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Objective: This study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models., Methods: We used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model., Results: Our boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490 / m m 3 yielded a sensitivity of 0.71 and specificity of 0.72., Conclusion: Our study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE., Significance: Although preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE., (© 2024. The Author(s).)

The development of an effective and broadly protective influenza vaccine against circulating and emerging strains remains elusive. In this study, we evaluated a potentially universal influenza vaccine based on single-component self-assembling protein nanoparticles (1c-SApNPs) presenting the conserved matrix protein 2 ectodomain (M2e) from influenza A and B viruses (IAV and IBV, respectively). We previously designed a tandem antigen comprising three IAV M2e domains of human, avian/swine, and human/swine origins (termed M2ex3). The M2ex3-presenting 1c-SApNPs conferred complete protection in mice against sequential lethal challenges with H1N1 and H3N2. To broaden this protection to cover IBVs, we designed a series of antigens incorporating different arrangements of three IAV M2e domains and three copies of IBV M2e. Tandem repeats of IAV and IBV (termed influenza A-B) M2e arrayed on the I3-01v9a 60-mer 1c-SApNP, when formulated with an oil-in-water emulsion adjuvant, generated greater M2e-specific immunogenicity and protective efficacy than the soluble influenza A-B M2e trimer, indicated by higher survival rates and reduced weight loss post-challenge. Importantly, one of the influenza A-B M2e SApNP constructs elicited 100% protection against a lethal influenza A/Puerto Rico/8/1934 (H1N1) challenge in mice and 70% protection against a lethal influenza B/Florida/4/2006 (Yamagata lineage) challenge, the latter of which has not been reported in the literature to date. Our study thus provides a promising M2e-based single-component universal vaccine candidate against the two major types of influenza virus circulating in humans.

Objective: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by metabolic, reproductive, and psychological manifestations. Growth and differentiation factor 15 (GDF-15) is a cytokine associated with metabolic and inflammatory disorders. Metformin is commonly used for the treatment of PCOS. We investigated the relationship between GDF-15 levels and PCOS, the effect of metformin on GDF-15 levels, and potential biologic pathways related to GDF-15., Subjects and Methods: The study included 35 women with PCOS and 32 women without PCOS (controls). Both groups were compared in terms of GDF-15 levels. Additional analysis was conducted on samples from 22 women with PCOS who were treated with either metformin (n = 7) or placebo (n = 15), retrieved from a previous randomized, controlled trial. Levels of GDF-15 were measured using MILLIPLEX. The biologic pathways related to GDF-15 were evaluated using the databases STRING, SIGNOR, and Pathway Commons. The statistical analysis was conducted using the software SPSS., Results: Levels of GDF-15 were higher in the PCOS group compared with the non-PCOS group (p = 0.039). Among women with PCOS, GDF-15 levels were higher in those treated with metformin compared with placebo (p = 0.007). The proteins related to GDF-15 overlapped between the databases, and a significant interaction was found between GDF-15 and proteins related to PCOS and its complications, including those related to estrogen response, oxidative stress, ovarian infertility, interleukin (IL)-18, IL-4, the ratio of advanced glycation end products to their receptor (AGE/RAGE), leptin, transforming growth factor beta (TGF-β), adipogenesis, and insulin., Conclusion: The findings of the present study suggest a relationship between GDF-15 and PCOS and a potential increase in GDF-15 levels with metformin treatment. An additional finding was that GDF-15 could be involved in biologic pathways related to PCOS complications., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Preeclampsia (PE) is the major cause of maternal-fetal mortality and morbidity. Its pathophysiology is not elucidated, but there is evidence for the role of visfatin/nicotinamide phosphoribosyl transferase (NAMPT), mainly due to its relation to endothelial dysfunction, a hallmark of PE. However, there is heterogeneous data regarding visfatin/NAMPT in healthy pregnancy (HP) and PE. Therefore, we performed a search on MEDLINE/PubMed using the terms "visfatin and preeclampsia" and "NAMPT and preeclampsia, and we selected 23 original articles: 12 articles reported increased levels in PE compared to HP, only four articles showed lower levels and eight articles did not find differences regarding visfatin/NAMPT in the groups studied. It is widely acknowledged that levels detected in plasma, serum, or placenta can be influenced by the size of the population and sample analyzed, as well as genetic factors. We further discussed the correlations of visfatin/NAMPT with clinical biomarkers in PE and inflammatory pathways. Considering the common inflammatory mechanisms between PE and visfatin/NAMPT, few studies have recently performed serum or plasma dosages. In conclusion, further studies are needed to highlight the potential role of visfatin/NAMPT in the pathophysiology of PE. This will provide comparative evidence to establish it as a biomarker for disease outcomes and treatment., Competing Interests: Declaration of Competing Interest The authors declare that no financial or non-financial interests are directly or indirectly related to the work submitted for peer review., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD., (© 2024 International Society for Neurochemistry.)

Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy., (© 2024. The Author(s).)

Objectives: Mycobacterium leprae is able to infect Schwann cells leading to neural damage. Neurotrophins are involved in nervous system plasticity and impact neural integrity during diseases. Investigate the association between single nucleotide polymorphisms in neurotrophin genes and leprosy phenotypes, especially neural damage., Design: We selected single nucleotide polymorphisms in neurotrophins or their receptors genes associated with neural disorders: rs6265 and rs11030099 of brain-derived neurotrophic factor (BDNF), rs6330 of BDNF, rs6332 in NT3 and rs2072446 of P75NTR. The association of genetic frequencies with leprosy phenotypes was investigated in a case-control study., Results: An association of the BDNF single nucleotide polymorphism rs11030099 with the number of affected nerves was demonstrated. The "AA+AC" genotypes were demonstrated to be protective against nerve impairment. However, this variation does not affect BDNF serum levels. BDNF is an important factor for myelination of Schwann cells and polymorphisms in this gene can be associated with leprosy outcome. Moreover, rs11030099 is located in the binding region for micro-RNA (miRNA) 26a that could be involved in control of BDNF expression. We demonstrated different expression levels of this miRNA in polar forms of leprosy., Conclusion: Our findings demonstrate for the first time an association between the polymorphism rs11030099 in the BDNF gene and neural commitment in leprosy and may indicate a possible role of miRNA-26a acting synergistically to these genetic variants in neural damage development., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of β-amyloid (Aβ) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy., Objective: This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO)., Methods: This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%., Results: The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group., Conclusion: GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Alzheimer's Disease (AD) is a multifactorial, progressive, and chronic neurodegenerative disorder associated with the aging process. Memory deficits, cognitive impairment, and motor dysfunction are characteristics of AD. It is estimated that, by 2050, 131.5 million people will have AD. There is evidence that the gastrointestinal microbiome and diet may contribute to the development of AD or act preventively. Communication between the brain and the intestine occurs through immune cells in the mucosa and endocrine cells, or via the vagus nerve. Aging promotes intestinal dysbiosis, characterized by an increase in pro-inflammatory pathogenic bacteria and a reduction in anti-inflammatory response-mediating bacteria, thus contributing to neuroinflammation and neuronal damage, ultimately leading to cognitive decline. Therefore, the microbiota-gut-brain axis has a significant impact on neurodegenerative disorders. Lipids may play a preventive or contributory role in the development of AD. High consumption of saturated and trans fats can increase cortisol release and lead to other chronic diseases associated with AD. Conversely, low levels of omega-3 polyunsaturated fatty acids may be linked to neurodegenerative diseases. Unlike other studies, this review aims to describe, in an integrative way, the interaction between the gastrointestinal microbiome, lipids, and AD, providing valuable insights into how the relationship between these factors affects disease progression, contributing to prevention and treatment strategies.

Introduction: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization., Methods: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries., Results: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome)., Discussion: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design., (© 2023 the Alzheimer's Association.)

COVID-19 continues to cause an increase in the number of cases and deaths worldwide. Due to the ever-mutating nature of the virus, frequent vaccination against COVID-19 is anticipated. Most of the approved SARS-CoV-2 vaccines are administered using the conventional intramuscular route, causing vaccine hesitancy. Thus, there is a need for an effective, non-invasive vaccination strategy against COVID-19. This study evaluated the synergistic effects of a subunit microparticulate vaccine delivered using microneedles. The microparticles encapsulated a highly immunogenic subunit protein of the SARS-CoV-2 virus, such as the spike protein's receptor binding domain (RBD). Adjuvants were also incorporated to enhance the spike RBD-specific immune response. Our vaccination study reveals that a microneedle-based vaccine delivering these microparticles induced spike RBD-specific IgM, IgG, IgG1, IgG2a, and IgA antibodies. The vaccine also generated high levels of CD4+ and CD8a+ molecules in the secondary lymphoid organs. Overall, dissolving microneedles delivery spike RBD antigen in microparticulate form induced a robust immune response, paving the way for an alternative self-administrable, non-invasive vaccination strategy against COVID-19.

