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Pseudomonas aeruginosa (P. aeruginosa) is a common nosocomial pathogen that can cause severe infections in critically ill patients. Due to its resistance to multiple drugs, it is challenging to treat, which can result in serious illness and death. Conventional treatments for infected wounds often involve the topical or systemic application of antibiotics, which can lead to systemic toxicity and the development of drug resistance. The combination of wound dressings that promote wound healing with nanoparticles (NPs) represents a revolutionary strategy for optimizing the safety and efficacy of antibiotics. This review assesses a systematic search to identify the latest approaches where the evaluation of wound dressings loaded with antibiotic NPs is conducted. The properties of NPs, the features of wound dressings, the antimicrobial activity and biocompatibility of the different strategies are analyzed. The results indicate that most research in this field is focused on dressings loaded with silver NPs (57.1%) or other inorganic materials (22.4%). Wound dressings loaded with polymeric NPs and carbon-based NPs represent 14.3% and 6.1% of the evaluated studies, respectively. Nevertheless, there are no clinical trials that have evaluated the efficacy of NPs-loaded wound dressings in patients. Further research is required to ensure the safety of these treatments and to translate the findings from the bench to the bedside.
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Antibacterianos , Vendajes , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Infecciones por Pseudomonas/tratamiento farmacológico , Nanopartículas/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Plata/administración & dosificaciónRESUMEN
Parkinson's disease (PD) is associated with a reduction in 26/20S proteasome and mitochondrial function and depletion of dopamine. Activation of mitochondrial function with the NAD+ precursor nicotinamide riboside (NR) is a potential therapeutic for PD. However, despite recently started clinical trials, analysis of NR in mammalian animal PD models is lacking and data in simpler PD models is limited. We analyzed the effect of NR in C. elegans and in mouse 26/20S proteasome inhibition models of PD. In C. elegans, NR rescued α-synuclein overexpression induced phenotypes likely by activating the mitochondrial unfolded protein response. However, in a proteasome inhibitor-induced mouse model of PD, NR first partially rescued behavioural dysfunction, but later resulted in decrease in dopamine and its related gene expression in the substantia nigra. Our results suggest that reduction in 26/20S function with long term NR treatment may increase risk for developing reduced nigrostriatal DA function.
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Purpose: To describe fluorescein angiography (FA) parameters observed in premature neonates with retinopathy of prematurity (ROP). Design: Retrospective case series. Subjects: Patients with ROP who underwent FA imaging using Retcam at Holtz Children's Hospital from November 2014 to October 2022. Methods: Fluorescein angiography images of the included patients were analyzed with a focus on the timing of angiography phases, including choroidal flush, retinal, and recirculation phases. Gestational age, birth weight (BW), age at imaging, treatment choice, and any FA complications were documented. Main Outcome Measures: Dose of fluorescein administered, onset and duration of each angiography phase, and FA findings in ROP-treated patients. Results: A total of 72 images of 72 eyes were reviewed. Image quality was deemed suitable for inclusion in 64 eyes (88.9%) of 43 patients. The mean gestational age and BW at birth were 24.4 ± 1.9 weeks and 607.8 ± 141.3 g, respectively. The mean postmenstrual age at FA imaging was 50.5 ± 40.8 weeks. All eyes (100%) received treatment with intravitreal injection of anti-VEGF at a mean age of 35.5 ± 2.4 weeks. The onset and duration of angiography phases were relatively variable within the cohort. Choroidal flush occurred at a mean time of 12.2 seconds (range: 6-22 seconds). A subsequent retinal phase was documented at a mean time of 11.96 seconds (range: 3-22 seconds). Recirculation phase was complete at an average time of 2.15 minutes (range: 1-5.45 minutes) postfluorescein injection. None of patients developed allergic reactions to fluorescein injection, such as rash, respiratory distress, tachycardia, fever, or local injection site reactions. Conclusions: Angiographic phases on FA in preterm infants with ROP are variable and may occur earlier than the established references for adults. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Introduction: Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance. Methods: This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis. Results and discussion: Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.
