Ethnic, geographical and altitude considerations and maternal mortality associated with HELLP syndrome in Ecuador: a population-based cohort study.

BACKGROUND: Eclampsia and pre-eclampsia rank as the third leading causes of maternal death in Ecuador, following pre-existing chronic diseases and postpartum haemorrhage, as reported by the Ecuadorian National Institute of Statistics and Census (INEC). In contrast, HELLP (Haemolysis, Elevated Liver enzymes, Low Platelet count) syndrome remains underexplored epidemiologically, not only in Latin America but globally. This study marks the first population-based investigation into HELLP syndrome incidence and mortality in Ecuador, examining geographical variations, altitude influences and ethnic backgrounds. METHODS: Conducted as a retrospective population-based cohort study from 2015 to 2017, this research delves into the incidence, risk factors and maternal mortality associated with HELLP syndrome in Ecuador. Utilising data from INEC and the Ecuadorian Ministry of Health, we identified HELLP syndrome cases through ICD-10 (International Classification of Diseases, tenth revision) coding in hospitalised individuals. Logistic regression analysis was employed to explore association, whilst geospatial statistical analysis focused on cantons to identify significant spatial clusters. Primary outcome measures include HELLP syndrome incidence and maternal mortality, supplying crucial insights into the syndrome's impact on maternal health in Ecuador. RESULTS: The incidence of HELLP syndrome is 0.76 (0.69-0.84)/ 1000 deliveries. Afro-Ecuadorian communities have a higher risk (Odds Ratio (OR) = 2.18 (1.03-4.63)) compared to Indigenous Ecuadorian communities. Living at mid-level or high altitude is a significant risk factor OR of 2.79 (2.19-3.55) and an OR 3.61 (2.58-5.03), respectively. Being an older mother was also identified as a risk factor. Women living more than 20 km from the obstetric unit have an OR of 2.55 (2.05-3.18). Moreover, we found that cantons with higher crude HELLP syndrome incidence also have lower numbers of physicians (R = 0.503, p-value < 0.001). The mortality incidence of women with HELLP syndrome is 21.22 (12.05-20.59)/1000 deliveries with HELLP syndrome diagnoses. CONCLUSIONS: High altitude, advanced maternal age and geographical distance between residence and health centres are risk factors for HELLP syndrome. Maternal mortality in women with HELLP syndrome is higher than pre-eclampsia and eclampsia but comparable with previous reports in other countries.

Unraveling druggable cancer-driving proteins and targeted drugs using artificial intelligence and multi-omics analyses.

The druggable proteome refers to proteins that can bind to small molecules with appropriate chemical affinity, inducing a favorable clinical response. Predicting druggable proteins through screening and in silico modeling is imperative for drug design. To contribute to this field, we developed an accurate predictive classifier for druggable cancer-driving proteins using amino acid composition descriptors of protein sequences and 13 machine learning linear and non-linear classifiers. The optimal classifier was achieved with the support vector machine method, utilizing 200 tri-amino acid composition descriptors. The high performance of the model is evident from an area under the receiver operating characteristics (AUROC) of 0.975 ± 0.003 and an accuracy of 0.929 ± 0.006 (threefold cross-validation). The machine learning prediction model was enhanced with multi-omics approaches, including the target-disease evidence score, the shortest pathways to cancer hallmarks, structure-based ligandability assessment, unfavorable prognostic protein analysis, and the oncogenic variome. Additionally, we performed a drug repurposing analysis to identify drugs with the highest affinity capable of targeting the best predicted proteins. As a result, we identified 79 key druggable cancer-driving proteins with the highest ligandability, and 23 of them demonstrated unfavorable prognostic significance across 16 TCGA PanCancer types: CDKN2A, BCL10, ACVR1, CASP8, JAG1, TSC1, NBN, PREX2, PPP2R1A, DNM2, VAV1, ASXL1, TPR, HRAS, BUB1B, ATG7, MARK3, SETD2, CCNE1, MUTYH, CDKN2C, RB1, and SMARCA4. Moreover, we prioritized 11 clinically relevant drugs targeting these proteins. This strategy effectively predicts and prioritizes biomarkers, therapeutic targets, and drugs for in-depth studies in clinical trials. Scripts are available at https://github.com/muntisa/machine-learning-for-druggable-proteins .

