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Lysosomal membrane damage represents a threat to cell viability. As such, cells have evolved sophisticated mechanisms to maintain lysosomal integrity. Small membrane lesions are detected and repaired by the endosomal sorting complex required for transport (ESCRT) machinery while more extensively damaged lysosomes are cleared by a galectin-dependent selective macroautophagic pathway (lysophagy). In this study, we identify a novel role for the autophagosome-lysosome tethering factor, TECPR1, in lysosomal membrane repair. Lysosomal damage promotes TECPR1 recruitment to damaged membranes via its N-terminal dysferlin domain. This recruitment occurs upstream of galectin and precedes the induction of lysophagy. At the damaged membrane, TECPR1 forms an alternative E3-like conjugation complex with the ATG12-ATG5 conjugate to regulate ATG16L1-independent unconventional LC3 lipidation. Abolishment of LC3 lipidation via ATG16L1/TECPR1 double knockout impairs lysosomal recovery following damage.
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Autofagia , Proteínas Associadas aos Microtúbulos , Proteínas Associadas aos Microtúbulos/metabolismo , Macroautofagia , Galectinas/metabolismo , Lisossomos/metabolismo , Proteínas Relacionadas à Autofagia/metabolismoRESUMO
BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/complicações , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Estudos Retrospectivos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Mieloblastina , RecidivaRESUMO
BACKGROUND: Giant cell arteritis (GCA) is an immune-mediated large-vessels vasculitis with complex etiology. Although the pathogenic mechanisms remain poorly understood, a central role for CD4+ T cells has been demonstrated. In this context, understanding the transcriptome dysregulation in GCA CD4+ T cells will yield new insights into its pathogenesis. METHODS: Transcriptome analysis was conducted on CD4+ T cells from 70 patients with GCA with different disease activity and treatment status (active patients before treatment and patients in remission with and without glucocorticoid treatment), and 28 healthy controls. The study also evaluated potential impacts of DNA methylation on gene expression alterations and assessed cross-talk with CD14+ monocytes. RESULTS: This study has uncovered a substantial number of genes and pathways potentially contributing to the pathogenicity of CD4+ T cells in GCA. Specifically, CD4+ T cells from GCA patients with active disease exhibited altered expression levels of genes involved in multiple immune-related processes, including various interleukins (IL) signaling pathways. Notably, IL-2, a decisive interleukin for regulatory T cells homeostasis, was among the most significant. Additionally, impaired apoptotic pathways appear crucial in GCA development. Our findings also suggest that histone-related epigenetic pathways may be implicated in promoting an inflammatory phenotype in GCA active patients. Finally, our study observed altered signaling communication, such as the Jagged-Notch signaling, between CD4+ T cells and monocytes that could have pathogenic relevance in GCA. CONCLUSIONS: Our study suggests the participation of novel cytokines and pathways and the occurrence of a disruption of monocyte-T cell crosstalk driving GCA pathogenesis.
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Linfócitos T CD4-Positivos , Perfilação da Expressão Gênica , Arterite de Células Gigantes , Monócitos , Transdução de Sinais , Transcriptoma , Humanos , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/genética , Monócitos/imunologia , Monócitos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Feminino , Masculino , Idoso , Metilação de DNA , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Epigênese Genética , Comunicação Celular/imunologia , Regulação da Expressão GênicaRESUMO
RATIONALE: Dispersity values are considered critical quality attributes for the quality control of poly(ethylene glycol) formulations due to the direct impact on drug performance. However, when these polymers are analysed using mass spectrometry, the design of the mass analyser can impact the oligomer response and affect the obtained dispersity values, so further understanding is needed. METHODS: The deconvoluted electrospray ionisation mass spectra of poly(ethylene glycol)s obtained using supercritical fluid chromatography (SFC) hyphenated to different mass analysers were compared, and visualisation diagrams were used to understand the differences in the dispersity value calculations. Five calibration approaches based on a surrogate single oligomer that represents the whole distribution, or the whole distribution itself, for response selection, were used to evaluate ionisation efficiency prior to quantitation. The impact of using an internal standard (ISTD) on the expanded uncertainty was also assessed. RESULTS: Although there were challenges related to the resolution of multiply charged species when low-resolution instruments were used, similar quantitation capabilities were obtained to those when high-resolution mass analysers were used. Evaluation of approaches using a surrogate oligomer or the whole distribution suggested the independence of both approaches and a constant ionisation efficiency across the oligomer chain length. The higher degree of chromatographic resolution of SFC allowed incorporating a monodispersed ISTD to improve the accuracy and precision of the method. CONCLUSIONS: The use of low resolution mass analysers was sufficient to provide accurate and precise dispersity values; however, higher resolution instruments were recommended for characterisation due to the improved mass resolution of ions. The introduction of a monodispersed ISTD improved precision without compromising the calculated dispersity value due to the lack of analyte suppression.
