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Researchers have dedicated efforts to refining genetic part assembly techniques, responding to the demand for complex DNA constructs. The optimization efforts, targeting enhanced efficiency, fidelity, and modularity, have yielded streamlined protocols. Among these, Golden Gate cloning has gained prominence, offering a modular and hierarchical approach for constructing complex DNA fragments. This method is instrumental in establishing a repository of reusable parts, effectively reducing the costs and proving highly valuable for high-throughput DNA assembly projects. In this review, we delve into the main protocol of Golden Gate cloning, providing refined insights to enhance protocols and address potential challenges. Additionally, we perform a thorough evaluation of the primary modular cloning toolkits adopted by the scientific community. The discussion includes an exploration of recent advances and challenges in the field, providing a comprehensive overview of the current state of Golden Gate cloning.
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Clonagem Molecular , Clonagem Molecular/métodos , DNA/genética , Vetores Genéticos/genéticaRESUMO
Violence against women continues to be a serious social and public health problem all over the world, despite its high level of social condemnation. The aim of this study is to include the concept of ambivalence in order to analyze the perceptions that young people have of intimate partner violence (IPV). We conducted a qualitative study based on 20 semi-structured interviews with young Spaniards (men and women) who were segmented according to involvement or not in activism against IPV. A critical discourse analysis was performed based on situational, attitudinal and temporal ambivalences. The results show the presence of ambivalent discourses that express a high level of condemnation towards IPV and, at the same time, justify certain violent practices when considering the situational framework. This leads to discursive contradictions when considering jealousy in a couple's relationship, the responsibilities of violence that women suffer and the social origin of IPV. These ambivalences are influenced by the social context, as those involved in activism against IPV express a more coherent discourse that does not justify or accept any kind of violence. Nonetheless, non-activists represent ambivalences in their attitudes towards IPV studied in this research. The results suggest the need to reflect on the strategies used with young people to eradicate IPV by considering the ambivalent nature of attitudes.
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Violência por Parceiro Íntimo , Humanos , Feminino , Violência por Parceiro Íntimo/psicologia , Masculino , Adulto Jovem , Adolescente , Adulto , Atitude , Pesquisa QualitativaRESUMO
Device-independent quantum key distribution (DIQKD) aims at generating secret keys between distant parties without the parties trusting their devices. We investigate a proposal for performing fully photonic DIQKD, based on single photon sources and heralding measurements at a central station placed between the two parties. We derive conditions to attain non-zero secret-key rates in terms of the photon efficiency, indistinguishability and the second order autocorrelation function of the single-photon sources. Exploiting new results on the security bound of such protocols allows us to reduce the requirements on the physical parameters of the setup. Our analysis shows that in the considered schemes, key rates of several hundreds of secret bits per second are within reach at distances of several tens of kilometers.
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OBJECTIVE: To analyze educational interventions in pediatric asthmatic patients to achieve an adequate inhalation technique and improve their self-management. DESIGN: Systematic review based on the PRISMA recommendations. DATA SOURCES: Pubmed, Scopus, Cuiden, Web of Science and Google Scholar databases were reviewed. STUDY SELECTION: Sixteen articles published between 2014 and 2021 were included, with access to full text, languages: English, French and Spanish and pediatric population: 0-18 years. DATA EXTRACTION: Two thousand three hundred and thirteen children were participated. The variables analyzed were: level of care, type of intervention, correct performance of the inhalation technique, follow-up of the technique, delivery of written recommendations, professional-educator category, variables related to respiratory pathology, school absenteeism, quality of life and economic costs. RESULTS: The health care level was primary, hospital and community care, where specialist doctors, nurses and pharmacists stood out as educators. The most prevalent educational interventions are on-site demonstration and delivery of recommendations or multimedia interventions. Several articles report that asthma education is not carried out correctly, others state that their technique improves after the intervention, but most of them highlight the importance of periodic review of the technique. CONCLUSIONS: The authors report improvement in the inhalation technique in all of them, as well as greater self-management of the disease and adherence to treatment. It is necessary to intensify the education of patients in the correct handling of the devices, and the follow-up and subsequent review to optimize the control of the disease.