Background: Polymorphisms in the CYP2C9 , VKORC1 , MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1 , *2 and *3 for CYP2C9 , -1639G>A for VKORC1 , 3435C>T for MDR1 , and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Breast cancer is the most common cancer and the most frequent cause of death in women. Doxorubicin, an anthracycline, is an important drug due to its efficacy in treating solid cancers, especially breast cancer. However, this drug is often responsible for cardiotoxicity that may affect more than 25% of patients. This study aimed to evaluate the red cell distribution width (RDW) in women with breast cancer to monitor adverse events associated with the use of doxorubicin. A prospective study of 80 women with breast malignancy undergoing neoadjuvant doxorubicin-based chemotherapy was conducted. The patients were evaluated at baseline (T0), just after the last cycle of chemotherapy with doxorubicin (T1), and 1 year after the treatment (T2). There was a significant increase over the time points for the RDW ( p < 0.001). There was a negative correlation between the RDW and C-reactive protein (CRP) levels at T1. The RDW did not show a significant difference between the groups classified according to cardiotoxicity. Based on these results, the RDW is a cost-effective test that shows a relationship with the doxorubicin response, but not with cardiotoxicity. It is a potential biomarker to evaluate patients with breast cancer after they receive chemotherapy with doxorubicin.

Background: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study., Method: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features., Results: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92)., Conclusions: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.

Purpose: To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS)., Methods: A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies., Results: Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment., Conclusion: We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Polycystic ovary syndrome (PCOS) is a condition that affects approximately 13% of reproductive age women and is characterized by androgen excess, menstrual irregularity and altered ovarian morphology. PCOS presents a complex etiology and pathophysiology, which still requires a detailed investigation of biochemical signatures to identify the molecules and mechanisms that govern it., Areas Covered: This narrative review summarizes the main molecular alterations found in the ovarian follicular fluid, endometrium and placenta of women with PCOS, and the genotypes potentially associated with the outcome of infertility treatments in PCOS., Expert Opinion: PCOS is associated with multiple alterations in growth factors, sex steroid hormones, reactive oxygen species, proinflammatory cytokines and adipokines, which contribute to follicle arrest/ anovulation or suboptimal corpus luteum function, and ultimately to menstrual irregularity and hyperandrogenic symptoms. A panel of PCOS biomarkers should include, besides ovarian products, markers of adipose tissue function, insulin resistance, vascular health, and low-grade chronic inflammation. The effects of ovarian stimulation drugs on infertile women with PCOS are likely to be modified by genetic factors, but the available evidence is heterogeneous; therefore, future studies should evaluate standard treatments and pre-specified outcomes of interest to provide more conclusive answers.

Venous thromboembolism (VTE) is an important cause of morbidity/mortality in cancer patients, and COMPASS-CAT score must be used to VTE-risk prediction. There is a relationship between cytokines and thrombus formation and/or resolution. This study aimed to investigate the VTE risk and cytokines level in breast cancer patients prior to chemotherapy with doxorubicin (DOXO). Eighty women with breast cancer and indication for DOXO treatment were selected. TNF, IL-1β, IL-6, and IL-10 were measured after the diagnosis and immediately before DOXO treatment. All 80 patients presented a high risk for VTE when evaluated by COMPASS-CAT model (score ≥7). A positive correlation was observed between IL-10 plasma levels and VTE risk score. Our data showed that higher IL-10 levels before chemotherapy are associated to increased risk of VTE in breast cancer patients. This finding suggests that IL-10 levels and the combination with COMPASS-CAT score could be good markers to predict increased risk of VTE in these patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We report SARS-CoV-2 genomic surveillance results between Belo Horizonte, Brazil's third and fourth case waves. Samples were obtained through a routine university monitoring COVID-19 program from the 9th to the 22nd epidemiological weeks (March and June 2022). We identified ten samples from the BA.1 clade (BA.1, BA.1.1, and BA.1.14.1 lineages) and 45 samples from the BA.2 clade (BA.2, BA.2.56, BA.2.9, BA.2.62, BA.2.23, BA.2.81, and BA.2.10). We observed progressive replacement of the BA.1 by the BA.2 clade. Furthermore, two XAG recombinants were found in the 22nd week. Diversification of the omicron variant seems to have contributed to the resurgence of cases in Belo Horizonte, similarly to what has been reported in South Africa., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Long noncoding RNAs (lncRNAs) undergo splicing and have multiple transcribed isoforms. Nevertheless, for lncRNAs, as well as for mRNA, measurements of expression are routinely performed only at the gene level. Metformin is the first-line oral therapy for type 2 diabetes mellitus and other metabolic diseases. However, its mechanism of action remains not thoroughly explained. Transcriptomic analyses using metformin in different cell types reveal that only protein-coding genes are considered. We aimed to characterize lncRNA isoforms that were differentially affected by metformin treatment on multiple human cell types (three cancer, two non-cancer) and to provide insights into the lncRNA regulation by this drug. We selected six series to perform a differential expression (DE) isoform analysis. We also inferred the biological roles for lncRNA DE isoforms using in silico tools. We found the same isoform of an lncRNA (AC016831.6-205) highly expressed in all six metformin series, which has a second exon putatively coding for a peptide with relevance to the drug action. Moreover, the other two lncRNA isoforms (ZBED5-AS1-207 and AC125807.2-201) may also behave as cis-regulatory elements to the expression of transcripts in their vicinity. Our results strongly reinforce the importance of considering DE isoforms of lncRNA for understanding metformin mechanisms at the molecular level.

