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OBJECTIVE: The Corollary Discharge (CD) mechanism inhibits self-generated speech sound perception, appearing disrupted in schizophrenia and potentially contributing to Anomalous Self-Experiences (ASEs). However, it remains unclear if this alteration and its correlation with ASEs extend to other psychotic disorders. METHODS: Electroencephalography was used to study the N1 Event-Related Potential (ERP) as an index of CD-mediated suppression in the auditory cortex across thirty-five participants with schizophrenia, twenty-six with bipolar disorder, and thirty healthy controls. Auditory N1 was elicited by two conditions: real-time listening to self-pronounced vowels while speaking through connected microphone and earphones (listen/talk -or talk condition in previous literature-) and passive listening to the same previously recorded self-uttered vowels (listen/no talk -or listen condition-). RESULTS: N1 ERP amplitude was lower in the listen/talk condition compared to listen/no talk across all groups. However, N1 suppression was significantly reduced in schizophrenia, with bipolar patients showing intermediate attenuation between both groups (i.e., non-significantly different from controls). Furthermore, N1 suppression inversely correlated with ASEs severity only in schizophrenia. CONCLUSIONS: Dysfunction of the CD mechanism may be a defining feature of schizophrenia, where it is connected to ASEs. SIGNIFICANCE: These results corroborate previous findings linking auditory N1 ERP suppression with disrupted CD mechanism in schizophrenia, but not in bipolar disorder.
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Isothermal microcalorimetry (IMC) is a potent analytical method for the real-time assessment of microbial metabolic activity, which serves as an indicator of microbial viability. This approach is highly relevant to the fields of probiotics and Live Biotherapeutic Products (LBPs), offering insights into microbial viability and growth kinetics. One important characteristic of IMC is its ability to measure microbial metabolic activity separately from cellular enumeration. This is particularly useful in situations where continuous tracking of bacterial activity is challenging. The focus on metabolic activity significantly benefits both probiotic research and industrial microbiology applications. IMC's versatility in handling different media matrices allows for the implementation of viability assessments under conditions that mirror those found in various industrial environments or biological models. In our study, we provide a proof of concept for the application of IMC in determining viability and growth dynamics and their correlation with bacterial count in probiotic organisms. Our findings reinforce the potential of IMC as a key method for process enhancement and accurate strain characterization within the probiotic sector. This supports the broader objective of refining the systematic approach and methods used during the development process, thereby providing detailed insights into probiotics and LBPs.
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Hemostatic powders (HP) are increasingly used to address limitations in conventional endoscopic techniques for gastrointestinal bleeding. HP is a relatively recent addition to the arsenal of hemostatic endoscopic procedures (HEPs) for gastrointestinal bleeding (GIB) due to benign and malignant lesions, which all life-threatening conditions. HP acts as a mechanical barrier and/or promotes platelet activation and coagulation cascade. Malignancy causes comprise 1-5% of all non-variceal upper gastrointestinal bleeding (NVUGIB). UI-EWD (NexPowder) is composed of oxidized dextran and succinic anhydride, which is converted to an adhesive hydrogel upon contact with moisture. The resulting hydrogel cross-links within itself and with adjacent tissue to create a mechanical barrier to promote hemostasis. As it does not require clot formation to achieve hemostasis, UI-EWD does not require active bleeding. This provides it a potential role in prophylaxis, such as post-procedure or following primary hemostasis achieved with conventional endoscopic techniques. While UI-EWD is the newest development in hemostatic powders for clinical use, initial results are promising. We report the case of a 51-year-old male with epidermoid esophageal stenosing carcinoma recently diagnosed and locally advanced. Started treatment concurrent chemotherapy and radiotherapy, being necessary a nasogastric tube for parenteral nutrition. Our patient came to the emergency unit due to hematemesis which came from a pressure ulcer with active bleeding shown in gastroscopy exploration, withdrawing the tube and spraying onto the surface of the bleeding site UI-EWD until the bleeding lesion was completely covered with the powder, doing successful hemostasis confirmed by hemostasis until 5 minutes after the endoscopic treatment. HP is highly effective in patients with NVUGIB when used either in combination with or as rescue therapy. Rapid development of hemostatic powders and growing clinical expertise has established these agents as a valuable strategy in gastrointestinal bleeding.
