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GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18â years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12â months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3â months and 1â day before starting treatment and 1, 3, 6 and 12â months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8â years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.
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Receptores de N-Metil-D-Aspartato , Serina , Humanos , Feminino , Masculino , Criança , Pré-Escolar , Adolescente , Serina/uso terapêutico , Serina/genética , Receptores de N-Metil-D-Aspartato/genética , Encefalopatias/genética , Encefalopatias/tratamento farmacológico , Resultado do Tratamento , Qualidade de VidaRESUMO
Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia, remains high. Infants with bronchopulmonary dysplasia have larger and fewer alveoli, a lung pathology that can persist into adulthood. Although recent data point to a role for hypoxia-inducible factor-1α (HIF-1α) in mediating pulmonary angiogenesis and alveolarization, the cell-specific role of HIF-1α remains incompletely understood. Thus, we hypothesized that HIF-1α, in a distinct subset of mesenchymal cells, mediates postnatal alveolarization. To test the hypothesis, we generated mice with a cell-specific deletion of HIF-1α by crossing SM22α promoter-driven Cre mice with HIF-1αflox/flox mice (SM22α-HIF-1α-/-), determined SM-22α-expressing cell identity using single-cell RNA sequencing, and interrogated samples from preterm infants. Deletion of HIF-1α in SM22α-expressing cells had no effect on lung structure at day 3 of life. However, at 8 days, there were fewer and larger alveoli, a difference that persisted into adulthood. Microvascular density, elastin organization, and peripheral branching of the lung vasculature were decreased in SM22α-HIF-1α-/- mice, compared with control mice. Single-cell RNA sequencing demonstrated that three mesenchymal cell subtypes express SM22α: myofibroblasts, airway smooth muscle cells, and vascular smooth muscle cells. Pulmonary vascular smooth muscle cells from SM22α-HIF-1α-/- mice had decreased angiopoietin-2 expression and, in coculture experiments, a diminished capacity to promote angiogenesis that was rescued by angiopoietin-2. Angiopoietin-2 expression in tracheal aspirates of preterm infants was inversely correlated with overall mechanical ventilation time, a marker of disease severity. We conclude that SM22α-specific HIF-1α expression drives peripheral angiogenesis and alveolarization in the lung, perhaps by promoting angiopoietin-2 expression.
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Angiopoietina-2 , Displasia Broncopulmonar , Subunidade alfa do Fator 1 Induzível por Hipóxia , Animais , Humanos , Recém-Nascido , Camundongos , Angiopoietina-2/metabolismo , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Recém-Nascido Prematuro , Pulmão/patologiaRESUMO
BACKGROUND: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. Our objectives were to associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification. METHODS: Preterms <32â weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3â T MRI in spontaneous sleep near term (AIRR (Attention to Infants at Respiratory Risks) study). Semi-manual PA flow quantification (phase-contrast MRI; no BPD n=28, mild BPD n=35 and moderate/severe BPD n=25) was complemented by cardiac function assessment (cine MRI). RESULTS: We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume right/left ratio, decreased mean relative area change and pathological right end-diastolic volume, to sensitively detect BPD-associated PVD while correcting for PMA (leave-one-out area under the curve 0.88, sensitivity 0.80 and specificity 0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA mid-systolic notching (t2; p=0.015) and cardiac index (p=1.67×10-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e. duration of mechanical ventilation (rs=0.63, p=2.20×10-4) and oxygen supplementation (rs=0.60, p=6.00×10-4). CONCLUSIONS: Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.
