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BACKGROUND: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy. METHODS: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method. RESULTS: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen's d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen's d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen's d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS. CONCLUSION: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults.
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BACKGROUND: Elevated rates of suicidal behavior were reported during the COVID-19 pandemic. However, information is scarce on patients' profiles during this period. Studies evoke the potential adverse effects of the mandatory lockdown, but they remain relatively speculative. METHODS: We monitored fluctuations in suicide attempts (SA) in six European countries. We gathered data, retrospectively for under 18-year-old SA episodes (1 January 2018 to 31 December 2021), through records of psychiatric emergency services. We collected clinical profiles individually. We extracted environmental indicators by month, as provided by Oxford COVID-19 Government Response Tracker (OxCGRT). We used the Pruned Exact Linear Time (PELT) method to identify breakpoints in SA episodes reported for each country, and logistic regressions to estimate changes in patients' characteristics after the breakpoints. Finally, we used a univariate and multivariate negative binomial model to assess the link between SA and OxCGRT indicators, accounting for the delay (lag) between the interventions and their impact on SA. RESULTS: The study comprised 2,833 children and adolescents (mean age = 15.1 years (SD 1.6); M: F sex-ratio = 1:5.4). A significant increase in SA was found either 6 or 10 months after the beginning of the pandemic, varying by country. Patients were more likely to be girls (aOR = 1.77 [1.34; 2.34]) and used SA methods "other than self-poisoning" (aOR = 1.34 [1.05; 1.7]). In the multivariate model, an association was found between SA and the contact tracing indicator with an 11 months delay, and the number of COVID-19 deaths with a 3-months delay. CONCLUSIONS: Findings confirmed a delayed increase in SA during the COVID-19 pandemic in children and adolescents as well as changes in patients' profiles. The duration and severity of the pandemic emerged as the strongest predictor in the rise of SA. If faced with a similar pandemic in the future, the gap between the onset of pandemic and the increase in suicide attempts presents an opportunity for prevention.
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Background: Successful Crohn's disease (CD) therapy relies on timely and precise management strategies. Endoscopic balloon dilation (EBD) has been applied as a first-line treatment for symptomatic CD-associated strictures due to its minimally invasive nature and the possibility of preserving intestinal length. Objective: The aim of the present study was to determine patient-related predictive factors associated with the need for surgery for CD-associated ileocolic strictures after technically successful EBD. Methods: All original studies published before December 2023 that reported the outcomes of patients treated with EBD for ileocolic strictures secondary to CD and described follow-up for at least 1 year were included. The difference in risk of needing surgery was calculated for 8 different patient characteristics (Sex, smoking habit, previous surgery, biologic therapy, steroids, immunosuppressors, nature of the stricture, and endoscopic disease activity). Results: There were significant differences in the risk of needing surgery after EBD among patients who underwent surgery and patients without a history of surgery (RD: -0.20 [-0.31, -0.08]), patients with endoscopic mucosal activity and patients in remission at the time of EBD (RD: 0.19 [0.04, 0.34]), patients using biologics at the time of EBD and patients not using biologics (RD: -0.09 [-0.16, -0.03]), and patients using steroids and those not using steroids at the time of EBD (RD: 0.16 [0.07, 0.26]). Conclusions: The use of biologics and endoscopic disease remission at the time of EBD were protective factors against the need for surgery. No previous surgery or use of steroids at the time of EBD was associated with the need for surgery during follow-up.
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The aim of this study was to evaluate the impact of non-thermal methods, using high hydrostatic pressure (HHP) and pulsed electric field (PEF), on the dual modification of quinoa starch and to analyze the microstructural, morphological, thermal, pasting, and texture properties. Starch was treated with HHP at 400 MPa for 10 min, while PEF was applied using voltages of 10 and 30 kV cm-1 for a total time of 90s. The modification techniques were effective in breaking down amylose molecules and amylopectin branches, where for the dual treatment, higher values of DP6-12 were found. The average diameter and gelatinization temperatures were elevated after HHP, thus forming clusters that require more energy for paste formation. The use of 30 kV cm-1 and 400 MPa (HP30) in starch facilitates the creation of new food products with better texture, stability and nutritional value, making them suitable for use in food emulsions and the cosmetics industry.
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Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3 h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000 mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100 mg/kg), hot plate test (12.5, 25, 50, and 100 mg/kg) and formalin (25, 50 and 100 mg/kg); open field test (100 mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100 mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000 mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100 mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25 mg/kg (11.3 ± 3.3 s) and 100 mg/kg (11.9 ± 0.9 s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100 mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100 mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.
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INTRODUCTION: Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. METHOD: Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. RESULTS: Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1-CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. CONCLUSIONS: We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.
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Antígeno B7-H1 , Células Dendríticas , Ganglios Linfáticos , Neoplasias de la Boca , Humanos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/metabolismo , Pronóstico , Femenino , Masculino , Ganglios Linfáticos/patología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Antígeno B7-H1/metabolismo , Persona de Mediana Edad , Anciano , Metástasis Linfática , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Biomarcadores de Tumor/metabolismo , AdultoRESUMEN
Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis.
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ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.
