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1.
Article in English | MEDLINE | ID: mdl-38690753

ABSTRACT

AIM: This study investigates the psychopathological characteristics of a sample of individuals at ultra-high risk for psychosis with and without comorbid attention-deficit hyperactivity disorder (ADHD). METHODS: Twenty-eight subjects (aged 13-21 years; 13 females) with attenuated psychosis syndrome (APS) were recruited in a cross-sectional study and divided into two groups, each with 14 patients, according to the presence or absence of ADHD. RESULTS: The APS group showed a significantly higher prevalence of negative symptoms than the APS + ADHD group. Other characteristics investigated (positive symptoms, aberrant salience, psychotic-like experiences and prodromal symptoms) did not differ between groups. CONCLUSIONS: The different profiles of negative symptoms in the APS with or without ADHD might suggest the presence of a specific subtype among individuals at ultra-high risk for psychosis. Longitudinal studies with larger samples will provide information about the role of negative symptoms in determining conversion to full psychosis in those people with 'pure' APS and those with APS + ADHD.

2.
J Infect Dis ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805191

ABSTRACT

Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the COVID-19 pandemic are scarce. We conducted a two-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.8% for SARS-CoV-2, often in association with rhinovirus or influenza A. This study provides valuable data to understand post-pandemic viral interactions, which is imperative for public health interventions.

3.
AJNR Am J Neuroradiol ; 45(5): 647-654, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38575319

ABSTRACT

BACKGROUND AND PURPOSE: There is a paucity of data on long-term neuroimaging findings from individuals who have developed the post-coronavirus 2019 (COVID-19) condition. Only 2 studies have investigated the correlations between cognitive assessment results and structural MR imaging in this population. This study aimed to elucidate the long-term cognitive outcomes of participants with the post-COVID-19 condition and to correlate these cognitive findings with structural MR imaging data in the post-COVID-19 condition. MATERIALS AND METHODS: A cohort of 53 participants with the post-COVID-19 condition underwent 3T brain MR imaging with T1 and FLAIR sequences obtained a median of 1.8 years after Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. A comprehensive neuropsychological battery was used to assess several cognitive domains in the same individuals. Correlations between cognitive domains and whole-brain voxel-based morphometry were performed. Different ROIs from FreeSurfer were used to perform the same correlations with other neuroimaging features. RESULTS: According to the Frascati criteria, more than one-half of the participants had deficits in the attentional (55%, n = 29) and executive (59%, n = 31) domains, while 40% (n = 21) had impairment in the memory domain. Only 1 participant (1.89%) showed problems in the visuospatial and visuoconstructive domains. We observed that reduced cortical thickness in the left parahippocampal region (t(48) = 2.28, P = .03) and the right caudal-middle-frontal region (t(48) = 2.20, P = .03) was positively correlated with the memory domain. CONCLUSIONS: Our findings suggest that cognitive impairment in individuals with the post-COVID-19 condition is associated with long-term alterations in the structure of the brain. These macrostructural changes may provide insight into the nature of cognitive symptoms.


Subject(s)
COVID-19 , Cognitive Dysfunction , Magnetic Resonance Imaging , Humans , Male , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/psychology , Female , Middle Aged , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Magnetic Resonance Imaging/methods , Follow-Up Studies , Adult , Aged , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Post-Acute COVID-19 Syndrome , Neuropsychological Tests , Brain Cortical Thickness , SARS-CoV-2
4.
J Infect ; 88(5): 106153, 2024 May.
Article in English | MEDLINE | ID: mdl-38588960

ABSTRACT

OBJECTIVES: This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023. METHODS: Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes. RESULTS: Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified. DISCUSSION: Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.