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BACKGROUND: There is limited evidence from antimicrobial stewardship programmes in less-resourced settings. This study aimed to improve the quality of antibacterial prescriptions by mitigating overuse and promoting the use of narrow-spectrum agents in intensive care units (ICUs) in a middle-income country. METHODS: We established a quality improvement collaborative (QIC) model involving nine Argentine ICUs over 11 months with a 16-week baseline period (BP) and a 32-week implementation period (IP). Our intervention package included audits and feedback on antibacterial use, facility-specific treatment guidelines, antibacterial timeouts, pharmacy-based interventions and education. The intervention was delivered in two learning sessions with three action periods along with coaching support and basic quality improvement training. RESULTS: We included 912 patients, 357 in BP and 555 in IP. The latter had higher APACHE II (17 (95% CI: 12 to 21) vs 15 (95% CI: 11 to 20), p=0.036), SOFA scores (6 (95% CI: 4 to 9) vs 5 (95% CI: 3 to 8), p=0.006), renal failure (41.6% vs 33.1%, p=0.009), sepsis (36.1% vs 31.6%, p<0.001) and septic shock (40.0% vs 33.8%, p<0.001). The days of antibacterial therapy (DOT) were similar between the groups (change in the slope from BP to IP 28.1 (95% CI: -17.4 to 73.5), p=0.2405). There were no differences in the antibacterial defined daily dose (DDD) between the groups (change in the slope from BP to IP 43.9, (95% CI: -12.3 to 100.0), p=0.1413).The rate of antibacterial de-escalation based on microbiological culture was higher during the IP (62.0% vs 45.3%, p<0.001).The infection prevention control (IPC) assessment framework was increased in eight ICUs. CONCLUSION: Implementing an antimicrobial stewardship program in ICUs in a middle-income country via a QIC demonstrated success in improving antibacterial de-escalation based on microbiological culture results, but not on DOT or DDD. In addition, eight out of nine ICUs improved their IPC Assessment Framework Score.
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The overuse of antimicrobial agents in medical and veterinary applications has led to the development of antimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. In this context, the use of transition metal complexes with photoactivatable properties, which can act as drug delivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In this work several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycotic drug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes as antifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. The complexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period of time. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT calculations. The complexes were tested against three different yeasts, which were selected based on their prevalence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligand showed the best activity against the three species under light, with minimal inhibitory concentration values of 0.88 µM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that of free clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were more active on yeast species than on cancer cell lines.
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Introduction: Four years after the start of the pandemic, there is limited evidence on the impact of COVID-19 on the women's health regardless of their reproductive status. Objective: The aim was to analyze the prevalence and associated factors of menstrual-related disturbances in formerly menstruating women following SARS-CoV-2 infection. Study design: A retrospective observational study of adult women in Spain was conducted during the month of December 2021 using an online survey (N = 17,512). The present analysis includes a subpopulation of SARS-CoV-2-infected and formerly menstruating women (n = 72). The collected data included general characteristics, medical history, and specific information on COVID-19. Chi-square and Mann-Whitney U-tests were performed. Bivariate logistic regression analysis was then performed to investigate possible associations between the occurrence of menstrual-related disturbances after SARS-CoV-2 infection. Results: 38.8% of participants experienced menstrual-related disturbances following COVID-19. Among these, unexpected vaginal bleeding (20.8%) was the most common event, followed by spotting (11.1%) ( Table 1). Other reported changes were in the length (shorter = 12.5%) and flow (heavier = 30.3%) of menstrual bleeding in comparison to their previous experience. Regression analysis revealed that being a perimenopausal woman [adjusted odds ratio (AOR) 4.721, CI 95%, 1.022-21.796, p = 0.047] and having a previous diagnosis of menorrhagia (AOR 5.824 CI 95%, 1.521-22.310, p = 0.010) were factors associated with the event. Conclusion: These findings could help health professionals provide their patients with up-to-date scientific information to empower them to actively manage their reproductive health, especially in societies where menstrual health is still taboo.
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This multicenter study sponsored by GETH-TC aimed to investigate the incidence and predictors of early (within the first 100 days) and late cardiac events (CE) (ECE and LCE) following allo-HCT in AML patients treated with anthracyclines, focusing on exploring the impact of PTCY on cardiac complications and the impact of CE on overall survival (OS) and non-relapse mortality (NRM). 1020 AML patients were included. PTCY was given to 450 (44.1%) adults. Overall, 94 (9.2) patients experienced CE and being arrythmias, pericardial complications, and heart failure the most prevalent ones. ECE occurred in 49 (4.8%) patients in a median of 13 days after allo-HCT, while LCE were diagnosed in 45 (4.4%) patients in a median of 3.6 years after transplant. Using PTCY increased the risk for ECE in multivariate analysis (HR 2.86, P=0.007), but did not not significantly affect the risk for LCE (HR 1.06, P=0.892). The impact of variables on outcomes revealed was investigated using multivariate regression analyses and revealed that the diagnosis of CE significantly decreased the likelihood of OS (HR 1.66, P=0.005) and increased the likelihood of NRM (HR 2.88, P<0.001). Furthermore, despite using PTCY increased the risk for ECE, its administration was found to be beneficial for OS (HR 0.71, P=0.026). The study suggests that while the incidence of CE was relatively low, it significantly impacted mortality. Standard doses of PTCY increased ECE risk but were associated with improved OS. Therefore, implementing protocols to prevent cardiac complications is recommended, considering the widespread adoption of PTCY in allo-HCT.