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Objectives. The COVID-19 pandemic, remote work and new technologies have heightened workplace pressures. Effective response and essential organizational changes require business leaders to be more adaptable, with managers' presence playing a pivotal role in successful implementation. The study assesses a brief mindfulness-based emotional regulation for managers (MBERM) intervention, to reduce workplace stress and enhance managerial well-being. Methods. An 8-week non-randomized controlled trial was conducted with a waiting list control group and an intervention group. Pre-post differences were measured by Student's t test or Wilcoxon test, and effect size calculated using the Hedge's g formula. The sample included 23 managers (17 men and six women) with average age 50 years. The study assessed anxiety and depressive symptoms, psychological flexibility, perceived self-efficacy, general work-related well-being, perceived stress and mindfulness. Results. Statistically significant changes were observed in the intervention group in depression, anxiety, work-related acceptance and action, general self-efficacy, exhaustion, alienation, stress and non-reactivity. The control group showed no statistically significant changes in any of the variables. Conclusion. The MBERM intervention could improve the emotional and work-related well-being of managers and reduce stress levels and burnout. Further study of this intervention is needed to promote adherence and ensure a long-term improvement.
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COVID-19 , Atención Plena , Estrés Laboral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proyectos Piloto , Estrés Laboral/prevención & control , Estrés Laboral/psicología , COVID-19/prevención & control , COVID-19/psicología , Depresión/prevención & control , Depresión/psicología , Adulto , Ansiedad/prevención & control , Ansiedad/psicología , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Lugar de Trabajo/psicología , Autoeficacia , SARS-CoV-2 , Personal Administrativo/psicología , Regulación EmocionalRESUMEN
Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1, Rbl1, Pten, and Trp53, which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes.
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Sistemas CRISPR-Cas , Neoplasias Pulmonares , Mutagénesis , Fosfohidrolasa PTEN , Carcinoma Pulmonar de Células Pequeñas , Proteína p53 Supresora de Tumor , Animales , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Fosfohidrolasa PTEN/genética , Proteína p53 Supresora de Tumor/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Humanos , Modelos Animales de Enfermedad , Proteína p107 Similar a la del Retinoblastoma/genética , Proteína p107 Similar a la del Retinoblastoma/metabolismo , Proteína de Retinoblastoma/genética , Proteína de Retinoblastoma/metabolismo , Edición Génica/métodosRESUMEN
INTRODUCTION: Multi-carbapenemase-producing Enterobacterales (M-CPE) are increasingly described. We characterized the M-CPE isolates prospectively recovered in our hospital (Madrid, Spain) over two years (2021-2022). METHODS: We collected 796 carbapenem resistant Enterobacterales (CRE) from clinical and surveillance samples. Carbapenemase production was confirmed with phenotypic (immunochromatographic, disk diffusion) and molecular (PCR, WGS) techniques. Antimicrobial susceptibility was evaluated by a standard broth microdilution method. Clinical and demographic data were collected. RESULTS: Overall, 23 M-CPE (10 Klebsiella pneumoniae, 6 Citrobacter freundii complex, 3 Escherichia coli, 2 Klebsiella oxytoca, and 2 Enterobacter hormaechei) isolates were recovered from 17 patients (3% with CPE, 0.26-0.28 cases per 1000 admissions). OXA-48 + KPC-3 (7/23) and KPC-3 + VIM-1 (5/23) were the most frequent carbapenemase combinations. All patients had prior antibiotics exposure, including carbapenems (8/17). High resistance rates to ceftazidime/avibactam (14/23), imipenem/relebactam (16/23) and meropenem/vaborbactam (7/23) were found. Ceftazidime/avibactam + aztreonam combination was synergistic in all metallo-ß-lactamase producers. Clonal and non-clonal related isolates were found, particularly in K. pneumoniae (5 ST29, 3 ST147, 3 ST307) and C. freundii (3 ST8, 2 ST125, 1 ST563). NDM-1 + OXA-48 was introduced with the ST147-K. pneumoniae high-risk clone linked to the transfer of a Ukrainian patient. We identified four possible nosocomial clonal transmission events between patients of the same clone with the same combination of carbapenemases (KPC-3 + VIM-1-ST29-K. pneumoniae, NDM-1 + OXA-48-ST147-K. pneumoniae and KPC-2 + VIM-1-ST145-K. oxytoca). Carbapenemase-encoding genes were located on different plasmids, except for VIM-1 + KPC-2-ST145-K. oxytoca. Cross-species transmission and a possible acquisition overtime was found, particularly between K. pneumoniae and E. coli producing OXA-48 + KPC-3. CONCLUSION: M-CPE is an emerging threat in our hospital. Co-production of different carbapenemases, including metallo-ß-lactamases, limits therapeutic options and depicts the need to reinforce infection control measures.