Subject(s)
Evolution, Molecular , Genome, Viral , Phylogeny , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Humans , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/immunology , Respiratory Syncytial Virus, Human/classification , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Child, Preschool , Child , Male , Infant , Female , Middle Aged , Spain/epidemiology , Adolescent , Adult , Genetic Variation , Antibodies, Monoclonal/immunology , Aged , Young Adult , Mutation , Whole Genome Sequencing , Antibodies, Viral/blood , Prevalence , High-Throughput Nucleotide Sequencing , Infant, Newborn
5.
Comput Struct Biotechnol J ; 25: 20-33, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38444982

ABSTRACT

The synthesis of silver nanoparticles with controlled physicochemical properties is essential for governing their intended functionalities and safety profiles. However, synthesis process involves multiple parameters that could influence the resulting properties. This challenge could be addressed with the development of predictive models that forecast endpoints based on key synthesis parameters. In this study, we manually extracted synthesis-related data from the literature and leveraged various machine learning algorithms. Data extraction included parameters such as reactant concentrations, experimental conditions, as well as physicochemical properties. The antibacterial efficiencies and toxicological profiles of the synthesized nanoparticles were also extracted. In a second step, based on data completeness, we employed regression algorithms to establish relationships between synthesis parameters and desired endpoints and to build predictive models. The models for core size and antibacterial efficiency were trained and validated using a cross-validation approach. Finally, the features' impact was evaluated via Shapley values to provide insights into the contribution of features to the predictions. Factors such as synthesis duration, scale of synthesis and the choice of capping agents emerged as the most significant predictors. This study demonstrated the potential of machine learning to aid in the rational design of synthesis process and paves the way for the safe-by-design principles development by providing insights into the optimization of the synthesis process to achieve the desired properties. Finally, this study provides a valuable dataset compiled from literature sources with significant time and effort from multiple researchers. Access to such datasets notably aids computational advances in the field of nanotechnology.

6.
Comp Immunol Microbiol Infect Dis ; 107: 102149, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38442544

ABSTRACT

We aimed to determine the antimicrobial susceptibility profile of pathogenic Escherichia coli strains isolated from fecal samples of calves and buffalo calves (2008-2013), in Minas Gerais, Brazil, as well as the frequency of O157 gene and strains carrying extended-spectrum beta-lactamases (ESBL) and mobile colistin resistance (mcr) genes. E. coli strains (n=518) were tested for susceptibility against ten antimicrobials. Tetracycline was the antimicrobial with the highest resistance rate (382/518), followed by ampicillin (321/518), sulfamethoxazole/trimethoprim (312/518), chloramphenicol (192/518), gentamicin (126/518), ciprofloxacin (148/518), cefazolin (89/518), colistin (54/518) and cefoxitin (34/518). Multidrug resistance (MDR) was observed in 381/518 isolates. No strain harbored mcr or O157 genes, whereas 19/99 were ESBL positive. The most prevalent pathotype and phylogroup were STEC and B1, respectively. Age, EHEC pathotype and resistance to aminoglycoside and cephem were significantly associated with MDR in the multivariate model. Overall, E. coli strains showed high rates of resistance to penicillin, tetracyclines and folate inhibitors, in addition to an alarming rate of MDR and ESBL-producing strains.


Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Animals , Escherichia coli , Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Escherichia coli Infections/epidemiology , Escherichia coli Infections/veterinary , Drug Resistance, Multiple, Bacterial/genetics , Drug Resistance, Bacterial , Microbial Sensitivity Tests/veterinary , Escherichia coli Proteins/genetics , beta-Lactamases/genetics
7.
Sci Total Environ ; 927: 171860, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38518823

