Cocoa and Carob Supplementation, Alone or in Combination with Metformin, Protects against Hepatorenal Injury in Zucker Diabetic Fatty Rats.

The liver and kidneys are crucial for glucose homeostasis and are seriously damaged in diabetes. Cocoa and carob possess antidiabetic activity, but their hepatorenal protective effects, especially when combined with antidiabetic drugs, are unknown. The aim of this study is to investigate the effects of a cocoa-carob-supplemented diet (CC), either alone or in combination with metformin, on liver and kidney damage in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model. Male ZDF animals received a control or CC-supplemented diet, with or without metformin, and Zucker lean rats were fed the control diet. The CC-supplemented diet improved glucose tolerance and insulin resistance and alleviated functional and structural alterations in the diabetic liver and renal cortex. The CC-supplemented diet also ameliorated oxidative stress, downregulated apoptosis, and improved insulin signalling and glucose homeostasis. The combination of CC and metformin boosted several benefits as certain parameters related to morphological and structural alterations, apoptosis, oxidative stress, glucose homeostasis, and insulin resistance, were improved in comparison to animals receiving the CC-supplemented diet or metformin alone; these include the following: apoptotic index, Bax, hepatic insulin receptor or glutathione content, among others. These results demonstrate that the CC-supplemented diet alleviates the hepatorenal damage in type 2 diabetic ZDF rats, highlighting its potential alone or as an adjuvant therapy.

Diversity of bacterial communities in wetlands of Calakmul Biosphere Reserve: a comparative analysis between conserved and semi-urbanized zones in pre-Mayan Train era.

BACKGROUND: The Calakmul Biosphere Reserve (CBR) is known for its rich animal and plant biodiversity, yet its microbial communities remain largely unknown. The reserve does not possess permanent bodies of water; nevertheless, seasonal depressions associated with fractures create wetlands, known locally as aguadas. Given the recent construction of the Maya train that crosses the CRB, it is essential to assess the biodiversity of its microorganisms and recognize their potential as a valuable source of goods. This evaluation is pivotal in mitigating potential mismanagement of the forest ecosystem. To enhance comprehension of microbial communities, we characterized the microbiota in three different wetlands. Ag-UD1 and Ag-UD2 wetlands are located in a zone without human disturbances, while the third, Ag-SU3, is in a semi-urbanized zone. Sampling was carried out over three years (2017, 2018, and 2019), enabling the monitoring of spatiotemporal variations in bacterial community diversity. The characterization of microbiome composition was conducted using 16S rRNA metabarcoding. Concurrently, the genomic potential of select samples was examined through shotgun metagenomics. RESULTS: Statistical analysis of alpha and beta diversity indices showed significant differences among the bacterial communities found in undisturbed sites Ag-UD1 and Ag-UD2 compared to Ag-SU3. However, no significant differences were observed among sites belonging to the undisturbed area. Furthermore, a comparative analysis at the zone level reveals substantial divergence among the communities, indicating that the geographic location of the samples significantly influences these patterns. The bacterial communities in the CBR wetlands predominantly consist of genera from phyla Actinobacteria, Acidobacteria, and Proteobacteria. CONCLUSION: This characterization has identified the composition of microbial communities and provided the initial overview of the metabolic capacities of the microbiomes inhabiting the aguadas across diverse conservation zones. The three sites exhibit distinct microbial compositions, suggesting that variables such as chemical composition, natural and anthropogenic disturbances, vegetation, and fauna may play a pivotal role in determining the microbial structure of the aguadas. This study establishes a foundational baseline for evaluating the impact of climatic factors and human interventions on critical environments such as wetlands.

Melanocytic cutaneous lesions in Sus ibericus, are these a cause for meat condemnation?

