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Objectives: Paternalistic care behavior in health contexts reduces involvement in the decision-making process and dissatisfaction in healthcare, which may negatively influence older adults' mental health. This study comprised two main objectives: (1) to explore older adults' experiences of paternalistic behavior in the context of health services and (2) analyze the influence of paternalistic behavior on older adults' mental health. Methods: The sample involved 416 participants aged 65 to 81 (M = 70.1 ± 5.73) with three different nationalities (English, Brazilian ad Portuguese). All interviews went through content analysis. Results: For the first objective, content analysis identified seven themes: (1) perceived inattention to the uniqueness of each person (81%); (2) feeling a duality of supporting and suppressing independence (79%); (3) selective disclosure of information to keep the person's spirit up (74%); (4) feeling neglected (66%); (5) feeling unable to make decisions (64%); (6) receiving opposition to the person's requests (60%); and (7) routine actions being considered as the best action (57%). For the second objective, three main themes emerged: (1) feeling anxious and stressed (88%); (2) feeling frustration and despair (87%); and (3) feeling injustice and anger (72%). Conclusions: Healthcare paternalism negatively affects older adults' mental health, emphasizing the need for their agency, involvement in decisions, and personalized care. These findings highlight the negative influence of paternalistic behavior on the mental health of older adults and may contribute to future targeted interventions and policy programs among the older population. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the ataxin-3 (ATXN3) gene. No effective treatment is available for this disorder, other than symptom-directed approaches. Bile acids have shown therapeutic efficacy in neurodegenerative disease models. Here, we pinpointed tauroursodeoxycholic acid (TUDCA) as an efficient therapeutic, improving the motor and neuropathological phenotype of SCA3 nematode and mouse models. Surprisingly, transcriptomic and functional in vivo data showed that TUDCA acts in neuronal tissue through the glucocorticoid receptor (GR), but independently of its canonical receptor, the farnesoid X receptor (FXR). TUDCA was predicted to bind to the GR, in a similar fashion to corticosteroid molecules. GR levels were decreased in disease-affected brain regions, likely due to increased protein degradation as a consequence of ATXN3 dysfunction being restored by TUDCA treatment. Analysis of a SCA3 clinical cohort showed intriguing correlations between the peripheral expression of GR and the predicted age at disease onset in presymptomatic subjects and FKBP5 expression with disease progression, suggesting this pathway as a potential source of biomarkers for future study. We have established a novel in vivo mechanism for the neuroprotective effects of TUDCA in SCA3 and propose this readily available drug for clinical trials in SCA3 patients. [ABSTRACT FROM AUTHOR]

A newly produced silk fibroin (SF) aerogel particulate system using a supercritical carbon dioxide (scCO2)-assisted drying technology is herein proposed for biomedical applications. Different concentrations of silk fibroin (3%, 5%, and 7% (w/v)) were explored to investigate the potential of this technology to produce size- and porosity-controlled particles. Laser diffraction, helium pycnometry, nitrogen adsorption–desorption analysis and Fourier Transform Infrared with Attenuated Total Reflectance (FTIR-ATR) spectroscopy were performed to characterize the physicochemical properties of the material. The enzymatic degradation profile of the SF aerogel particles was evaluated by immersion in protease XIV solution, and the biological properties by cell viability and cell proliferation assays. The obtained aerogel particles were mesoporous with high and concentration dependent specific surface area (203–326 m2/g). They displayed significant antioxidant activity and sustained degradation in the presence of protease XIV enzyme. The in vitro assessment using human dermal fibroblasts (HDF) confirm the particles' biocompatibility, as well as the enhancement in cell viability and proliferation. [ABSTRACT FROM AUTHOR]

Thermoplastic resin transfer molding (T-RTM) technology was applied to synthesize graphene nanoplatelets-based nanocomposites via anionic ring-opening polymerization (AROP). Polyamide 6 (PA6) was obtained by AROP and was used as the polymeric matrix of the developed nanocomposites. The non-isothermal crystallization behavior of PA6 and nanocomposites was analyzed by differential scanning calorimetry (DSC). Nanocomposites with 0.5 wt.% of graphene nanoplatelets (GNPs) with two different diameter sizes were prepared. Results have shown that the crystallization temperature shifted to higher values in the presence of GNPs. This behavior is more noticeable for the nanocomposite prepared with smaller GNPs (PA6/GN). The crystallization kinetic behavior of all samples was assessed by Avrami and Liu's models. It was observed that GNPs increased the crystallization rate, thus revealing a nucleating ability, and also validated the reduction of half-time crystallization values. Such tendency was also supported by the lower activation energy values determined by Friedman's method. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the most frequent neoplasms and is associated with serious oncologic emergencies (OE). We performed a retrospective study to characterize OE in lung cancer patients admitted to the pulmonology department to determine the effects of the SARS-CoV2 pandemic. Materials and Methods: A total number of 82 patients were admitted with an emergency, mostly brain metastasis (n=37; 45.1%), followed by superior vena cava syndrome (n=13; 15.9%), cardiac tamponade (n=7; 8.5%), large pleural effusion (n=7; 8.5%), severe pulmonary embolism (n=6; 7.3%), spinal cord syndrome (n=6; 7.3%), massive hemoptysis (n=3; 3.7%), stridor (n=2; 2.4%) and atelectasis (n=1; 1.2%). Clinical and pathological data were retrieved from clinical charts including demographic information, smoking status, cancer histology, clinical stage at diagnosis, anticancer treatment, time between LC diagnosis until the OE, outcomes of OE treatment, and overall survival after OE. Results: The predominant histology was adenocarcinoma (n=59; 71.9%) and 86.8% of the patients (n=71) were in stage IV. OE was the disease presentation in 45.2% (n=37) and 6-month mortality was 75.6%. Neurologic emergencies were associated with a lower risk of 6-month mortality compared to cardiovascular and respiratory [OR 0.255 (CI 0.72-0.90), p=0.035)]. Younger patients (p=0.011), metastatic disease (p=0.02), no cancer treatment (p<0.001), and small cell carcinoma (SCLC) (p=0.016) had a shorter time between cancer diagnosis and the event. Conclusion: OE occurred mostly in men with metastatic adenocarcinomas. Younger patients, SCLC, metastatic disease, and no cancer treatment were associated with a shorter time between lung cancer diagnosis until the occurrence of an OE and brain metastasis with a better prognosis. There were no differences between patients admitted in 2019 and 2020 that could be related to the access to healthcare services during the SARS-COV2 pandemic. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is the result of various environmental, bacterial and genetic stimuli, which culminate in the disruption of the skin's barrier function. Characterized by highly pruritic skin lesions, xerosis and an array of comorbidities among which skin infections are the most common, this condition results in both a significant loss of quality of life and in the need for life-long treatments (e.g., corticosteroids, monoclonal antibodies and regular antibiotic intake), all of which may have harmful secondary effects. This, in conjunction with AD's rising prevalence, made the development of alternative treatment strategies the focus of both the scientific community and the pharmaceutical industry. Given their potential to both manage the skin microbiome, fight infections and even modulate the local immune response, the use of antimicrobial peptides (AMPs) from more diverse origins has become one of the most promising alternative solutions for AD management, with some being already used with some success towards this end. However, their production and use also exhibit some limitations. The current work seeks to compile the available information and provide a better understanding of the state of the art in the understanding of AMPs' true potential in addressing AD. [ABSTRACT FROM AUTHOR]