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BACKGROUND: Genetic substrate reduction therapy (gSRT), which involves the use of nucleic acids to downregulate the genes involved in the biosynthesis of storage substances, has been investigated in the treatment of lysosomal storage diseases (LSDs). OBJECTIVE: To analyze the application of gSRT to the treatment of LSDs, identifying the silencing tools and delivery systems used, and the main challenges for its development and clinical translation, highlighting the contribution of nanotechnology to overcome them. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines was performed. PubMed, Scopus, and Web of Science databases were used for searching terms related to LSDs and gene-silencing strategies and tools. RESULTS: Fabry, Gaucher, and Pompe diseases and mucopolysaccharidoses I and III are the only LSDs for which gSRT has been studied, siRNA and lipid nanoparticles being the silencing strategy and the delivery system most frequently employed, respectively. Only in one recently published study was CRISPR/Cas9 applied to treat Fabry disease. Specific tissue targeting, availability of relevant cell and animal LSD models, and the rare disease condition are the main challenges with gSRT for the treatment of these diseases. Out of the 11 studies identified, only two gSRT studies were evaluated in animal models. CONCLUSIONS: Nucleic acid therapies are expanding the clinical tools and therapies currently available for LSDs. Recent advances in CRISPR/Cas9 technology and the growing impact of nanotechnology are expected to boost the clinical translation of gSRT in the near future, and not only for LSDs.
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Terapia Genética , Enfermedades por Almacenamiento Lisosomal , Nanopartículas , Humanos , Enfermedades por Almacenamiento Lisosomal/terapia , Enfermedades por Almacenamiento Lisosomal/genética , Terapia Genética/métodos , Animales , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/uso terapéutico , Sistemas CRISPR-Cas , Silenciador del Gen , Sistemas de Liberación de Medicamentos , LiposomasRESUMEN
Lung cancer is the leading cause of cancer mortality worldwide. KRAS oncogenes are responsible for at least a quarter of lung adenocarcinomas, the main subtype of lung cancer. After four decades of intense research, selective inhibitors of KRAS oncoproteins are finally reaching the clinic. Yet, their effect on overall survival is limited due to the rapid appearance of drug resistance, a likely consequence of the high intratumoral heterogeneity characteristic of these tumors. In this study, we have attempted to identify those functional alterations that result from KRAS oncoprotein expression during the earliest stages of tumor development. Such functional changes are likely to be maintained during the entire process of tumor progression regardless of additional co-occurring mutations. Single-cell RNA sequencing analysis of murine alveolar type 2 cells expressing a resident Kras oncogene revealed impairment of the type I interferon pathway, a feature maintained throughout tumor progression. This alteration was also present in advanced murine and human tumors harboring additional mutations in the p53 or LKB1 tumor suppressors. Restoration of type I interferon (IFN) signaling by IFN-ß or constitutive active stimulator of interferon genes (STING) expression had a profound influence on the tumor microenvironment, switching them from immunologically "cold" to immunologically "hot" tumors. Therefore, enhancement of the type I IFN pathway predisposes KRAS mutant lung tumors to immunotherapy treatments, regardless of co-occurring mutations in p53 or LKB1.