ABSTRACT

Safe-and-sustainable-by-design (SSbD) nanomaterials (NMs) or NM-containing products are a priority. Silver (Ag) NMs have a vast array of applications, including biomedical and other products, even as nanopesticides. Thus, their release to the environment is expected to increase. The aim of the present study was to assess the ecotoxicity of the SSbD Ag NM to the soil model species Enchytraeus crypticus (Oligochaeta). The Ag NM tested consists in a SSbD Ag with biomedical applications, a hydroxyethyl cellulose (HEC) coated Ag NMs (AgHEC) and its toxicity was compared to the naked Ag NMs (Ag-Sigma), an Ag-based biomedical product (PLLA-Ag: Poly l-Lactide microfibers doped with Ag), and AgNO3. Effects were assessed both in soil and aqueous media, following the standard OECD guideline in soil (28 days) and the OECD extension (56 days), and short-term pulse (5 days) in aqueous media: reconstituted water (ISO water) and soil:water (S:W) extracts, followed by a 21-days recovery period in soil. Ag materials were thoroughly characterized as synthesized and during the test in media and animals. Results in S:W showed AgHEC was more toxic than Ag-Sigma (ca. 150 times) and PLLA-Ag (ca. 2.5 times), associated with a higher Ag uptake. Higher toxicity was related to a smaller hydrodynamic size and higher suspension stability, which in turn resulted in a higher bioavailability of Ag NMs and released ions, particularly in S:W. Toxicity was correlated with the main physicochemical features, providing useful prediction of AgNMs bioactivity. The ability to test E. crypticus in a range of media with different and/or increasing complexity (water, S:W extracts, soil) provided an excellent source to interpret results and is here recommended.


Subject(s)
Metal Nanoparticles , Oligochaeta , Silver , Soil Pollutants , Soil , Silver/toxicity , Animals , Soil Pollutants/analysis , Oligochaeta/drug effects , Soil/chemistry , Metal Nanoparticles/toxicity , Nanostructures/toxicity , Invertebrates/drug effects
8.
Polymers (Basel) ; 16(3)2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38337308

ABSTRACT

The development of polymeric biocomposites containing natural fibers has grown over the years due to the properties achieved and its eco-friendly nature. Thus, biocomposites involving a polymer from a renewable source (Biopolyethylene (BioPE)) and babassu fibers (BFs), compatibilized with polyethylene grafted with maleic anhydride (MA) and acrylic acid (AA) (PE-g-MA and PE-g-AA, respectively) were obtained using melt mixing and injection molded into tensile, impact, and HDT specimens. Babassu fiber was characterized with Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), and scanning electron microscopy (SEM). The biocomposites were characterized using torque rheometry, TGA, tensile strength, impact strength, thermomechanical properties, Shore D hardness, and SEM. The data indicate that the torque during the processing of compatibilized biocomposites was higher than that of BioPE/BF biocomposites, which was taken as an indication of a possible reaction between the functional groups. Compatibilization led to a substantial improvement in the elastic modulus, tensile strength, HDT, and VST and a decrease in Shore D hardness. These results were justified with SEM micrographs, which showed babassu fibers better adhered to the surface of the biopolyethylene matrix, as well as an encapsulation of these fibers. The system investigated is environmentally sustainable, and the results are promising for the technology of polymeric composites.

9.
Epilepsia ; 65(3): e41-e46, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38243753

ABSTRACT

Trilostane is a 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase inhibitor able to produce a manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis in the kainic acid (KA) model of temporal lobe epilepsy. It is unknown whether trilostane may have a similar effect on the progression of epilepsy severity, as observed in KA-treated rats. Consequently, we investigated the effects of trilostane (50 mg/kg/day, 1 week) in epileptic rats, given 64 days after KA administration. Seizures were monitored by video-electrocorticographic recordings before and during the treatment with trilostane or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography-electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other neurosteroids augmented in both the neocortex and hippocampus. Only pregnanolone levels were not upregulated by trilostane. As expected, a significant increase in the seizure occurrence was observed in rats receiving the vehicle, but not in the trilostane group. This suggests that the increased availability of neurosteroids produced a disease-modifying effect in the brain of epileptic rats.


Subject(s)
Epilepsy , Neurosteroids , Rats , Animals , Neurosteroids/pharmacology , Pregnanolone/pharmacology , Epilepsy/chemically induced , Epilepsy/drug therapy , Brain , Seizures/chemically induced , Seizures/drug therapy
10.
Phytother Res ; 38(3): 1400-1461, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38232725

ABSTRACT

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.