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Displasia Broncopulmonar , Hipertensão Pulmonar , Doenças Vasculares , Recém-Nascido , Lactente , Humanos , Artéria Pulmonar/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Displasia Broncopulmonar/diagnóstico por imagem , Imageamento por Ressonância Magnética , Doenças Vasculares/complicaçõesRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection may be associated with a prothrombotic state, predisposing patients for a progressive disease course. We investigated whether rivaroxaban, a direct oral anticoagulant factor Xa inhibitor, would reduce coronavirus disease 2019 (COVID-19) progression. METHODS: Adults (Nâ =â 497) with mild COVID-19 symptoms and at high risk for COVID-19 progression based on age, body mass index, or comorbidity were randomized 1:1 to either daily oral rivaroxaban 10 mg (Nâ =â 246) or placebo equivalent (Nâ =â 251) for 21 days and followed to day 35. Primary end points were safety and progression. Absolute difference in progression risk was assessed using a stratified Miettinen and Nurminen method. RESULTS: The study was terminated after 497 of the target 600 participants were enrolled due to a prespecified interim analysis of the first 200 participants that crossed the futility boundary for the primary efficacy end point in the intent-to-treat population. Enrollees were 85% aged <65 years; 60% female; 27% Hispanic, Black, or other minorities; and 69% with ≥2 comorbidities. Rivaroxaban was well tolerated. Disease progression rates were 46 of 222 (20.7%) in rivaroxaban vs 44 of 222 (19.8%) in placebo groups, with a risk difference of -1.0 (95% confidence interval, -6.4 to 8.4; Pâ =â .78). CONCLUSIONS: We did not demonstrate an impact of rivaroxaban on disease progression in high-risk adults with mild COVID-19. There remains a critical public health gap in identifying scalable effective therapies for high-risk people in the outpatient setting to prevent COVID-19 progression.
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Tratamento Farmacológico da COVID-19 , Adulto , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Rivaroxabana/uso terapêutico , SARS-CoV-2 , Resultado do TratamentoRESUMO
Although hepcidin synthesis is stimulated by inflammation and inhibited by Fe deficiency, the strength of their opposing effects on serum hepcidin (SHep) in humans remains unclear. It was recently shown that an inflammatory stimulus in anaemic women did not increase SHep or decrease Fe absorption. The enhancing effect of ascorbic acid on Fe absorption may not be effective during inflammation because of increased SHep. Our study aim was to test whether reducing inflammation in Fe-depleted overweight (OW) women with low-grade inflammation would lower SHep and improve Fe absorption with and without ascorbic acid, compared with normal-weight (NW) women without inflammation. Before and after 14 d of anti-inflammatory treatment (3 × 600 mg ibuprofen daily) in OW and NW women (n 36; 19-46 years of age), we measured SHep and fractional Fe absorption (FIA) (erythrocyte Fe incorporation) from 57Fe- and 58Fe-labelled test meals with and without ascorbic acid. There were significant group effects on IL-6, C-reactive protein, serum ferritin and SHep (for all, P < 0·05). There was a significant treatment effect on SHep (P < 0·05): in OW women, treatment decreased IL-6 by approximately 30 % and SHep by approximately 45 %. However, there were no significant treatment or group effects on FIA. Body Fe stores (BIS) were a significant positive predictor of SHep before and after treatment (P < 0·001), but IL-6 was not. Reducing chronic inflammation in OW women halved SHep but did not affect Fe absorption with or without ascorbic acid, and the main predictor of Fe absorption was BIS.