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ABSTRACT: Gorlin syndrome, also known as basal cell nevus syndrome, is an autosomal dominant genetic disorder that predisposes humans to tumors. In most cases, this syndrome results from inactivating mutations in the patched homologue 1 gene. Basal cell carcinomas are one of the main characteristics of this syndrome and serve as a major diagnostic criterion. Gorlin syndrome shows a variable phenotype, and recently, other less common mutations in the suppressor of fused homologue or patched homologue 2 genes have been documented in individuals with this syndrome. We present the case of a patient with early-onset basal cell carcinomas and a mild Gorlin syndrome phenotype, attributed to a de novo patched homologue 2 variant of uncertain significance, which has not been previously reported in the literature.
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Síndrome do Nevo Basocelular , Feminino , Humanos , Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/patologia , Fenótipo , Mutação , Receptor Patched-2/genéticaRESUMO
This paper presents the analysis of a pilot anaerobic digestion plant that operates with organic fraction of municipal solid waste (OFMSW) from a wholesale market and can treat up to 500 kg d-1. The process was monitored for a period of 524 days during which the residue was characterized and the biogas production and methane content were recorded. The organic load rate (OLR) of volatile solids (VS) was 0.89 kg m-3 d-1 and the Hydraulic Retention Time (HRT) was 25 d during the process. The yield was 82 Nm3 tons OFMSW-1 biogas, equivalent to 586 Nm3 tons CH4 VS-1. The results obtained in the pilot plant were used to carry out a technical-economic evaluation of a plant that treats 50 tons of OFMSW from wholesale markets. A production of 3769 Nm3 d-1 of biogas and 2080 Nm3 d-1 of methane is estimated, generating 35.1 MWh d-1 when converted to electricity.
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Eliminação de Resíduos , Resíduos Sólidos , Resíduos Sólidos/análise , Eliminação de Resíduos/métodos , Anaerobiose , Biocombustíveis , Reatores Biológicos , MetanoRESUMO
Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.
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Senescência Celular , Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Humanos , Senescência Celular/imunologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Animais , Pulmão/imunologia , Pulmão/patologia , ImunidadeRESUMO
PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.
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Conjuntivite , Transtornos de Fotossensibilidade , Prurigo , Dermatopatias Genéticas , Animais , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , México/epidemiologia , Prurigo/complicações , Prurigo/epidemiologia , Prurigo/patologia , Estudos Prospectivos , Povos IndígenasRESUMO
Salivary secretory dysfunction in SS-patients is associated with altered proteostasis, upregulation of ATF6α and components of the ERAD complex, such as SEL1L, and downregulation of XBP-1s and GRP78. Hsa-miR-424-5p is downregulated and hsa-miR-513c-3p is overexpressed in salivary glands from SS-patients. These miRNAs emerged as candidates that could regulate ATF6/SEL1L and XBP-1s/GRP78 levels, respectively. This study aimed to evaluate the effect of IFN-γ on hsa-miR-424-5p and hsa-miR-513c-3p expression and how these miRNAs regulate their targets. In labial salivary glands (LSG) biopsies from 9 SS-patients and 7 control subjects and IFN-γ-stimulated 3D-acini were analyzed. hsa-miR-424-5p and hsa-miR-513c-3p levels were measured by TaqMan assays and their localization by ISH. mRNA, protein levels, and localization of ATF6, SEL1L, HERP, XBP-1s and GRP78 were determined by qPCR, Western blot, or immunofluorescence. Functional and interaction assays were also performed. In LSGs from SS-patients and IFN-γ-stimulated 3D-acini, hsa-miR-424-5p was downregulated and ATF6α and SEL1L were upregulated. ATF6α and SEL1L were decreased after hsa-miR-424-5p overexpression, while ATF6α, SEL1L and HERP increased after hsa-miR-424-5p silencing. Interaction assays revealed that hsa-miR-424-5p targets ATF6α directly. hsa-miR-513c-3p was upregulated and XBP-1s and GRP78 were downregulated. XBP-1s and GRP78 were decreased after hsa-miR-513c-3p overexpression, while increases in XBP-1s and GRP78 were observed after hsa-miR-513c-3p silencing. Furthermore, we determined that hsa-miR-513c-3p targets XBP-1s directly. Significant correlations were found between both miRNA levels and clinical parameters. In conclusion, IFN-γ-dependent hsa-miR-424-5p and hsa-miR-513c-3p levels affect the expression of important factors involved in cellular proteostasis that control secretory function in LSG from SS-patients.
