Search Results (104)

Background/Objectives: The timely initiation of antiretroviral therapy (ART) in persons living with HIV (PLWH) can improve clinical outcomes. However, ART commencement is often delayed. Portugal, despite having one of the highest new HIV diagnosis rates within the European Union, has limited available national-level data. Prior evidence from 2017 to 2018 suggests that the average time to ART initiation exceeds the recommendations for optimal patient benefits. This study aimed to determine the number of days from the first hospital appointment to the commencement of ART among newly diagnosed PLWH in Portugal between 2017 and 2022 at the national level and across different hospitals. It was hypothesized that newly diagnosed PLWH in Portugal experience a delay in ART initiation beyond the recommended timeframe. Methods: A retrospective analysis of records from Portuguese public tertiary care hospitals, which manage most HIV patients, was conducted. Descriptive statistics (measures of central tendency, dispersion, and frequency) were applied, along with association tests and a binary logistic regression model to examine factors influencing the timing of ART initiation. Results: A total of 2229 cases (out of 3434 received) from 19 hospitals were considered eligible. The median time interval between the first hospital appointment and ART initiation was 29.00 days, with a decreasing tendency between 2017 and 2022. Patients initiating therapy after 14 days had higher CD4 levels and lower viral loads compared to those starting within 14 days, with statistical significance. Conclusions: Continuous and regular monitoring of key indicators, such as the time to ART initiation, is pivotal for assessing the effectiveness of HIV treatment programs and pinpointing areas in need of improvement. Full article

This study offers fresh insights into the technical and stylistic exchanges between Flemish and Portuguese panel painting during the late 15th and early 16th centuries. By comparing two contemporaneous works, we trace Flemish influence in Portugal through a detailed materials and techniques analysis. Non-invasive, in situ methods—including energy dispersive X-ray fluorescence (XRF), macro-photography (MP), infrared reflectography (IRR), and dendrochronology—were used to examine each painting’s wooden support, ground layer, underdrawing, and pigment stratigraphy. Select micro-sampling analyses—micro-Fourier-transform infrared spectroscopy (μ-FTIR), scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), and micro-Raman spectroscopy (µ-Raman)—provided complementary data on binder and pigment composition. While both paintings share nearly identical pigments and layering sequences and employ comparable coating techniques, their ground compositions differ subtly. Notably, the Flemish work features extensive gold-leaf application, whereas underdrawing execution takes on principal importance in the Portuguese example. Together, these findings reveal that Jorge Afonso’s workshop developed a distinct Portuguese method—rooted in Flemish practices disseminated by Quentin Metsys—yet adapted to local materials and aesthetic priorities. Full article

Adverse childhood experiences, such as abuse, are a risk factor for mental health and poor socio-emotional development in adulthood. Assessing these experiences in specific populations allows for the identification of patterns and the implementation of preventive interventions. Objective: To evaluate the psychometric properties of the abbreviated version of the Adverse Childhood Experiences Abuse Form (ACE-ASF) in Ecuadorian youth, aiming to ensure the validity, reliability, and consistency of the instrument in accurately measuring abuse dimensions in this Ecuadorian population. Methodology: An instrumental study was conducted on the psychometric properties of the eight-item ACE-ASF, applying it to a sample of 840 university students (52.1% females and 47.9% males). The evaluation focused on analyzing the factorial structure and internal consistency of the instrument in this sample. Results: The two-factor model showed a satisfactory fit across all levels of invariance (configural, metric, scalar, and strict), with acceptable fit indices (CFI, TLI, GFI, RMSEA, and SRMR). The internal consistency was adequate, as assessed using the McDonald’s omega and Cronbach’s alpha coefficients. Convergent and discriminant validity were confirmed using the AVE and HTMT indices, ensuring proper differentiation between the dimensions assessed. Conclusion: The ACE-ASF proved to be a valid and reliable instrument for assessing abuse experiences in Ecuadorian youth. Its two-factor structure reflects distinct yet related dimensions, providing a useful tool for identifying adverse childhood experiences in this population. Full article