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Ácido Ascórbico/administração & dosagem , Hepcidinas , Inflamação/tratamento farmacológico , Ferro/metabolismo , Sobrepeso , Adulto , Feminino , Hepcidinas/sangue , Humanos , Ibuprofeno/uso terapêutico , Interleucina-6 , Absorção Intestinal , Pessoa de Meia-Idade , Adulto JovemRESUMO
Phenology has been useful to better understand the climate-vegetation relationship, and it is considered an indicator of climate change impact. Phenological data have been generated through multiple remote sensing techniques and ground-based observations through professional or citizen science. The combination of both techniques is known as cross-scale phenological monitoring. However, no comparative analysis has been carried out to assess the advantages and disadvantages of each of these techniques to characterize the phenological cycle of forest ecosystem species. This work is a content-analysis-based review of scientific literature published between 2000 and 2018 related to cross-scale monitoring methods, to estimate the phenological variation in different forest ecosystems worldwide. For this study, 97 publications related to cross-scale phenological monitoring were selected. We found that 71% of the articles aimed to corroborate the data generated through satellite imagery using surface data from either phenocams, flux towers, or from citizen science networks. More publications were published by authors in the USA (30%), Canada (8%), and China (7%). The most commonly used vegetation index was the normalized difference vegetation index (65%). Some deficiencies in the evaluation of the phenological phases of autumn when compared with surface observations were found. Flux towers and phenocams were included as alternatives for ground-based monitoring. Cross-scale phenological monitoring has the potential to characterize the phenological response of vegetation accurately due to data combinations at two different observation scales. This work contributes to specifying the methodologies used in gathering phenological parameters of the world's forest ecosystems.
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Ecossistema , Florestas , Mudança Climática , Imagens de Satélites , Estações do AnoRESUMO
Mast cells (MCs) participate in allergy, inflammation, and defense against pathogens. They release multiple immune mediators via exocytosis, a process that requires SNARE proteins, including syntaxins (Stxs). The identity of the Stxs involved in MC exocytosis remains controversial. Here, we studied the roles of Stx3 and -4 in fully developed MCs from conditional knockout mice by electrophysiology and EM, and found that Stx3, and not Stx4, is crucial for MC exocytosis. The main defect seen in Stx3-deficient MCs was their inability to engage multigranular compound exocytosis, while leaving most single-vesicle fusion events intact. We used this defect to show that this form of exocytosis is not only required to accelerate MC degranulation but also essential to achieve full degranulation. The exocytic defect was severe but not absolute, indicating that an Stx other than Stx3 and -4 is also required for exocytosis in MCs. The removal of Stx3 affected only regulated exocytosis, leaving other MC effector responses intact, including the secretion of cytokines via constitutive exocytosis. Our in vivo model of passive systemic anaphylaxis showed that the residual exocytic function of Stx3-deficient MCs was sufficient to drive a full anaphylactic response in mice.
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Exocitose , Mastócitos/citologia , Proteínas Qa-SNARE/metabolismo , Animais , Contagem de Células , Degranulação Celular , Diferenciação Celular , Técnicas de Inativação de Genes , Cinética , Camundongos , Proteínas Qa-SNARE/deficiência , Proteínas Qa-SNARE/genéticaRESUMO
BACKGROUND: Hematopoietic cell transplantation (HCT) outcomes, including infectious complications, change between centers and countries. Thus, the aim of this study was to report the incidence of infections and isolated pathogens among recipients of HCT and the association with mortality at a tertiary referral center in Mexico. METHODS: Two hundred and eighty-two patients undergoing autologous or allogeneic HCT between January 2005 and December 2018 at the National Institute of Medical Sciences and Nutricion Salvador Zubiran were included. RESULTS: In autologous HCT (n = 176), within the preengraftment and the early postengraftment, 130 (74%) and 31 (18%) recipients presented infections, respectively. Within the preengraftment, the early postengraftment, and the late postengraftment, 81 (76%), 34 (33%), and 58 (60%) allogeneic HCT recipients presented infections, respectively. Non-relapse mortality (NRM) as a result of infections occurred in 1 (0.6%) and 5 (5%) autologous and allogeneic HCT recipients, respectively. CONCLUSIONS: Our results demonstrated that despite our limited resources, infections were not a significant burden for NRM among HCT recipients. More importantly, the isolation rates were higher than international studies, which could be explained by the existence of a specialized infectious diseases department and laboratory, which we consider key elements for the establishment of an HCT program worldwide.