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MicroRNAs , Glândulas Salivares , Síndrome de Sjogren , Humanos , Chaperona BiP do Retículo Endoplasmático , Interferon gama/genética , Interferon gama/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas/genética , Proteínas/metabolismo , Glândulas Salivares/metabolismo , Síndrome de Sjogren/genética , Síndrome de Sjogren/metabolismoRESUMO
OBJECTIVE: The objective of this study was to analyse the clinico-serological and histological phenotypes of patients with SSc with associated myopathy. METHODS: From November 2002 to September 2020, 52 patients with SSc underwent a muscle biopsy for suspected myopathy. We established two subgroups according to the histological findings based on the presence of isolated fibrosis or fibrosis together with significant inflammation. These patterns were designated as fibrosing and inflammatory, respectively. Clinical data, antibody profile, electrophysiologic studies, muscle biopsy findings and data regarding treatment, mortality and survival were compared between the two groups. RESULTS: Fourteen biopsies had a fibrosing pattern, whereas 26 showed an inflammatory pattern that could be classified (according to the predominant pattern) into DM (n = 7), necrotizing myopathy (n = 4) and non-specific myositis (n = 15). Additionally, 12 muscle biopsies were reported as neurogenic atrophy (n = 2), or normal muscle or minimal changes (n = 10). Compared with the inflammatory group, SSc patients with the fibrosing pattern presented a higher prevalence of ischaemic heart disease (38.5% vs 3.8%, P = 0.011), conduction abnormalities or arrhythmias (61.5% vs 26.9%, P = 0.036), anti-topo I antibodies (42.9% vs 11.5%, P = 0.044), greater median ESR (53.5 mm/h vs 32.5 mm/h, P = 0.013), with poor response to treatment and a higher mortality (42.9% vs 3.8%, P = 0.004) and lower cumulative survival (P = 0.035). CONCLUSIONS: Patients with SSc-associated myopathy require a comprehensive approach that encompasses clinical, serological and histopathological aspects, given their outcome predictive capacity. At least two different phenotypes can be drawn, considering clinico-pathological features. Significant differences are delineated between both a fibrotic and an inflammatory phenotype.
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Doenças Musculares , Escleroderma Sistêmico , Humanos , Doenças Musculares/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Fibrose , Biópsia , FenótipoRESUMO
Poly(ethylene glycols) are complex polymers often added to pharmaceutical formulations to improve drug solubility and delivery. One of the main challenges when using chromatographic techniques coupled to mass spectrometry is the unselective ionization of poly(ethylene glycols) oligomers. Additionally, when the chain length is large enough, multiple charged species are formed, further complicating the mass spectra and processing. This study uses the advanced oligomer separation provided by supercritical fluid chromatography with a mass spectrometry approach that selectively ionizes poly(ethylene glycols) as ammoniated molecules to simplify data analysis and facilitate batch-to-batch comparisons. Several visual representations of the response of the ionization events based on the polymer molecular weight and the repeating unit were used to elucidate trends in ionization. Evaluation of the influence of the oligomer length and end-group on the electrospray ionization of the polymer allowed the development of a process to enable selective ionization for these complex polymers.