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PURPOSE: Study the effect on the tear film in blepharospasm (BEB), facial hemispasm (FH), or aberrant regeneration (AR) treated with Botulinum Toxin (BTX-A). METHODS: A prospective study was used to evaluate the tear film in patients with BEB, FH, or AR treated with BTX-A. Schirmer tests, break-up time (BUT), optical coherence tomography (OCT) meniscus measurement, the Ocular Surface Disease Index (OSDI) questionnaire, and Oxford scale were documented before; 1 month after; and 3 months after BTX-A treatment. Comparisons were made with the Friedman test and Wilcoxon matched-pairs signed rank test was used. A p-value <0.05 was considered statistically significant. RESULTS: A total of 35 eyes from 27 patients were included. The mean patient age was 66.81 ± 12.94 years and 18 (66.7%) were female. Ten (37%) patients had BEB, six (22.2%) had FH, and 11 (40.74%) had AR. BTX-A improved the lid spasms. One month after BTX-A, Schirmer tests showed slight increments (Schirmer 1 p = 0.009; Schirmer 2 p = 0.05) and at 3 months they became similar to pre-treatment (p = 0.5). The BUT test was not significantly different at 1 month (p = 0.450) or at 3 months. On OCT 1 month after BTX-A, there was an increase in tear meniscus area (p = 0.004), height (p = 0.007), and depth (p = 0.004), and at 3 months the measurements also became similar to the pre-BTX-A values. No significant changes in the OSDI (p = 0.717) and Oxford scale (p = 0.255). CONCLUSION: OCT is a good tool to detect the increase in tear meniscus after periocular BTX-A in BEB, FH, and AR.
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Plasmids are extrachromosomal genetic elements commonly found in bacteria. Plasmids are known to fuel bacterial evolution through horizontal gene transfer (HGT), but recent analyses indicate that they can also promote intragenomic adaptations. However, the role of plasmids as catalysts of bacterial evolution beyond HGT remains poorly explored. In this study, we investigate the impact of a widespread conjugative plasmid, pOXA-48, on the evolution of various multidrug-resistant clinical enterobacteria. Combining experimental and within-patient evolution analyses, we unveil that plasmid pOXA-48 promotes bacterial evolution through the transposition of plasmid-encoded insertion sequence 1 (IS1) elements. Specifically, IS1-mediated gene inactivations expedite the adaptation rate of clinical strains in vitro and foster within-patient adaptation in the gut microbiota. We decipher the mechanism underlying the plasmid-mediated surge in IS1 transposition, revealing a negative feedback loop regulated by the genomic copy number of IS1. Given the overrepresentation of IS elements in bacterial plasmids, our findings propose that plasmid-mediated IS transposition represents a crucial mechanism for swift bacterial adaptation.
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In this work, we focused on the bioactivity and antibacterial behavior of PLA-based electrospun fibers, efibers, reinforced with both MgO and Mg(OH)2 nanoparticles, NPs. The evolution of PLA-based efibers was followed in terms of morphology, FTIR, XRD, and visual appearance. The bioactivity was discussed in terms of hydroxyapatite growth after 28 days, considered as T28, of immersion in simulated body fluid, SBF. In particular, the biomineralization process evidenced after immersion in SBF started at T14 in both systems. The number of precipitated crystals increased by increasing the amount of both NPs. The chemical composition of the precipitated crystals was also characterized in terms of the Ca/P molar ratio after T28 of immersion in SBF, indicating the presence of hydroxyapatite on the surface of both reinforced efibers. Moreover, a reduction in the average diameter of the PLA-based efibers was observed, reaching a maximum reduction of 46 and 60% in the average diameter of neat PLA and PLA:OLA efibers, respectively, after 28 days of immersion in SBF. The antibacterial behavior of the MgO and Mg(OH)2 NPs in the PLA-based electrospun fibers was tested against Escherichia coli, E. coli, as the Gram-negative bacteria, and Staphylococcus aureus, S. aureus, as the Gram-positive bacteria, obtaining the best antibacterial activity against the Gram-negative bacteria E. coli of 21 ± 2% and 34 ± 6% for the highest concentration of MgO and Mg(OH)2 NPs, respectively.