Carboxymethyl cellulose use in industry is ubiquitous. Though it is recognized as safe by the EFSA and FDA, newer works have raised concerns related to its safety, as in vivo studies showed evidence of gut dysbiosis associated with CMC's presence. Herein lies the question, is CMC a gut pro-inflammatory compound? As no work addressed this question, we sought to understand whether CMC was pro-inflammatory through the immunomodulation of GI tract epithelial cells. The results showed that while CMC was not cytotoxic up to 25 mg/mL towards Caco-2, HT29-MTX and Hep G2 cells, it had an overall pro-inflammatory behavior. In a Caco-2 monolayer, CMC by itself increased IL-6, IL-8 and TNF-α secretion, with the latter increasing by 1924%, and with these increases being 9.7 times superior to the one obtained for the IL-1β pro-inflammation control. In co-culture models, an increase in secretion in the apical side, particularly for IL-6 (692% increase), was observed, and when RAW 264.7 was added, data showed a more complex scenario as stimulation of pro-inflammatory (IL-6, MCP-1 and TNF-α) and anti-inflammatory (IL-10 and IFN-β) cytokines in the basal side was observed. Considering these results, CMC may exert a pro-inflammatory effect in the intestinal lumen, and despite more studies being required, the incorporation of CMC in foodstuffs must be carefully considered in the future to minimize potential GI tract dysbiosis. [ABSTRACT FROM AUTHOR]

MoS2 nanoflowers (NFs) obtained through a hydrothermal approach were used as the substrate for the deposition of tiny spherical bimetallic AuAg or monometallic Au nanoparticles (NPs), leading to novel photothermal-assisted catalysts with different hybrid nanostructures and showing improved catalytic performance under NIR laser irradiation. The catalytic reduction of pollutant 4-nitrophenol (4-NF) to the valuable product 4-aminophenol (4-AF) was evaluated. The hydrothermal synthesis of MoS2 NFs provides a material with a broad absorption in the Vis-NIR region of the electromagnetic spectrum. The in situ grafting of alloyed AuAg and Au NPs of very small size (2.0–2.5 nm) was possible through the decomposition of organometallic complexes [Au2Ag2(C6F5)4(OEt2)2]n and [Au(C6F5)(tht)] (tht = tetrahydrothiophene) using triisopropilsilane as reducing agent, leading to nanohybrids 1–4. The new nanohybrid materials display photothermal properties arising from NIR light absorption of the MoS2 NFs component. The AuAg-MoS2 nanohybrid 2 showed excellent photothermal-assisted catalytic activity for the reduction of 4-NF, which is better than that of the monometallic Au-MoS2 nanohybrid 4. The obtained nanohybrids were characterised by transmission electron microscopy (TEM), High Angle Annular Dark Field—Scanning Transmission Electron Microscopy—Energy Dispersive X-ray Spectroscopy (HAADF-STEM-EDS), X-ray photoelectron spectroscopy and UV-Vis-NIR spectroscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer represents a highly prevalent form of cancer worldwide, with timely detection and treatment being crucial for achieving a high survival rate. Manual segmentation, which is the process of manually identifying different anatomical structures or tissues within an image, is the most prevalent detection method. However, it is a time-consuming and subjective task constrained by the radiologists' expertise, which underpins the demand for automated segmentation methods. In this study, we conduct a comprehensive and rigorous comparison of multiple prevalent deep learning-based automatic segmentation models for the prostate gland and both peripheral and transition zones, using multi-parametric MRI data. Prostate cancer is one of the most common forms of cancer globally, affecting roughly one in every eight men according to the American Cancer Society. Although the survival rate for prostate cancer is significantly high given the very high incidence rate, there is an urgent need to improve and develop new clinical aid systems to help detect and treat prostate cancer in a timely manner. In this retrospective study, our contributions are twofold: First, we perform a comparative unified study of different commonly used segmentation models for prostate gland and zone (peripheral and transition) segmentation. Second, we present and evaluate an additional research question regarding the effectiveness of using an object detector as a pre-processing step to aid in the segmentation process. We perform a thorough evaluation of the deep learning models on two public datasets, where one is used for cross-validation and the other as an external test set. Overall, the results reveal that the choice of model is relatively inconsequential, as the majority produce non-significantly different scores, apart from nnU-Net which consistently outperforms others, and that the models trained on data cropped by the object detector often generalize better, despite performing worse during cross-validation. [ABSTRACT FROM AUTHOR]

ATXN2 gene, encoding for ataxin-2, is located in a trait locus for obesity. Atxn2 knockout (KO) mice are obese and insulin resistant; however, the cause f or this phenotype is still unknown. Moreover, several findings suggest ataxin-2 as a metabolic regulator, but the role of this protein in the hypothalamus was never studied before. The aim of this work was to understand if ataxin-2 modulation in the hypothalamus could play a role in metabolic regulation. Ataxin-2 was overexpressed/re-established in the hypothalamus of C57Bl6/Atxn2 KO mice fed either a chow or a high-fat diet (HFD). This deliv ery was achieved through stereotaxic injection of lentiviral vectors encoding for ataxin-2. We show, for the first time, that HFD decreases ataxin-2 levels in mouse hypothalamus and liver. Specific hypothalamic ataxin-2 overexpression prevents HFD-induced obesity and insulin resistance. Ataxin-2 re-establishment in Atxn2 KO mice improved metabolic dysfunction without changing body weight. Furthermore, we observed altered clock gene expression in Atxn2 KO that might be causative of metabolic dysfunction. Interestingly, ataxin-2 hypothalamic re-establishment rescued these circadian alterations. Thus, ataxin-2 in the hypothalamus is a determinant for weight, insulin sensitivity and clock gene expression. Ataxin-2's potential role in the circadian clock, through the regulation of clock genes, might be a relevant mechanism to regulate metabolism. Overall, this work shows hypothalamic ataxin-2 as a new player in metabolism regulation, which might contribute to the development of new strategies for metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: to identify the sociodemographic profile and the characteristics of interpersonal violence against older adults during the first year of the COVID-19 pandemic in a capital city from the Brazilian Southeast region. Method: a descriptive and exploratory research study with a cross-sectional design based on the notifications of suspected or confirmed cases of violence against older adults between March 2020 and March 2021. A univariate statistical analysis and Fisher's exact test (p<0.05) were performed. Results: a total of 2,681 notifications were recorded during the period. The main victims were individuals aged between 60 and 64 years old, female, white-skinned and with low schooling levels. The instances of violence were more frequent in the victims' homes. Physical and psychological violence predominated, through physical force/beatings and threats, respectively. Most of the aggressors were male, younger than the victims and generally their children or intimate partners. The aggressions were perpetrated more than once and were driven by generational conflicts. There was low referral to entities for the protection of older adults. Conclusion: the sociodemographic profile found evidences vulnerable victims, subjected to many types of violence, and at a potential risk against their overall health. [ABSTRACT FROM AUTHOR]