Eco-alternative treatments for Vibrio parahaemolyticus and V. cholerae biofilms from shrimp industry through Eucalyptus (Eucalyptus globulus) and Guava (Psidium guajava) extracts: A road for an Ecuadorian sustainable economy.

Understanding how environmental variables influence biofilm formation becomes relevant for managing Vibrio biofilm-related infections in shrimp production. Therefore, we evaluated the impact of temperature, time, and initial inoculum in the biofilm development of these two Vibrio species using a multifactorial experimental design. Planktonic growth inhibition and inhibition/eradication of Vibrio biofilms, more exactly V. parahaemolyticus (VP87 and VP275) and V. cholerae (VC112) isolated from shrimp farms were evaluated by Eucalyptus and Guava aqueous leaf extracts and compared to tetracycline and ceftriaxone. Preliminary results showed that the best growth conditions of biofilm development for V. parahaemolyticus were 24 h and 24°C (p <0.001), while V. cholerae biofilms were 72 h and 30°C (p <0.001). Multivariate linear regression ANOVA was applied using colony-forming unit (CFU) counting assays as a reference, and R-squared values were applied as goodness-of-fit measurements for biofilm analysis. Then, both plant extracts were analyzed with HPLC using double online detection by diode array detector (DAD) and mass spectrometry (MS) for the evaluation of their chemical composition, where the main identified compounds for Eucalyptus extract were cypellogin A, cypellogin B, and cypellocarpin C, while guavinoside A, B, and C compounds were the main compounds for Guava extract. For planktonic growth inhibition, Eucalyptus extract showed its maximum effect at 200 µg/mL with an inhibition of 75% (p < 0.0001) against all Vibrio strains, while Guava extract exhibited its maximum inhibition at 1600 µg/mL with an inhibition of 70% (p < 0.0001). Both biofilm inhibition and eradication assays were performed by the two conditions (24 h at 24°C and 72 h at 30°C) on Vibrio strains according to desirability analysis. Regarding 24 h at 24°C, differences were observed in the CFU counting between antibiotics and plant extracts, where both plant extracts demonstrated a higher reduction of viable cells when compared with both antibiotics at 8x, 16x, and 32x MIC values (Eucalyptus extract: 1600, 3200, and 6400 µg/mL; while Guava extract: 12800, 25600, and 52000 µg/mL). Concerning 72 h at 30°C, results showed a less notorious biomass inhibition by Guava leaf extract and tetracycline. However, Eucalyptus extract significantly reduced the total number of viable cells within Vibrio biofilms from 2x to 32x MIC values (400-6400 µg/mL) when compared to the same MIC values of ceftriaxone (5-80 µg/mL), which was not able to reduce viable cells. Eucalyptus extract demonstrated similar results at both growth conditions, showing an average inhibition of approximately 80% at 400 µg/mL concentration for all Vibrio isolates (p < 0.0001). Moreover, eradication biofilm assays demonstrated significant eradication against all Vibrio strains at both growth conditions, but biofilm eradication values were substantially lower. Both extract plants demonstrated a higher reduction of viable cells when compared with both antibiotics at 8x, 16x, and 32x MIC values at both growth sets, where Eucalyptus extract at 800 µg/mL reduced 70% of biomass and 90% of viable cells for all Vibrio strains (p < 0.0001). Overall results suggested a viable alternative against vibriosis in the shrimp industry in Ecuador.

Exploring the Multifaceted Biological Activities of Anthocyanins Isolated from Two Andean Berries.

