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  • 1
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-4-11)
    Abstract: A collection of 259 staphylococci of 13 different species [212 coagulase-negative (CoNS) and 47 coagulase-positive (CoPS)] recovered from nasotracheal samples of 87 healthy nestling white storks was tested by the spot-on-lawn method for antimicrobial-activity (AA) against 14 indicator bacteria. Moreover, extracts of AP isolates were obtained [cell-free-supernatants (CFS) both crude and concentrated and butanol extracts] and tested against the 14 indicator bacteria. The microbiota modulation capacity of AP isolates was tested considering: (a) intra-sample AA, against all Gram-positive bacteria recovered in the same stork nasotracheal sample; (b) inter-sample AA against a selection of representative Gram-positive bacteria of the nasotracheal microbiota of all the storks (30 isolates of 29 different species and nine genera). In addition, enzymatic susceptibility test was carried out in selected AP isolates and bacteriocin encoding genes was studied by PCR/sequencing. In this respect, nine isolates (3.5%; seven CoNS and two CoPS) showed AA against at least one indicator bacteria and were considered antimicrobial-producing (AP) isolates. The AP isolates showed AA only for Gram-positive bacteria. Three of these AP isolates ( S. hominis X3764, S. sciuri X4000, and S. chromogenes X4620) revealed AA on all extract conditions; other four AP isolates only showed activity in extracts after concentration; the remaining two AP isolates did not show AA in any of extract conditions. As for the microbiota modulation evaluation, three of the nine AP-isolates revealed intra-sample AA. It is to highlight the potent inter-sample AA of the X3764 isolate inhibiting 73% of the 29 representative Gram-positive species of the nasotracheal stork microbiota population. On the other hand, enzymatic analysis carried out in the two highest AP isolates (X3764 and X4000) verified the proteinaceous nature of the antimicrobial compound and PCR analysis revealed the presence of lantibiotic-like encoding genes in the nine AP isolates. In conclusion, these results show that nasotracheal staphylococci of healthy storks, and especially CoNS, produce antimicrobial substances that could be important in the modulations of their nasal microbiota.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 2
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 10 ( 2023-5-19)
    Abstract: Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer. Methods: Hepsin levels in plasma from resected and metastatic colorectal cancer patients were analyzed by ELISA. The effect of hepsin levels on cell migration, invasion, and proliferation, as well as on the activation of crucial cancer signaling pathways, was performed in vitro using colorectal cancer cells. A thrombin generation assay determined the procoagulant function of hepsin from these cells. A virtual screening of a database containing more than 2000 FDA-approved compounds was performed to screen hepsin inhibitors, and selected compounds were tested in vitro for their ability to suppress hepsin effects in colorectal cancer cells. Xenotransplantation assays were done in zebrafish larvae to study the impact of venetoclax on invasion promoted by hepsin. Results: Our results showed higher plasma hepsin levels in metastatic patients, among which, hepsin was higher in those suffering thrombosis. Hepsin overexpression increased colorectal cancer cell invasion, Erk1/2 and STAT3 phosphorylation, and thrombin generation in plasma. In addition, we identified venetoclax as a potent hepsin inhibitor that reduced the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells. Interestingly, pretreatment with Venetoclax of cells overexpressing hepsin reduced their invasiveness in vivo . Discussion: Our results demonstrate that hepsin overexpression correlates with a more aggressive and prothrombotic tumor phenotype. Likewise, they demonstrate the antitumor role of venetoclax as a hepsin inhibitor, laying the groundwork for molecular-targeted therapy for colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2814330-9
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  • 3
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-2-16)
    Abstract: Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. Methods To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. Results Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. Discussion In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-4-21)
    Abstract: COVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose. Methods We have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant. Results All these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination. Conclusion This work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 14 ( 2023-3-2)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-3-2)
    Abstract: Nasal carriage of coagulase-positive staphylococci (CoPS) in healthy dogs could indicate increased risks of colonization for in-contact people or vice versa. This study determined the nasal carriage rate of CoPS among healthy dogs and in-contact people, their genotypic characteristics and phylogenetic relatedness. Methods Nasal samples were collected from 27 households (34 dogs and 41 humans) in Spain. Staphylococci were identified by MALDI-TOF-MS, their antimicrobial resistance (AMR) genes and spa -types were tested by PCR/sequencing. The relatedness of CoPS from the same households was assessed by core genome single nucleotide polymorphisms (SNPs) analyses. Results Staphylococcus aureus carriage was found in 34.1% of humans (including one methicillin-resistant S. aureus MRSA-CC5-t2220-SCC mec type-IV2B) and 5.9% of dogs; Staphylococcus pseudintermedius in 2.4% of humans and 32.4% of dogs; while Staphylococcus coagulans was only detected in dogs (5.4%). Remarkably, one human co-carried S. aureus / S. pseudintermedius , while a dog co-carried the three CoPS species. Household density was significantly associated with S. pseudintermedius carriage in households with & gt; than 1 dog and & gt;than 1 human (OR = 18.10, 95% CI: 1.24–260.93, p  = 0.034). Closely related ( & lt;15 SNPs) S. aureus or S. pseudintermedius were found in humans or dogs in three households. About 56.3% S. aureus carriers (dog or human) harboured diverse within-host spa -types or AMR genotypes. Ten clonal complexes (CCs) were detected among the S. aureus , of which methicillin-susceptible S. aureus -CC398-IEC-type C (t1451 and t571) was the most frequent, but exclusive to humans. S. aureus and S. pseudintermedius isolates harboured resistance genes or mutations associated to 9 classes of antimicrobials including linezolid (G2261A & amp; T1584A point mutations in 23S rDNA). The S. coagulans isolates were susceptible to all antimicrobials. Most of the S. pseudintermedius carried lukS/F-I, siet, and sient genes, and all S. aureus were negative for lukS/F -PV , tst-1, eta and etb genes. Discussion Clonally related human-to-human MSSA and dog-to-human MSSP were found. The detection of the MSSA-CC398 clade highlights the need for its continuous surveillance from One Health perspective.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-4-26)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-4-26)