Objective: To analyze the efficiency of São Paulo municipalities with spending on the Primary Health Care subfunction in 2018 and its association with location, population size, wealth generated in the municipality (GDP - Gross Domestic Product) and budget expenditures with this public policy. Methodology: Exploratory descriptive and explanatory study with São Paulo municipalities in six similar clusters of population and GDP. It uses the settled expense as input, the Number of ESF Teams, Percentage of ESF Coverage, Number of Basic Health Units and Percentage of Live Births of mothers who performed more than 7 consultations in the prenatal period as an output. The efficiency level of each municipality is shown on georeferenced maps. Pearson's correlation is used to estimate the levels of associations between quantitative variables. Results: 102 municipalities have a maximum level of efficiency, distributed among the five groups. Municipalities with a low number of inhabitants and GDP tend to be more inefficient. Efficiency has a low correlation with population size, GDP or public spending. The municipalities with the lowest levels of efficiency are neighbors of São Paulo (Metropolitan Region) or small cities scattered throughout the territory. Theoretical Contributions: identifies that the management (formulation, implementation and evaluation) of the primary health care policy must consider different programs that focus on its location in the territory, population and wealth of the municipalities. There are references to the benchmarks for good practices in managing Primary Health Care policies. [ABSTRACT FROM AUTHOR]

Simple Summary: We have previously identified deflamin, an oligomeric protein isolated from the white lupine seeds (Lupinus albus) with anti-MMPs and anti-inflammatory properties. Given the involvement of MMPs and inflammation in the carcinogenesis process, we aimed to assess deflamin's role in cancer development and progression. Using colorectal cancer cell lines and zebrafish xenotransplant models, we found that deflamin exhibits anti-MMP-2 and anti-MMP-9 activity, being able to reduce tumor size and metastasis formation in vivo. Deflamin was shown to impair cancer cell migration and invasion, as well as collagen remodeling and angiogenesis in the tumor microenvironment, highly impacting cancer behavior. Overall, our results unravel the nutraceutical potential of deflamin in colorectal cancer treatment. Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a crucial role in tumor microenvironment remodeling, contributing to inflammatory and angiogenic processes, and ultimately promoting tumor maintenance and progression. Several studies on bioactive polypeptides isolated from legumes have shown anti-migratory, anti-MMPs, and anti-tumor effects, potentially constituting novel strategies for both the prevention and progression of cancer. In this work, we investigated the anti-tumor role of deflamin, a protein oligomer isolated from white lupine seeds (Lupinus albus) reported to inhibit MMP-9 and cell migration in colorectal cancer (CRC) cell lines. We found that deflamin exerts an inhibitory effect on tumor growth and metastasis formation, contributing to increased tumor apoptosis in the xenotransplanted zebrafish larvae model. Furthermore, deflamin resulted not only in a significant reduction in MMP-2 and MMP-9 activity but also in impaired cancer cell migration and invasion in vitro. Using the xenograft zebrafish model, we observed that deflamin inhibits collagen degradation and angiogenesis in the tumor microenvironment in vivo. Overall, our work reveals the potential of deflamin as an agent against CRC development and progression. [ABSTRACT FROM AUTHOR]

There is an increase in the popularity of craft beer, which is produced by small, independent, and traditional breweries. Since craft beer popularity is rising in Portugal this research focused on assessing physicochemical parameters, total phenolic content (TPC) and the antioxidant capacity of Portuguese craft beers and raw materials used in beer production. In this experimental study, 19 beer samples were analyzed. Parameters such as pH, Total Acidity, Reducing Sugar Content and TPC were evaluated. For the determination of antioxidant activity, DPPH scavenging activity and metal chelating activity (MCA) were analyzed in all samples. Craft beers demonstrated a high phenolic content (ranging from 343.78 mg GAE/L to 2172.49 mg GAE/L), significantly different from industrial beers. Craft beers demonstrated a higher inhibition of DPPH radicals and higher MCA than the raw materials. DPPH inhibition ranged from 36.5% to 96.0% for malt and 64.7% to 79.6% in hops samples. MCA also varied between the different samples, with results of 12.0% to 24.8% in malt samples and 3.8% to 23.5% in hops. Raw materials can potentially influence the antioxidant activity of the resulting beer. Positive correlations between TPC and physicochemical properties can be useful to help consumers choose beers with added value for health. [ABSTRACT FROM AUTHOR]

In recent years bioactive textiles have risen to the forefront of consumers perception due to their potential protection against virus, fungi and bacteria. However, traditional textile staining is an eco-damaging process that and current methods of textile functionalization are expensive, complicated and with great environmental impact. With that in mind, this work sought to show a possible solution for this problematic through the usage of a novel one step textile dyeing and functionalization method based upon nanoencapsulated textile dyes (NTDs). To do so navy blue everzol NTDs were produced with chitosan, cotton dyed, characterized through FTIR and SEM and biological potential evaluated through biocompatibility screening and antimicrobial activity against skin pathogens. The data obtained showed that NTDs effectively dyed the target textile through a coating of the cotton fibre and that NTDs formed hydrogen bonds with the cellulose fibre via electrostatic interactions of the chitosan amino groups with cotton sulphate groups. From a biocompatibility perspective NTDs dyed cotton had no deleterious effects upon a skin cell line, as it promoted cellular metabolism of HaCat cells, while traditionally died cotton reduced it by 10%. Last but not least, NTDs dyed cotton showed significant antimicrobial activity as it reduced viable counts of MRSA, MSSA and A. baumannii between 1 and 2 log of CFU while traditional dyed cotton had no antimicrobial activity. Considering these results the novel method proposed shows is a viable and ecological alternative for the development of antimicrobial textiles with potential biomedical applications. [ABSTRACT FROM AUTHOR]

Traditionally synthetic textile dyes are hazardous and toxic compounds devoid of any biological activity. As nanoencapsulation of yellow everzol textile dye with chitosan has been shown to produce biocompatible nanoparticles which were still capable of dyeing textiles, this work aims to further characterize the biocompatibility of yellow everzol nanoparticles (NPs) and to ascertain if the produced nanoencapsulated dyes possess any biological activity against various skin pathogens in vitro assays and in a cell infection model. The results showed that the NPs had no deleterious effects on the HaCat cells' metabolism and cell wall, contrary to the high toxicity of the dye. The biological activity evaluation showed that NPs had a significant antimicrobial activity, with low MICs (0.5–2 mg/mL) and MBCs (1–3 mg/mL) being registered. Additionally, NPs inhibited biofilm formation of all tested microorganisms (inhibitions between 30 and 87%) and biofilm quorum sensing. Lastly, the dye NPs were effective in managing MRSA infection of HaCat cells as they significantly reduced intracellular and extracellular bacterial counts. [ABSTRACT FROM AUTHOR]

Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD. [ABSTRACT FROM AUTHOR]