Natural pigments extracted from plant species are used in foods, cosmetics, and pharmaceuticals. This study evaluates the comprehensive biological activities of anthocyanins isolated from Andean blueberry (Vaccinium floribundum Kunth) and Andean blackberry (Rubus glaucus Benth), focusing on their antimicrobial, antioxidant, antitumoral, anti-inflammatory, and hemolytic properties. Chemical characterization revealed significant anthocyanin content with complex mass spectrometric profiles indicating diverse glycosylation patterns that may influence their bioactivity. The antimicrobial assays showed that the extracts were particularly effective against Gram-positive bacteria, with minimal inhibitory concentrations (MICs) as low as 1 mg/mL for Rubus glaucus, indicating strong potential for therapeutic use. The antioxidant capacity of the berries was substantial, albeit slightly lower than that of ascorbic acid. The extracts also exhibited notable antitumoral activity in various cancer cell lines, showing promise as adjunctive or preventive treatments. The anti-inflammatory effects were confirmed by inhibiting nitric oxide production in macrophage cells, highlighting their potential in managing inflammatory diseases. In terms of hemolytic activity, Rubus glaucus exhibited dose-dependent effects, potentially attributable to anthocyanins and phenolics, while Vaccinium floribundum demonstrated no significant hemolytic activity, underscoring its safety. These findings suggest that anthocyanins from Andean berries possess potent biological activities, which could be leveraged for health benefits in pharmaceutical and nutraceutical applications. Further studies are needed to isolate specific bioactive compounds and investigate their synergistic effects in clinical and real-world contexts.

A chemical analysis of the Pelargonium species: P. odoratissimum, P. graveolens, and P. zonale identifies secondary metabolites with activity against gram-positive bacteria with multidrug-resistance.

The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds.

Prediction of compound-target interaction using several artificial intelligence algorithms and comparison with a consensus-based strategy.

For understanding a chemical compound's mechanism of action and its side effects, as well as for drug discovery, it is crucial to predict its possible protein targets. This study examines 15 developed target-centric models (TCM) employing different molecular descriptions and machine learning algorithms. They were contrasted with 17 third-party models implemented as web tools (WTCM). In both sets of models, consensus strategies were implemented as potential improvement over individual predictions. The findings indicate that TCM reach f1-score values greater than 0.8. Comparing both approaches, the best TCM achieves values of 0.75, 0.61, 0.25 and 0.38 for true positive/negative rates (TPR, TNR) and false negative/positive rates (FNR, FPR); outperforming the best WTCM. Moreover, the consensus strategy proves to have the most relevant results in the top 20 % of target profiles. TCM consensus reach TPR and FNR values of 0.98 and 0; while on WTCM reach values of 0.75 and 0.24. The implemented computational tool with the TCM and their consensus strategy at: https://bioquimio.udla.edu.ec/tidentification01/ . Scientific Contribution: We compare and discuss the performances of 17 public compound-target interaction prediction models and 15 new constructions. We also explore a compound-target interaction prioritization strategy using a consensus approach, and we analyzed the challenging involved in interactions modeling.

Evaluation of the polyphenolic profile of native Ecuadorian stingless bee honeys (Tribe: Meliponini) and their antibiofilm activity on susceptible and multidrug-resistant pathogens: An exploratory analysis.

Biofilms are associated with infections that are resistant to conventional therapies, contributing to the antimicrobial resistance crisis. The need for alternative approaches against biofilms is well-known. Although natural products like stingless bee honeys (tribe: Meliponini) constitute an alternative treatment, much is still unknown. Our main goal was to evaluate the antibiofilm activity of stingless bee honey samples against multidrug-resistant (MDR) pathogens through biomass assays, fluorescence (cell count and viability), and scanning electron (structural composition) microscopy. We analyzed thirty-five honey samples at 15% (v/v) produced by ten different stingless bee species (Cephalotrigona sp., Melipona sp., M. cramptoni, M. fuscopilosa, M. grandis, M. indecisa, M. mimetica, M. nigrifacies, Scaptotrigona problanca, and Tetragonisca angustula) from five provinces of Ecuador (Tungurahua, Pastaza, El Oro, Los Ríos, and Loja) against 24-h biofilms of Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, and Candida tropicalis. The present honey set belonged to our previous study, where the samples were collected in 2018-2019 and their physicochemical parameters, chemical composition, mineral elements, and minimal inhibitory concentration (MIC) were screened. However, the polyphenolic profile and their antibiofilm activity on susceptible and multidrug-resistant pathogens were still unknown. According to polyphenolic profile of the honey samples, significant differences were observed according to their geographical origin in terms of the qualitative profiles. The five best honey samples (OR24.1, LR34, LO40, LO48, and LO53) belonging to S. problanca, Melipona sp., and M. indecisa were selected for further analysis due to their high biomass reduction values, identification of the stingless bee specimens, and previously reported physicochemical parameters. This subset of honey samples showed a range of 63-80% biofilm inhibition through biomass assays. Fluorescence microscopy (FM) analysis evidenced statistical log reduction in the cell count of honey-treated samples in all pathogens (P <0.05), except for S. aureus ATCC 25923. Concerning cell viability, C. tropicalis, K. pneumoniae ATCC 33495, and K. pneumoniae KPC significantly decreased (P <0.01) by 21.67, 25.69, and 45.62%, respectively. Finally, scanning electron microscopy (SEM) analysis demonstrated structural biofilm disruption through cell morphological parameters (such as area, size, and form). In relation to their polyphenolic profile, medioresinol was only found in the honey of Loja, while scopoletin, kaempferol, and quercetin were only identified in honey of Los Rios, and dihydrocaffeic and dihydroxyphenylacetic acids were only detected in honey of El Oro. All the five honey samples showed dihydrocoumaroylhexose, luteolin, and kaempferol rutinoside. To the authors' best knowledge, this is the first study to analyze stingless bees honey-treated biofilms of susceptible and/or MDR strains of S. aureus, K. pneumoniae, and Candida species.