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Asma , Qualidade de Vida , Criança , Humanos , Asma/terapiaRESUMO
OBJECTIVE: Risk assessment of patients with chest pain is based on clinical parameters; however, without a scoring system, such as risk stratification scales, estimates are less precise and accurate. The aim of this paper was to compare the HEART, GRACE score and clinical parameters in the prediction of major cardiovascular events (cardiovascular mortality or acute myocardial infarction) during hospitalization, in patients with chest pain attended in the emergency department. METHODS: A descriptive observational study of patients with ischemic chest pain, who attended to the Miguel Servet University Hospital emergency department (Zaragoza, Spain) during one year was carried out. HEART and GRACE scores were calculated retrospectively from clinical history. Quantitative variables were expressed as mean (±standard deviation), and qualitative variables as frequencies and percentages. A bivariate analysis was carried out using the chi-square test. The performance of the scales and clinical parameters was compared by calculating the area under the curve. The primary outcome was the occurrence of a major cardiovascular event (cardiovascular mortality or acute myocardial infarction) during hospital admission. RESULTS: 306 patients were registered (66.3% men, n=203), with a mean age of 71.45±12.85 years and a 48.7% history of ischemic heart disease. The areas under the curve for HEART scales, GRACE and clinical parameters were 0.80 (95% CI: 0.73-0.86), 0.79 (95% CI: 0.72-0.85) and 0.74 (95% CI: 0.68-0.80), respectively. During hospitalization, the incidence of the primary event was 13.4% and no low-risk patient, in both scales, presented a major cardiovascular event. CONCLUSIONS: In patients with ischemic chest pain attended in the emergency department, the GRACE and HEART scale have a greater area under curve than clinical parameters.
OBJECTIVE: La valoración del riesgo de los pacientes con dolor torácico se basa en los parámetros clínicos. Sin embargo, sin un sistema de puntuación, como las escalas de estratificación del riesgo, las estimaciones son menos precisas y exactas. El objetivo de este estudio fue comparar las escalas HEART, GRACE Score y los parámetros clínicos en la predicción de eventos mayores cardiovasculares (mortalidad cardiovascular o infarto agudo de miocardio) durante la hospitalización, en pacientes con dolor torácico atendidos en Urgencias. METHODS: Se realizó un estudio observacional descriptivo de pacientes que, durante un año, acudieron a Urgencias del Hospital Universitario Miguel Servet (Zaragoza) por dolor torácico de tipo isquémico. Las puntuaciones HEART y GRACE se calcularon retrospectivamente a partir de las historias clínicas. Las variables cuantitativas se expresaron como media (±desviación estándar), y las cualitativas como frecuencias y porcentajes. Se llevó a cabo un análisis bivariante mediante la prueba chi cuadrado. El rendimiento de las escalas y parámetros clínicos se comparó mediante el cálculo del área bajo la curva. El resultado primario fue la ocurrencia de un evento mayor cardiovascular (mortalidad cardiovascular o infarto agudo de miocardio) durante el ingreso hospitalario. RESULTS: Se registraron 306 pacientes (66,3% eran hombres, n=203), con edad media de 71,45±12,85 años y un 48,7% de antecedentes de cardiopatía isquémica. El área bajo la curva, para el evento primario, de las escalas HEART, GRACE y parámetros clínicos fue 0,80 (IC al 95%: 0,73-0,86), 0,79 (IC al 95%: 0,72- 0,85) y 0,74 (IC del 95%: 0,68-0,80), respectivamente. Durante la hospitalización, la incidencia del evento primario fue del 13,4% y ningún paciente de bajo riesgo, en ambas escalas, presentó un evento mayor cardiovascular. CONCLUSIONS: En pacientes con dolor torácico de tipo isquémico atendidos en Urgencias, tanto la escala GRACE como la escala HEART presentan un área bajo la curva más alta que los parámetros clínicos.
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Dor no Peito , Infarto do Miocárdio , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Estudos Prospectivos , Espanha/epidemiologia , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Medição de Risco , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações , Serviço Hospitalar de Emergência , Fatores de RiscoRESUMO
Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the â¼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs.