Subject(s)
Brain Injuries, Traumatic , Neurodegenerative Diseases , Stilbenes , Humans , Resveratrol , Neurodegenerative Diseases/drug therapy , Brain Injuries, Traumatic/drug therapy
11.
Angew Chem Int Ed Engl ; 63(12): e202319308, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38231568

ABSTRACT

Direct and stereodivergent Michael additions of N-acyl 1,3-thiazinane-2-thiones to α,ß-unsaturated aldehydes catalyzed by chiral nickel(II) complexes are reported. The reactions proceed with a remarkable regio-, diastereo-, and enantioselectivity, so access to any of the four potential Michael stereoisomers is granted through the appropriate choice of the chiral ligand of the nickel(II) complex. Simple removal of the heterocyclic scaffold furnishes a wide array of either syn or anti enantiomerically pure derivatives, which can be exploited for the asymmetric synthesis of biologically active compounds, as demonstrated in a new approach to tapentadol. In turn, a mechanism, based on theoretical calculations, is proposed to account for the stereochemical outcome of these transformations.

12.
Prev Vet Med ; 224: 106101, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38244415

ABSTRACT

Our study explored the patterns of bovine brucellosis dissemination in Minas Gerais state, Brazil, by examining data on passive surveillance of bovine brucellosis cases from the Instituto Mineiro de Agropecuaria (IMA) (Animal Health Authority), as well as cattle population and bovine brucellosis testing, from 2011 to 2018 by means of a spatiotemporal analysis. We plotted cases, populations and testing distributions and performed spatial autocorrelation (Moran's I test) and local indicators of spatial autocorrelation (LISA) analyses. Moreover, we assessed the correlation of the spatial distribution and the compiled data (brucellosis cases, cattle populations, and brucellosis testing) by Lee's test. Our results showed that bovine brucellosis cases occurred mainly in the Triângulo Mineiro, Alto Paranaíba and Northwest regions, which reported cases in all analyzed years (2011 to 2018). The cattle population of Minas Gerais was concentrated in the same regions as bovine brucellosis cases, and the performed tests through the analyzed years (2011 to 2018). Moran's I test results of the case data showed significant spatial autocorrelation in 2011, 2015 and 2018 (p value < 0.05), and from 2011 to 2018, the population and testing data were also significant in Moran's I test (p value < 0.01). The results of cluster analysis (LISA) of cases showed clusters mainly in the Triângulo Mineiro, Alto Paranaíba, Northwest and South regions in 2011, 2015 and 2018. The local clusters for cattle populations and brucellosis testing were also observed in the same regions as bovine brucellosis cases in all years (2011 to 2018). The correlation results between clusters (Lee's test) were 0.22 (p value < 0.01) in 2011, 0.15 (p value < 0.01) in 2015 and 0.43 (p value <0.01) in 2018 between cases and populations, and 0.25 (p value <0.01) in 2011, 0.14 (p value <0.01) in 2015 and 0.38 (p value < 0.01) in 2018 for testing and cases. Therefore, our results showed that brucellosis cases were distributed together with cattle populations and brucellosis testing data, indicating that brucellosis in cattle in Minas Gerais state is being identified where there are more animals and where more tests are performed.


Subject(s)
Brucellosis, Bovine , Brucellosis , Cattle Diseases , Cattle , Animals , Brazil/epidemiology , Brucellosis, Bovine/epidemiology , Brucellosis/epidemiology , Brucellosis/veterinary , Spatio-Temporal Analysis , Spatial Analysis , Cattle Diseases/epidemiology
13.
Sci Total Environ ; 913: 169748, 2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38160813