Exploring the Chemistry of Ocimum Species under Specific Extractions and Chromatographic Methods: A Systematic Review.

Ocimum is considered the largest genus in the Lamiacea family. The genus includes basil, a group of aromatic plants with a wide range of culinary uses that nowadays draws attention for its medicinal and pharmaceutical potential. This systematic review intends to explore the chemical composition of nonessential oils and their variation across different Ocimum species. Moreover, we aimed to identify the state of knowledge regarding the molecular space in this genus as well as the different methods of extraction/identification and geographical location. Seventy-nine eligible articles were selected for the final analysis, from which we extracted more than 300 molecules. We found that the countries with the highest number of studies into Ocimum species are India, Nigeria, Brazil, and Egypt. However, from all known species of Ocimum, only 12 were found to have an extensive chemical characterization, particularly Ocimum basilicum and Ocimum tenuiflorum. Our study focused especially on alcoholic, hydroalcoholic, and water extracts, in which the main techniques for compound identifications are GC-MS, LC-MS, and LC-UV. Across the compiled molecules, we found a wide variety of compounds, especially flavonoids, phenolic acids, and terpenoids, suggesting that this genus could be a very useful source of possible bioactive compounds. The information collected in this review also emphasizes the huge gap between the vast number of Ocimum species discovered and the number of studies in each of them that determined the chemical characterization.

Molecular Modeling and In Vitro Evaluation of Piplartine Analogs against Oral Squamous Cell Carcinoma.

Cancer is a principal cause of death in the world, and providing a better quality of life and reducing mortality through effective pharmacological treatment remains a challenge. Among malignant tumor types, squamous cell carcinoma-esophageal cancer (EC) is usually located in the mouth, with approximately 90% located mainly on the tongue and floor of the mouth. Piplartine is an alkamide found in certain species of the genus Piper and presents many pharmacological properties including antitumor activity. In the present study, the cytotoxic potential of a collection of piplartine analogs against human oral SCC9 carcinoma cells was evaluated. The analogs were prepared via Fischer esterification reactions, alkyl and aryl halide esterification, and a coupling reaction with PyBOP using the natural compound 3,4,5-trimethoxybenzoic acid as a starting material. The products were structurally characterized using 1H and 13C nuclear magnetic resonance, infrared spectroscopy, and high-resolution mass spectrometry for the unpublished compounds. The compound 4-methoxy-benzyl 3,4,5-trimethoxybenzoate (9) presented an IC50 of 46.21 µM, high selectively (SI > 16), and caused apoptosis in SCC9 cancer cells. The molecular modeling study suggested a multi-target mechanism of action for the antitumor activity of compound 9 with CRM1 as the main target receptor.

Cinnamomum sp. and Pelargonium odoratissimum as the Main Contributors to the Antibacterial Activity of the Medicinal Drink Horchata: A Study Based on the Antibacterial and Chemical Analysis of 21 Plants.