The Alentejano pig (Sus ibericus) is an autochthonous breed of swine from Portugal phylogenetically close to the Iberian breed that is known to develop melanocytic lesions. In this study, 34 melanocytic skin lesions were identified and collected from Alentejano pigs slaughtered for human consumption for further routine histologic assessment. The samples were classified into 4 age ranges: 1 (1 to 6 months), 2 (7 to 12 months) 3 (13 to 24 months), and 4 (more than 25 months). All the lesions were considered benign after the histopathological assessment, of which 52.9% and 47.1%, were classified as melanosis and melanocytomas, respectively. Regarding the age ranges, a statistical difference between the groups was observed, indicating that the probability of melanosis presentation was higher at the age range 4 and for melanocytomas at the age range 3. While no malignant lesions were observed in this study, it was concluded that benign melanocytic lesions are commonly found in Alentejano pig carcasses. Further research is necessary to accurately distinguish between malignant and benign lesions, which is crucial for official veterinarians to make decisions regarding meat approval or condemnation.

Antibacterial activity of Nocardia spp. and Streptomyces sp. on multidrug-resistant pathogens causing neonatal sepsis.

Neonatal sepsis leads to severe morbidity and occasionally death among neonates within the first week following birth, particularly in low- and middle-income countries. Empirical therapy includes antibiotics recommended by WHO. However, these have been ineffective against antimicrobial multidrug-resistant bacterial strains such as Klebsiella spp, Escherichia coli, and Staphylococcus aureus species. To counter this problem, new molecules and alternative sources of compounds with antibacterial activity are sought as options. Actinobacteria, particularly pathogenic strains, have revealed a biotechnological potential still underexplored. This study aimed to determine the presence of biosynthetic gene clusters and the antimicrobial activity of actinobacterial strains isolated from clinical cases against multidrug-resistant bacteria implicated in neonatal sepsis. In total, 15 strains isolated from clinical cases of actinomycetoma were used. PCR screening for the PKS-I, PKS-II, NRPS-I, and NRPS-II biosynthetic systems determined their secondary metabolite-producing potential. The strains were subsequently assayed for antimicrobial activity by the perpendicular cross streak method against Escherichia fergusonii Sec 23, Klebsiella pneumoniae subsp. pneumoniae H1064, Klebsiella variicola H776, Klebsiella oxytoca H793, and Klebsiella pneumoniae subsp. ozaenae H7595, previously classified as multidrug-resistant. Finally, the strains were identified by 16S rRNA gene sequence analysis. It was found that 100% of the actinobacteria had biosynthetic systems. The most frequent biosynthetic system was NRPS-I (100%), and the most frequent combination was NRPS-I and PKS-II (27%). All 15 strains showed antimicrobial activity. The strain with the highest antimicrobial activity was Streptomyces albus 94.1572, as it inhibited the growth of the five multidrug-resistant bacteria evaluated.

Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 in APAP-induced hepatotoxicity. The molecular mechanisms that regulate the balance between cell death and survival and the response to oxidative stress induced by APAP was assessed in cultured human hepatocyte-derived (Huh7) cells treated with pharmacological inhibitors of ALK receptors and with modulated expression of ALK2 or ALK3 by lentiviral infection, and in a mouse model of APAP-induced hepatotoxicity. Inhibition of ALK3 signalling with the pharmacological inhibitor DMH2, or by silencing of ALK3, showed a decreased cell death both by necrosis and apoptosis after APAP treatment. Also, upon APAP challenge, ROS generation was ameliorated and, thus, ROS-mediated JNK and P38 MAPK phosphorylation was reduced in ALK3-inhibited cells compared to control cells. These results were also observed in an experimental model of APAP-induced ALF in which post-treatment with DMH2 after APAP administration significantly reduced liver tissue damage, apoptosis and oxidative stress. This study shows the protective effect of ALK3 receptor inhibition against APAP-induced hepatotoxicity. Furthermore, findings obtained from the animal model suggest that BMP signalling might be a new pharmacological target for the treatment of ALF.

(-)-Epicatechin and colonic metabolite 2,3-dihydroxybenzoic acid, alone or in combination with metformin, protect cardiomyocytes from high glucose/high palmitic acid-induced damage by regulating redox status, apoptosis and autophagy.