Background: About 5-10% of breast cancer cases are related to genetic and hereditary factors. The application of Next Generation Sequencing (NGS) in oncology has allowed the identification of genetic variants present in several genes related to the increased risk of breast cancer. This study aimed to determine the frequency of germline genetic variants in patients with a family and/or personal history of breast cancer., Methods: An analysis of positive reports from NGS panels was carried out in female individuals with a personal and/or family history of breast cancer, present in the database of a private laboratory in Brazil., Results: From about 2000 reports, 183 individuals presented 219 different germline genetic variants. The genes with the highest number of variants were BRCA2 (16.0%), ATM (15.0%) and BRCA1 (12.8%). Among the variants found, 78 were either pathogenic or probably pathogenic, accounting for 35% of all variants discovered. The gene with the highest proportion of pathogenic/probably pathogenic variants was TP53 (80%) and the most frequent pathogenic variant was also reported in this gene (c.1010G > A p.(Arg337His)). Furthermore, the study obtained a high proportion of variants of uncertain significance (VUS) (65%) and approximately 32% of the variants found were in genes of moderate penetrance., Conclusions: Our results could improve the risk estimation and clinical follow-up of Brazilian patients with a history of breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people. RT-PCR remains the gold standard for diagnosing COVID-19. However, new methods, such as other molecular techniques and immunoassays emerged. Also, the need for accessible tests with quick results boosted the development of point of care tests (POCT) that are fast, and automated, with high precision and accuracy. This assay reduces the dependence on laboratory conditions and mass testing of the population, dispersing the pressure regarding screening and detection. This review summarizes the advances in the diagnostic field since the pandemic started, emphasizing various laboratory techniques for detecting COVID-19. We reviewed the main existing diagnostic methods, as well as POCT under development, starting with RT-PCR detection, but also exploring other nucleic acid techniques, such as digital PCR, loop-mediated isothermal amplification-based assay (RT-LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS), and immunoassay tests, and nanoparticle-based biosensors, developed as portable instruments for the rapid standard diagnosis of COVID-19., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study, we demonstrate how encapsulating a conserved influenza ectodomain matrix-2 protein virus-like particle (M2e5x VLP) into a pre-crosslinked bovine serum albumin (BSA) polymeric matrix enhances in vitro antigen immunogenicity and in vivo efficacy. The spray-dried M2e5x VLP-loaded BSA microparticles (MPs) showed enhanced stimulation of antigen presenting cells (APCs), as confirmed through nitrite production and increased antigen-cell interactions seen in real time using live-cell imaging. Next, to further boost the immunogenicity of M2e5x VLP microparticles, M2e5x MPs were combined with Alhydrogel ® and monophosphoryl lipid-A (MPL-A ® ) adjuvant microparticles. M2e5x VLP MPs and the combination VLP M2e5x VLP + Alhydrogel ® + MPL-A ® MPs elicited a significant increase in the expression of antigen-presenting molecules in dendritic cells compared to M2e5x VLP alone. Lastly, for preliminary evaluation of in vivo efficacy, the vaccine was administered in mice through the skin using an ablative laser. The M2e5x VLP + Alhydrogel ® + MPL-A ® MPs were shown to induce high levels of M2e-specific IgG antibodies. Further, a challenge with live influenza revealed heightened T-cell stimulation in immune organs of mice immunized with M2e5x VLP + Alhydrogel ® + MPL-A ® MPs. Hence, we utilized the advantages of both VLP and polymeric delivery platforms to enhance antigen immunogenicity and adaptive immunity in vivo.