Several arguments have been made to substantiate the need for natural antimicrobials for the food industry. With blueberry extracts, the most compelling are both their healthy connotation and the possibility of obtaining a multipurpose solution that can be an antioxidant, colorant, and antimicrobial. From an antimicrobial perspective, as blueberry/anthocyanin-rich extracts have been associated with a capacity to inhibit harmful bacteria while causing little to no inhibition on potential probiotic microorganisms, the study of potential benefits that come from synergies between the extract and probiotics may be of particular interest. Therefore, the present work aimed to evaluate the effect of an anthocyanin-rich extract on the adhesion of five different probiotics as well as their effect on the probiotics' capacity to compete with or block pathogen adhesion to a mucin/BSA-treated surface. The results showed that, despite some loss of probiotic adhesion, the combined presence of extract and probiotic is more effective in reducing the overall amount of adhered viable pathogen cells than the PROBIOTIC alone, regardless of the probiotic/pathogen system considered. Furthermore, in some instances, the combination of the extract with Bifidobacterium animalis Bo allowed for almost complete inhibition of pathogen adhesion. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected disease caused by protozoan parasites of the Leishmania genus. Benzylamines are a class of compounds selectively designed to inhibit the squalene synthase (SQS) that catalyzes the first committed reaction on the sterol biosynthesis pathway. Herein, we studied seven new benzylamines (SBC 37–43) against Leishmania amazonensis. After the first screening of cell viability, two inhibitors (SBC 39 and SBC 40) were selected. Against intracellular amastigotes, SBC 39 and SBC 40 presented selectivity indexes of 117.7 and 180, respectively, indicating high selectivity. Analysis of the sterol composition revealed a depletion of endogenous 24-alkylated sterols such as episterol and 5-dehydroepisterol, with a concomitant accumulation of fecosterol, implying a disturbance in cellular lipid content. This result suggests a blockade of de novo sterol synthesis at the level of SQS and C-5 desaturase. Furthermore, physiological analysis and electron microscopy revealed three main alterations: (1) in the mitochondrion; (2) the presence of lipid bodies and autophagosomes; and (3) the appearance of projections in the plasma membrane. In conclusion, our results support the notion that benzylamines have a potent effect against Leishmania amazonensis and should be an exciting novel pharmaceutical lead for developing new chemotherapeutic alternatives to treat leishmaniasis. [ABSTRACT FROM AUTHOR]

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate. [ABSTRACT FROM AUTHOR]

Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder (ND). While most research in NDs has been following a neuron-centric point of view, microglia are now recognized as crucial in the brain. Previous work revealed alterations that point to an increased activation state of microglia in the brain of CMVMJD135 mice, a MJD mouse model that replicates the motor symptoms and neuropathology of the human condition. Here, we investigated the extent to which microglia are actively contributing to MJD pathogenesis and symptom progression. For this, we used PLX3397 to reduce the number of microglia in the brain of CMVMJD135 mice. In addition, a set of statistical and machine learning models were further implemented to analyze the impact of PLX3397 on the morphology of the surviving microglia. Then, a battery of behavioral tests was used to evaluate the impact of microglial depletion on the motor phenotype of CMVMJD135 mice. Although PLX3397 treatment substantially reduced microglia density in the affected brain regions, it did not affect the motor deficits seen in CMVMJD135 mice. In addition to reducing the number of microglia, the treatment with PLX3397 induced morphological changes suggestive of activation in the surviving microglia, the microglia of wild-type animals becoming similar to those of CMVMJD135 animals. These results suggest that microglial cells are not key contributors for MJD progression. Furthermore, the impact of PLX3397 on microglial activation should be taken into account in the interpretation of findings of ND modification seen upon treatment with this CSF1R inhibitor. [ABSTRACT FROM AUTHOR]

Chronic wounds are one of the most frequent complications that are associated with diabetes mellitus. The overproduction of reactive oxygen species (ROS) is a key factor in the delayed healing of a chronic wound. In the present work, we develop a novel in situ-forming silk sericin-based hydrogel (SSH) that is produced by a simple methodology using horseradish peroxidase (HRP) crosslinking as an advanced dressing for wound healing. The antioxidant and angiogenic effects were assessed in vitro and in vivo after in situ application using an excisional wound-healing model in a genetically-induced diabetic db/db mice and though the chick embryo choriollantoic membrane (CAM) assay, respectively. Wounds in diabetic db/db mice that were treated with SSH closed with reduced granulation tissue, decreased wound edge distance, and wound thickness, when compared to Tegaderm, a dressing that is commonly used in the clinic. The hydrogel also promoted a deposition of collagen fibers with smaller diameter which may have had a boost effect in re-epithelialization. SSH treatment slightly induced two important endogenous antioxidant defenses, superoxide dismutase and catalase. A CAM assay made it possible to observe that SSH led to an increase in the number of newly formed vessels without inducing an inflammatory reaction. The present hydrogel may result in a multi-purpose technology with angiogenic, antioxidant, and anti-inflammatory properties, while advancing efficient and organized tissue regeneration. [ABSTRACT FROM AUTHOR]

Previous studies have highlighted the positive effects of Estradiol (E2) replacement therapy and physical exercise on skeletal muscle during menopause. However, the comparison effects of exercise training (ET) and estradiol replacement therapy during menopause on skeletal muscle have not been investigated to date. This study aimed to compare the effects of endurance exercise training versus E2 replacement therapy on mitochondrial density, redox status, and inflammatory biomarkers in the skeletal muscle of ovariectomized rats. Thirty female Wistar rats (12-week-old) were randomly assigned into three groups: Untrained ovariectomized rats (UN-OVX, n = 10); untrained ovariectomized rats treated with estradiol replacement therapy (E2-OVX); and, trained ovariectomized rats (TR-OVX). After ovariectomy, the E2-OVX rats were treated subcutaneously with E2 (implanted Silastic® capsule containing 360 μg of 17β-estradiol/mL) while the TR-OVX group performed an exercise training protocol (50–70% of maximal running speed on a treadmill, 60 min/day, 5 days/week for 8 weeks). After euthanasia, the soleus muscle was processed for histological and biochemical evaluations. Only exercise prevented the reduction of maximal oxygen consumption and increased mechanical efficiency (ME). While mitochondrial muscle density, total antioxidant capacity (FRAP), catalase (CAT) activity, and interleukin 10 levels were higher in TR-OVX, only OVX-E2 presented higher CAT activity and lower interleukin 6 levels. Endurance exercise training compared with E2 replacement therapy maintains the aerobic capacity improving the ME of OVX rats. In addition, only endurance exercise training raises the skeletal muscle mitochondrial content and tends to balance the redox and inflammatory status in the skeletal muscle of OVX rats. [ABSTRACT FROM AUTHOR]