Horchata, a herbal infusion drink from Ecuador containing a mixture of medicinal plants, has been reported to exhibit anti-inflammatory, analgesic, diuretic, and antioxidant activity. The antibacterial activity of each of the plants contained in the horchata mixture has not been fully evaluated. Thus, in this study, we analysed the antibacterial activity of 21 plants used in horchata, collected from the Ecuadorian Andes region, against bacterial strains of clinical importance. The methanolic extract of Cinnamomum sp. showed minimal inhibitory concentration (MIC) values of 250 µg/mL against Staphylococcus aureus ATCC25923 and Methicillin-resistant S. aureus (MRSA), while Pelargonium odoratissimum exhibited a MIC value of 500 µg/mL towards S. aureus ATCC25923. The high-performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS) analyses identified in Cinnamomum sp. epicatechin tannins, cinnamaldehyde, and prehelminthosporol molecules, whereas in P. odoratissimum, gallocatechin and epigallocatechin tannins, some flavonoids, and gallic acid and derivatives were identified. Finally, Cinnamomum sp. and P. odoratissimum showed partial inhibition of biofilm formation of S. aureus ATCC25923 and MRSA. Overall, our findings revealed which of the plants used in horchata are responsible for the antibacterial activity attributed to this herbal drink and exhibit the potential for Cinnamomum sp. and P. odoratissimum secondary metabolites to be explored as scaffolds in drug development.

Canonical or noncanonical? Structural plasticity of serine protease-binding loops in Kunitz-STI protease inhibitors.

The Kunitz-Soybean Trypsin Inhibitor (Kunitz-STI) family is a large family of proteins with most of its members being protease inhibitors. The versatility of the inhibitory profile and the structural plasticity of these proteins, make this family a promising scaffold for designing new multifunctional proteins. Historically, Kunitz-STI inhibitors have been classified as canonical serine protease inhibitors, but new inhibitors with novel inhibition mechanisms have been described in recent years. Different inhibition mechanisms could be the result of different evolutionary pathways. In the present work, we performed a structural analysis of all the crystallographic structures available for Kunitz-STI inhibitors to characterize serine protease-binding loop structural features and locations. Our study suggests a relationship between the conformation of serine protease-binding loops and the inhibition mechanism, their location in the ß-trefoil fold, and the plant source of the inhibitors. The classical canonical inhibitors of this family are restricted to plants from the Fabales order and bind their targets via the ß4-ß5 loop, whereas serine protease-binding loops in inhibitors from other plants lie mainly in the ß5-ß6 and ß9-ß10 loops. In addition, we found that the ß5-ß6 loop is used to inhibit two different families of serine proteases through a steric blockade inhibition mechanism. This work will help to change the general perception that all Kunitz-STI inhibitors are canonical inhibitors and proteins with protease-binding loops adopting noncanonical conformations are exceptions. Additionally, our results will help in the identification of protease-binding loops in uncharacterized or newly discovered inhibitors, and in the design of multifunctional proteins.

Evolutionary analysis of endogenous intronic retroviruses in primates reveals an enrichment in transcription binding sites associated with key regulatory processes.

Background: Endogenous retroviruses (ERVs) are the result of the integration of retroviruses into host DNA following germline infection. Endogenous retroviruses are made up of three main genes: gag, pol, and env, each of which encodes viral proteins that can be conserved or not. ERVs have been observed in a wide range of vertebrate genomes and their functions are associated with viral silencing and gene regulation. Results: In this work, we studied the evolutionary history of endogenous retroviruses associated with five human genes (INPP5B, DET1, PSMA1, USH2A, and MACROD2), which are located within intron sections. To verify the retroviral origin of the candidates, several approaches were used to detect and locate ERV elements. Both orthologous and paralogous genes were identified by Ensembl and then analyzed for ERV presence using RetroTector. A phylogenetic tree was reconstructed to identify the minimum time point of ERV acquisition. From that search, we detected ERVs throughout the primate lineage and in some other groups. Also, we identified the minimum origin of the ERVs from the parvorder Catarrhini to the Homininae subfamily. Conclusions: With the data collected, and by observing the transcription factors annotated inside ERVs, we propose that these elements play a relevant role in gene expression regulation and they probably possess important features for tumorigenesis control.

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules.