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Países em Desenvolvimento , Transplante de Células-Tronco Hematopoéticas , Infecções/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Incidência , México , Centros de Atenção Terciária , Transplante AutólogoRESUMO
INTRODUCTION: Various biomarkers based on blood counts have been useful for the prognosis of patients critically ill with COVID-19. OBJECTIVE: To describe the usefulness of the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and lymphocyte-to-platelet (LPR) ratios for the prognosis of mortality and ventilatory support requirement for COVID-19. METHOD: Retrospective cohort of clinical records of patients with COVID-19 who required hospital care. RESULTS: One-hundred and -twenty-five cases were analyzed; mean age was 51 years, and 60 % were of the male gender; 21.6 % had type 2 diabetes mellitus, and 18.4 % had hypertension. Mean leukocyte count was 9.5 x 103/µL, with a neutrophil mean of 8.0 x 103/µL. Mean NLR was 12.01, while for MLR it was 0.442, and for LPR, 373.07. Regarding the area under the curve, the following values were recorded for mortality: 0.594 for NLR, 0.628 for MLR and 0.505 for LPR; as for mechanical ventilation, the values were 0.581 for NLR, 0.619 for MLR and 0.547 for LPR. In the univariate analysis, an NLR value > 13 (OR: 2.750, p = 0.001) and an MLR of > 0.5 (OR: 2.069, p = 0.047) were associated with mortality; LPR showed no impact on mortality or respiratory support. CONCLUSION: NLR and MLR are useful for predicting mortality in patients with COVID-19.
INTRODUCCIÓN: Diversos biomarcadores basados en conteos sanguíneos han sido de utilidad para el pronóstico de los pacientes en estado crítico por COVID-19. OBJETIVO: Describir la utilidad de los índices neutrófilo/linfocito (INL), monocito/linfocito (IML) y linfocito/plaqueta (IPL) para el pronóstico de la mortalidad y necesidad de soporte ventilatorio por COVID-19. MÉTODO: Cohorte retrospectiva de registros clínicos de pacientes con COVID-19 que requirieron atención hospitalaria. RESULTADOS: Se analizaron 125 casos, la edad media fue de 51 años y 60 %, del sexo masculino; 21.6 % padecía diabetes mellitus tipo 2 y 18.4 %, hipertensión. La media de leucocitos fue 9.5 × 103/µL y la de neutrófilos, de 8.0 × 103/µL. La media del INL fue de 12.01; del IML, de 0.442 y del IPL, de 373.07. Respecto al área bajo la curva se registraron los siguientes valores en cuanto a mortalidad: INL, 0.594; IML, 0.628 e ILP, 0.505; en cuanto a ventilación mecánica: INL, 0.581; IML, 0.619 e ILP, 0.547. En el análisis univariado, INL > 13 (RM = 2.750, p = 0.001) e IML > 0.5 (RM = 2.069, p = 0.047) se asociaron a mortalidad; ILP no mostró impacto en la mortalidad ni en el soporte respiratorio. CONCLUSIÓN: INL e IML son de utilidad para predecir la mortalidad en pacientes con COVID-19.
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COVID-19/sangue , COVID-19/mortalidade , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , Estudos de Coortes , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Contagem de Plaquetas , Prognóstico , Estudos RetrospectivosRESUMO
Mast cells (MCs) are involved in host defenses against pathogens and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of Caenorhabditis elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and we studied their roles using global and conditional knock-out (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia. This protection correlated with lower plasma histamine levels and with histological evidence of defective MC degranulation but not with changes in MC development, distribution, numbers, or morphology. In vitro assays revealed that the defective response in Munc13-4-deficient MCs was limited to regulated exocytosis, leaving other MC secretory effector responses intact. Single cell capacitance measurements in MCs from mouse mutants differing in Munc13-4 expression levels in their MCs revealed that as levels of Munc13-4 decrease, the rate of exocytosis declines first, and then the total amount of exocytosis decreases. A requirement for Munc13-2 in MC exocytosis was revealed only in the absence of Munc13-4. Electrophysiology and EM studies uncovered that the number of multigranular compound events (i.e. granule-to-granule homotypic fusion) was severely reduced in the absence of Munc13-4. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in MCs, and that this MC effector response is required for a full anaphylactic response.