ABSTRACT

Lipid-based nanoparticles (LNPs) are advanced materials (AdMa), particularly relevant for drug delivery of poorly water-soluble compounds, while also providing protection, stabilization, and controlled release of the drugs/active substances. The toxicological data available often focus on the specific applications of the LNPs-drug tested, with indication of low toxicity. However, the ecotoxicological effects of LNPs are currently unknown. In the present study, we investigated the ecotoxicity of a formulation of Lipid Surfactant Submicron Particles (LSSPs) loaded with melatonin at 1 mg/mL. The LSSPs formulation has been developed to be fully compliant with regulatory for its potential use in the market and all components are food additives. The same formulation without the thickening agent xanthan gum (stabilizer in water phase) designated as LSSP-xg, was also tested. Two soil model invertebrate species were tested in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola). Effects were assessed based on the OECD standard guideline (28 days) and its extension, the longer-term exposure (56 days). Assessed endpoints were survival, reproduction, and size. LSSPs and LSSP-xg were toxic to E. crypticus and F. candida reducing their survival and reproduction in a dose-dependent way: e.g., 28-day exposure: E. crypticus: LC/EC50 = 30/15 mg LSSPs/kg soil and F. candida LC/EC50 = 55/44 mg LSSPs/kg soil, with similar values for LSSP-xg. Size was also reduced for F. candida but was the least sensitive endpoint. There were no indications that toxicity increased with longer term exposure. The results provide relevant information on ecotoxicity of a AdMa and highlights the need for awareness of the potential risks, even on products and additives usually used in food or cosmetic industry. Further information on single components and on their specific assembly is necessary for the interpretation of results, as it is not fully clear what causes the toxicity in this specific AdMa. This represents a typical challenge for AdMa hazard assessment scenario.


Subject(s)
Arthropods , Melatonin , Oligochaeta , Soil Pollutants , Animals , Melatonin/pharmacology , Surface-Active Agents/toxicity , Soil , Reproduction , Lipoproteins/pharmacology , Water , Soil Pollutants/analysis
14.
Nanotoxicology ; 17(6-7): 529-544, 2023.
Article in English | MEDLINE | ID: mdl-37885250

ABSTRACT

Nanoinformatics demands accurate predictive models to assess the potential hazards of nanomaterials (NMs). However, limited data availability and the diverse nature of NMs physicochemical properties and their interaction with biological media, hinder the development of robust nano-Quantitative Structure-Activity Relationship (QSAR) models. This article proposes an approach that combines artificially data generation techniques and topological projections to address the challenges of insufficient dataset sizes and their limited representativeness of the chemical space. By leveraging the rich information embedded in the topological features, this methodology enhances the representation of the chemical space, enabling a more an exploration of the structure-activity relationships. We demonstrate the efficacy of our approach through extensive experiments, employing various machine learning regression algorithms to validate the methodology. Finally, we compare two different resampling approaches based on different modeling scenarios. The results showcase a significant improved predictive performance of QSAR models demonstrating a promising strategy to overcome the limitations of small datasets in the field of nanoinformatics. The proposed approach offers noteworthy potential for advancing nanoinformatics research within the nanosafety domain by enabling the development of more accurate predictive models for assessing the potential hazards associated with NMs.


Subject(s)
Nanostructures , Quantitative Structure-Activity Relationship , Algorithms , Nanostructures/toxicity , Machine Learning
15.
Elife ; 122023 Oct 27.
Article in English | MEDLINE | ID: mdl-37888959

ABSTRACT

Candida albicans, an opportunistic human pathogen, poses a significant threat to human health and is associated with significant socio-economic burden. Current antifungal treatments fail, at least in part, because C. albicans can initiate a strong drug tolerance response that allows some cells to grow at drug concentrations above their minimal inhibitory concentration. To better characterize this cytoprotective tolerance program at the molecular single-cell level, we used a nanoliter droplet-based transcriptomics platform to profile thousands of individual fungal cells and establish their subpopulation characteristics in the absence and presence of antifungal drugs. Profiles of untreated cells exhibit heterogeneous expression that correlates with cell cycle stage with distinct metabolic and stress responses. At 2 days post-fluconazole exposure (a time when tolerance is measurable), surviving cells bifurcate into two major subpopulations: one characterized by the upregulation of genes encoding ribosomal proteins, rRNA processing machinery, and mitochondrial cellular respiration capacity, termed the Ribo-dominant (Rd) state; and the other enriched for genes encoding stress responses and related processes, termed the Stress-dominant (Sd) state. This bifurcation persists at 3 and 6 days post-treatment. We provide evidence that the ribosome assembly stress response (RASTR) is activated in these subpopulations and may facilitate cell survival.