Extracellular vesicles (EVs) can transport molecules that combat viruses, such as RNA against SARS-CoV-2. Bacterial coinfections can help establish certain viruses and worsen diseases. Thus, we designed a model to induce the secretion of polydisperse EVs shown with SARS-CoV-2 and bacterial coinfection using macrophages and E. coli fractions as in vitro inducers. We obtained short and large macrophage EVs. The E. coli fraction was designated as SDS-soluble bacterial membrane fraction and its associated proteins (SDS-SBMF). The proteins were identified using a mass spectrometer. SDS-SBMF contained mainly OmpF, OmpA, OmpC, OmpX, and lpp. The SDS-SBMF macrophages induced the secretion of polydisperse EVs at 30 min, reaching optimal secretion at 120 min, as observed via scanning electron microscopy and confocal microscopy. Macrophage EVs contained mainly HSP7C, actin, apolipoprotein, GAPDH, annexin A5, PKM, moesin, and cofilin. We observed an increase in EVs in the bloodstream of patients with SARS-CoV-2 and bacterial coinfection, in addition to the presence of SARS-CoV-2 genes (E, ORF) in EVs. This in vitro method for inducing EVs has the potential to be used to obtain larger samples for study and for the detection of diagnostic and prognostic biomarkers of different diseases. Full article

Most donor human milk (HM) banks use Holder pasteurization (HoP) to ensure microbiological safety, although it can degrade essential bioactive factors for newborns. This study evaluates the innovative ultra-high-pressure homogenization (UHPH) technology as a potential alternative. Listeria innocua, Staphylococcus carnosus, Franconibacter helveticus (formerly named Cronobacter helveticus) and Escherichia coli strains were used as surrogates for common HM pathogens according to European Milk Bank Association (EMBA) guidelines, to evaluate the efficacy of new technologies. A reconstituted powder milk formula inoculated with these strains was used to determine the most efficient conditions (those to achieve a lethality of ≥5 Log), applying treatments from 150 to 300 MPa. These treatments were later validated using inoculated HM with the same strains. Immunoglobulin (sIgA, IgG, IgM) retention was also evaluated and compared with HoP. Results showed that UHPH treatments at 200 MPa achieved a lethality > 5 Log for all strains, except for St. carnosus, which required 250 MPa for complete inactivation in HM. Unlike HoP, UHPH at 200 and 250 MPa did not significantly reduce the basal concentration of sIgA, IgG, or IgM compared with raw HM. These findings suggest UHPH as a promising alternative to HoP, maintaining both microbiological safety and immunological quality. Full article

Background: Small intestinal bacterial overgrowth (SIBO) is a dysbiosis marked by an excessive proliferation of bacteria in the small intestine, resulting in abdominal symptoms that significantly affect patients’ quality of life. Objectives: This study aims to evaluate the impact of a comprehensive therapeutic approach in improving the quality of life of patients with SIBO. Methods: For this purpose, standardized questionnaires were used at baseline, 30 days and 90 days, including the IBS-QOL (Irritable Bowel Syndrome Quality of Life Questionnaire), the GSRS (Gastrointestinal Symptom Rating Scale), the EuroQOL-5D, and the Bristol Scale. Results: The results show that a comprehensive approach, combining pharmacological treatment, appropriate dietary intervention, and strategies aimed at improving gut microbiota and intestinal permeability, produces a sustained improvement in the quality of life of a significant proportion of patients who participated in the study. Furthermore, the results suggest that, although gas normalization is a relevant indicator, clinical improvement and quality of life depend considerably on patients’ subjective perception of their health. Conclusions: This finding underscores the importance of recognizing SIBO as a prevalent condition that requires accurate diagnoses and individualized treatments to improve patients’ well-being. Full article