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Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Anafilaxia , Animais , Modelos Animais de Doenças , Exocitose/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Mastócitos/metabolismo , Mastócitos/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Isoformas de Proteínas , Transporte ProteicoRESUMO
The application of six novel α,ß-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the presence of aq. NaOH. Whereas dipeptides 4 and 6 in conjunction with 4-dimethylaminopyridine (DMAP) and thiourea as a hydrogen bond donor proved to be highly efficient organocatalytic systems in the enantioselective reaction between isobutyraldehyde and various nitroolefins.
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Dipeptídeos/química , 4-Aminopiridina/análogos & derivados , 4-Aminopiridina/química , Aldeídos/química , Alcenos/química , Catálise , Ligação de Hidrogênio , Maleimidas/química , Nitrocompostos/química , Solventes , Estereoisomerismo , Tioureia/químicaRESUMO
Microplastics (MPs) composed of different polymers with various shapes, within a vast granulometric distribution (1 µm - 5 mm) and with a wide variety of physicochemical surface and bulk characteristics spiral around the globe, with different atmospheric, oceanic, cryospheric, and terrestrial residence times, while interacting with other pollutants and biota. The challenges of microplastic pollution are related to the complex relationships between the microplastic generation mechanisms (physical, chemical, and biological), their physicochemical properties, their interactions with other pollutants and microorganisms, the changes in their properties with aging, and their small sizes that facilitate their diffusion and transportation between the air, water, land, and biota, thereby promoting their ubiquity. Early career researchers (ERCs) constitute an essential part of the scientific community committed to overcoming the challenges of microplastic pollution with their new ideas and innovative scientific perspectives for the development of remediation technologies. However, because of the enormous amount of scientific information available, it may be difficult for ERCs to determine the complexity of this environmental issue. This mini-review aims to provide a quick and updated overview of the essential insights of microplastic pollution to ERCs to help them acquire the background needed to develop highly innovative physical, chemical, and biological remediation technologies, as well as valorization proposals and environmental education and awareness campaigns. Moreover, the recommendations for the development of holistic microplastic pollution remediation strategies presented here can help ERCs propose technologies considering the environmental, social, and practical dimensions of microplastic pollution while fulfilling the current government policies to manage this plastic waste.
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Poluentes Ambientais , Poluentes Químicos da Água , Microplásticos , Plásticos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , EcossistemaRESUMO
Keeping surfaces clean can reduce the spread of infections. In particular, to decrease the potential for SARS CoV-2 contamination, performing disinfection of high-touching surfaces. Several ceramic tiles and porcelain stoneware tiles with antimicrobial properties are already available on the market. However, the widespread use of antimicrobial glazed stoneware tiles may require to replace the ceramic surfaces already present in many buildings. The unfeasibility of such replacement can be due to both product durability (lifetime of a tile is usually long) and/or monetary restrictions. Furthermore, as porcelain stoneware per se does not have antimicrobial activity, these materials are fabricated by adding chemical agents able to provide antimicrobial properties. This approach requires a compatibility between the antimicrobial agents and the glaze formulation, as well as a careful control of the firing cycle and the final properties of the ceramic products. It follows that the final cost of antimicrobial tiles is not competitive with that of conventional tiles. In the latter, the persistence of potential pathogens on the surfaces is a crucial problem to face: the longer a pathogen survives on a surface, the longer it may be a source of transmission and thus endanger susceptible subjects. In this work, bacteria's capacity to adhere and to be effectively removed from two conventional glazed porcelain stoneware tiles (under dirty and clean conditions) was investigated. Two different glazes were tested, one mainly glassy (glossy) and the other mainly crystalline (matt). The sanitization procedures were carried out by chemical and chemo-mechanical procedures. The results showed that chemo-mechanical sanitization was the most effective, and the best results could be obtained on the stoneware tiles coated with the mainly glassy glaze, with the lowest porosity and the lower roughness values and water contact angles, especially under clean conditions.