Many drugs currently used to treat fungal diseases are becoming less effective. This is partly due to the rise of antifungal resistance, where certain fungal cells acquire mutations that enable them to thrive and proliferate despite the medication. Antifungal tolerance also contributes to this problem, wherein certain cells can continue to grow and multiply, while other ­ genetically identical ones ­ cannot. This variability is partly due to differences in gene expression within the cells. The specific nature of these differences has remained elusive, mainly because their study requires the use of expensive and challenging single-cell technologies. To address this challenge, Dumeaux et al. adapted an existing technique to perform single-cell transcriptomics in the pathogenic yeast Candida albicans. Their approach was cost effective and made it possible to examine the gene expression in thousands of individual cells within a population that had either been treated with antifungal drugs or were left untreated. After two to three days following exposure to the antifungal treatment, C. albicans cells commonly exhibited one of two states: one subgroup, the 'Ribo-dominant' cells, predominantly expressed genes for ribosomal proteins, while the other group, the 'Stress-dominant' cells, upregulated their expression of stress-response genes. This suggests that drug tolerance may be related to different gene expression patterns in growing cell subpopulations compared with non-growing subpopulations. The findings also indicate that the so-called 'ribosome assembly stress response' known to help baker's yeast cells to survive, might also aid C. albicans in surviving exposure to antifungal treatments. The innovative use of single-cell transcriptomics in this study could be applied to other species of fungi to study differences in cell communication under diverse growth conditions. Moreover, the unique gene expression patterns in C. albicans identified by Dumeaux et al. may help to design new antifungal treatments that target pathways linked to drug resistance.


Subject(s)
Antifungal Agents , Candida albicans , Humans , Antifungal Agents/pharmacology , Candida albicans/genetics , Fluconazole/pharmacology , Microbial Sensitivity Tests , Mitochondria , Drug Resistance, Fungal
16.
Lett Appl Microbiol ; 76(11)2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37881107

ABSTRACT

The LightMix® Modular Mycoplasma Macrolide and LightMix® Modular parC Fluoroquinolone Resistance assays (TIB Molbiol) were evaluated using sequential Mycoplasma genitalium positive (n = 125) and negative (n = 93) clinical samples. Results were compared to the results of an established commercial assay (ResistancePlus MG assay, SpeeDx Pty Ltd) or Sanger sequencing (for parC). Detection of M. genitalium by the TIB Molbiol assay had a high agreement with the reference assay, with a positive percent agreement (PPA) of 97.6 [95% confidence interval (CI): 93.1-99.5] and negative percent agreement (NPA) of 95.7 (95% CI: 89.5-98.8). From 105 positive samples, macrolide resistance detection had a PPA of 100% (95% CI: 93.7-100) and NPA of 81.3% (95% CI: 67.4-91.1). For the detection of fluroquinolone resistance mutation G248T/S83I or "other mutation" in the quinolone resistance determinant region, from 95 samples there was 100% (95% CI: 86.3-100) sensitivity and 100% (95% CI: 94.5-100) specificity. The understanding of the basis for fluoroquinolone treatment failure is still developing; it is therefore important to use the output of parC-based resistance assays with caution to avoid the inappropriate use of antibiotic therapies, especially considering the limited number of alternative treatments.