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Cromossomos Artificiais de Levedura , Genoma Fúngico , Saccharomyces cerevisiae , Perfilação da Expressão Gênica , Proteômica , Saccharomyces cerevisiae/genética , Biologia Sintética , RNA de Transferência/genética , Cromossomos Artificiais de Levedura/genéticaRESUMO
Background: The use of health surveys has been key in the scientific community to promptly communicate results about the health impact of COVID-19. But what information was collected, where, when and how, and who was the study population? Objective: To describe the methodological characteristics used in large health surveys conducted in Spain early on in the COVID-19 pandemic. Methods: Scoping review. Inclusion criteria: observational studies published between January 2020 and December 2021, with sample sizes of over 2,000 persons resident in Spain. Databases consulted: PubMed, CINAHL, Literatura Latinoamericana y del Caribe en CC de la Salud, Scopus, PsycINFO, Embase, Sociological Abstracts, Dialnet and Web of Science Core Collection. We analyzed the characteristics of the literature references, methodologies and information gathered in the surveys selected. Fifty five studies were included. Results: Sixty percentage of the studies included had mental health as their main topic and 75% were conducted on the general adult population. Thirteen percentage had a longitudinal design, 93% used the internet to gather information and the same percentage used non-probability sampling. Thirty percentage made some type of sampling correction to reduce coverage or non-response biases, but not selection biases. Sixty seven percentage did not state the availability of their data. Conclusions: Consistent with the extensive use of non-probability sampling without any bias correction in the extraordinary setting created by COVID-19, quality population frameworks are required so that probability and representative samples can be extracted quickly to promptly address other health crises, as well as to reduce potential coverage, non-response and particularly selection biases by utilizing reweighting techniques. The low data accessibility despite the huge opportunity that COVID-19 provided for Open Science-based research is striking.
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COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , Pandemias , Espanha/epidemiologia , Inquéritos Epidemiológicos , Bases de Dados FactuaisRESUMO
Tauopathy is characterized by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule-associated protein tau. The neuronal changes evident in tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by co-expression of WldS. In a Drosophila model of tauopathy in which expression of human 0N3R tau protein leads to progressive age-dependent phenotypes, WldS was expressed with and without activation of the downstream pathway. The olfactory receptor neuron circuit OR47b was used for these studies in adults, and the larval motor neuron system was employed in larvae. Tau phenotypes studied included neurodegeneration, axonal transport, synaptic deficits and locomotor behaviour. Impact on total tau was ascertained by assessing total, phosphorylated and misfolded tau levels by immunohistochemistry. Activation of the pathway downstream of WldS completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldS was activated several weeks after tau-mediated degeneration had become established. Though total tau levels were not altered, the protected neurons displayed significantly reduced MC1 immunoreactivity suggestive of clearance of misfolded tau, as well as a trend for a decline in tau species phosphorylated at the AT8 and PHF1 epitopes. In contrast, WldS expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in tau-expressing larvae. This collectively implies that the pathway mediating the protective effect of WldS intersects with the mechanism(s) of degeneration initiated by tau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.
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Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.
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Doença de Alzheimer , Tauopatias , Animais , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Proteínas tau/metabolismo , Tauopatias/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Drosophila/metabolismo , Autofagia/genética , FosforilaçãoRESUMO
The aim of this research is the development of new colonic release systems of meloxicam (MLX) a non-steroidal anti-inflammatory drug (NSAIDs) with pH and time-dependent vehicles for cancer or autoimmune diseases. The colon has a higher pH than the rest of the gastrointestinal tract (GIT) and this can be used as a modified release strategy. Eudragit® polymers are the most widely used synthetic products in the design of colonic release formulations because they might offer mucoadhesiveness and pH-dependent release. Colonic delivery systems produced with pH-dependent and permeable polymers (FS-30D) or with pH-independent and low permeability polymers (NM-30D), must dissolve at a pH range of 6.0-7.0 to delay the release of the drug and prevent degradation in the GIT, before reaching the colon. The conditions prepared to simulate a gastrointestinal transit showed the CNM multiparticulate system, composed of Eudragit® NM and cellulose, as the best release option for MLX with a more sustained release with respect to the other formulations. CNM formulation followed Higuchi and First-order release kinetics, thus MLX release was controlled by a combination of diffusion and polymers swelling/eroding processes.