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Microplastics are a significant environmental threat and the lack of efficient removal techniques further amplifies this crisis. Photocatalytic semiconducting nanoparticles have the potential to degrade micropollutants, among them microplastics. The hydrodynamic effects leading to the propulsion of micromotors can lead to the accumulation of microplastics in close vicinity of the micromotor. Incorporating these different properties into a single photocatalytic micromotor (self-propulsion, phoretic assembly of passive colloids and photocatalytic oxidation of contaminants), we achieve a highly scalable, inherently-asymmetric Pac-Man TiO2 micromotor with the ability to actively collect and degrade microplastics. The target microplastics are homogeneous polystyrene microspheres (PS) to facilitate the optical degradation measurements. We cross-correlate the degradation with catalytic activity studies and critically evaluate the timescales required for all involved processes.
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There is a growing demand for interpreter-mediated cognitive assessments for dementia. However, most interpreters lack specialist knowledge of dementia and cognitive assessment tools. This can negatively affect the way instructions and responses are conveyed between clinicians and patients, undermining clinicians' ability to accurately assess for cognitive impairment. This article reports on the co-design of an online dementia training package, MINDSET, which aims to address this gap. Two iterative online co-design workshops were conducted in October and November 2021, using a World Café approach. Sixteen clinicians, interpreters, and multilingual family carers of a person with dementia participated. Based on these workshops, training and assessment materials were developed and tested with 12 interpreters from April to June 2022. The training package comprises online modules: 1) Knowledge of Dementia and Australia's Aged Care System, 2) Briefings and Introductions, 3) Interpreting Skills, 4) Interpreting Ethics, and 5) Cross-cultural Communication. The codesign process highlighted divergent perspectives between clinicians and interpreters on an interpreter's role during a cognitive assessment, but it also facilitated negotiation and consensus building, which enriched the training content. The training is now developed and will be evaluated in a randomized control trial and subsequent implementation study.
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Demência , Multilinguismo , Humanos , Idoso , Tradução , Barreiras de Comunicação , CogniçãoRESUMO
Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.
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Microbioma Gastrointestinal , Tenericutes , Masculino , Humanos , Feminino , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/fisiologia , Gorduras na Dieta/metabolismo , Bile , Bactérias/genética , MamíferosRESUMO
Microplastics (MPs) are plastic particles with sizes between 1 µm and 5 mm with a ubiquitous presence in aquatic ecosystems. MPs harm marine life and can cause severe health problems for humans. Advanced oxidation processes (AOPs) that involve the in-situ generation of highly oxidant hydroxyl radicals can be an alternative to fight MPs pollution. Of all the AOPs, photocatalysis has been proven a clean technology to overcome microplastic pollution. This work proposes novel C,N-TiO2/SiO2 photocatalysts with proper visible-active properties to degrade polyethylene terephthalate (PET) MPs. Photocatalysis was performed in an aqueous medium and at room temperature, evaluating the influence of two pH values (pH 6 and 8). The results demonstrated that the degradation of the PET MPs by C,N-TiO2/SiO2 semiconductors is possible, achieving mass losses between 9.35 and 16.22 %.