Subject(s)
Mycoplasma Infections , Mycoplasma genitalium , Humans , Anti-Bacterial Agents/pharmacology , Fluoroquinolones , Macrolides , Mycoplasma genitalium/genetics , Drug Resistance, Bacterial/genetics , Mycoplasma Infections/diagnosis , Mutation , RNA, Ribosomal, 23S/genetics , Prevalence
17.
Cir. Esp. (Ed. impr.) ; 101(10): 701-707, oct. 2023. tab, ilus
Article in Spanish | IBECS | ID: ibc-226496

ABSTRACT

Introducción: La incidencia de pólipos vesiculares es del 0,3-12%. Es importante diferenciar los seudopólipos (pólipos de colesterol, adenomiomatosis o pólipos inflamatorios) de los pólipos verdaderos (adenomas y adenocarcinomas). Los principales factores de riesgo de malignización son el tamaño superior a 6-10mm, crecimiento rápido del mismo, morfología sésil, etnia india y colangitis esclerosante primaria. La ecografía es el gold standard para su diagnóstico. Sin embargo, la mayoría de los pólipos diagnosticados por ecografía son seudopólipos. El objetivo del estudio es analizar si la ecografía es precisa para diagnosticar los pólipos verdaderos en los pacientes cuya indicación quirúrgica ha sido este diagnóstico ecográfico. Métodos: Estudio observacional retrospectivo de los pacientes intervenidos en nuestro centro, desde el año 2007 al 2019, de colecistectomía electiva por presentar pólipos vesiculares. La cirugía se indicó en pacientes sintomáticos y/o con factores de riesgo. El estudio fue aprobado por el Comité Ético de Investigación Clínica de nuestro hospital. Resultados: Se han incluido 124 pacientes. En todos ellos se ha realizado colecistectomía laparoscópica. La edad media fue de 55,4 años y el 61% eran mujeres. El 65% tenían síntomas biliares. En nuestro estudio, solo 3 pacientes presentaron pólipos verdaderos (2,4%). Todos ellos, fueron adenomas tubulares. El resto de los pacientes resultaron falsos positivos (97,6%). El tamaño de los adenomas fue de 11, 6 y 5mm. La cirugía se indicó por tamaño o por clínica asociada. Conclusiones: La ecografía no es precisa para el diagnóstico de pólipos vesiculares verdaderos. La validación de otras pruebas complementarias para el diagnóstico de pólipos en pacientes asintomáticos podría ser relevante para evitar cirugías innecesarias. (AU)


Introduction: The incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the potential to become malignant, and true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are size>6-10mm, rapid growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. However, most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyze whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. Methods: We conducted a retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study was approved by the Clinical Research Ethics Committee of our hospital. Results: Our study included 124 patients who had undergone elective laparoscopic cholecystectomy. Mean age was 55.4 years, and 61% were women. In total, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2.4%), all of which were tubular adenomas. The remainig patients were false positives (97.6%). The adenoma sizes were 11, 6 and 5mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. Conclusion: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. The validation of other complementary tests for the diagnose gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Polyps/diagnostic imaging , Gallbladder Diseases/diagnostic imaging , Ultrasonography , Retrospective Studies , Risk Factors , Cholecystectomy , Gallbladder Diseases/surgery
18.
Cir Esp (Engl Ed) ; 101(10): 701-707, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37748643

ABSTRACT

INTRODUCTION: Incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the capacity to become malignant, from true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are >6-10 mm, growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. Most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyse whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. METHODS: Retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study has been approved by the Clinical Research Ethics Committee of our hospital. RESULTS: We included 124 patients in our study. An elective laparoscopic cholecystectomy was performed in all of them. The mean age was 55,4 years and 61% were women. Of all patients, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2,4%). All of them were tubular adenomas. The rest of patients were false positives (97,6%). The adenoma size was 11, 6 and 5 mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. CONCLUSION: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. Validation of other complementary tests for the diagnosis of gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries.