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Vector-borne diseases are a major public health problem. Amongst them, dengue, Zika and chikungunya illnesses are increasing their incidence and geographical expansion. Since vector control is the main measure to prevent these diseases, this systematic review aims to determine the effectiveness of environmental interventions for the prevention of the transmission of these three diseases, as well as for the reduction of their burden. Experimental studies of environmental management interventions aimed at vector control were included. The outcome variables of interest were disease burden indicators and entomological indicators. Of the 923 references initially retrieved, after discarding those that were duplicated or didn't comply with the inclusion criteria, a total of 7 articles were included. All included studies carried out environmental manipulation interventions and only 1 carried out an environmental modification intervention. Regarding the outcome variables, all used entomological indicators (larval or pupae indices). Of those, pupae indices are better indicators of vector abundance. In 4 out of the 6 studies, there was a statistically significant reduction of the pupae indices related to the elimination of small containers, manipulation of large tanks and cleaning outdoor spaces. These interventions are easy to implement and involve little resources, which acquires special importance regarding areas with limited resources. Although it is assumed that a reduction of mosquitoes would lead to a reduction or the risk of transmission, a little evidence proving this has been published. It would be advisable that, in addition to entomological indicators, epidemiological, environmental and sociodemographic factors would be taken into consideration, bearing in mind that mosquito density is one of the many factors that influence the transmission of these viruses. None of the papers included used disease indicators, not allowing to demonstrate if environmental interventions contribute to reduce disease burden.
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Aedes , Febre de Chikungunya , Dengue , Infecção por Zika virus , Zika virus , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/prevenção & controle , Dengue/epidemiologia , Dengue/prevenção & controle , Humanos , Controle de Mosquitos , Mosquitos Vetores , Pupa , Infecção por Zika virus/prevenção & controleRESUMO
The prevalence of pediatric respiratory diseases in Spain is 23%. Inhalation is the preferred route of administration but there are frequent errors in the performance of the inhalation technique leading a poor control of the disease. The aim of this research was to detect errors in the execution of the inhalation technique at a Pediatric Pulmonology Unit in a hospital of Aragón (Spain). In order to improve the administration of inhaled medication, an educational intervention for 1 year by nursing was conducted. This interventional study, including children aged 1 to 15 years with an inhalation therapy and who attended the Pediatric Pulmonology Unit, was conducted between September 2017 and September 2018. Logistic Regression models were conducted in SPSS. This study involved 393 children (61.1% boys). Before the intervention, 39.4% achieved a correct inhalation technique increasing up to 62.1% after the intervention. Those who had their first visit to the Unit, young children and girls had a higher risk of incorrect performance than those with subsequent visits, older children, and boys, respectively. The most common errors in the inhalation technique were not performing adequate apnoea after inhaling and not rinsing the mouth at the end of the procedure. The education given by nurses to pediatric patients improved the inhalation technique, achieving better control of the disease and use of the health system.
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Papel do Profissional de Enfermagem , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Adolescente , Criança , Pré-Escolar , Escolaridade , Feminino , Humanos , Masculino , Nebulizadores e Vaporizadores , Preparações Farmacêuticas , Doença Pulmonar Obstrutiva Crônica/diagnósticoRESUMO
White-rot fungi secrete a repertoire of high-redox potential oxidoreductases to efficiently decompose lignin. Of these enzymes, versatile peroxidases (VPs) are the most promiscuous biocatalysts. VPs are attractive enzymes for research and industrial use but their recombinant production is extremely challenging. To date, only a single VP has been structurally characterized and optimized for recombinant functional expression, stability, and activity. Computational enzyme optimization methods can be applied to many enzymes in parallel but they require accurate structures. Here, we demonstrate that model structures computed by deep-learning-based ab initio structure prediction methods are reliable starting points for one-shot PROSS stability-design calculations. Four designed VPs encoding as many as 43 mutations relative to the wildtype enzymes are functionally expressed in yeast, whereas their wildtype parents are not. Three of these designs exhibit substantial and useful diversity in their reactivity profiles and tolerance to environmental conditions. The reliability of the new generation of structure predictors and design methods increases the scale and scope of computational enzyme optimization, enabling efficient discovery and exploitation of the functional diversity in natural enzyme families directly from genomic databases.