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BACKGROUND: Although respiratory symptoms are the most prominent manifestations of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially the omicron variant, may cause neurological manifestations such as seizures. It remains unclear if specific variants of the virus increase the risk of seizures more than others. MATERIAL AND METHODS: This was a retrospective multicenter study of pediatric (zero to 16 years) patients with COVID-19 who attended five pediatric emergency departments in Madrid, Spain, between March 2020 and July 2022. An analysis of demographics, medical history, and seizure characteristics was conducted. The data obtained were correlated with the incidence of the different strains of SARS-CoV-2 in the Community of Madrid. RESULTS: A total of 2411 seizures (infectious and noninfectious) were recorded, and 35 of them (1.4%) were positive for SARS-CoV-2. Of those 35 patients, 18 (51.4%) reported a history of previous seizures. The highest percentage of cases occurred when the omicron variant was the most prevalent (28 [80%] vs 7 [20%] before omicron variant). Typical febrile seizures accounted for 52.9% of the cases. No treatment was required in more than half (57.1%) of the cases. CONCLUSION: during the emergence of the omicron variant, there has been an increase in the number of COVID-19-associated seizures. These findings highlight the need for SARS-CoV-2 screening in patients with febrile and afebrile seizures, in addition to other microbiological, biochemical, or neuroimaging tests, depending on the patient's age and clinical presentation.
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COVID-19 , SARS-CoV-2 , Convulsiones , Humanos , COVID-19/complicaciones , Niño , Masculino , Femenino , Preescolar , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/epidemiología , Adolescente , Lactante , España/epidemiología , Recién NacidoRESUMEN
Objectives: We performed a multicentre study (2020-2022) to compare the in vitro activity of ozenoxacin and comparator agents against Staphylococcus aureus and Streptococcus pyogenes clinical isolates from skin and soft-tissue infections (SSTI). Methods: A total of 1725 isolates (1454 S. aureus and 271 S. pyogenes) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria. Results: Ozenoxacin exhibited high in vitro activity against S. aureus (MIC50/90â=â0.002/0.12â mg/L) and S. pyogenes (MIC50/90â=â0.015/0.03â mg/L), inhibiting 99% of the isolates at MICâ≤â0.5â mg/L and at MICâ≤â0.06, respectively. The most active comparators against S. aureus were retapamulin (MIC90â=â0.12â mg/L), fusidic acid (MIC90â=â0.25â mg/L) and mupirocin (MIC90â=â0.5â mg/L); and against S. pyogenes were retapamulin (MIC90â=â0.03â mg/L), clindamycin (MIC90â=â0.12â mg/L) and mupirocin (MIC90â=â0.25â mg/L). Ciprofloxacin and methicillin resistant rates for S. aureus were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible S. aureus than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates. Conclusions: Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.
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OBJECTIVE: To identify findings in the scientific literature relevant to the strategic lines proposed by the Humanising Intensive Care Project in the context of paediatric intensive care units. DESIGN: Narrative review. METHODS: A literature search was conducted in the databases PubMed, Scopus, CINHAL, and Cochrane Library. Specific indexing terms and search strategies adapted to each database were designed. The inclusion of publications was based on two criteria: 1) related to the paediatric intensive care unit and 2) addresses at least one of the topics related to the strategic lines of the Humanising Intensive Care Project. Study selection was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the quality of the included studies was assessed using the Mixed Method Appraisal tool. RESULTS: A total of 100 articles from 19 different countries were included, covering the period between 2019 and 2021. Nineteen different design types were identified. Thirty-two studies were cross-sectional observational studies, while 15 had an experimental approach. The articles were distributed among the seven strategic lines of the Humanising Intensive Care Project. CONCLUSIONS: Synthesising the knowledge related to humanisation in paediatric intensive care units will allow progress to be made in improving quality in these units. However, there is disparity in the amount of experimental research overall. IMPLICATIONS FOR CLINICAL PRACTICE: There is a disparity in the available research related to the different strategic lines, and it is necessary to carry out more exhaustive research on topics such as the presence and participation of the family in care or the management of post-paediatric intensive care syndrome.