Functionalization of nanoparticles surfaces have been widely used to improve diagnostic and therapeutic biological outcome. Several methods can be applied to modify nanoparticle surface; however, in this article we focus toward a simple and less time-consuming method. We applied an adsorption method on already formulated nanostructured lipid carriers (NLC) to functionalize these nanoparticles with three distinct peptides sequences. We selected a cell-penetrating peptide (CPP), a lysine modified model amphipathic peptide (Lys(N3)-MAP), CPP/drug complex, and the neuropeptide Y. The aim of this work is to evaluate the effect of several parameters such as peptide concentration, different types of NLC, different types of peptides, and incubation medium on the physicochemical proprieties of NLC and determine if adsorption occurs. The preliminary results from zeta potential analysis indicate some evidence that this method was successful in adsorbing three types of peptides onto NLC. Several non-covalent interactions appear to be involved in peptide adsorption with the possibility of three adsorption peptide hypothesis that may occur with NLC in solution. Moreover, and for the first time, in silico docking analysis demonstrated strong interaction between CPP MAP and NPY Y1 receptor with high score values when compared to standard antagonist and NPY. [ABSTRACT FROM AUTHOR]

Background: Hospitalizations due to Ambulatory Care Sensitive Conditions (ACSC) have been used as an indicator of access to primary care and monitoring of its performance. Objective: To analyze the behavioral trend of ACSC among elderly in Minas Gerais, Brazil, from 2010 to 2015. Method: Ecological study based on data from the Hospital Information System (SIH) of the Unified Health System (SUS), concerning the hospitalization of the elderly aged 60-79 years. ACSC rates were calculated, global, specific by ACSC and by health administrative region. Results: A total of 126,757 ACSC occurred in the period (8.8% of all hospitalizations by SUS). The overall rate decreased from 10.4 to 9.4 (p/1,000). The causes of hospitalization showed a reduction in the risk of hospitalization for hypertension, nutritional deficiencies, and infectious gastroenteritis, but increased the risk of hospitalization for kidney and urinary tract infection. The ACSC rates also varied according to the health regions: regions with low population density, lower per capita GDP and worse health infrastructure showed higher rates. Conclusion: The variation of the indicator among health regions may reflect socioeconomic disparities and the organization and supply of health services. Raising inpatient rates for some of the ACSC may indicate the need for PHC services to increase efforts to care for the elderly who suffer from comorbidity more often. [ABSTRACT FROM AUTHOR]

The association between lifestyle factors and mental health has been evaluated in isolation; however, there has been a lack of information about lifestyle patterns and Common Mental Disorders (CMD) in adolescents. Therefore, the present study aims to assess the association between sets of lifestyle patterns and the occurrence of CMD in Brazilian adolescents evaluated in a national school-based cross-sectional survey. The outcome variable considered was presence of CMD. Lifestyle patterns were identified from the Principal Component Analysis. Consumption of foods, water and alcoholic beverages, sleep, physical activity, and smoking were used to identify patterns as explanatory variables. Sociodemographic characteristics, administrative dependence of the school and, nutritional status, were considered adjustment factors in the regression model. A total of 70,427 adolescents were evaluated. The principal component analysis identified three lifestyle patterns: high consumption of ultra-processed foods and low consumption of unprocessed or minimally processed foods (pattern 1); high consumption of alcoholic beverages and tobacco in the last 30 days (pattern 2); and high consumption of water and high level of physical activity (pattern 3). In the adjusted model, in patterns 1 and 2, the third tertile presented greater chance of CMD (OR 1.68; CI 95% 1.51–1.87 and OR 1.38; CI 95% 1.19–1.60, respectively). In pattern 3, the second (OR 0.88; CI 95% 0.80–0.96) and the third (OR 0.80; CI 95% 0.72–0.88) tertiles presented lower chances of CMD among the adolescents evaluated. Therefore, we suggest that health-promoting practices aimed at adolescents include multiple behaviors, with the objective of ensuring physical, mental, and social well-being. [ABSTRACT FROM AUTHOR]

Detecting MLH1 promoter methylation is highly relevant to differentiate between possible Lynch syndrome patients or patients with sporadic causes of MLH1/PMS2 deficiency in colorectal (CRC) and endometrial cancers. Here, we aimed to develop a test for assessing MLH1 promoter methylation based in next generation sequencing (NGS), and to evaluate the concordance of MLH1 methylation and BRAF -V600 mutation status in CRC. For that, we performed a series of experiments with DNA from tumor, saliva and commercial control samples and our in house developed amplicon-based NGS test. In patients' samples, MLH1 methylation above 10% was only observed in tumors with MLH1/PMS2 loss. We confirmed the reproducibility and accuracy of MLH1 promoter analysis performing a serial dilution experiment with completely methylated and unmethylated control DNAs and a comparison between two NGS platforms (Ion Proton and Illumina). In MLH1/PMS2 deficient tumors, the MLH1 methylation status was concordant with the BRAF mutation status in 90% (18/20) of the cases. Our amplicon-based NGS test showed a great sensitivity and specificity for detecting MLH1 methylation in CRC samples, with a high agreement with the evaluation of BRAF mutation. This simple and affordable test could be used as a reflex test to identify patients with sporadic causes of MLH1/PMS2 deficiency in CRC, aiding to genetic test referral and identification of Lynch syndrome patients. • Detecting MLH1 promoter methylation is highly relevant to identify Lynch syndrome patients. • Amplicon based NGS is a simple and low-cost method for detecting MLH1 methylation. • The test showed high agreement with BRAF mutation status in colorectal cancer. [ABSTRACT FROM AUTHOR]

This work aimed to study the effect of the incorporation of graphene nanoplatelets (GRA 0.5% and 1% (w/w)) on the matrices of biobased polymers composed of starch-based materials (B20) and poly(butylene succinate) (PBS) using pine rosin (RES) as a compatibilizer. Three formulations were produced (B20/RES/PBS, B20/RES/PBS/GRA0.5%, and B20/RES/PBS/GRA1%), and their mechanical properties (tensile, flexural, hardness, and impact), rheological behavior, thermal properties (thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC)), chemical analysis (Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy), and contact angle were evaluated. Hardness (Shore D), tensile, and flexural moduli increased, whereas elongation at break and toughness decreased as GRA content increased. FTIR studies strongly supported the existence of interactions between polymeric matrices and the large surface area of GRA. The viscosity flow curves were well fitted to the Cross-Williams-Landel-Ferry (Cross-WLF) model, and the three formulations exhibited non-Newtonian (shear-thinning) behavior. The analysis of water contact angles indicated that the formulation surfaces have hydrophilic behavior. All the samples are thermally stable, and the results of this study can be used to optimize the application of biobased graphene-based composites for applications in injection molding industries. [ABSTRACT FROM AUTHOR]

Nowadays, with consumers' requirements shifting towards more natural solutions and the advent of nutraceutical-based approaches, new alternatives for obesity management are being developed. This work aimed to show, for the first time, the potential of avocado oil-fortified cheese as a viable foodstuff for obesity management through complex in vitro cellular models. The results showed that oleic and palmitic acids' permeability through the Caco-2/HT29-MTX membrane peaked at the 2h mark, with the highest apparent permeability being registered for oleic acid (0.14 cm/s). Additionally, the permeated compounds were capable of modulating the metabolism of adipocytes present in the basal compartment, significantly reducing adipokine (leptin) and cytokine (MPC-1, IL-10, and TNF-α) production. The permeates (containing 3.30 µg/mL of palmitic acid and 2.16 µg/mL of oleic acid) also presented an overall anti-inflammatory activity upon Raw 264.7 macrophages, reducing IL-6 and TNF-α secretion. Despite in vivo assays being required, the data showed the potential of a functional dairy product as a valid food matrix to aid in obesity management. [ABSTRACT FROM AUTHOR]