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Basidiomycota , Peroxidases , Lignina , Peroxidases/química , Peroxidases/genética , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: The global health emergency caused by the current COVID-19 pandemic is resulting in a huge challenge at all levels. The use of masks may reduce the spread of the infection by minimising the excretion of Flügge droplets. The objective of this study was to compile the evidence available on the use of masks in relation to respiratory infections. METHODOLOGY: An umbrella review (review of systematic reviews) was conducted. Two reviewers independently carried out the screening process, data extraction and data analysis. Discrepancies were resolved with a third reviewer, and the assessment of the risk of bias of the studies was carried out using the AMSTAR 2 tool. The Rayyan QCRI program was used for the screening process. RESULTS: A total of eight systematic reviews were included. The studies analysed the use of masks in the general population, in long-term care facilities, in hospitals and at mass gatherings, and compared the effectiveness thereof in preventing infection. The results of this review revealed that the use of masks is associated with a protective effect against respiratory infections in healthcare facilities, in long-term care facilities and at mass gatherings. CONCLUSIONS: In light of the results, it seems reasonable to recommend the use of masks to the general population, but this use should be accompanied by a training programme to improve compliance, as not using them properly may increase the risk of infection.
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COVID-19 , Infecções Respiratórias , Humanos , Máscaras , Pandemias , Infecções Respiratórias/prevenção & controle , SARS-CoV-2 , Revisões Sistemáticas como AssuntoAssuntos
Miosite , Doenças Orbitárias , Miosite Orbital , Humanos , Miosite/diagnóstico , Miosite Orbital/diagnósticoRESUMO
PURPOSE: Multiple Chemical Sensitivity is a condition principally suffered by women. As with fibromyalgia and chronic fatigue syndrome, Multiple Chemical Sensitivity is usually included among the so called "contested illnesses", defined as illnesses whose cause, diagnosis, prevalence and even existence are subject to controversy. This article seeks to explore how women with Multiple Chemical Sensitivity experience this contested illness, through their own descriptions of diagnostic processes, search for treatment and encounters with different health professionals. We aim to observe these experiences in detail and to identify aspects that could improve care for Multiple Chemical Sensitivity sufferers. METHOD: Qualitative design. We performed personal in-depth interviews, which were recorded and transcribed to conduct a qualitative content analysis supported by Atlas.ti-7. SUBJECTS/PATIENTS: 22 women diagnosed with Multiple Chemical Sensitivity in Spain. RESULTS: Two main categories were identified in the interviews: (1) unavoidable barriers: patients' exposure to chemicals and the absence of treatment, and (2) Skepticism on the part of care providers and lack of recognition in the process of diagnosis. CONCLUSION: Training and above all awareness raising strategies are needed to address health professionals' prejudices regarding the existence of contested illnesses such as Multiple Chemical Sensitivity. These prejudices hinder diagnosis and medical follow-up, and add negative emotions to the physical limitations already suffered by patients.IMPLICATIONS FOR REHABILITATION Multiple Chemical SensitivityIt is important to promote a compassionate and empathetic attitude among health providers, in order to avoid rejection and delegitimization of the experiences of women with Multiple Chemical Sensitivity.Multiple Chemical Sensitivity protocols should be developed and implemented to give skills to health professionals to assist patients with Multiple Chemical Sensitivity.These protocols should include avoidance of exposure to chemicals present in healthcare facilities.Training programs for health providers should include not only knowledge, but awareness raising about the characteristics and severity of contested illnesses such as Multiple Chemical Sensitivity.Health providers should avoid stigmatizing patients by psychologizing their symptoms and be aware of the existence of stereotypes regarding women suffering from Multiple Chemical Sensitivity.
