grow in several monosaccharides tested (including glucose and xylose), but after being grown in maltose, the uptake of 14C-glucose and 14C-xylose was detected. While SsXUT1 lacks lysine residues with high ubiquitinylation potential in its N-terminal domain and displays only one in its C-terminal domain, both SpXUT1 and SaXUT1 transporters have several such residues in their C-terminal domains. A truncated version of SpXUT1 gene, deprived of the respective 3'-end, was cloned in DLG-K1 and allowed growth and fermentation in glucose or xylose. In another approach, two arrestins known to be involved in the ubiquitinylation and endocytosis of sugar transporters (ROD1 and ROG3) were knocked out, but only the rog3 mutant allowed a significant improvement of growth and fermentation in glucose when either of the XUT permeases were expressed. Therefore, for the efficient heterologous expression of monosaccharide (e.g., glucose/xylose) transporters in S. cerevisiae, we propose either the removal of lysines involved in ubiquitinylation and endocytosis or the use of chassis strains hampered in the specific mechanism of membrane protein turnover.