Enhancing Sustainability in PLA Membrane Preparation through the Use of Biobased Solvents.

For the first time, ultrafiltration (UF) green membranes were prepared through a sustainable route by using PLA as a biopolymer and dihydrolevoclucosenone, whose trade name is Cyrene™ (Cyr), dimethyl isosorbide (DMI), and ethyl lactate (EL) as biobased solvents. The influence of physical-chemical properties of the solvent on the final membrane morphology and performance was evaluated. The variation of polymer concentration in the casting solution, as well as the presence of Pluronic® (Plu) as a pore former agent, were assessed as well. The obtained results highlighted that the final morphology of a membrane was strictly connected with the interplaying of thermodynamic factors as well as kinetic ones, primarily dope solution viscosity. The pore size of the resulting PLA membranes ranged from 0.02 to 0.09 µm. Membrane thickness and porosity varied in the range of 0.090-0.133 mm of 75-87%, respectively, and DMI led to the most porous membranes. The addition of Plu to the casting solution showed a beneficial effect on the membrane contact angle, allowing the formation of hydrophilic membranes (contact angle < 90°), and promoted the increase of pore size as well as the reduction of membrane crystallinity. PLA membranes were tested for pure water permeability (10-390 L/m2 h bar).

A roadmap towards safe and sustainable by design nanotechnology: Implementation for nano-silver-based antimicrobial textile coatings production by ASINA project.

This report demonstrates a case study within the ASINA project, aimed at instantiating a roadmap with quantitative metrics for Safe(r) and (more) Sustainable by Design (SSbD) options. We begin with a description of ASINA's methodology across the product lifecycle, outlining the quantitative elements within: Physical-Chemical Features (PCFs), Key Decision Factors (KDFs), and Key Performance Indicators (KPIs). Subsequently, we delve in a proposed decision support tool for implementing the SSbD objectives across various dimensions-functionality, cost, environment, and human health safety-within a broader European context. We then provide an overview of the technical processes involved, including design rationales, experimental procedures, and tools/models developed within ASINA in delivering nano-silver-based antimicrobial textile coatings. The result is pragmatic, actionable metrics intended to be estimated and assessed in future SSbD applications and to be adopted in a common SSbD roadmap aligned with the EU's Green Deal objectives. The methodological approach is transparently and thoroughly described to inform similar projects through the integration of KPIs into SSbD and foster data-driven decision-making. Specific results and project data are beyond this work's scope, which is to demonstrate the ASINA roadmap and thus foster SSbD-oriented innovation in nanotechnology.

Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children.

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

Respiratory viral coinfections in pediatric patients in the primary care setting: a multicenter prospective study within the COPEDICAT network.

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.

Psychopathological characteristics in ultra-high risk for psychosis with and without comorbid ADHD.

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.

Genomic evolution of human respiratory syncytial virus during a decade (2013-2023): bridging the path to monoclonal antibody surveillance.

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.

Reduced Cortical Thickness Correlates of Cognitive Dysfunction in Post-COVID-19 Condition: Insights from a Long-Term Follow-up.

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.

Design rules applied to silver nanoparticles synthesis: A practical example of machine learning application.

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.

Safe and sustainable by design Ag nanomaterials: A case study to evaluate the bio-reactivity in the environment using a soil model invertebrate.

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.

Antimicrobial resistance and public and animal health risks associated with pathogenic Escherichia coli isolated from calves.

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.

Toward Producing Biopolyethylene/Babassu Fiber Biocomposites with Improved Mechanical and Thermomechanical Properties.

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.

Seizure progression is slowed by enhancing neurosteroid availability in the brain of epileptic rats.

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.

A spatiotemporal analysis of bovine brucellosis cases in Minas Gerais state, Brazil, from 2011 to 2018.

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.

Direct, Stereodivergent, and Catalytic Michael Additions of Thioimides to α,ß-Unsaturated Aldehydes - Total Synthesis of Tapentadol.

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.

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence.

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.

Advanced materials - Food grade melatonin-loaded Lipid Surfactant Submicron Particles (LSSP)-environmental impacts.

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.

Development and validity of an algorithm for planning intravenous medication administration in infants / Desarrollo y validación de un algoritmo para la planificación de la administración de medicamentos intravenosos en neonatos / Elaboração e validação de algoritmo para o planejamento da administração de medicamentos intravenosos em neonatos

ABSTRACT Objective: to develop and validate the content of an algorithm for planning intravenous medication administration in infants. Method: this is a methodological study of technology development and validity. A scoping review was carried out, which supported the creation of an algorithm by the researchers and its subsequent validity by 13 expert nurses, which took place between November 2021 and March 2022. Items with a Content Validity Index ≥ 0.8 were considered acceptable. Results: thirty-one references were included in the scoping review, organized into five categories: "recommendation for intravenous access", "polypharmacy-related care", "care prior to intravenous medication administration", "venous catheter handling-related care" and "medication infusion-related care". This division supported the algorithm development, which was validated after three rounds, with an overall Content Validity Index of the instrument of 0.91. Conclusion: algorithm validity indicates reliability and accuracy of its content.

RESUMEN Objetivo: desarrollar y validar el contenido de un algoritmo para la planificación de la administración de medicamentos intravenosos en neonatos. Método: se trata de un estudio metodológico de desarrollo y validación de tecnología. Se realizó una revisión de alcance que apoyó la creación del algoritmo por parte de los investigadores y su posterior validación por 13 enfermeras especialistas, que se llevó a cabo entre noviembre de 2021 y marzo de 2022. Se consideraron aceptables los ítems con un Índice de Validez de Contenido ≥ 0,8. Resultados: se incluyeron 31 referencias en la revisión de alcance, organizadas en cinco categorías: "indicación de acceso intravenoso", "cuidados relacionados con la polifarmacia", "cuidados previos a la administración de medicamentos intravenosos", "cuidados relacionados con la manipulación del catéter venoso" y "cuidados relacionados con la infusión de medicamentos". Esta división apoyó el desarrollo del algoritmo, que fue validado después de tres rondas, con un Índice de Validez de Contenido global del instrumento de 0,91. Conclusión: la validación del algoritmo indica confiabilidad y precisión de su contenido.

RESUMO Objetivo: elaborar e validar o conteúdo de um algoritmo para o planejamento da administração de medicamentos intravenosos em neonatos. Método: estudo metodológico de elaboração e de validação de tecnologia. Foi realizada a revisão de escopo que subsidiou a elaboração do algoritmo pelas pesquisadoras e sua posterior validação por 13 enfermeiros especialistas, a qual ocorreu entre novembro de 2021 e março de 2022. Foram considerados aceitáveis os itens com Índice de Validade de Conteúdo ≥ 0,8. Resultados: foram incluídas 31 referências na revisão de escopo, organizadas em cinco categorias: "indicação de acesso intravenoso", "cuidados relacionados à polifarmácia", "cuidados prévios à administração de medicamentos intravenosos", "cuidados relacionados à manipulação do cateter venoso" e "cuidados relacionados à infusão de medicamentos". Essa divisão subsidiou a elaboração do algoritmo, que foi validado após três rodadas, com Índice de Validade de Conteúdo geral do instrumento de 0,91. Conclusão: a validação do algoritmo indica confiabilidade e precisão do seu conteúdo.

Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to antifungal compounds.

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.

Evaluation of TIB Molbiol LightMix® assays for detection of Mycoplasma genitalium and key resistance mutations for macrolides and fluoroquinolones.

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.

Artificial augmented dataset for the enhancement of nano-QSARs models. A methodology based on topological projections.

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.