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Sensibilidade Química Múltipla , Atitude do Pessoal de Saúde , Feminino , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , EspanhaRESUMO
INTRODUCTION: The global health emergency caused by the current COVID-19 pandemic is resulting in a huge challenge at all levels. The use of masks may reduce the spread of the infection by minimising the excretion of Flügge droplets. The objective of this study was to compile the evidence available on the use of masks in relation to respiratory infections. METHODOLOGY: An umbrella review (review of systematic reviews) was conducted. Two reviewers independently carried out the screening process, data extraction and data analysis. Discrepancies were resolved with a third reviewer, and the assessment of the risk of bias of the studies was carried out using the AMSTAR 2 tool. The Rayyan QCRI program was used for the screening process. RESULTS: A total of eight systematic reviews were included. The studies analysed the use of masks in the general population, in long-term care facilities, in hospitals and at mass gatherings, and compared the effectiveness thereof in preventing infection. The results of this review revealed that the use of masks is associated with a protective effect against respiratory infections in healthcare facilities, in long-term care facilities and at mass gatherings. CONCLUSIONS: In light of the results, it seems reasonable to recommend the use of masks to the general population, but this use should be accompanied by a training programme to improve compliance, as not using them properly may increase the risk of infection.
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MicroRNAs (miRNAs) regulate gene expression posttranscriptionally and control biological processes (BPs), including fibrogenesis. Kidney fibrosis remains a clinical challenge and miRNAs may represent a valid therapeutic avenue. We show that miR-9-5p protected from renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). This was reflected in reduced expression of pro-fibrotic markers, decreased number of infiltrating monocytes/macrophages, and diminished tubular epithelial cell injury and transforming growth factor-beta 1 (TGF-ß1)-dependent de-differentiation in human kidney proximal tubular (HKC-8) cells. RNA-sequencing (RNA-Seq) studies in the UUO model revealed that treatment with miR-9-5p prevented the downregulation of genes related to key metabolic pathways, including mitochondrial function, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and glycolysis. Studies in human tubular epithelial cells demonstrated that miR-9-5p impeded TGF-ß1-induced bioenergetics derangement. The expression of the FAO-related axis peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-peroxisome proliferator-activated receptor alpha (PPARα) was reduced by UUO, although preserved by the administration of miR-9-5p. We found that in mice null for the mitochondrial master regulator PGC-1α, miR-9-5p was unable to promote a protective effect in the UUO model. We propose that miR-9-5p elicits a protective response to chronic kidney injury and renal fibrosis by inducing reprogramming of the metabolic derangement and mitochondrial dysfunction affecting tubular epithelial cells.
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Reprogramação Celular , Fibrose/prevenção & controle , Regulação da Expressão Gênica , Nefropatias/prevenção & controle , MicroRNAs/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia , Obstrução Ureteral/prevenção & controle , Animais , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transcriptoma , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologiaRESUMO
BACKGROUND: Fertility in recent decades in European countries such as Norway, Spain or United Kingdom has declined, while in others such as Portugal, it has remained relatively constant, and in others such as Germany fertility rated have risen. The determinants of this change in reproductive pattern can be explained by the cultural, social, and economic changes that took place in our society. Objective: to identify the principal reasons and independent determinants associated with the postponement of motherhood and document any association between the time taken to achieve successful pregnancy and maternal age, as well as the level of anxiety of these women. METHODS: An observational study, including 326 women, was conducted in Spain with primiparous women, in which data was collected on sociodemographic, health, and pregnancy-related factors. Comparison of means (t-test or analysis of variance) and the analysis of covariance was used to estimate adjusted means for potential confounders. RESULTS: Women in stable relationships became mothers at older ages (31.83±0.29) than those who were not (28.75±0.78) (p<0.001). Women who delayed motherhood for medical reasons had a mean age of 34.15 ± 0.88 years, compared to a mean of 30.52±0.36 years for personal reasons, and 27.51±1.39 years for other reasons. Mothers with an older age had a higher level of anxiety (p<0.05). The average time required to achieve pregnancy increased as maternal age increased, with an average time of 24 months for women with a mean age of 35.23±0.71 years compared to <3 months for women with a mean age of 29.44±0.39 years. Women ≥ 35 years were more likely to need medical assistance to achieve pregnancy (aOR = 12.07, 95% CI: 1.50-97.05; p = 0.019). CONCLUSIONS: Medical reasons were among those cited for delaying motherhood. The postponement of motherhood was associated with difficulty to achieve a successful pregnancy and a higher level of anxiety.