(-)-Epicatechin (EC) and a main colonic phenolic acid derived from flavonoid intake, 2,3-dihydroxybenzoic acid (DHBA), display antioxidant and antidiabetic activities. Diabetic cardiomyopathy (DCM) is one of the main causes of mortality in patients with diabetes, lacking a suitable treatment. Hyperglycaemia and dyslipidaemia are mainly responsible for oxidative stress and altered apoptosis and autophagy in cardiomyocytes during DCM. In this context, phenolic compounds could be suitable candidates for alleviating DCM, but have scarcely been investigated or their use in combination with antidiabetic drugs. This study evaluates the effects of EC, DHBA and antidiabetic drug metformin (MET), alone or all combined (MIX), on redox status, autophagy and apoptosis in H9c2 cardiomyocytes challenged with high concentrations of glucose (HG) and palmitic acid (PA). Under HG + PA conditions, EC, DHBA, MET and MIX equally improved redox status, reduced apoptosis induction and ameliorated autophagy inhibition. Mechanistically, all treatments alleviated HG + PA-induced oxidative stress by reinforcing antioxidant defences (∼40% increase in glutathione, ∼30% diminution in GPx activity and ∼15% increase in SOD activity) and reducing ROS generation (∼20%), protein oxidation (∼35%) and JNK phosphorylation (∼200%). Additionally, all treatments mitigated HG + PA-induced apoptosis and activated autophagy by decreasing Bax (∼15-25%), caspase-3 (∼20-40%) and p62 (∼20-40%), and increasing Bcl-2, beclin-1 and LC3-II/LC3-I (∼40-60%, ∼15-20%, and ∼25-30%, respectively). JNK inhibition improved protective changes to redox status, apoptosis and autophagy that were observed in EC-, DHBA- and MIX-mediated protection. Despite no additive or synergistic effects being detected when phenolic compounds and MET were combined, these results provide the first evidence for the benefits of EC and DHBA, comparable to those of MET alone, to ameliorate cardiomyocyte damage, that involve an improvement in antioxidant competence, autophagy and apoptosis, these effects being mediated at least by targeting JNK.

Synergistic Effect of a Flavonoid-Rich Cocoa-Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats.

The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes.

Antibacterial activity of Nocardia spp. and Streptomyces sp. on multidrug-resistant pathogens causing neonatal sepsis

ABSTRACT Neonatal sepsis leads to severe morbidity and occasionally death among neonates within the first week following birth, particularly in low- and middle-income countries. Empirical therapy includes antibiotics recommended by WHO. However, these have been ineffective against antimicrobial multidrug-resistant bacterial strains such as Klebsiella spp, Escherichia coli, and Staphylococcus aureus species. To counter this problem, new molecules and alternative sources of compounds with antibacterial activity are sought as options. Actinobacteria, particularly pathogenic strains, have revealed a biotechnological potential still underexplored. This study aimed to determine the presence of biosynthetic gene clusters and the antimicrobial activity of actinobacterial strains isolated from clinical cases against multidrug-resistant bacteria implicated in neonatal sepsis. In total, 15 strains isolated from clinical cases of actinomycetoma were used. PCR screening for the PKS-I, PKS-II, NRPS-I, and NRPS-II biosynthetic systems determined their secondary metabolite-producing potential. The strains were subsequently assayed for antimicrobial activity by the perpendicular cross streak method against Escherichia fergusonii Sec 23, Klebsiella pneumoniae subsp. pneumoniae H1064, Klebsiella variicola H776, Klebsiella oxytoca H793, and Klebsiella pneumoniae subsp. ozaenae H7595, previously classified as multidrug-resistant. Finally, the strains were identified by 16S rRNA gene sequence analysis. It was found that 100% of the actinobacteria had biosynthetic systems. The most frequent biosynthetic system was NRPS-I (100%), and the most frequent combination was NRPS-I and PKS-II (27%). All 15 strains showed antimicrobial activity. The strain with the highest antimicrobial activity was Streptomyces albus 94.1572, as it inhibited the growth of the five multidrug-resistant bacteria evaluated.

Cedrela domatifolia (Meliaceae), un nuevo registro de cedro para el Perú

Cedrela domatifolia W. Palacios es registrada por primera vez para Perú en el valle de Chanchamayo, departamento de Junín. Con esta adición se elevan a 11 especies del género Cedrela (Meliaceae) en el Perú. La característica vegetativa más resaltante de C. domatifolia son los domacios prominentes, situados en las axilas de los nervios secundarios de las láminas por el envés. En caracteres florales, los pétalos son de color rojo a fucsia, una característica no común en el género.