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Inhibidores de Puntos de Control Inmunológico , Interferón Tipo I , Neoplasias Pulmonares , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Transducción de Señal , Animales , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ratones , Interferón Tipo I/metabolismo , Interferón Tipo I/genética , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Proteínas Quinasas Activadas por AMPRESUMEN
Purpose: Additional monitoring (AM) medicines include (i) medicines containing a new active substance; (ii) biological medicines; (iii) medicines with conditional approval or authorized in special situations; (iv) medicines which require further studies; (v) medicines that have specific requirements regarding the reporting of suspected adverse drug reactions (ADRs). When AM medicines are marketed, their most common ADRs are known, but safety information is limited because relatively rare ADRs are often not detected in clinical trials. Their AM status warrants real-world studies to identify other safety issues; however, such studies are lacking. Correct use and adherence to dosage regimen by patients are key factors for the evaluation of the safety and efficacy of medicines. The objective of this work was assessing the impact on safety, adherence, use and knowledge (U&K) about medicines and patient's quality of life (QOL), of community pharmacist (CP)-led interventions in a new service focused on AM medicines targeted at three prevalent chronic diseases: diabetes mellitus type 2, chronic obstructive pulmonary disease and cardiovascular disease. Patients and Methods: A prospective interventional cohort study was conducted with a 6-month follow-up in 27 community pharmacies (145 patients). Safety, adherence to treatment, patient U&K and QOL were assessed at follow-up visits (months 0, 3 and 6). Results: The number of detected ADRs was 163 with 41 patients referred to the doctor. At baseline, 24.1% of the patients were non-adherent, mainly due to unintentional causes. After six months and 130 interventions by CPs on adherence, a significant reduction to lower than 5.8% was achieved. The inadequate U&K of medicines also decreased, from 47.6% to 7.9% after 182 interventions. Also, the patient's QOL improved. Conclusion: A new patient-centered pharmacy service provides some evidence on the important role of CP in assisting the proper and safe use of AM medicines, improving patient health outcomes.
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Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.
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New industries are proliferating in the recovery of agri-food wastes, such as those involved in the revaluation of alperujo, generated in the production of olive oil. Despite the potential environmental benefits, their activity is not exempt from new forms of emissions, aggravated by the massification of waste treatments. This work reports a six-month field campaign carried out in an alperujo desiccation plant which can serve as a proxy for these emerging industries in the Mediterranean countries. The study focused on air quality parameters, covering criteria pollutants, metals and microbiological load of particulate matter and the characterization of volatile organic compounds (VOCs). The results show a slight contribution of the factory to the NOx levels in the surroundings (3.0-12.5 µg/m3). Statistically significant effects were not observed for ozone, CO, SO2, or PM10. Concerning the levels of metals, concentrations were low and calculated health risk indexes indicated safe conditions in the area. The most abundant elements were Na (6.5 × 102 ng/m3), K (4.0 × 102 ng/m3), Al (2.7 × 102 ng/m3), Zn (2.1 × 102 ng/m3), Ca (2.16 × 102 ng/m3), Fe (3.6 × 101 ng/m3) and Mg (3.2 × 101 ng/m3). Bacterial counts, with a mean value of 15.9 CFU/m3, showed a seasonal shift, mainly explained by weather (air moisture and temperature) and PM2.5 concentration. The genomic analysis showed Cutibacterium as the dominant genus during the cold months while Bacillus predominated in the warm season. The VOCs with higher average concentrations were acetic acid (130 µg/m3), nonanoic acid (124 µg/m3), benzoic acid (29.7 µg/m3), octanoic acid (19.9 µg/m3) and nonanal (4.70 µg/m3), with the rest of compounds in concentrations below 4 µg/m3. Odorant pollutants with the greatest contribution to olfactory nuisance were aldehydes (from pentanaldehyde to decanaldehyde), acetic acid and phenol. Although the observable effects of the waste treatments were low, several parameters showed an influence on the environment which should be assessed to foresee and prevent long-term consequences.
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Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.
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Endolysins, proteins encoded by phages to lyse their hosts and release their progeny, have evolved to adapt to the structural features of each host. The endolysins from Staphylococcus-infecting phages typically feature complex architectures with two enzymatically active domains (EADs) and one cell wall-binding domain (CBD) belonging to the bacterial SH3 (SH3b) superfamily. This study focuses on three SH3b-like CBDs from representative staphylococcal phage endolysins (LysRODI, LysC1C and LysIPLA5) that were structurally and functionally characterized. While RODI_CBD and C1C_CBD were assigned to the well-known SH3_5 family, a new family, SH3b_T (PF24246), was identified using the CBD from LysIPLA5 as a model. GFP-fused CBDs were created to assess their differential binding to a collection of staphylococcal strains. IPLA5_CBD showed enhanced binding to Staphylococcus epidermidis, while RODI_CBD and C1C_CBD exhibited distinct binding profiles, with RODI_CBD targeting Staphylococcus aureus specifically and C1C_CBD displaying broad binding. Sequence comparisons suggested that a few differences in key amino acids could be responsible for the latter binding difference. The CBDs modulated the activity spectrum of synthetic EAD-CBD combinations in accordance with the previous binding profiles, but in a manner that was also dependent on the EAD present in the fusion protein. These results serve as a context for the diversity and versatility of SH3b domains in staphylococcal endolysins, providing insights on how (i) the CBDs from this superfamily have diverged to adapt to diverse bacterial ligands in spite of sharing a common fold; and (ii) the evolution of specificity relies on the EAD-CBD combination rather than solely the CBD.