We used a population genomic approach to unravel the population structure, genetic differentiation, and genetic diversity of three widespread wild bee species across the Iberian Peninsula, Andrena agilissima, Andrena flavipes and Lasioglossum malachurum. Our results demonstrated that genetic lineages in the Ebro River valley or near the Pyrenees mountains are different from the rest of Iberia. This relatively congruent pattern across species once more supports the hypothesis of "refugia within refugia" in the Iberian Peninsula. The results for A. flavipes and A. agilissima showed an unexpected pattern of genetic differentiation, with the generalist polylectic A. flavipes having lower levels of genetic diversity (Ho = 0.0807, He = 0.2883) and higher differentiation (FST = 0.5611), while the specialist oligolectic A. agilissima had higher genetic diversity (Ho = 0.2104, He = 0.3282) and lower differentiation values (FST = 0.0957). For L. malachurum, the smallest and the only social species showed the lowest inbreeding coefficient (FIS = 0.1009) and the lowest differentiation level (FST = 0.0663). Overall, our results, suggest that this pattern of population structure and genetic diversity could be explained by the combined role of past climate changes and the life-history traits of the species (i.e., size, sociality and host-plant specialization), supporting the role of the Iberian refugia as a biodiversity hotspot. [ABSTRACT FROM AUTHOR]

Conservantes alimentares, como o benzoato de sódio, são amplamente utilizados para preservar alimentos, entretanto seu consumo exagerado pode gerar complicações na saúde e na gestação. A gestação é um processo que exige a ocorrência de eventos morfofisiológicos essenciais para o seu sucesso, tais como a invasão trofoblástica e o remodelamento vascular. Estes eventos sofrem influência das células Natural Killer uterinas (uNK), células imunológicas que atingem 70% da representatividade linfocitária no útero gestante de murinos e seres humanos. Este trabalho teve como objetivo avaliar os efeitos da administração em excesso de benzoato de sódio para camundongos prenhes em parâmetros gestacionais e comportamentais da prole. Camundongos fêmeas da linhagem Swiss receberam o tratamento diário com benzoato de sódio via gavagem orogástrica nas concentrações de: (grupo 1) 150 mg/kg e (grupo 2) 300 mg/kg; e grupo controle, que recebeu apenas salina. O tratamento foi feito do dia de gestação 1 (GD1) ao GD9. No GD10 as fêmeas foram eutanasiadas para coleta de sítios de implantação, rim, coração e fígado. Os sítios de implantação foram submetidos à coloração de Hematoxilina e Eosina (HE) para avaliação da morfometria das artérias, e à histoquímica de lectina DBA para a análise esterológica dos subtipos de célulasuNK. Foi possível observar que a administração do conservante reduziu o númerode células uNK DBA+ com consequente aumento no número de células uNK DBAlow, e causou aumento na espessura da parede das artérias endometriais no grupo 2. A administraçao do conservante benzoato de sódio afetou parametros gestacionais relacionados às células iminológicas maternas e às artérias endometrias, sugerindo que o conservante está afetando de modo negativo a gestação. No momento, estudos estão em andamento para análise histológica dos tecidos cardíaco, hepático e renal e análise comportamental da prole. [ABSTRACT FROM AUTHOR]

This work aims to evaluate the influence of two starch-based materials (B16 and B20) on the moisture sorption isotherms, determined at 30, 40, and 50 °C, where B16 contains 5% (w/w) more starch than B20. Thermodynamic functions (differential enthalpy (∆Hdif), differential entropy (∆Sdif), integral enthalpy (Δhint), integral entropy (ΔSint), free Gibbs energy (∆G), and spreading pressure (φ)) were used to understand the water-binding behaviors and the energy requirements to remove the moisture content from the surface of these materials. The moisture sorption isotherms exhibited type III behavior, and the Guggenheim–Anderson–de Boer (GAB) model was the most suitable to fit the experimental moisture adsorption data. The adsorption isotherms of microparticles were enthalpy-controlled, with isokinetic temperature values of 221.45 and 279.77 K for B16 and B20, respectively, being higher than the harmonic mean temperature (312.94 K). The values of ∆G were positive (45.274 and 44.307 kJmol−1 for B16 and B20, respectively), indicating a non-spontaneous process. The spreading pressure values increased with increasing water activity (aw) for all isotherms. Higher values of ∆Hdif and ∆Sdif obtained from B16 confirmed its higher number of sorption sites available for binding with water molecules when compared to B20, making it less suitable for application in the food packaging industry. [ABSTRACT FROM AUTHOR]

Spent yeast waste streams are a byproduct obtained from fermentation process and have been shown to be a rich secondary source of bioactive compounds such as phenolic compounds and peptides. The latter are of particular interest for skin care and cosmetics as they have been shown to be safe and hypoallergenic while simultaneously being able to exert various effects upon the epidermis modulating immune response and targeting skin metabolites, such as collagen production. As the potential of spent yeast's peptides has been mainly explored for food-related applications, this work sought to understand if peptide fractions previously extracted from fermentation engineered spent yeast (Saccharomyces cerevisiae) waste streams possess biological potential for skin-related applications. To that end, cytotoxic effects on HaCat and HDFa cells and whether they were capable of exerting a positive effect upon the production of skin metabolites relevant for skin health, such as collagen, hyaluronic acid, fibronectin and elastin, were evaluated. The results showed that the peptide fractions assayed were not cytotoxic up to the highest concentration tested (500 µg/mL) for both cell lines tested. Furthermore, all peptide fractions showed a capacity to modulate the various target metabolites production with an overall positive effect being observed for the four fractions over the six selected targets (pro-collagen IαI, hyaluronic acid, fibronectin, cytokeratin-14, elastin, and aquaporin-9). Concerning the evaluated fractions, the overall best performance (Gpep > 1 kDa) was of an average promotion of 41.25% over the six metabolites and two cell lines assessed at a concentration of 100 µg/mL. These results showed that the peptide fractions assayed in this work have potential for future applications in skin-related products at relatively low concentrations, thus providing an alternative solution for one of the fermentation industry's waste streams and creating a novel and highly valuable bioactive ingredient with encompassing activity to be applied in future skin care formulations. [ABSTRACT FROM AUTHOR]