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Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos , Ecossistema , Polietilenotereftalatos , Dióxido de Silício/química , Poluentes Químicos da Água/análiseRESUMO
Introduction: The number of Australian residents with dementia is projected to double by 2058, with 28% currently being migrants from non-Anglophone countries. There will be growing demand for professional interpreters for cognitive assessments and dementia-related health consultations in the future. Interpreting cognitive assessments can be challenging for interpreters; inaccurate interpreting can influence assessment outcomes. The Improving Interpreting for Dementia Assessments (MINDSET) project will upskill interpreters through an online training course in dementia and cognitive assessments. The training has been co-designed with key stakeholders from the interpreting sector, dementia-related services, and family caregivers, and has been user-tested with 12 interpreters. The training aims to improve the quality of interpreter-mediated communication during cognitive assessments, and thereby improve the accuracy and acceptability of cognitive assessments with older people who have limited English proficiency. Methods: We are conducting a single-blinded randomized controlled trial to evaluate the effectiveness of the training. We aim to enroll 150 interpreters, and allocate them to equal parallel groups. The intervention group will receive access to the MINDSET training, which comprises 4 hours of resources covering five domains: dementia knowledge, cross-cultural communication, briefings and debriefings, interpreting skills, and interpreting ethics. The control group will be assigned to a wait list, and will receive access to the training after the trial. Participants will be assessed according to the five domains, via the Dementia Knowledge and Assessment Scale, multiple-choice questions, video-simulated assessments, and ethical scenarios. Assessments will occur at baseline (prior to the intervention group completing the training), 3 months after enrollment, and 6 months after enrollment. Results: The trial is ongoing. Recruitment began in June 2022. Discussion: This is the first time a training resource for interpreters in dementia has been trialed. If successful it may represent a technologically innovative way to offer training to both trainee and practicing interpreters. Highlights: Interpreters are crucial in facilitating cognitive assessments for allophone speakers.Interpreters would benefit from training to improve assessment accuracy.Our study has co-designed specialized dementia training for interpreters.This is a protocol to evaluate the training's efficacy in a randomized controlled trial.
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Introduction: Infection by the hepatitis C virus (HCV) is an important cause of chronic liver disease, considered a public health problem worldwide with high morbidity and mortality due to limited access to diagnostic tests in developing countries. Only a small percentage know their infection status and receive timely treatment. It is critical to make diagnostic tests for HCV infection accessible and to provide timely treatment, which not only reduces the spread of infection but also stops the progression of HCV disease without symptoms. Objective: To determine the prevalence of chronic infection by HCV in patients with risk factors by using rapid tests in Cartagena, Colombia, and describe their epidemiological characteristics. Methodology: A cross-sectional descriptive observational study was carried out on asymptomatic adults with risk factors for HCV infection in the city of Cartagena between December 2017 and November 2019. A rapid immunochromatographic test was performed to detect antibodies, characterizing the population. Results: In total, 1,023 patients were identified who met the inclusion criteria, 58.5% women and 41.4% men, obtaining nine positive results, confirming chronic infection with viral load for HCV, finding seven cases of genotype 1b and two genotype 1a. Conclusion: In our study, a prevalence of hepatitis C infection of 0.9% was found in asymptomatic individuals with risk factors, which allows us to deduce that the active search for cases in risk groups constitutes a pillar for the identification of the disease, the initiation of antiviral therapy, and decreased morbidity and mortality.
RESUMO
Continuous myoelectric prediction of intended limb dynamics has the ability to provide transparent control of a prosthesis by the user. However, the impact on these models of adding a human user into the control loop is less clear. Here, the ability of a User Response Model (URM) to continuously predict EMG activity from gait kinematics and kinetics collected during three mobility tasks (level-ground walking, stair ascent, and stair descent) was examined. Multiple-input, multiple-output NARX-based URMs were developed with two outputs (ankle plantarflexor and dorsiflexor) and variable inputs (ankle kinetics, and shank and/or ankle kinematics). Accuracy in predicting the tibialis anterior and medial gastrocnemius EMG was comparable across URMs regardless of the number of inputs. Stair descent had the lowest accuracy among the mobility tasks. No significant differences in normalized root-mean-square error and cross-correlation were found between URMs with five and nine inputs. A URM that continuously predicts EMG activity from gait kinetics and kinematics could be used to simulate human-in-the-loop myoelectric control of a transtibial prosthesis and examine the stability of the system to changes in the environment or due to control errors.