A new record of Cedrela domatifolia W. Palacios is presented in Chanchamayo Valley, department of Junin, which adds to 11 the number of Cedrela (Meliaceae) species recorded in Peru. The most notorious vegetative character of the species are the prominent domatia in the axils of the secondary nerves of blades. At floral characters, the petals are red to fuchsia, an uncommon feature in the genus.

Emergence of Raoultella ornithinolytica in human infections from different hospitals in Ecuador with OXA-48-producing resistance.

Purpose: The purpose of this study was to highlight the clinical and molecular features of 13 Raoultella ornithinolytica strains isolated from clinical environments in Ecuador, and to perform comparative genomics with previously published genomes of Raoultella spp. As Raoultella is primarily found in environmental, clinical settings, we focused our work on identifying mechanisms of resistance that can provide this bacterium an advantage to establish and persist in hospital environments. Methods: We analyzed 13 strains of Raoultella ornithinolytica isolated from patients with healthcare associated infections (HAI) in three hospitals in Quito and one in Santo Domingo de Los Tsáchilas, Ecuador, between November 2017 and April 2018. These isolates were subjected to phenotypic antimicrobial susceptibility testing, end-point polymerase chain reaction (PCR) to detect the presence of carbapenemases and whole-genome sequencing. Results: Polymerase chain reaction revealed that seven isolates were positive isolates for blaOXA-48 and one for blaKPC-2 gene. Of the seven strains that presented the blaOXA-48 gene, six harbored it on an IncFII plasmid, one was inserted into the bacterial chromosome. The blaKPC gene was detected in an IncM2/IncR plasmid. From the bioinformatics analysis, nine genomes had the gene blaOXA-48, originating from Ecuador. Moreover, all R. ornithinolytica strains contained the ORN-1 gene, which confers resistance for ß-lactams, such as penicillins and cephalosporins. Comparative genome analysis of the strains showed that the pangenome of R. ornithinolytica is considered an open pangenome, with 27.77% of core genes, which could be explained by the fact that the antibiotic resistance genes in the ancestral reconstruction are relatively new, suggesting that this genome is constantly incorporating new genes. Conclusion: These results reveal the genome plasticity of R. ornithinolytica, particularly in acquiring antibiotic-resistance genes. The genomic surveillance and infectious control of these uncommon species are important since they may contribute to the burden of antimicrobial resistance and human health.

Dietary Supplementation with a Cocoa-Carob Blend Modulates Gut Microbiota and Prevents Intestinal Oxidative Stress and Barrier Dysfunction in Zucker Diabetic Rats.

We have recently developed a cocoa-carob blend (CCB) rich in polyphenols with antidiabetic properties. In this study, we investigated whether its benefits could be related to gut health and gut microbiota (GM) composition and the likely phenolic metabolites involved. Zucker diabetic fatty rats were fed on a standard or a CCB-rich diet for 12 weeks. Intestinal barrier structure and oxidative and inflammatory biomarkers were analyzed in colonic samples. GM composition and phenolic metabolites were evaluated from feces. The results show that CCB improved mucin and tight-junction proteins and counteracted gut oxidative stress and inflammation by regulating sirtuin-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) levels. CCB also modulated the composition of the GM, showing increases in Akkermansia and Bacteroides and decreases in Ruminococcus genera. Correlation analysis strengthened the associations between these genera and improved pathological variables in diabetic animals. Moreover, 12 phenolic metabolites were identified in CCB feces, being2,3-dihydroxybenzoic and 3,4,5-trihydroxybenzoic acids significantly associated with increased levels of Akkermansia and Oscillospira genera. Our findings support the potential use of CCB to prevent intestinal damage and dysbiosis in T2D, which would help to delay the progression of this pathology.

Evaluation of the Ability to Form Biofilms in KPC-Producing and ESBL-Producing Klebsiella pneumoniae Isolated from Clinical Samples.