The production of high-quality coffee seedlings is essential to meet the demands of the coffee sector, requiring more efficient and sustainable water management practices. In this context, the use of hydroretentive polymers, particularly biodegradable ones, emerges as a promising alternative to optimize water use, reduce the environmental impact associated with synthetic polymers, and improve the agronomic traits of seedlings. Therefore, this study aimed to evaluate the effects of different irrigation intervals and hydroretentive polymer doses on the water consumption and agronomic characteristics of Coffea arabica L. seedlings. This study was conducted in a protected environment using a randomized block design with split plots and four replicates. The plots consisted of two irrigation intervals (2 and 4 days), and the subplots included four doses of hydroretentive polymer (0%, 0.25%, 0.5%, and 1%), applied in 0.5 dm³ polypropylene bags. Results showed that the 0.5% polymer dose combined with a 2-day irrigation interval resulted in the highest water consumption, while the combination of 0% polymer and a 4-day irrigation interval led to the lowest water consumption. The 0.25% hydroretentive polymer dose with irrigation every 2 days showed the best performance in gas exchange, promoting photosynthesis without causing water saturation. This management also promoted better seedling growth, increasing biomass, height, leaf area, and root volume compared to longer irrigation intervals. The crop coefficients (Kc × Ks) were 0.20, 0.28, and 0.45 during the periods of 0–50, 51–80, and 81–150 days after sowing, respectively. A dose of 0.25% hydroretentive polymer with a 2-day irrigation interval is recommended for the production of Arabica coffee seedlings, contributing to agricultural practices aligned with environmental preservation and productive efficiency. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) is one of the most common medical conditions in pregnancy, with adverse effects on maternal and neonatal outcomes. Evidence suggests a beneficial effect of plant-based dietary patterns, rich in foods derived from plant sources and low in animal foods, on type 2 diabetes; however, their effects on GDM remain unclear. We aimed to investigate the association between pre-pregnancy provegetarian food patterns and the incidence of GDM in a Spanish cohort. Materials and Methods: This subsample of the Seguimiento Universidad de Navarra (SUN) cohort analyzed 3589 Spanish university graduate pregnant women with a mean (standard deviation) age of 28 (±4.3) who were initially free of pre-existing diabetes at baseline. Dietary food consumption was evaluated through a validated, 136-item semi-quantitative food frequency questionnaire. The pre-pregnancy provegetarian food pattern was obtained by assigning positive scores to plant-based food groups and reverse scores to animal food groups. Energy-adjusted quintiles were applied to allocate points to construct the provegetarian food pattern, ranging from 12 to 60 points. Logistic regression models were performed to estimate the odds ratios (OR) of GDM across quintiles of a pre-pregnancy provegetarian food pattern, using the lowest quintile as the reference category. Results: We identified 178 incidence cases of GDM. Women in the highest quintile (Q5) of provegetarian food pattern before pregnancy exhibited a 42% relative reduction in the odds of GDM [adjusted OR (95% CI) Q5 vs. Q1: 0.58 (0.35, 0.97); p-trend = 0.109]. Higher consumption of meat and dairy before pregnancy was associated with a significantly increased risk of GDM [adjusted OR (95% CI) Q5 vs. Q1: 1.94 (1.19, 3.16); p-trend = 0.005] and [adjusted OR (95% CI) Q5 vs. Q1: 1.77 (1.07, 2.94); p-trend = 0.082], respectively. Conclusions: Higher pre-pregnancy consumption of a provegetarian food pattern was associated with a lower risk of developing GDM in Spanish women. Further studies are needed to confirm these findings. Full article

In this study, we consider the importance of applying legal protection and management measures to natural tourist areas. We assess the sensitivity of these areas with respect to tourist demand, which drives the need for protective and corrective measures, such as carrying capacities controlled via admissions; in particular, we analyse the protective features that exist in a transboundary biosphere reserve, the Gêres–Xurés Baixa Limia Reserve, which occupies territory in northern Spain, southern Galicia (Spain) and northern Portugal. Our objective is to assess the relevance and effectiveness of the features used by both countries to protect their natural spaces while guaranteeing sustainability and environmental development. These measures ensure that the value of their resources is not compromised for future generations or negatively affected by tourist use. To carry out the analysis, we first conducted a geographical study of the area to characterize the different areas found in this biosphere reserve. Subsequently, we analysed the regulatory norms used for protection in both countries, and we explain the management mechanisms that have been implemented in both countries. This approach enables us to compare the relative importance assigned by each country for the sustainable management of the chosen territory and tourist space. Furthermore, we can compare the use of control measures for sustainable and respectful tourism planning, such as guiding plans, use plans and management and protective regulations. Full article