Subject(s)
Adenoma , Colorectal Neoplasms , Gallbladder Diseases , Gallbladder Neoplasms , Gastrointestinal Neoplasms , Polyps , Female , Humans , Male , Adenoma/diagnostic imaging , Adenoma/surgery , Cholecystectomy , Colorectal Neoplasms/surgery , Gallbladder Diseases/diagnostic imaging , Gallbladder Diseases/surgery , Gallbladder Neoplasms/diagnostic imaging , Gallbladder Neoplasms/surgery , Gastrointestinal Neoplasms/surgery , Polyps/diagnostic imaging , Polyps/surgery , Prospective Studies , Ultrasonography , Retrospective Studies
19.
PLoS One ; 18(9): e0288737, 2023.
Article in English | MEDLINE | ID: mdl-37713377

ABSTRACT

Toxicity evaluation of engineered nanomaterials is challenging due to the ever increasing number of materials and because nanomaterials (NMs) frequently interfere with commonly used assays. Hence, there is a need for robust, high-throughput assays with which to assess their hazard potential. The present study aimed at evaluating the applicability of a genotoxicity assay based on the immunostaining and foci counting of the DNA repair protein 53BP1 (p53-binding protein 1), in a high-throughput format, for NM genotoxicity assessment. For benchmarking purposes, we first applied the assay to a set of eight known genotoxic agents, as well as X-ray irradiation (1 Gy). Then, a panel of NMs and nanobiomaterials (NBMs) was evaluated with respect to their impact on cell viability and genotoxicity, and to their potential to induce reactive oxygen species (ROS) production. The genotoxicity recorded using the 53BP1 assay was confirmed using the micronucleus assay, also scored via automated (high-throughput) microscopy. The 53BP1 assay successfully identified genotoxic compounds on the HCT116 human intestinal cell line. None of the tested NMs showed any genotoxicity using the 53BP1 assay, except the positive control consisting in (CoO)(NiO) NMs, while only TiO2 NMs showed positive outcome in the micronucleus assay. Only Fe3O4 NMs caused significant elevation of ROS, not correlated to DNA damage. Therefore, owing to its adequate predictivity of the genotoxicity of most of the tested benchmark substance and its ease of implementation in a high throughput format, the 53BP1 assay could be proposed as a complementary high-throughput screening genotoxicity assay, in the context of the development of New Approach Methodologies.


Subject(s)
Nanostructures , Tumor Suppressor Protein p53 , Humans , Reactive Oxygen Species , Benchmarking , DNA Damage
20.
Polymers (Basel) ; 15(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37631490

ABSTRACT

In this work, blends based on poly (lactic acid) (PLA)/acrylonitrile-butadiene-styrene (ABS) compatibilized with maleic anhydride-grafted (SEBS-g-MA) were prepared in a co-rotational twin-screw extruder by varying the concentrations of the compatibilizing agent. The influence of the compatibilizing agent on the morphology, mechanical, thermal, thermomechanical, and rheological properties of the prepared materials was analyzed. The effect of annealing on the properties of the blends was also investigated using injection-molded samples. The X-ray diffraction (XRD) results proved that the increments in crystallinity were an effect of annealing in the PLA/ABS/SEBS-g-MA blends, resonating at higher heat deflection temperatures (HDTs). The impact strength of the PLA/ABS blends compatibilized with 10 wt% SEBS-g-MA was significantly increased when compared to the PLA/ABS blends. However, the hardness and elastic modulus of the blends decreased when compared to neat PLA. The refined morphology shown in the scanning electron microscopy (SEM) analyses corroborated the improved impact strength promoted by SEBS-g-MA. The torque rheometer degradation study also supported the increased compatibility between SEBS-g-MA, PLA, and ABS. The TGA results show that the PLA/ABS and PLA/ABS/SEBS-g-MA blends are more thermally stable than the neat PLA polymer at higher temperatures. The results showed that the ideal composition is the heat-treated PLA/ABS/SEBS-g-MA (60/30/10 wt%), given the high impact strength and HDT results. The results of this work in terms of mechanical improvement with the use of compatibilizers and annealing suggest that the PLA/ABS/SEBS-g-MA system can be used in the production of 3D-printing filaments.

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