The appearance of Klebsiella pneumoniae strains producing extended-spectrum ß-lactamase (ESBL), and carbapenemase (KPC) has turned into a significant public health issue. ESBL- and KPC-producing K. pneumoniae's ability to form biofilms is a significant concern as it can promote the spread of antibiotic resistance and prolong infections in healthcare facilities. A total of 45 K. pneumoniae strains were isolated from human infections. Antibiograms were performed for 17 antibiotics, ESBL production was tested by Etest ESBL PM/PML, a rapid test was used to detect KPC carbapenemases, and resistance genes were detected by PCR. Biofilm production was detected by the microtiter plate method. A total of 73% of multidrug resistance was found, with the highest resistance rates to ampicillin, trimethoprim-sulfamethoxazole, cefotaxime, amoxicillin-clavulanic acid, and aztreonam. Simultaneously, the most effective antibiotics were tetracycline and amikacin. blaCTX-M, blaTEM, blaSHV, aac(3)-II, aadA1, tetA, cmlA, catA, gyrA, gyrB, parC, sul1, sul2, sul3, blaKPC, blaOXA, and blaPER genes were detected. Biofilm production showed that 80% of K. pneumoniae strains were biofilm producers. Most ESBL- and KPC-producing isolates were weak biofilm producers (40.0% and 60.0%, respectively). There was no correlation between the ability to form stronger biofilms and the presence of ESBL and KPC enzymes in K. pneumoniae isolates.

Evidence of natural selection and dominance of SARS-CoV-2 variant Lambda (C.37) over variants of concern in Cusco, Peru.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage C.37 (Lambda) has spread rapidly in Peru and other Latin American countries. However, most studies in Peru have focused on Lima, the capital city, without knowing the dynamics of the spread of the variant in other departments. Cusco, Peru, is one of the most popular departments in the country for tourists, so the introduction of new variants of SARS-CoV-2 might occur despite closure of the borders. Therefore, in this work, we analyzed the variants circulating in Cusco. The aim of this work was to better understand the distribution of SARS-CoV-2 lineages circulating in Cusco and to characterize the genomes of these strains. To this end, 46 SARS-CoV-2 genomes from vaccinated and unvaccinated patients were sequenced in the first half of 2021. The genomes were analyzed using phylogenetic and natural selection methods. Phylogenetic trees from Cusco showed dominance of the Lambda lineage over the variants of concern (VOCs), and there was no clustering of variants by district. Natural selection analysis revealed mutations, mainly in the spike protein, at positions 75, 246, 247, 707, 769, and 1020. In addition, we found that unvaccinated patients accumulated more new mutations than did vaccinated patients, and these included the F101Y mutation in ORF7a, E419A in NSP3, a deletion in S (21,618-22,501), and a deletion in ORF3a (25,437-26,122).

Urinary Metabolomics Study on the Protective Role of Cocoa in Zucker Diabetic Rats via 1H-NMR-Based Approach.

Cocoa constitutes one of the richest sources of dietary flavonoids with demonstrated anti-diabetic potential. However, the metabolic impact of cocoa intake in a diabetic context remains unexplored. In this study, metabolomics tools have been used to investigate the potential metabolic changes induced by cocoa in type 2 diabetes (T2D). To this end, male Zucker diabetic fatty rats were fed on standard (ZDF) or 10% cocoa-rich diet (ZDF-C) from week 10 to 20 of life. Cocoa supplementation clearly decreased serum glucose levels, improved glucose metabolism and produced significant changes in the urine metabolome of ZDF animals. Fourteen differential urinary metabolites were identified, with eight of them significantly modified by cocoa. An analysis of pathways revealed that butanoate metabolism and the synthesis and degradation of branched-chain amino acids and ketone bodies are involved in the beneficial impact of cocoa on diabetes. Moreover, correlation analysis indicated major associations between some of these urine metabolites (mainly valine, leucine, and isoleucine) and body weight, glycemia, insulin sensitivity, and glycated hemoglobin levels. Overall, this untargeted metabolomics approach provides a clear metabolic fingerprint associated to chronic cocoa intake that can be used as a marker for the improvement of glucose homeostasis in a diabetic context.