Ever since coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, was declared a pandemic on March 11, 2020, by the WHO, a concerted effort has been made to find compounds capable of acting on the virus and preventing its replication. In this context, researchers have refocused part of their attention on certain natural compounds that have shown promising effects on the virus. Considering the importance of this topic in the current context, this study aimed to present a critical review and analysis of the main reports of plant-derived compounds as possible inhibitors of the two SARS-CoV-2 proteases: main protease (Mpro) and Papain-like protease (PLpro). From the search in the PubMed database, a total of 165 published articles were found that met the search patterns. A total of 590 unique molecules were identified from a total of 122 articles as potential protease inhibitors. At the same time, 114 molecules reported as natural products and with annotation of theoretical support and antiviral effects were extracted from the COVID-19 Help database. After combining the molecules extracted from articles and those obtained from the database, we identified 648 unique molecules predicted as potential inhibitors of Mpro and/or PLpro. According to our results, several of the predicted compounds with higher theoretical confidence are present in many plants used in traditional medicine and even food, such as flavonoids, carboxylic acids, phenolic acids, triterpenes, terpenes phytosterols, and triterpenoids. These are potential inhibitors of Mpro and PLpro. Although the predictions of several molecules against SARS-CoV-2 are promising, little experimental information was found regarding certain families of compounds. Only 45 out of the 648 unique molecules have experimental data validating them as inhibitors of Mpro or PLpro, with the most frequent scaffold present in these 45 compounds being the flavone. The novelty of this work lies in the analysis of the structural diversity of the chemical space among the molecules predicted as inhibitors of SARS-CoV-2 Mpro and PLpro proteases and the comparison to those molecules experimentally validated. This work emphasizes the need for experimental validation of certain families of compounds, preferentially combining classical enzymatic assays with interaction-based methods. Furthermore, we recommend checking the presence of Pan-Assay Interference Compounds (PAINS) and the presence of molecules previously reported as inhibitors of Mpro or PLpro to optimize resources and time in the discovery of new SARS-CoV-2 antivirals from plant-derived molecules.

Influence of Altitudes and Development Stages on the Chemical Composition, Antioxidant, and Antimicrobial Capacity of the Wild Andean Blueberry (Vaccinium floribundum Kunth).

The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry (Vaccinium floribundum Kunth), also known as mortiño, presents a unique combination of several phytochemicals, which play a synergistic role in its characterization as a functional food. We aimed to expose the possible variations that exist in the profile of the phenolic compounds as well as the antioxidant and antimicrobial capacity of the wild Andean blueberry with respect to three ripeness stages and two different altitudes. We found that polyphenols are the predominant compounds in the berry during the early ripeness stage and are the main bioactive compounds that give rise to the antioxidant capacity and inhibition effect on the growth of gram-positive and gram-negative bacteria. Moreover, the accumulation of ascorbic acid, free amino acids, and anthocyanins increases as the ripening process progresses, and they were the main bioactive compounds in the ripe berry. The latter compounds influence the production of the typical bluish or reddish coloration of ripe blueberries. In addition, it was determined that environmental conditions at high altitudes could have a positive influence in all cases. Overall, our data provide evidence regarding the high functional value of the wild Andean blueberry.

Evaluation of the biofilm life cycle between Candida albicans and Candida tropicalis.

Candida tropicalis is an emergent pathogen with a high rate of mortality associated with its biofilm formation. Biofilm formation has important repercussions on the public health system. However, little is still known about its biofilm life cycle. The present study analyzed the biofilm life cycle of Candida albicans and C. tropicalis during various timepoints (24, 48, 72, and 96 h) through biomass assays, colony-forming unit (CFU) counting, and epifluorescence and scanning electron microscopies. Our results showed a significant difference between C. albicans and C. tropicalis biofilms in each biomass and viability assay. All-time samples in the biomass and viability assays confirmed statistical differences between the Candida species through pairwise Wilcoxon tests (p < 0.05). C. albicans demonstrated a lower biomass growth but reached nearly the same level of C. tropicalis biomass at 96 h, while the CFU counting assays exhibited a superior number of viable cells within the C. tropicalis biofilm. Statistical differences were also found between C. albicans and C. tropicalis biofilms from 48- and 72-h microscopies, demonstrating C. tropicalis with a higher number of total cells within biofilms and C. albicans cells with a superior cell area and higher matrix production. Therefore, the present study proved the higher biofilm production of C. tropicalis.