Background/objectives: To compare the prevalence of intra-ocular inflammation (IOI) between brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD) after intra-vitreal injections (IVI) and to compare the IOI odds ratios (ORs) of both therapies with the prevalence of septic endophthalmitis after IVI that was previously reported in the literature. Methods: A total of 468 IVI of brolucizumab (117 eyes) were compared with 2884 IVI of aflibercept (305 eyes) regarding IOI and occlusive retinal vasculitis (RV) from December 2021 to June 2023 in this retrospective study. The OR was calculated for both anti-VEGF agents and was compared with the relative risk of septic endophthalmitis after IVI. Results: There were four eyes with unilateral IOI related to brolucizumab (3.42%), one presenting uveitis (0.85%), two vitritis (1.71%) and the last one presenting occlusive RV (0.85%), compared with two eyes presenting unilateral IOI (anterior uveitis, 0.66%) and none with RV from the aflibercept cohort. The incidence of IOI per injection with brolucizumab (0.855%) was significantly higher compared with aflibercept (0.069%, p = 0.004). The OR of IOI related to brolucizumab IVI compared with septic endophthalmitis was 20 times greater (1.49 for aflibercept, p = 0.646, versus 20.15 for brolucizumab, p < 0.001). The OR of RV with brolucizumab compared with septic endophthalmitis was 4.6. Conclusion: Data from our department suggest a much higher risk of IOI and occlusive retinal vasculitis after brolucizumab when compared with aflibercept. The risk of IOI and severe sight-threatening complications related to brolucizumab is greater than the risk of septic endophthalmitis after any IVI. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the human body and serves multiple functions such as barrier protection and thermoregulation. The maintenance of its integrity and healthy structure is of paramount importance. Accordingly, technological advances in cosmetic sciences have been directed towards optimizing these factors. Plant-derived ingredients have been explored for their bioactivity profiles and sustainable sources. Grape by-products contain a group of bioactive molecules that display important biological activities. Nonetheless, many of these molecules (e.g., phenolic compounds) are unstable and susceptible to degradation. So, their encapsulation using nano/microsystems (i.e., microdispersions) has been explored as a promising solution. In this work, two grape seed extracts were obtained, one from a single grape variety (GSE-Ov) and another from a mix of five grape varieties (GSE-Sv). These extracts were analysed for their antioxidant and antimicrobial activities, as well as their chemical composition and molecular structure. The extract that showed the most promising properties was GSE-Ov with a DPPH IC50 of 0.079 mg mL−1. This extract was encapsulated in soy lecithin microdispersions coated with pectin, with an encapsulation efficiency of 88.8%. They showed an in vitro release of polyphenols of 59.4% during 24 h. The particles displayed a zeta potential of −20.3 mV and an average diameter of 13.6 µm. Microdispersions proved to be safe under 5 and 2.5 mg mL−1 in HaCaT and HDF cell models, respectively. Additionally, they demonstrated anti-inflammatory activity against IL-1α when tested at 2 mg mL−1. This work enabled the valorisation of a by-product from the wine industry by using natural extracts in skincare products. [ABSTRACT FROM AUTHOR]

Efforts are intensifying to identify new biofuel sources in response to the pressing need to mitigate environmental pollutants, such as greenhouse gases, which are key contributors to global warming and various worldwide calamities. Algae and microalgae present themselves as excellent alternatives for solid-gaseous fuel production, given their renewable nature and non-polluting characteristics. However, making biomass production from these organisms economically feasible remains a challenge. This article collates various studies on the use of lignocellulosic waste, transforming it from environmental waste to valuable organic supplements for algae and microalgae cultivation. The focus is on enhancing biomass production and the metabolites derived from these biomasses. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. Design: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 μmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. Setting: Forty-eight poorest municipalities in the South Region of Brazil. Participants: Children (n 1503) aged 12–59 months. Results: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). Conclusions: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country. [ABSTRACT FROM AUTHOR]

In recent years, pomegranate oil has obtained more attention due to its content of conjugated linolenic acids and possible application in the prevention of many diseases. The purpose of this work was to evaluate the potential ability of pomegranate oil to modulate obesity-related metabolism and immune response using in vitro models. In this regard, pomegranate oil was characterized in terms of fatty acids profile, tocopherols and phytosterols, and antioxidant capacity. After evaluation of the safety profile, pomegranate oil's capacity to modulate obesity-related metabolism was evaluated through adipolysis and adipokines secretion quantification in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation assay in Hep G2 hepatocytes. The immunomodulatory activity was evaluated in Caco-2 cells by quantification of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. This oil showed high antioxidant capacity and was mainly composed of conjugated fatty acid, namely punicic acid. Its chemical composition was responsible for its capacity to reduce the lipid accumulation in Hep G2 cells and 3T3-L1 differentiated adipocytes. In short, pomegranate oil shows great potential for the development of functional foods and nutraceuticals targeting obesity. [ABSTRACT FROM AUTHOR]

Virome and 16/18S analyses were performed on 304 longitudinal fecal samples of eight infants. The gut virota--the collection of all viruses present in the gut--was dominated by bacteriophages, which were nearly absent at birth and emerged rapidly within the first weeks after birth. Over 85% of phage reads correspond to 305 near-complete genomes, most of which (70.5%) were individual infant-specific, including two crAs-sphages, whereas 7.8% of phages were present in at least 50% of infants. Bacterial hosts could be predicted for 80% of phages, mainly infecting Firmicutes. Strong temporal correlations between phages and their predicted bacterial hosts were identified for >40% of our phages, and together with the observation of a decreasing fraction of phages with a temperate lifestyle further suggest that phages are induced from early-colonizing bacteria. The vast majority (>86%) of identified eukaryotic viruses, known to cause gastroenteritis, occurred without clinical signs, and an increase in the rate of infection occurred after day-care entrance. On average, 112 genomic contigs of distinct anelloviruses could be identified per infant, some of which were shed at > 1 y. The identified plant viruses reflected the infant diet. Finally, the sporadic identification of fungi and parasites argues against the presence of such stable communities in the study population. Overall, this work provides a very high temporal resolution on how the different members of the infant gut microbiota, and especially the virome, develop over time in the gut of healthy infants, and might serve as valuable baseline knowledge for further studies investigating the effect of perturbations in the infant gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Several strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data. Methods: Length/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The following cutoffs for residuals were tested to flag those: -3/+3, -4/+4, -5/+5, -6/+6. The selected child growth indicators included length/height-for-age z-scores and weight-for-age z-scores, classified according to the WHO charts. Results: The dataset included 50,154,738 records from 10,775,496 children. Boys and girls had 5.74% and 5.31% of length/height and 5.19% and 4.74% of weight values flagged as population outliers, respectively. After removing those, the percentage of longitudinal outliers varied from 0.02% (<-6/>+6) to 1.47% (<-3/>+3) for length/height and from 0.07 to 1.44% for weight in boys. In girls, the percentage of longitudinal outliers varied from 0.01 to 1.50% for length/height and from 0.08 to 1.45% for weight. The initial removal of population outliers played the most substantial role in the growth trajectories as it was the first step in the cleaning process, while the additional removal of longitudinal outliers had lower influence on those, regardless of the cutoff adopted. The prevalence of the selected indicators were also affected by both population and longitudinal (to a lesser extent) outliers. Conclusions: Although both population and longitudinal outliers can detect biologically implausible values in child growth data, removing population outliers seemed more relevant in this large administrative dataset, especially in calculating summary statistics. However, both types of outliers need to be identified and removed for the proper evaluation of trajectories. [ABSTRACT FROM AUTHOR]