Aims: Chronic lymphocytic leukemia (CLL) involves the proliferation and increase of B-lymphocytes in the peripheral blood, bone marrow and lymphoid organs. This study evaluated the microRNAs miR-197, miR-26a and miR-27a as potential biomarkers for CLL. Patients & Methods: Eighty-two patients with CLL and 62 control subjects (CT) were investigated for these targets, using quantitative PCR (qPCR). Results: A significant reduction of all microRNAs was observed in CLL compared to the controls (p < 0.001). Significant negative correlations were observed for the clinical staging groups. After adjusting for multiple logistic regression analysis, miR-197 and miR-26a remained as possible independent risk factors related to the CLL. Conclusions: Our data indicated good performance of this microRNAs as potential biomarkers in CLL.

Background: Atrial fibrillation (AF) is an arrhythmia that involves structural and electrophysiological abnormalities. Many of the AF-related clinical conditions are associated with an increase in inflammatory and oxidative factors. Haptoglobin (Hp) is an acute phase protein whose biological role is to promote clearance of free hemoglobin (Hb). In addition, for being considered an inflammatory marker, Hp represents a protective mechanism against the oxidative effects of Hb. The Hp1-Hp2 polymorphism at Hp locus can lead to three phenotypes related to structural and functional differences in the protein. The objective of this study were to evaluate Hp levels and Hp1-Hp2 polymorphism at Hp locus in patients with AF compared to a control group., Methods and Results: This study included 65 patients with AF and 54 individuals without the arrhythmia. Biochemical parameters were determined using Vitros system, plasma levels of Hp were measured in serum samples by using ELISA method and polymorphisms were verified by PCR technique. Plasma Hp levels, as well as allelic and genotypic frequency, were not associated with AF. The levels of Hp also did not differ among the genotypes according to the applied models., Conclusions: The results suggest that Hp levels and Hp1-Hp2 polymorphism are not associated to AF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Infertility has become a global health problem, increasing the number of couples looking for in vitro fertilization (IVF). Despite advances and technical improvements, some couples remain childless due to the high complexity of the technique. The use of machine learning (ML) in the prediction of pregnancy, computing factors that could interfere in the effectiveness of the treatment, is an important tool to optimize these factors and reach the success of pregnancy. The aim of this study was to apply ML models to determine variables related to pregnancy after IVF in a public health service, including pre-implantation variables. This study included 771 women who underwent IVF treatment at Hospital das Clínicas, Federal University of Minas Gerais, between 2013 and 2019. We used the following Machine Learning algorithms: Logistic Regression, Random Forest, XG Boost and Support Vector Machines. The Random Forest algorithm achieved the best performance, with better accuracy, sensitivity and area under the ROC curve to predict the success of IVF evaluated by pregnancy frequency. We also trained a specific model only for women older than 35 years old. Variables in the Random Forest model related to pregnancy after in vitro fertilization., (© 2022. International Federation for Medical and Biological Engineering.)

M2e VLP was previously described as a vaccine that incorporates the extracellular region of the matrix 2 protein (M2e), which is highly conserved amongst all the strains of influenza. In this study, we analyzed activation status of dendritic cells (DCs) after exposure to M2e VLP, stimulating DCs with M2e VLP and co-culturing the stimulated DCs with T cells to observe innate and adaptive immune responses. The M2e VLP microparticle was prepared by encapsulating into a polymer matrix using the one-step spray drying method. Adjuvants Alhydrogel®, MPL-A® or Addavax TM were used to enhance the DC stimulatory effects by the M2e VLP microparticle. The M2e VLP microparticle yield was found to be 92% and the encapsulation yield was around 84% with a size of approximately 2.78 μm. There was no short-term cytotoxicity found in DCs and macrophages with concentrations up to 1500 μg/mL of M2e VLP microparticle, however long-term exposure resulted in 25% decrease in viability of cells with concentrations more than or equal to 500 μg/mL. The M2e VLP microparticle vaccine with Alhydrogel® and MPL-A® induced high levels of TNFα in both DCs and macrophages. The high levels of MHC I, II, CD28, B7-1, ICAM-1, LFA-1 expression and IL-12 release in the M2e VLP microparticle group with Alhydrogel® suggests that the M2e VLP vaccine with this adjuvant activated T cells via the Th2 pathway. The increased expression of MHC I, II, CD40, CD154, ICAM-1 and LFA-1 on DCs and the release of IL-12 in the M2e VLP microparticle culture of DCs with MPL-A® demonstrated that the M2e VLP vaccine with this adjuvant activated T cells via the Th1 pathway. The decrease in fluorescence in the Alhydrogel® and MPL-A® group illustrates the proliferation of T cells took place following exposure of DCs to the M2e VLP microparticle with these adjuvants. The M2e VLP microparticle exhibited higher stimulatory responses of DCs than the M2e VLP in suspension. Furthermore, the presence of Alhydrogel® and MPL-A® enhanced the stimulatory effects of DCs by the M2e VLP microparticle (MP) vaccine., (Copyright © 2022. Published by Elsevier B.V.)