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ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.
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Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopénica Idiopática , Piridinas , Pirimidinas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Anciano , Oxazinas/uso terapéutico , Oxazinas/efectos adversos , Anciano de 80 o más Años , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Morfolinas/uso terapéutico , Morfolinas/efectos adversos , Piridinas/uso terapéutico , Piridinas/efectos adversos , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Quinasa Syk/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Recuento de Plaquetas , Estudios ProspectivosRESUMEN
OBJECTIVE: To establish a methodology for objectively estimating the Lens Equatorial Plane (LEP) from clinical images, comparing LEP with dilated versus non-dilated pupils. METHODS: A cohort of 91 eyes from 60 patients undergoing preoperative assessments for cataract surgery was evaluated. Anterior Segment Optical Coherence Tomography (AS-OCT) images were analysed under conditions of pharmacologically induced pupil dilation versus a non-dilated pupil. Geometrical parameters, including LEP, intersection diameter (ID), lens thickness (LT), anterior and posterior lens thickness were automatically calculated by applying standard image processing techniques to clinical AS-OCT images. RESULTS: Significant differences in lens parameters, including LEP, were observed between dilated and non-dilated conditions (all p < 0.001). A strong linear correlation was found across all geometrical variables under both conditions (r[LEP] = 0.64, r[ID] = 0.78, r[LT] = 0.99, all p < 0.001); enabling reliable correction of these differences. CONCLUSION: The study introduces an objective methodology for LEP calculation, emphasising the need to consider the eye's physiological state during preoperative measurements. Incorporating LEP into future intraocular lens (IOL) power calculation formulas and replacing the habitual effective lens position may potentially improve the accuracy of IOL power estimation and thus postoperative visual outcomes.
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Cristalino , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Cristalino/diagnóstico por imagen , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pupila/fisiología , Reproducibilidad de los Resultados , Extracción de Catarata , Biometría/métodos , Anciano de 80 o más Años , Midriáticos/administración & dosificación , Midriáticos/farmacologíaRESUMEN
Water pollution from industrial or household waste, containing dyes from the textile industry, poses a significant environmental challenge requiring immediate attention. In this study, we have developed a crosslinked-smart-polymer film based on 2-(dimethylamino)ethyl methacrylate copolymerized with other hydrophilic and hydrophobic commercial monomers, and its efficacy in removing 21 different textile dyes was assessed. The smart polymer effectively interacts with and adsorbs dyes, inducing a noticeable colour change. UV-Vis spectroscopy analysis confirmed a removal efficiency exceeding 90 % for anionic dyes, with external diffusion identified as the primary influencing factor on process kinetics, consistent with both pseudo-first-order kinetics and the Crank-Dual model. Isothermal studies revealed distinct adsorption behaviors, with indigo carmine adhering to a Freundlich isotherm while others conformed to the Langmuir model. Permeation and fluorescence analyses corroborated isotherm observations, verifying surface adsorption. Significantly, our proof-of-concept demonstrated the resilience of the smart-film to common fabric softeners and detergents without compromising adsorption capacity. Additionally, the material exhibited reusability (for at least 5 cycles), durability, and good thermal and mechanical properties, with T5 and T10 values of 265 °C and 342 °C, respectively, a Tg of 168 °C, and a water swelling percentage of 54.3 %, thus confirming its stability and suitability for industrial application. ENVIRONMENTAL IMPLICATION: Dyes released during laundry processes should be classified as "hazardous materials" owing to their significant toxicity towards aquatic organisms, with the potential to disrupt ecosystems and harm aquatic biodiversity. This paper discusses the development of a novel acrylic material in film form, engineered to extract toxic anionic dyes. This study directly contributes to mitigating the environmental impact associated with the fashion industry and the domestic use of textiles. It can be implemented on both an industrial and personal scale, thereby encouraging more sustainable practices and promoting collaborative citizen science efforts towards.
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BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia. METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit ß1 (KCNAB1) and ß2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells. RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls. CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.