    Abstract: Bacteriocins are antimicrobial peptides with relevance in the modulation of human and animal microbiota that have gained interest in biomedical and biotechnological applications. In this study, the production of bacteriocin-like inhibitory substances (BLIS) was tested among a collection of 890 staphylococci of different origins (humans, animals, food, and the environment) and species, both coagulase-positive (CoPS, 238 isolates of 3 species) and coagulase-negative staphylococci (CoNS, 652 isolates of 26 species). Of the 890 staphylococci, 60 (6.7%) showed antimicrobial activity by the spot-on-lawn method against at least one of the 25 indicator bacteria tested. BLIS-producer (BLIS + ) isolates were detected in 8.8% of CoPS and 6.0% of CoNS. The staphylococcal species with the highest percentages of BLIS + isolates were S. chromogenes (38.5%), S. pseudintermedius (26.7%), and S. warneri (23.1%). The production of BLIS was more frequently detected among isolates of pets, wild animals, and food. Moreover, 13 BLIS + isolates showed wide antimicrobial activiy spectrum, and 7 of these isolates (of species S. aureus , S. pseudintermedius , S. sciuri , and S. hominis ) demonstrated antimicrobial activity against more than 70% of the indicator bacteria tested. The genetic characterization (by PCR and sequencing) of the 60 BLIS + isolates revealed the detection of (a) 11 CoNS and CoPS isolates carrying putative lantibiotic-like genes; (b) 3 S. pseudintermedius isolates harboring the genes of BacSp222 bacteriocin; and (c) 2 S. chromogenes isolates that presented the gene of a putative cyclic bacteriocin (uberolysin-like), being the first report in this CoNS species. Antimicrobial susceptibility testing was performed in BLIS + isolates and one-third of the CoNS isolates showed susceptibility to all antibiotics tested, which also lacked the virulence genes studied. These BLIS + CoNS are good candidates for further characterization studies.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Psychology Vol. 12 ( 2021-10-8)
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 12 ( 2021-10-8)
    Abstract: Inventory of Depression and Anxiety Symptoms-II (IDAS-II) constitutes a useful measurement tool with demonstrated psychometric properties that is contributing to the advancement of knowledge of emotional disorders within transdiagnostic models. To implement its use in clinical settings it is important that the scores can be interpreted in order to guide clinical decisions. This study aims to develops normative data for the Spanish version of the IDAS-II. An anonymous online survey was applied to 1,072 subjects, recruited through a stratified random sampling procedure taking into account population gender, age, and geographical region of Spain. Results show that women tend to score higher than men, particularly on the Dysphoria, General Depression, Appetite Gain, and Lassitude scales. Largest effect sizes for differences in the scores according to age were found for Lassitude, Dysphoria, and General Depression. Therefore, normative data according to gender and age group for each IDAS-II scale is provided. The norms provided in this work complement those already available, facilitating the decision-making of clinical professionals. Evidence of unidimensionality is provided for the 19 IDAS-II scales that allows researchers and clinicians to use specific IDAS-II scales independently.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2563826-9
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  • 8
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-10-29)
    Abstract: Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA 1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and & lt;5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA 1c ) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. Results Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06)] , as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [β=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA 1c levels and changes in GCF [β=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [β=-0.31 (95%CI -0.44, -0.18)] , and other cognitive tests. Conclusions Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk. Clinical Trial Registration http://www.isrctn.com/ISRCTN89898870 , identifier ISRCTN: 89898870.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 9
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 11 ( 2020-8-26)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 10
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 10 ( 2022-5-31)
    Abstract: During early skin-to-skin contact (ESSC), alterations in peripheral oxygen saturation (SpO 2 ) and heart rate (HR) have been frequently observed. Objectives This study aimed to determine the incidence of cardiorespiratory events (CREs) during ESSC in healthy term newborns (HTNs) and estimate the association of maternal and neonatal prognostic factors with the risk of CREs. Methods A pooled analysis of the cohort from a clinical trial involving healthy mother–child dyads during ESSC was performed. Pulse oximetry was employed to continuously monitor SpO 2 and HR within 2 h after birth. The individual and combined prognostic relevance of the demographic and clinical characteristics of dyads for the occurrence of a CRE (SpO 2 & lt;91% or HR & lt;111 or & gt;180 bpm) was analyzed through logistic regression models. Results Of the 254 children assessed, 169 [66.5%; 95% confidence interval (95% CI), 60.5–72.5%] had at least one CRE. The characteristics that increased the risk of CRE were maternal age ≥35 years (odds ratio, 2.21; 95% CI, 1.19–4.09), primiparity (1.96; 1.03–3.72), gestational body mass index (BMI) & gt;25 kg/m 2 (1.92; 1.05–3.53), and birth time between 09:00 p.m. and 08:59 a.m. (2.47; 1.02–5.97). Conclusion CREs were more frequent in HTNs born during nighttime and in HTNs born to first-time mothers, mothers ≥35 years, and mothers with a gestational BMI & gt;25 kg/m 2 . These predictor variables can be determined during childbirth. Identification of neonates at higher risk of developing CREs would allow for closer surveillance during ESSC.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711999-3
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