Background: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data., Methods: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2)., Results: Higher IL-10 levels were observed in the case group compared to controls at T1 ( p = .006) and T2 ( p = .046). The IL-1β, IL-6 and TNF levels did not change during treatment in each group ( p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 ( p  < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed ( p = .048 and p = .004, respectively)., Conclusion: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Purpose: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms., Methods: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS., Results: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster., Conclusion: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS., (© 2021. Italian Society of Endocrinology (SIE).)

The induction of broadly neutralizing antibodies (bNAbs) that target the hemagglutinin stalk domain is a promising strategy for the development of "universal" influenza virus vaccines. bNAbs can be boosted in adults by sequential exposure to heterosubtypic viruses through natural infection or vaccination. However, little is known about if or how bNAbs are induced by vaccination in more immunologically naive children. Here, we describe the impact of repeated seasonal influenza vaccination and vaccine type on induction of bNAbs against group 1 influenza viruses in a pediatric cohort enrolled in randomized controlled trials of seasonal influenza vaccination. Repeated seasonal vaccination results in significant boosting of a durable bNAb response. Boosting of serological bNAb titers is comparable within inactivated and live attenuated (LAIV) vaccinees and declines with age. These data provide insights into vaccine-elicited bNAb induction in children, which have important implications for the design of universal influenza vaccine modalities in this critical population., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Hydroxyurea has long been used for the treatment of sickle cell anemia (SCA), and its clinical effectiveness is related to the induction of fetal hemoglobin (HbF), a major modifier of SCA phenotypes. However, there is substantial variability in response to hydroxyurea among patients with SCA. While some patients show an increase in HbF levels and an ameliorated clinical condition under low doses of hydroxyurea, other patients present a poor effect or even develop toxicity. However, the effects of genetic polymorphisms on increasing HbF levels in response to hydroxyurea in patients with SCA (Hb SS) have been less explored. Therefore, we performed a systematic review to assess whether single-nucleotide polymorphisms (SNPs) affect HbF levels in patients with SCA treated with hydroxyurea. Moreover, we performed pathway analysis using the set of genes with SNPs found to be associated with changes in HbF levels in response to hydroxyurea among the included studies. The systematic literature search was conducted on Medline/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science. Seven cohort studies were included following our inclusion and exclusion criteria. From the 728 genetic polymorphisms examined in the included studies, 50 different SNPs of 17 genes were found to be associated with HbF changes in patients with SCA treated with hydroxyurea, which are known to affect baseline HbF but are not restricted to them. Enrichment analysis of this gene set revealed reactome pathways with the lowest adjusted p -values and highest combined scores related to VEGF ligand-receptor interactions (R-HSA-194313; R-HSA-195399) and the urea cycle (R-HSA-70635). Pharmacogenetic studies of response to hydroxyurea therapy in patients with SCA are still scarce and markedly heterogeneous regarding candidate genes and SNPs examined for association with HbF changes and outcomes, suggesting that further studies are needed. The reviewed findings highlighted that similar to baseline HbF, changes in HbF levels upon hydroxyurea therapy are likely to be regulated by multiple loci. There is evidence that SNPs in intron 2 of BCL11A affect HbF changes in response to hydroxyurea therapy, a potential application that might improve the clinical management of SCA. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=208790)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sales, Nogueira, Tosatti, Gomes and Luizon.)

Background: A cheap and minimum-invasive method for early identification of Alzheimer's disease (AD) pathogenesis is key to disease management and the success of emerging treatments targeting the prodromal phases of the disease., Objective: To develop a machine learning-based blood panel to predict the progression from mild cognitive impairment (MCI) to dementia due to AD within a four-year time-to-conversion horizon., Methods: We created over one billion models to predict the probability of conversion from MCI to dementia due to AD and chose the best-performing one. We used Alzheimer's Disease Neuroimaging Initiative (ADNI) data of 379 MCI individuals in the baseline visit, from which 176 converted to AD dementia., Results: We developed a machine learning-based panel composed of 12 plasma proteins (ApoB, Calcitonin, C-peptide, CRP, IGFBP-2, Interleukin-3, Interleukin-8, PARC, Serotransferrin, THP, TLSP 1-309, and TN-C), and which yielded an AUC of 0.91, accuracy of 0.91, sensitivity of 0.84, and specificity of 0.98 for predicting the risk of MCI patients converting to dementia due to AD in a horizon of up to four years., Conclusion: The proposed machine learning model was able to accurately predict the risk of MCI patients converting to dementia due to AD in a horizon of up to four years, suggesting that this model could be used as a minimum-invasive tool for clinical decision support. Further studies are needed to better clarify the possible pathophysiological links with the reported proteins.