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Canales de Potasio con Entrada de Voltaje , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/inmunología , Esquizofrenia/fisiopatología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Canales de Potasio con Entrada de Voltaje/metabolismo , Técnicas de Placa-Clamp , Linfocitos/metabolismo , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de los fármacos , ProteómicaRESUMEN
Albumin is undoubtedly the most studied protein thanks to its widespread diffusion and biochemistry; despite its binding ability towards different dyes, provoking dye's colour change, has been exploited for decades for quantification purposes, the joint effect of working pH, ionic strength, and dye's pKa still remains only sporadically discussed. In the present study, the interaction of Bovine Serum Albumin (BSA) with five dyes belonging to the sulfonephthalein group, Bromophenol Blue (BPB, pKa = 3.75), Bromocresol Green (BCG, pKa = 4.42), Chlorophenol Red (CPR, pKa = 5.74), Bromocresol Purple (BCP, pKa = 6.05) and Bromothymol Blue (BTB, pKa = 6.72), is investigated at four working pH values (3.5, 6.0, 7.5 and 9.0) and two ionic strength conditions by UV-Vis spectroscopy. Principal Component Analysis is then applied to rationalize dye behavior upon BSA addition at each pH value and to summarize the protein effect on dyes' spectral features, identifying three general behaviors. The most relevant systems are then submitted to further characterization involving a solution equilibria study aimed at determining conditional binding constants for the selected DSA-dye adducts and fluorescence, CD, and 1H NMR spectroscopy to evaluate the binding effect on the species involved.
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Colorantes , Albúmina Sérica Bovina , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Colorantes/química , Bovinos , Concentración de Iones de Hidrógeno , Concentración Osmolar , Animales , Soluciones , Espectrofotometría Ultravioleta , Unión Proteica , Azul de Bromofenol/química , Azul de Bromofenol/metabolismo , Espectrometría de Fluorescencia , Verde de Bromocresol/química , Verde de Bromocresol/metabolismo , Análisis de Componente Principal , Púrpura de Bromocresol/química , Púrpura de Bromocresol/metabolismoRESUMEN
Machine learning (ML) methods are proliferating in scientific research. However, the adoption of these methods has been accompanied by failures of validity, reproducibility, and generalizability. These failures can hinder scientific progress, lead to false consensus around invalid claims, and undermine the credibility of ML-based science. ML methods are often applied and fail in similar ways across disciplines. Motivated by this observation, our goal is to provide clear recommendations for conducting and reporting ML-based science. Drawing from an extensive review of past literature, we present the REFORMS checklist (recommendations for machine-learning-based science). It consists of 32 questions and a paired set of guidelines. REFORMS was developed on the basis of a consensus of 19 researchers across computer science, data science, mathematics, social sciences, and biomedical sciences. REFORMS can serve as a resource for researchers when designing and implementing a study, for referees when reviewing papers, and for journals when enforcing standards for transparency and reproducibility.
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Consenso , Aprendizaje Automático , Humanos , Reproducibilidad de los Resultados , CienciaRESUMEN
Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from the same episode of otitis, or even different episodes affecting the same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrated the value of WGS for disentangling the epidemiology of this yeast species.
We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.
Asunto(s)
Antifúngicos , Azoles , Enfermedades de los Perros , Farmacorresistencia Fúngica , Variación Genética , Malassezia , Pruebas de Sensibilidad Microbiana , Perros , Animales , Malassezia/genética , Malassezia/efectos de los fármacos , Malassezia/aislamiento & purificación , Malassezia/clasificación , Azoles/farmacología , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/epidemiología , Antifúngicos/farmacología , Prevalencia , Otitis/microbiología , Otitis/epidemiología , Otitis/veterinaria , Dermatitis/microbiología , Dermatitis/veterinaria , Dermatitis/epidemiología , Dermatomicosis/microbiología , Dermatomicosis/veterinaria , Dermatomicosis/epidemiología , Secuenciación Completa del Genoma , Esterol 14-Desmetilasa/genéticaRESUMEN
Incidents related to patient safety are a problem of great impact in Intensive Care Medicine (ICM). Multiple strategies have been developed to identify them, analyze, and develop policies aim at reducing their incidence and minimizing their effects and consequences. The development of a safety culture, an adequate organizational and structural design of the ICM, which contemplates the implementation of effective safe practices, with a provision of human resources adjusted to the care activity carried out and the periodic analysis of the different events and their factors, will allow us to bring the risk of critical patient care closer to zero, as would be desirable.