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PURPOSE: The Clavien-Dindo Classification (CDC) and the Comprehensive Complication Index (CCI®) are both widely used methods for reporting postoperative complications. Several studies have compared the CCI® with the CDC in evaluating postoperative complications of major abdominal surgery. However, there are no published reports comparing both indexes in single-stage laparoscopic common bile duct exploration with cholecystectomy (LCBDE) for the treatment of common bile duct stones. This study aimed to compare the accuracy of the CCI® and the CDC in evaluating the complications of LCBDE. METHODS: In total, 249 patients were included. Spearman's rank test was used to calculate the correlation coefficient between CCI® and CDC with length of postoperative stay (LOS), reoperation, readmission, and mortality rates. Student t-test and Fisher's exact test were used to study, if higher ASA, age, larger surgical time, history of previous abdominal surgery, preoperative ERCP, and intraoperative cholangitis finding were associated with higher CDC grade or higher CCI® score. RESULTS: Mean CCI® was 5.17 ± 12.8. CCI® ranges overlap among three CDC grades: II (20.90-36.20), IIIa (26.20-34.60), and IIIb (33.70-52.10). Age > 60 years, ASA ≥ III, and intraoperative cholangitis finding were associated with higher CCI® (p = 0.010, p = 0.044, and p = 0.031) but not with CDC ≥ IIIa (p = 0.158, p = 0.209, and p = 0.062). In patients with complications, LOS presented a significantly higher correlation with CCI® than with CDC (p = 0.044). CONCLUSION: In LCBDE, the CCI® assesses better the magnitude of postoperative complications in patients older than 60 years, with a high ASA as well as in those who present intraoperative cholangitis. In addition, the CCI® correlates better with LOS in patients with complications.
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Colecistectomia Laparoscópica , Coledocolitíase , Cálculos Biliares , Laparoscopia , Humanos , Pessoa de Meia-Idade , Coledocolitíase/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Cálculos Biliares/cirurgia , Abdome , Colecistectomia Laparoscópica/métodos , Tempo de Internação , Estudos RetrospectivosRESUMO
Functionalized textiles have been increasingly used for enhancing antimicrobial or antiviral (antipathogenic) action. Those pathogens can cause recurring diseases by direct or indirect transmission. Particularly, airborne microorganisms may cause respiratory diseases or skin infections like allergies and acne and the use of inorganic agents such as metal and metal oxides has proven effective in antipathogen applications. This review is a tutorial on how to obtain functional fabric with processes easily applied for industrial scale. Also, this paper summarizes relevant textiles and respective incorporated inorganic agents, including their antipathogenic mechanism of action. In addition, the processing methods and functional finishing, on a laboratory and industrial scale, to obtain a functional textile are shown. Characterization techniques, including antipathogenic activity and durability, mechanical properties, safety, and environmental issues, are presented. Challenges and perspectives on the broader use of antipathogenic fabrics are discussed.
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PURPOSE: To evaluate the efficacy of applying a combination of intrameniscal and intraarticular infiltrations of Platelet-Rich Plasma (PRP) in patients with meniscal tears, analyzing its failure rate and clinical evolution, as well as factors that may influence the positive response to this treatment. METHODS: Three hundred and ninety-two cases out of 696 met the inclusion criteria and were included in this work. Survival and patient-reported outcome measure (PROM) were collected and analyzed. Survival rate was defined as the percentage of patients who did not undergo meniscus surgery during their follow-up time. Patients were asked to complete the Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6 months and 18 months. Other patient- and pathology-related variables were collected. Blood and PRP samples were randomly tested as a quality control measure. Survival and comparative statistical tests, and multivariate regression were performed for the analysis of the variables. RESULTS: The PRP applied had a platelet concentration factor of 1.9X in respect to blood levels, with no leukocytes or erythrocytes. Thirty-eight patients required surgical intervention after treatment reaching a survival rate of 90.3% with an estimated mean survival time of 54.4 months. The type of injury (P = 0.002) and the presence of chondropathy were risk factors for surgical intervention after PRP treatment (P = 0.043). All KOOS scores showed a significant statistical increase from baseline to 6 months (N = 93) and 18 months (N = 66) (P < 0.0001). The number of cases with minimal clinically important improvement (MCII) at 6 months and 18 months post-treatment was 65 (69.9%) and 43 (65.2%), respectively. CONCLUSION: The combination of intrameniscal and intraarticular PRP infiltrations is a valid conservative treatment for meniscal injuries avoiding the need for surgical intervention. Its efficacy is higher in horizontal tears and decreases when joint degeneration is present. LEVEL OF EVIDENCE: Level IV.