Irisin is a recently discovered adipomyokine involved in the regulation of glucose and lipid, which also exhibits anti-inflammatory and neuroprotective properties. Here we aimed to compare irisin peripheral levels between individuals with behavioral variant frontotemporal dementia (bvFTD) and cognitively healthy matched controls, in addition to investigating whether there is a correlation between irisin and pro-inflammatory cytokines (IL-6 and TNF) concentrations. Twenty-nine individuals participated in this study, being 18 patients with probable bvFTD and 11 controls. Irisin, IL-6 and TNF levels were measured in EDTA plasma through ELISA. There was no difference of the levels of irisin between the groups (p = 0.964). However, in the bvFTD, but not in control group, the levels of irisin were positively correlated with the concentration of IL-6 (r = 0.637, p = 0.006) and TNF (r = 0.517, p = 0.034). The results suggest that the production of irisin in bvFTD could be related to chronic inflammatory and neurodegenerative states in these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Transdermal vaccination route using biodegradable microneedles is a rapidly progressing field of research and applications. The fear of painful needles is one of the primary reasons most people avoid getting vaccinated. Therefore, developing an alternative pain-free method of vaccination using microneedles has been a significant research area. Microneedles comprise arrays of micron-sized needles that offer a pain-free method of delivering actives across the skin. Apart from being pain-free, microneedles provide various advantages over conventional vaccination routes such as intramuscular and subcutaneous. Microneedle vaccines induce a robust immune response as the needles ranging from 50 to 900 μm in length can efficiently deliver the vaccine to the epidermis and the dermis region, which contains many Langerhans and dendritic cells. The microneedle array looks like band-aid patches and offers the advantages of avoiding cold-chain storage and self-administration flexibility. The slow release of vaccine antigens is an important advantage of using microneedles. The vaccine antigens in the microneedles can be in solution or suspension form, encapsulated in nano or microparticles, and nucleic acid-based. The use of microneedles to deliver particle-based vaccines is gaining importance because of the combined advantages of particulate vaccine and pain-free immunization. The future of microneedle-based vaccines looks promising however, addressing some limitations such as dosing inadequacy, stability and sterility will lead to successful use of microneedles for vaccine delivery. This review illustrates the recent research in the field of microneedle-based vaccination.

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease. The prevalence of FH has previously been reported as 1 in 500 in the general population. This study aimed to evaluate the proprotein convertase subtilisin/kexin 9 (PCSK9) levels, lipid profile and thrombin generation in FH patients undergoing treatment or not., Methods: Eighty individuals with FH were selected and distributed in 2 groups: individuals treated with statins alone or conjugate therapy (statin + ezetimibe) (T = 53) and those non treated (NT = 27). PCSK9 levels were determined by ELISA, the lipid profile by colorimetric enzyme method and thrombin generation assay (TGA) by CAT method., Results: Individuals treated with conjugate therapy (statin + ezetimibe) showed a significant reduction in the levels of total cholesterol (TC) low density lipoprotein cholesterol (LDLc) and in the potential for thrombin generation (ETP with low and high concentration of tissue factor), compared to the treated individuals with monotherapy (statins). PCSK9 was positively correlated with increased levels of TC, LDLc and triglycerides, while TGA parameters were positively correlated with PCSK9 and lipid profile., Conclusion: PCSK9 levels appear to be associated with components of the lipid and hemostatic profiles, in addition to being influenced by age. In general, our findings suggest that combined therapy for the treatment of FH is associated with a significant improvement in both lipid and hemostatic profiles assessed by TGA, suggesting a reduction in atherogenic and thrombogenic risks and, therefore, more promising compared to the use of statin monotherapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD -0·29 (95 % CI -0·56, -0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.