Clustering Analysis of the Multi-Microbial Consortium by Lactobacillus Species Against Vaginal Dysbiosis Among Ecuadorian Women.

The vaginal microbiota plays vital protection in women. This probiotic activity is caused not only by individual Lactobacillus species but also by its multi-microbial interaction. However, the probiotic activity promoted by multi-microbial consortia is still unknown. The aim of this study was the individual and collective analysis on the prevalence of five vaginal lactobacilli (Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, and Lactobacillus acidophilus) among healthy women and women with bacterial vaginosis (BV) or aerobic vaginitis (AV). PCR assays were realized on 436 vaginal samples from a previous study. Chi-square, univariable, and multivariable logistic regression analyses with the Benjamini-Hochberg adjustment evaluated associations between these lactobacilli and vaginal microbiota. Multi-microbial clustering model was also realized through Ward's Minimum Variance Clustering Method with Euclidean squared distance for hierarchical clustering to determine the probiotic relationship between lactobacilli and vaginal dysbiosis. Concerning the individual effect, L. acidophilus, L. jensenii, and L. crispatus showed the highest normalized importance values against vaginal dysbiosis (100%, 79.3%, and 74.8%, respectively). However, only L. acidophilus and L. jensenii exhibited statistical values (p = 0.035 and p = 0.050, respectively). L. acidophilus showed a significant prevalence on healthy microbiota against both dysbioses (BV, p = 0.041; and AV, p = 0.045). L. jensenii only demonstrated significant protection against AV (p = 0.012). Finally, our results evidenced a strong multi-microbial consortium by L. iners, L. jensenii, L. gasseri, and L. acidophilus against AV (p = 0.020) and BV (p = 0.009), lacking protection in the absence of L. gasseri and L. acidophilus.

Genetic Variations of the DPYD Gene and Its Relationship with Ancestry Proportions in Different Ecuadorian Trihybrid Populations.

Dihydropyrimidine dehydrogenase is one of the main pharmacological metabolizers of fluoropyrimidines, a group of drugs widely used in clinical oncology. Around 20 to 30% of patients treated with fluoropyrimidines experience severe toxicity caused by a partial or total decrease in enzymatic activity. This decrease is due to molecular variants in the DPYD gene. Their prevalence and allelic frequencies vary considerably worldwide, so their description in heterogeneous groups such as the Ecuadorian population will allow for the description of pharmacogenetic variants and proper characterization of this population. Thus, we genotyped all the molecular variants with a predictive value for DPYD in a total of 410 Ecuadorian individuals belonging to Mestizo, Afro-Ecuadorian, and Indigenous ethnic groups. Moreover, we developed a genetic ancestry analysis using 46 autosomal ancestry informative markers. We determined 20 genetic variations in 5 amplified regions, including 3 novel single nucleotide variants. The allele frequencies for DPYD variants c.1627G>A (*5, rs1801159), c.1129-15T>C (rs56293913), c.1218G>A (rs61622928), rs1337752, rs141050810, rs2786783, rs2811178, and g.97450142G>A (chr1, GRCh38.p13) are significantly related to Native American and African ancestry proportions. In addition, the FST calculated from these variants demonstrates the closeness between Indigenous and Mestizo populations, and evidences genetic divergence between Afro-Ecuadorian groups when compared with Mestizo and Indigenous ethnic groups. In conclusion, the genetic variability in the DPYD gene is related to the genetic component of ancestral populations in different Ecuadorian ethnic groups. The absence and low frequency of variants with predictive value for fluoropyrimidine toxicity such as DPYD *2A, HapB3, and c.2846A>T (prevalent in populations with European ancestry) is consistent with the genetic background found.

Metabolomic profile and computational analysis for the identification of the potential anti-inflammatory mechanisms of action of the traditional medicinal plants Ocimum basilicum and Ocimum tenuiflorum.