Metabolic regulation of (-)-epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid on the glucose uptake, lipid accumulation and insulin signalling in cardiac H9c2 cells.

Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake have been suggested to exert healthful effects, although their mechanism of action remains unknown. Heart damage is highly prevalent in metabolic diseases, and the failure of this organ is a major cause of death worldwide. In this study, the modulation of the energy metabolism and insulin signalling by the mentioned compounds in cardiac H9c2 cells was evaluated. Incubation of cells with EC (1-20 µM) and 2,3-dihydroxybenzoic acid (DHBA, 10 µM) reduced glucose uptake, and both compounds decreased lipid accumulation at concentrations higher than 0.5 µM. EC and DHBA also increased the tyrosine phosphorylated and total insulin receptor (IR) levels, and activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in cardiac H9c2 cells. Interestingly, EC and DHBA did not modify glucose transporters (SGLT-1 and GLUT-1) levels, and increased GLUT-4 values. In addition, EC and DHBA decreased cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) values, and enhanced carnitine palmitoyl transferase 1 (CPT1) and proliferator activated receptor α (PPARα) levels. By using specific inhibitors of AKT and 5'-AMP-activated protein kinase (AMPK), the participation of both proteins in EC- and DHBA-mediated regulation on glucose uptake and lipid accumulation was shown. Taken together, EC and DHBA modulate glucose uptake and lipid accumulation via AKT and AMPK, and reinforce the insulin signalling by activating key proteins of this pathway in H9c2 cells.

Satisfaction with testicular prosthesis: a Portuguese questionnaire-based study in testicular cancer survivors.

Radical orchiectomy in testicular cancer patients can have a negative impact on body image and self-esteem. Reconstructive surgery with testicular prosthesis might mitigate this burden. We conducted a questionnaire-based study aiming to evaluate our patients' satisfaction with testicular prosthesis. Overall satisfaction was rated as excellent or good in 97.7%. The main complaints were related to the prosthesis' inappropriate texture (45.5%), size (18.1%) or position (15.9%). Among men interviewed, 59% considered that having a normal looking scrotum was either extremely important or important for their self-esteem. The majority (88.2%) stated they would make the same decision again, and nearly all patients would recommend it to other men with testicular cancer. We believe testicular implants should always be offered, leaving the final decision to the patient.

Supplementation with a Cocoa-Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats.

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa-carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

Antimicrobial Resistance Genes and Diversity of Clones among Faecal ESBL-Producing Escherichia coli Isolated from Healthy and Sick Dogs Living in Portugal.

The purpose of this study was to analyse the prevalence and genetic characteristics of ESBL and acquired-AmpC (qAmpC)-producing Escherichia coli isolates from healthy and sick dogs in Portugal. Three hundred and sixty-one faecal samples from sick and healthy dogs were seeded on MacConkey agar supplemented with cefotaxime (2 µg/mL) for cefotaxime-resistant (CTXR) E. coli recovery. Antimicrobial susceptibility testing for 15 antibiotics was performed and the ESBL-phenotype of the E. coli isolates was screened. Detection of antimicrobial resistance and virulence genes, and molecular typing of the isolates (phylogroups, multilocus-sequence-typing, and specific-ST131) were performed by PCR (and sequencing when required). CTXRE. coli isolates were obtained in 51/361 faecal samples analysed (14.1%), originating from 36/234 sick dogs and 15/127 healthy dogs. Forty-seven ESBL-producing E. coli isolates were recovered from 32 sick (13.7%) and 15 healthy animals (11.8%). Different variants of blaCTX-M genes were detected among 45/47 ESBL-producers: blaCTX-M-15 (n = 26), blaCTX-M-1 (n = 10), blaCTX-M-32 (n = 3), blaCTX-M-55 (n = 3), blaCTX-M-14 (n = 2), and blaCTX-M-variant (n = 1); one ESBL-positive isolate co-produced CTX-M-15 and CMY-2 enzymes. Moreover, two additional CTXR ESBL-negative E. coli isolates were CMY-2-producers (qAmpC). Ten different sequence types were identified (ST/phylogenetic-group/ß-lactamase): ST131/B2/CTX-M-15, ST617/A/CTX-M-55, ST3078/B1/CTX-M-32, ST542/A/CTX-M-14, ST57/D/CTX-M-1, ST12/B2/CTX-M-15, ST6448/B1/CTX-M-15 + CMY-2, ST5766/A/CTX-M-32, ST115/D/CMY-2 and a new-ST/D/CMY-2. Five variants of CTX-M enzymes (CTX-M-15 and CTX-M-1 predominant) and eight different clonal complexes were detected from canine ESBL-producing E. coli isolates. Although at a lower rate, CMY-2 ß-lactamase was also found. Dogs remain frequent carriers of ESBL and/or qAmpC-producing E. coli with a potential zoonotic role.