Skeletal muscle regeneration after injury is a complex process involving inflammatory signaling and myoblast activation. Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) are key mediators, but their effects on gene expression in proliferating myoblasts are unclear. We performed the RNA sequencing of TNF-α treated C2C12 myoblasts to elucidate the signaling pathways and gene networks regulated by TNF-α during myoblast proliferation. The TNF-α (10 ng/mL) treatment of C2C12 cells led to 958 differentially expressed genes compared to the controls. Pathway analysis revealed significant regulation of TNF-α signaling, along with the chemokine and IL-17 pathways. Key upregulated genes included cytokines (e.g., IL-6), chemokines (e.g., CCL7), and matrix metalloproteinases (MMPs). TNF-α increased myogenic factor 5 (Myf5) but decreased MyoD protein levels and stimulated the release of MMP-9, MMP-10, and MMP-13. TNF-α also upregulates versican and myostatin mRNA. Overall, our study demonstrates the TNF-α modulation of distinct gene expression patterns and signaling pathways that likely contribute to enhanced myoblast proliferation while suppressing premature differentiation after muscle injury. Elucidating the mechanisms involved in skeletal muscle regeneration can aid in the development of regeneration-enhancing therapeutics. Full article

Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC₅₀ values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy. Full article

Through the shikimate pathway, a massive metabolic flux connects the central carbon metabolism with the synthesis of chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as other compounds, including salicylate or folate. The alternative metabolic channeling of chorismate involves a key branch-point, finely regulated by aromatic amino acid levels. Chorismate mutase catalyzes the conversion of chorismate to prephenate, a precursor of phenylalanine and tyrosine and thus a vast repertoire of fundamental derived compounds, such as flavonoids or lignin. The regulation of this enzyme has been addressed in several plant species, but no study has included conifers or other gymnosperms, despite the importance of the phenolic metabolism for these plants in processes such as lignification and wood formation. Here, we show that maritime pine (Pinus pinaster Aiton) has two genes that encode for chorismate mutase, PpCM1 and PpCM2. Our investigations reveal that these genes encode plastidial isoenzymes displaying activities enhanced by tryptophan and repressed by phenylalanine and tyrosine. Using phylogenetic studies, we have provided new insights into the possible evolutionary origin of the cytosolic chorismate mutases in angiosperms involved in the synthesis of phenylalanine outside the plastid. Studies based on different platforms of gene expression and co-expression analysis have allowed us to propose that PpCM2 plays a central role in the phenylalanine synthesis pathway associated with lignification. Full article

Currently, Mediterranean forests are experiencing the deleterious effects of global warming, which mainly include increased temperatures and decreased precipitation in the region. Relict Abies pinsapo fir forests, endemic in the southern Iberian Peninsula, are especially sensitive to these recent environmental disturbances, and identifying the genes involved in the response of this endangered tree species to climate-driven stresses is of paramount importance for mitigating their effects. Genomic resources for A. pinsapo allow for the analysis of candidate genes reacting to warming and aridity in their natural habitats. Several members of the complex gene families encoding late embryogenesis abundant proteins (LEAs) and heat shock proteins (HSPs) have been found to exhibit differential expression patterns between wet and dry seasons when samples from distinct geographical locations and dissimilar exposures to the effects of climate change were analyzed. The observed changes were more perceptible in the roots of trees, particularly in declining forests distributed at lower altitudes in the more vulnerable mountains. These findings align with previous studies and lay the groundwork for further research on the molecular level. Molecular and genomic approaches offer valuable insights for mitigating climate stress and safeguarding this endangered conifer. Full article

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading. Full article

Agriculture is one of the most important industries in the world. In this context, the importance of Brazil as a strategic country to meet a range of SDG’s targets linked to food security, fighting against hunger, and poverty reduction is undeniable. This study aimed to highlight the production and dissemination of scientific research developed by Brazilian institutions, and to identify prominent authors and institutions based on articles related to sustainability, agriculture, livestock, and agribusiness. A bibliometric analysis was developed based on a sample of 3139 documents published between 2000 and 2022, comprising 21,380 authors that were then analyzed using the Biblioshiny package. As result, the term “sustainability” showed growth as it branched out to semantically similar terms, such as “sustainable agriculture” and “sustainable intensification”; and “crop–livestock integration” and “agroforestry” were highlighted as important in the development of future research. The majority of documents were produced by the University of São Paulo (~33%), the State University of São Paulo (~15%), and the Federal University of Rio Grande do Sul (~11%), suggesting that their researchers could act as coordinators in future research through the formation of multi-collaborative groups to jointly lead to the participatory elaboration of public policies that promote more sustainable paths for agricultural production. Full article