Cardiovascular adverse events in patients with breast cancer undergoing chemotherapy (CT) are frequent due to the high cardiotoxic potential of treatments, especially doxorubicin (DOXO). This study aimed to evaluate the association of plasma levels of various biomarkers with cardiotoxicity in women with breast cancer on DOXO-based chemotherapy. In this single center prospective cohort, 80 breast cancer patients who used DOXO as a first-line treatment for cancer were evaluated. Patients were assessed at three time points: before CT (T0), 1 week after (T1) and 12 months after DOXO treatment (T2). The predominant histological classification was ductal carcinoma, n = 72 (90.0%); the most frequent molecular classification was Human epidermal growth factor receptor-type 2 positive (HER2+), n = 34 (43.0%). In patients submitted to complementary treatment with trastuzumab (n = 23), there was no association with cardio-specific biomarkers. Evaluating the clinical variables and the laboratory parameters in T1 and T2 in relation to T0, the reduction any time of N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), triglycerides and hematocrit levels showed an association with higher cardiotoxicity risk. In addition, increased levels of troponin I (cTnI) and glycated hemoglobin (HbA 1 c) showed an independent association with the occurrence of cardiotoxicity. These results suggest that the evaluation of these laboratory tests should be included routinely to identify breast cancer patients under DOXO treatment at cardiotoxicity risk.

Diabetes mellitus (DM) is a metabolic disorder characterised by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism. Several studies demonstrated that foods typical of the Mediterranean diet (MedDiet), including vegetables, fruits, oilseeds, extra virgin olive oil and fish, can promote health benefits for individuals at risk of or with type 2 diabetes (T2DM). In this review, we summarised randomised clinical trials, cohort studies, meta-analyses and systematic reviews that evaluated the effects of the MedDiet on metabolic control of T2DM. The data suggest that the MedDiet influences cardiovascular risk factors, including blood pressure, lipid profile, insulin resistance, inflammation and glucose metabolism, in T2DM patients. In conclusion, the MedDiet appears to protect patients from macro- and microangiopathy and should be considering in the management of diabetic patients.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais - Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.

Background: Cardiotoxicity is a common and serious adverse effect of anthracycline therapy in breast cancer patients. The current criteria for cardiotoxicity are based on imaging and cardiac biomarkers. However, there is a need for new biomarkers to help with early diagnosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression. Several miRNAs have been associated with cardiovascular diseases and are biomarkers under investigation for cancer treatment-related cardiotoxicity., Methods: We performed a systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science and Embase, until April 2020. Cohort studies that reported miRNA biomarkers in breast cancer patients with anthracycline-induced cardiotoxicity and non-cardiotoxicity patients were included. Moreover, we searched the miRTarBase for experimentally validated miRNA-target interactions., Results: Among the 209 studies retrieved, five fulfilled the inclusion criteria. Let-7f, miR-1, miR-20a, miR-126 and miR-210 were validated in two population-based cohorts. The pro-angiogenic miRNAs let-7f, miR-20a, miR-126 and miR-210 were significantly down-regulated in epirubicin-cardiotoxicity when compared to the non-cardiotoxicity group. miR-1 has been shown to provide diagnostic and prognostic information in the setting of myocardial infarction, but changes in its levels are controversial in doxorubicin-treated breast cancer patients with cardiotoxicity. Reactome pathways relevant to cardiotoxicity were found from the target genes for let-7f, miR-1, miR-20a, miR-126 and miR-210 at miRTarBase., Conclusion: The data suggest that let-7f, miR-1, miR-20a, miR-126 and miR-210 are associated with anthracycline-based cardiotoxicity during chemotherapy in breast cancer patients., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of gestation) and late- (LOPE, ≥34 weeks of gestation). DNA methylation (DNAm) may help to understand the abnormal placentation in PE. Therefore, we performed a systematic review to assess the role of global DNAm on pathophysiology of PE, focused on fetal and maternal tissues of placenta from pregnant with PE, including EOPE and LOPE. We searched the databases EMBASE, Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Scielo and Google Scholar, and followed the MOOSE guidelines. Moreover, we performed pathway analysis with the overlapping genes from the included studies. Twelve out of 24 included studies in the qualitative analysis considered the classification into EOPE and LOPE. We did not found heterogeneity in the criteria used for diagnosis of PE, and a few studies evaluated whether confounding factors would influence placental DNAm. Fourteen out of 24 included studies showed hypomethylation in placental tissue from pregnant with PE compared to controls. The differences in DNAm are specific to genes or differentially methylated regions, and more evident in EOPE and preterm PE compared to controls, rather than LOPE and term PE. The overlapping genes from included studies revealed pathways relevant to pathophysiology of PE. Our findings highlighted the heterogeneous results of the included studies, mainly focused on North America and China. Replication studies in different populations should use the same placental tissues, techniques to assess DNAm and pipelines for bioinformatic analysis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)