Hutchinson‐Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin, and musculoskeletal age‐related dysfunctions. In most cases, these children die of age‐related cardiovascular dysfunction by their early teenage years. The absence of effective treatments for HGPS underscores the critical need to explore novel safe therapeutic strategies. In this study, we show that treatment with the hormone ghrelin increases autophagy, decreases progerin levels, and alleviates other cellular hallmarks of premature aging in human HGPS fibroblasts. Additionally, using a HGPS mouse model (LmnaG609G/G609G mice), we demonstrate that ghrelin administration effectively rescues molecular and histopathological progeroid features, prevents progressive weight loss in later stages, reverses the lipodystrophic phenotype, and extends lifespan of these short‐lived mice. Therefore, our findings uncover the potential of modulating ghrelin signaling offers new treatment targets and translational approaches that may improve outcomes and enhance the quality of life for patients with HGPS and other age‐related pathologies. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the most common movement disorder, characterized by the progressive loss of dopaminergic neurons from the nigrostriatal system. Currently, there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Mesenchymal stem cells (MSCs) are one of the most extensively studied cell sources for regenerative medicine applications, particularly due to the release of soluble factors and vesicles, known as secretome. The main goal of this work was to address the therapeutic potential of the secretome collected from bone-marrow-derived MSCs (BM-MSCs) using different models of the disease. Firstly, we took advantage of an optimized human midbrain-specific organoid system to model PD in vitro using a neurotoxin-induced model through 6-hydroxydopamine (6-OHDA) exposure. In vivo, we evaluated the effects of BM-MSC secretome comparing two different routes of secretome administration: intracerebral injections (a two-site single administration) against multiple systemic administration. The secretome of BM-MSCs was able to protect from dopaminergic neuronal loss, these effects being more evident in vivo. The BM-MSC secretome led to motor function recovery and dopaminergic loss protection; however, multiple systemic administrations resulted in larger therapeutic effects, making this result extremely relevant for potential future clinical applications. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has been described in many neurodegenerative disorders; however, there is less information regarding mitochondrial deficits in Machado–Joseph disease (MJD), a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ATXN3 gene. In the present study, we characterized the changes in mitochondrial function and biogenesis markers in two MJD models, CMVMJD135 (MJD135) transgenic mice at a fully established phenotype stage and tetracycline-regulated PC6-3 Q108 cell line expressing mutant ataxin-3 (mATXN3). We detected mATXN3 in the mitochondrial fractions of PC6-3 Q108 cells, suggesting the interaction of expanded ATXN3 with the organelle. Interestingly, in both the cerebella of the MJD135 mouse model and in PC6-3 Q108 cells, we found decreased mitochondrial respiration, ATP production and mitochondrial membrane potential, strongly suggesting mitochondrial dysfunction in MJD. Also, in PC6-3 Q108 cells, an additional enhanced glycolytic flux was observed. Supporting the functional deficits observed in MJD mitochondria, MJD135 mouse cerebellum and PC6-3 Q108 cells showed reduced cytochrome c mRNA and protein levels. Overall, our findings show compromised mitochondrial function associated with decreased cytochrome c levels in both cell and animal models of MJD. [ABSTRACT FROM AUTHOR]

Objective: To describe the time trends and socio-economic inequalities in infant and young child feeding practices in accordance with the Brazilian deprivation index (BDI). Design: This time-series study analysed the prevalence of multiple breast-feeding and complementary feeding indicators based on data from the Brazilian Food and Nutrition Surveillance System, 2008–2019. Prais–Winsten regression models were used to analyse time trends. Annual percent change (APC) and 95 % CI were calculated. Setting: Primary health care services, Brazil. Participants: Totally, 911 735 Brazilian children under 2 years old. Results: Breast-feeding and complementary feeding practices differed between the extreme BDI quintiles. Overall, the results were more favourable in the municipalities with less deprivation (Q1). Improvements in some complementary feeding indicators were observed over time and evidenced such disparities: minimum dietary diversity (Q1: Δ 47·8–52·2 %, APC + 1·44, P = 0·006), minimum acceptable diet (Q1: Δ 34·5–40·5 %, APC + 5·17, P = 0·004) and consumption of meat and/or eggs (Q1: Δ 59·7–80·3 %, APC + 6·26, P < 0·001; and Q5: Δ 65·7–70·7 %, APC + 2·20, P = 0·041). Stable trends in exclusive breast-feeding and decreasing trends in the consumption of sweetened drinks and ultra-processed foods were also observed regardless the level of the deprivation. Conclusions: Improvements in some complementary food indicators were observed over time. However, the improvements were not equally distributed among the BDI quintiles, with children from the municipalities with less deprivation benefiting the most. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression. [ABSTRACT FROM AUTHOR]

This work aims to present an historical review of the ecosystem services provided by anadromous fish (i.e., species that migrate from the sea to the river to spawn) throughout Human time, as well as of the main related threats, focusing on the Iberian Peninsula region. Anadromous fish provide important provision, cultural, regulatory and supporting ecosystem services across their distribution range and have been extensively exploited by humans since prehistoric times. In the Iberian Peninsula, sea lamprey, allis and twaite shads, sea trout, Atlantic salmon and European sturgeon were once abundantly present in several river basins covering what is now Portuguese and Spanish territory. These species have suffered a severe decline across their distribution range, mainly due to habitat loss and overexploitation. Considered regal delicacies, these fishes were once a statement on the tables of the highest social classes, a much appreciated bounty for the poorer population and are still an important part of the local gastronomy and economy. Such high economic and cultural interest encouraged intensive fishing. Currently, management efforts are being implemented, pairing habitat rehabilitation (e.g., construction of fish passes in obstacles to migration such as weirs and dams) with sustainable fisheries. Considering the present climate change scenario, these species are bound to endure increased pressures, demanding novel management approaches to ensure population numbers that are able to secure their sustainable exploitation. [ABSTRACT FROM AUTHOR]

Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as key factors in endothelial repair. In a rat model of IUGR induced by a maternal low-protein diet, we observed an altered functionality of ECFCs in 6-month-old males, which was associated with arterial hypertension related to oxidative stress and stress-induced premature senescence (SIPS). Resveratrol (R), a polyphenol compound, was found to improve cardiovascular function. In this study, we investigated whether resveratrol could reverse ECFC dysfunctions in the IUGR group. ECFCs were isolated from IUGR and control (CTRL) males and were treated with R (1 μM) or dimethylsulfoxide (DMSO) for 48 h. In the IUGR-ECFCs, R increased proliferation (5′-bromo-2′-deoxyuridine (BrdU) incorporation, p < 0.001) and improved capillary-like outgrowth sprout formation (in Matrigel), nitric oxide (NO) production (fluorescent dye, p < 0.01), and endothelial nitric oxide synthase (eNOS) expression (immunofluorescence, p < 0.001). In addition, R decreased oxidative stress with reduced superoxide anion production (fluorescent dye, p < 0.001); increased Cu/Zn superoxide dismutase expression (Western blot, p < 0.05); and reversed SIPS with decreased beta-galactosidase activity (p < 0.001), and decreased p16ink4a (p < 0.05) and increased Sirtuin-1 (p < 0.05) expressions (Western blot). No effects of R were observed in the CTRL-ECFCs. These results suggest that R reverses long-term ECFC dysfunctions related to IUGR. [ABSTRACT FROM AUTHOR]