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Ansiedade/diagnóstico , Idade Materna , Mães/psicologia , Gravidez/psicologia , Tempo para Engravidar , Adulto , Fatores Etários , Ansiedade/psicologia , Feminino , Humanos , Mães/estatística & dados numéricos , Gravidez/estatística & dados numéricos , Espanha , Fatores de TempoRESUMO
OBJECTIVE: Sex is a determining factor in the differences with which men and women are treated in the emergency room. The objective was to analyze the profile in patients with chest paint attended in emergency department, and the gender inequalities in the diagnosis and treatment. METHODS: Descriptive observational study of patients, who attended to the Miguel Servet University Hospital emergency department, with ischemic chest pain during 2017. Sociodemographic and clinical variables of treatment and evolution were analyzed. Bivariate and multivariate analysis was performed through the statistical program SPSS. RESULTS: 351 cases were registered (235 men and 116 women). The women were older (median age 75.5 years, against, 71.4 years in men, p=0.003), went to the hospital during summer time (p=0.021) and took most often of benzodiazepines (p=0.001), antidepressants (p<0.001) and diuretics drugs (p=0.039). The women had greater proportion of arterial hypertension (p=0.001). The men came more to the emergency department during autumn period (p=0.008), and had more history of ischemic heart disease (p=0.003) and percutaneous coronary intervention (p<0.001). The time of completion of the first electrocardiogram was greater in women (p<0.001), and were diagnosed with a higher frequency of atypical chest pain (p=0.003), unlike men, more diagnosed of acute coronary syndrome (p=0.028) and subjected to invasive treatment (p<0.001). CONCLUSIONS: There are differences according to sex in the antecedents, delay in performing the first electrocardiogram and use of invasive treatment. Its consideration from the emergency department, without influence of value judgments and with the determination of values disaggregated by sex, can improve the attention and evolution of these patients.
OBJETIVO: El sexo es determinante en las diferencias con que hombres y mujeres son atendidos en Urgencias. El objetivo de este estudio fue analizar el perfil clínico de los pacientes atendidos en Urgencias por dolor torácico isquémico, y la presencia de inequidades según sexo en el diagnóstico y tratamiento. METODOS: Se realizó un estudio observacional descriptivo de los pacientes que acudieron a Urgencias del Hospital Universitario Miguel Servet (Zaragoza) por dolor torácico isquémico en 2017. Se recogieron variables sociodemográficas y clínicas de tratamiento y evolución mediante la historia clínica. Se realizó análisis bivariante y multivariante mediante el paquete estadístico SPSS. RESULTADOS: Se registraron 351 casos (235 hombres, 116 mujeres). Las mujeres fueron mayores que los hombres (edad mediana de 75,5 años frente a 71,4 años en hombres, p=0,003), acudieron más durante el verano (p=0,021), tomaron con mayor frecuencia benzodiacepinas (p=0,001), antidepresivos (p<0,001) y diuréticos (p=0,039), y presentaron con mayor proporción hipertensión arterial (p=0,001). Los hombres acudieron más durante el otoño (p=0,008) y presentaron más antecedentes de cardiopatía isquémica (p=0,003) e intervención coronaria percutánea (p<0,001). El tiempo de realización del electrocardiograma fue mayor en mujeres (p<0,001), y estas fueron diagnosticadas con mayor frecuencia de dolor torácico atípico (p=0,003), a diferencia de los hombres, más diagnosticados de síndrome coronario agudo (p=0,028) y sometidos a tratamiento invasor (p<0,001). CONCLUSIONES: Existen diferencias según el sexo en los antecedentes, demora en la realización del electrocardiograma y uso de tratamiento invasor. Su consideración desde Urgencias, sin influencia de juicios de valor y con la determinación de valores desagregados por sexo, puede mejorar la atención y evolución de estos pacientes.