Ocimum basilicum and Ocimum tenuiflorum are two basil species widely used medicinally as an anti-inflammatory, antimicrobial and cardioprotective agent. This study focuses on the chemical characterization of the majoritarian compounds of both species and their anti-inflammatory potential. Up to 22 compounds such as various types of salvianolic acids, derivatives of rosmaniric acid and flavones were identified in both plants. The identified compounds were very similar between both plants and are consistent with previous finding in other studies in Portugal and Italy. Based on the identified molecules a consensus target prediction was carried out. Among the main predicted target proteins, we found a high representation of the carbonic anhydrase family (CA2, CA7 and CA12) and several key proteins from the arachidonic pathway (LOX5, PLA2, COX1 and COX2). Both pathways are well related to inflammation. The interaction between the compounds and these targets were explored through molecular docking and molecular dynamics simulation. Our results suggest that some molecules present in both plants can induce an anti-inflammatory response through a non-steroidal mechanism of action connected to the carbon dioxide metabolism.

Prevalence of biofilms in Candida spp. bloodstream infections: A meta-analysis.

CONTEXT: Candida-related infections are nowadays a serious Public Health Problem emerging multidrug-resistant strains. Candida biofilm also leads bloodstream infections to invasive systemic infections. OBJECTIVE: The present meta-analysis aimed to analyze Candida biofilm rate, type, and antifungal resistance among hospitalized patients between 1995 and 2020. DATA SOURCES: Web of Science, Scopus, PubMed, and Google Scholar databases were searched for English papers using the following medical subject heading terms (MESH): "invasive candidiasis"; "bloodstream infections"; "biofilm formation"; "biofilm-related infections"; "mortality"; and "prevalence". STUDY SELECTION: The major inclusion criteria included reporting the rate of biofilm formation and the prevalence of biofilm-related to Candida species, including observational studies (more exactly, cohort, retrospective, and case-control studies). Furthermore, data regarding the mortality rate, the geographical location of the study set, and the use of anti-fungal agents in clinical isolates were also extracted from the studies. DATA EXTRACTION: Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. DATA SYNTHESIS: A total of 31 studies from publicly available databases met our inclusion criteria. The biofilm formation in the data set varied greatly from 16 to 100% in blood samples. Most of the studies belonged to Europe (17/31) and Asia (9/31). Forest plot showed a pooled rate of biofilm formation of 80.0% (CI: 67-90), with high heterogeneity (Q = 2567.45, I2 = 98.83, τ2 = 0.150) in random effects model (p < 0.001). The funnel plot and Egger's linear regression test failed to find publication bias (p = 0.896). The mortality rate in Candida-related bloodstream infections was 37.9% of which 70.0% were from biofilm-associated infections. Furthermore, Candida isolates were also characterized in low, intermediate, or high biofilm formers through their level of biofilm mass (crystal violet staining or XTT assays) after a 24h growth. When comparing between countries, statistical differences were obtained (p = 0.0074), showing the lower and higher biofilm prevalence values in Italy and Spain, respectively. The prevalence of low, intermediate, and high biofilms were 36.2, 18.9, and 35.0% (p < 0.0001), respectively. C. tropicalis was the prevalent species in high biofilm formation (67.5%) showing statistically significant differences when compared to other Candida species, except for C. krusei and C. glabrata. Finally, the rates of antifungal resistance to fluconazole, voriconazole, and caspofungin related to biofilm were 70.5, 67.9 and 72.8% (p < 0.001), respectively. CONCLUSIONS: Early detection of biofilms and a better characterization of Candida spp. bloodstream infections should be considered, which eventually will help preserve public health resources and ultimately diminish mortality among patients.

Comparative organizational network analysis considering formal power-based networks and organizational hierarchies.

Comparative organizational network analysis makes it possible to identify the similarities and differences between organizations according to the content of their networks. This research is a comparative study of organizational networks based on formal power. To accomplish this goal, networks were developed in three organizations from different sectors with workers distributed in high, middle and operational levels in the organizational hierarchy. For the study, 100% of the workers within the identified networks were included. The results indicated that, considering centrality and connectivity network indices, there were no statistically significant differences between organizations according to formal power network behavior. However, we obtained statistically significant differences in terms connectivity and centrality considering the workers' hierarchy. The representative nodes of high and middle hierarchical levels had higher indices of connectivity and centrality than the nodes representative of the operational level. This study makes it possible to identify the formal roles within networks based on legitimate power, which can serve as a basis for decision-making processes and resource allocations, for the strategic use of the networks created.