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity.

Type 2 diabetes (T2D) and obesity are relevant worldwide chronic diseases. A common complication in both pathologies is the dysregulation of the insulin-signaling pathway that is crucial to maintain an accurate glucose homeostasis. Flavonoids are naturally occurring phenolic compounds abundant in fruits, vegetables and seeds. Rising evidence supports a role for the flavonoids against T2D and obesity, and at present, these compounds are considered as important potential chemopreventive agents. This review summarizes in vitro and in vivo studies providing data related to the effects of flavonoids and flavonoid-rich foods on the modulation of the insulin route during T2D and obesity. Notably, few human studies have evaluated the regulatory effect of these phenolic compounds at molecular level on the insulin pathway. In this context, it is also important to note that the mechanism of action for the flavonoids is not fully characterized and that a proper dosage to obtain a beneficial effect on health has not been defined yet. Further investigations will contribute to solve all these critical challenges and will enable the use of flavonoids to prevent, delay or support the treatment of T2D and obesity.

Herramientas digitales como un aliado informativo en el Perú para el autocuidado en tiempos de COVID-19 / Digital tools as information aids for self-care in the time of COVID-19 in Peru

Este estudio tuvo como objetivo analizar las métricas disponibles de las herramientas digitales que fomentan el autocuidado para comprender sus efectos en la población en tiempos de COVID-19. Se realizó una búsqueda sobre sitios web, aplicaciones móviles y redes sociales que ofrecían información a la población sobre la COVID-19, los cuales debían pertenecer al gobierno peruano o a instituciones oficiales relacionadas con la salud. Se revisaron las métricas disponibles de cada herramienta digital para una posterior evaluación de uso. Los sitios web identificados brindaban información referente a la COVID-19, así como datos actualizados sobre los casos existentes, la autoevaluación para descartar la enfermedad y el reporte de resultados de la prueba para su diagnóstico. El sitio web más visitado fue el del Gobierno del Perú, el cual contenía la página web del Ministerio de Salud. Asimismo, la aplicación móvil del Gobierno del Perú PerúEnTusManos fue la más descargada por parte de la población peruana. Las redes sociales, en colaboración con estas herramientas digitales en el Perú, vienen siendo utilizadas activamente para informar e interactuar con la población en estos tiempos de COVID-19. Por lo tanto, por la rápida adaptabilidad que tienen los sitios web y las aplicaciones móviles, estas se han convertido en el Perú en una herramienta informativa ideal para hacer frente a la pandemia de la COVID-19(AU)

The purpose of the study was to analyze the metrics available for digital tools fostering self-care to understand their effects on the population in the time of COVID-19. A search was conducted about websites, mobile applications and social networks offering information to the population about COVID-19 and belonging to the Peruvian government or health-related official institutions. A review was performed of the metrics available for each digital tool with a view to an eventual evaluation of their use. The websites identified provided information about COVID-19 as well as updated data about existing cases, self-evaluation to rule out the disease and the report of results of diagnostic tests. The most visited website was that of the Government of Peru, which contained the website of the Ministry of Health. The mobile application of the Government of Peru PerúEnTusManos was the most commonly downloaded by the Peruvian population. Social networks, in joint cooperation with these digital tools, are actively used in Peru to inform and interact with the population in the time of COVID-19. Due to the rapid adaptability of websites and mobile applications, these have become an ideal information tool in Peru to face the COVID-19 pandemic(AU)