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BACKGROUND: Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models. RESULTS: As expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra. CONCLUSIONS: Shotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/genética , ARN Ribosómico 16S/genética , Microbioma Gastrointestinal/genética , Heces/microbiología , Metagenómica/métodos , Bacterias/genética , Bacterias/clasificación , Análisis de Secuencia de ADN/métodos , Masculino , Metagenoma , FemeninoRESUMEN
BACKGROUND: Smoking is associated with an increased risk of HPV infection. However, the use of e-cigarettes and marijuana, number of cigarettes, and serum cotinine concentrations in relation with HPV (6, 11, 16, 18) and high-risk HPV (16 or 18) infections in underserved and understudied populations remain poorly understood. METHODS: Data included 687 males and 664 females among whom 489 were White, 375 were Black and 342 were Hispanics from the NHANES 2013-2016 with HPV and high-risk HPV infections. Smoking history included current and past smokers, number of cigarettes, use of e-cigarettes, marijuana, and serum cotinine levels. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: High-risk HPV infection was associated with current smoking history plus ≥ 20 cigarettes/day (OR=1.92, 95 % CI=1.09, 3.37) in the overall population. E-cigarettes use (5 days) was positively associated with high-risk HPV infection (OR=2.43, 95 % CI=1.13, 5.22) in the overall population, with similar findings with e-cigarette (past 30 days) among women and Whites. CONCLUSION: High number of cigarettes, e-cigarette usage and marijuana were associated with HPV and high-risk HPV infections in the overall population. Most of these associations remained significant when stratified by gender and race/ethnicity. Increasing use of e-cigarettes and marijuana in these population warrants further investigation for the prevention of HPV infection and related cancers.
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Investigating the contribution of mindfulness training to psychological well-being and quality of life in the university setting is of interest. The objective of the study is to present a comparative analysis of the scores in the variables of self-efficacy, resilience, coping strategies, and communication skills before and after the application of an intervention program based on mindfulness. An ex post facto cross-sectional design and a convenience sample of participants were adopted. The participants were students belonging to Education Sciences who benefited from the activities of the program. Instruments were administered to assess mindfulness, self-efficacy, resilience, coping strategies, and communication skills. The correlations of the mindfulness variable with the other psychoeducational variables evaluated were also analyzed. The results indicate an increase in the scores in the selected variables of mindfulness, resilience, communication skills, and some of the coping strategies considered productive or functional such as problem solving, self-criticism, emotional expression, desiderative thinking, social support, and cognitive restructuring. Statistically significant correlations were also observed between the variable mindfulness and those of perceived self-efficacy, resilience, coping strategies, and communication skills. The development of mindfulness training programs in the university setting is necessary to contribute to the improvement of more adaptive coping skills and the promotion of resilience.
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INTRODUCTION: The study of Candida glabrata genes associated with fluconazole resistance, from a molecular perspective, increases the understanding of the phenomenon with a view to its clinical applicability. OBJECTIVE: We sought to establish the predictive molecular profile of fluconazole resistance in Candida glabrata by analyzing the ERG11, ERG3, CgCDR1, and CgSNQ2 genes. METHOD: Expression was quantified using RT-qPCR. Metrics were obtained through molecular docking and Fisher discriminant functions. Additionally, a predictive classification was made against the susceptibility of C. glabrata to fluconazole. RESULTS: The relative expression of the ERG3, CgCDR1, and CgSNQ2 genes was higher in the fluconazole-resistant strains than in the fluconazole-susceptible, dose-dependent strains. The gene with the highest relative expression in the fluconazole-exposed strains was CgCDR1, and in both the resistant and susceptible, dose-dependent strains exposed to fluconazole, this was also the case. The molecular docking model generated a median number of contacts between fluconazole and ERG11 that was lower than the median number of contacts between fluconazole and ERG3, -CgCDR1, and -CgSNQ2. The predicted classification through the multivariate model for fluconazole susceptibility achieved an accuracy of 73.5%. CONCLUSION: The resistant strains had significant expression levels of genes encoding efflux pumps and the ERG3 gene. Molecular analysis makes the identification of a low affinity between fluconazole and its pharmacological target possible, which may explain the lower intrinsic susceptibility of the fungus to fluconazole.