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Doenças das Cartilagens , Osteoartrite do Joelho , Osteoartrite , Plasma Rico em Plaquetas , Humanos , Taxa de Sobrevida , Resultado do Tratamento , Tratamento Conservador , Injeções Intra-Articulares , Osteoartrite do Joelho/patologiaRESUMO
The literature reports the presence of multiresistant microorganisms in wastewater discharged from municipal and hospital wastewater treatment plants (WWTPs). This has led to questions concerning the disinfection efficiency of the treatments applied. Thus, this study aimed to assess the efficiency of different chemical oxidation methods to disinfect and to degrade bacterial plasmids present in hospital wastewaters, to avoid the dispersion of antibiotic resistance genes in the environment. The methods tested were UV254nm alone or associated with an Ag or Ti-photocatalyst in photo-peroxonization (UV254 nm/H2O2/O3/Ag2O/Ag2CO3@PU or UV254 nm/H2O2/O3/TiO2@PU) under different pH conditions (4, 7, and 10). The application of plasmid DNA electrophoresis to hospital wastewater treated using an advanced oxidation process (AOP) achieved the total structural denaturation of microorganism plasmids at the three pH values tested. Also, UV254 nm alone was partially efficient in the disinfection of hospital wastewater. AOPs performed with the two functionalized catalysts resulted in 100% disinfection after 10 min at the three pH values tested. No intact plasmids were observed after 20 min of treatment with photocatalysis. This study could contribute to the development and improvement of wastewater treatment aimed at mitigating the spread of multiresistant microorganisms in the environment.
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Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Peróxido de Hidrogênio/química , DNA , Bactérias/genética , Plasmídeos/genética , Oxirredução , Hospitais , Purificação da Água/métodos , Desinfecção/métodosRESUMO
OBJECTIVE: To design and validate a nomophobia scale in children aged 9-13 years. DESIGN: Cross-sectional descriptive observational study. SITE: The pilot study was carried out in December 2019 with students from a school in Ávila and another in Madrid. The field study was carried out during the months of January to March 2020, collecting data from 592 students from a school in Badajoz and 3 from Ávila. PARTICIPANTS: Students of both sexes from 4th, 5th and 6th of Primary Education and from 1st and 2nd of Compulsory Secondary Education, from public and private schools. METHOD: The study has been divided in 2 phases. PHASE I: consisted of the preparation of a 40-item questionnaire with the advice of a panel of experts. This questionnaire was passed, within the pilot study, to 312 children enrolled in Primary Education or Compulsory Secondary Education. After analyzing the results, the 40-item scale was modified to improve the understanding of the schoolchildren and a field study was carried out with 592 participants. PHASE II: consisted of an exploratory factorial analysis carried out using the principal components method, which provided the distribution of the items in 7 components. After the confirmatory factorial analysis, the final 32-item scale was defined. RESULTS: This scale was shown to produce valid and reliable scores. CONCLUSIONS: The validation of this scale will be useful to identify children at risk of nomophobia, allowing educators, parents and health professionals to detect this phenomenon early in order to prevent pathological smartphone use.
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Smartphone , Estudantes , Masculino , Feminino , Humanos , Criança , Adolescente , Estudos Transversais , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Giant cell arteritis (GCA) is a complex systemic vasculitis mediated by the interplay between both genetic and epigenetic factors. Monocytes are crucial players of the inflammation occurring in GCA. Therefore, characterisation of the monocyte methylome and transcriptome in GCA would be helpful to better understand disease pathogenesis. METHODS: We performed an integrated epigenome-and transcriptome-wide association study in CD14+ monocytes from 82 patients with GCA, cross-sectionally classified into three different clinical statuses (active, in remission with or without glucocorticoid (GC) treatment), and 31 healthy controls. RESULTS: We identified a global methylation and gene expression dysregulation in GCA monocytes. Specifically, monocytes from active patients showed a more proinflammatory phenotype compared with healthy controls and patients in remission. In addition to inflammatory pathways known to be involved in active GCA, such as response to IL-6 and IL-1, we identified response to IL-11 as a new pathway potentially implicated in GCA. Furthermore, monocytes from patients in remission with treatment showed downregulation of genes involved in inflammatory processes as well as overexpression of GC receptor-target genes. Finally, we identified changes in DNA methylation correlating with alterations in expression levels of genes with a potential role in GCA pathogenesis, such as ITGA7 and CD63, as well as genes mediating the molecular response to GC, including FKBP5, ETS2, ZBTB16 and ADAMTS2. CONCLUSION: Our results revealed profound alterations in the methylation and transcriptomic profiles of monocytes from GCA patients, uncovering novel genes and pathways involved in GCA pathogenesis and in the molecular response to GC treatment.
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We present a method for evaluating the quality of optical glass using a high-resolution wavefront sensor, the wavefront phase imaging (WFPI) sensor. As shadowgraphy is a widely used method for inspecting striae in optical glass, it does not provide a quantitative metric that represents the potential optical quality of the glass and should be based on the operator's experience. We compare the proposed method in two experiments. First, we compare it with the results obtained by shadowgraphy on a variety of samples. Second, we compare the results of a single-point chromatic confocal profilometer on a calibrated sample. The WFPI shows results comparable to the reference method in both cases but provides more information than shadowgraphy and avoids the human factor in the measurement.
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Skin lesions are not uncommon in children, and most of them are benign. However, they can be a matter of concern. Although in most cases the diagnosis can be suspected based on clinical history and physical examination, in some cases clinical findings are nonspecific. High-frequency color Doppler US is a noninvasive technique that can play a relevant role in these cases and give important anatomical information for final clinical management. US can be helpful to avoid unnecessary surgery, plan a surgical excision and avoid advanced imaging studies such as MRI and CT, which have a lower resolution for the skin. Different lesions can look similar on US, and clinical correlation is always important. The purpose of this article is to show a variety of skin lesions that occur in children, emphasizing clinical-sonographic correlation, and to familiarize pediatric radiologists with the US technique and sonographic appearance of common skin lesions in children.
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Imageamento por Ressonância Magnética , Pele , Criança , Humanos , Pele/diagnóstico por imagem , Ultrassonografia , Ultrassonografia Doppler em Cores/métodosRESUMO
INTRODUCTION: In complex and deformed knees, soft tissue release (STR) is required to obtain symmetry in the femorotibial gap. The objective of this study was to attempt to predict the need for soft tissue release using surgical navigation in total knee replacement (TKR). METHODS: Prospective and non-randomized study. One hundred thirty knees. At the start of navigation, an attempt was made to correct the femorotibial mechanical axis by applying force to the medial or lateral side of the knee (varus-valgus stress angle test). A gap balanced technique with computer-assisted surgery (CAS) was performed in all cases. The ligaments were tensioned, and using CAS visualization and control, progressive STR was performed in the medial or lateral side until a symmetry of the femorotibial gap was achieved. RESULTS: Eighty-two patients had a varus axis ≥ 3° and 38 had a valgus axis (P < 0.001). STR was performed under navigation control in 38.5% of cases, lateral release (LR) in 12 cases, and medial release (MR) in 38 cases. After performing the varus-valgus stress angle test (VVSAT), the axis of 0° could be restored at some point during the manoeuvre in 28 cases. STR was required in 44.6% of varus cases and 27% of valgus cases (P = 0.05). A significant relationship was found between the previous deformity and the need for MR (P < 0.001) or LR (P = 0.001). STR was more common in male patients (P = 0.002) and as obesity increased. CONCLUSION: This study shows that pre-operative factors favouring the need to perform STR in a TKR implant can be defined.