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Monoterpenos Acíclicos , Analgésicos , Antiinflamatorios , Edema , Lippia , Aceites Volátiles , Hojas de la Planta , Animales , Lippia/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Brasil , Analgésicos/farmacología , Analgésicos/aislamiento & purificación , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Masculino , Hojas de la Planta/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Monoterpenos Acíclicos/farmacología , Plantas Medicinales/química , Dolor/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Dimensión del Dolor/efectos de los fármacosRESUMEN
Despite the many advances in drug research, natural products are still being explored as a promising source for discovering new bioactive compounds to treat global diseases such as tuberculosis. However, there is a lack of studies and information about coastal natural products, which thrive in the transitional environment between two different ecosystems and produce unique secondary metabolites. Mangroves, estuaries, and mudflats make up areas for coastal species and have shown promising results in antituberculosis research, some of them are present in hotspot areas. This review focuses on research conducted in coastal environments and explores the reasons why these natural products tend to outperform non-coastal ones against the causative agent of tuberculosis, Mycobacterium tuberculosis.
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OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is a technically complex procedure. The scissor knife mechanism may potentially provide easier and safer colorectal ESD. The aim of this meta-analysis is to evaluate the efficacy and safety of scissor-assisted vs. conventional ESD for colorectal lesions. METHODS: A search strategy was conducted in MEDLINE, Embase, and Lilacs databases from January 1990 to November 2023 according to PRISMA guidelines. Fixed and random-effects models were used for statistical analysis. Heterogeneity was assessed using I2 test. Risk of bias was assessed using the ROBINS-I and RoB-2 tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of five studies (three retrospective and two randomized controlled trials, including a total of 1575 colorectal ESD) were selected. The intraoperative perforation rate was statistically lower (risk difference [RD] -0.02; 95% confidence interval [CI] -0.04 to -0.01; P = 0.001; I2 = 0%) and the self-completion rate was statistically higher (RD 0.14; 95% CI 0.06, 0.23; P = 0.0006; I2 = 0%) in the scissor-assisted group compared with the conventional ESD group. There was no statistical difference in R0 resection rate, en bloc resection rate, mean procedure time, or delayed bleeding rate between the groups. CONCLUSION: Scissor knife-assisted ESD is as effective as conventional knife-assisted ESD for colorectal lesions with lower intraoperative perforation rate and a higher self-completion rate.
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Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.
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AIMS: Yttrium (Y) holds significant industrial and economic importance, being listed as a critical element on the European list of critical elements, thus emphasizing the high priority for its recovery. Bacterial strategies play a crucial role in the biorecovery of metals, offering a promising and environmentally friendly approach. Therefore, gaining a comprehensive understanding of the underlying mechanisms behind bacterial resistance, as well as the processes of bioaccumulation and biotransformation, is of paramount importance. METHODS AND RESULTS: A total of 207 Alphaproteobacteria strains from the University of Coimbra Bacteria Culture Collection were tested for Y-resistance. Among these, strain Mesorhizobium qingshengii J19 exhibited high resistance (up to 4 mM Y) and remarkable Y accumulation capacity, particularly in the cell membrane. Electron microscopy revealed Y-phosphate interactions, while X-ray diffraction identified Y(PO3)3·9H2O biocrystals produced by J19 cells. CONCLUSION: This study elucidates Y immobilization through biomineralization within phosphate biocrystals using M. qingshengii J19 cells.
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Biomineralización , Mesorhizobium , Fosfatos , Itrio , Fosfatos/metabolismo , Mesorhizobium/metabolismo , Mesorhizobium/fisiologíaRESUMEN
The aim of this research is to identify the main factors associated with patients' payment perception and the effects of these factors on payment perception. Patients admitted between January and December 2016 at an emergency department of a public hospital in Lisbon, Portugal, were included in this study, with a representative sample size of 382 patients. A 5% margin of error and a 95% confidence interval were used, and all the data were collected between May and November 2017. To test the mediation models, stepwise multiple linear regression analysis was used. The effect of doctors on payment perception through satisfaction and through perceived quality of healthcare (PQHC) is explained by 3% and 4% of the variation, respectively, with statistically significant results (Pâ <â .01). Moreover, the effect of privacy and meeting expectations on payment perception through PQHC is explained by 4% and 4% of the variation, with statistically significant results (Pâ <â .01). Doctors play a crucial role in understanding the patients' payment perception (with direct and indirect effects). Mediators, in turn, strengthen this effect, in which the contribution of PQHC is more significant than that of satisfaction.
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Servicio de Urgencia en Hospital , Satisfacción del Paciente , Calidad de la Atención de Salud , Humanos , Satisfacción del Paciente/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Femenino , Portugal , Persona de Mediana Edad , Adulto , Anciano , PercepciónRESUMEN
The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.
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Moléculas de Adhesión Celular , Virus del Dengue , Evolución Molecular , Interacciones Huésped-Patógeno , Receptores de Superficie Celular , Proteínas del Envoltorio Viral , Envoltura Viral , Humanos , Brasil , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/química , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/metabolismo , Interacciones Huésped-Patógeno/genética , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/química , Simulación de Dinámica Molecular , Filogenia , Unión Proteica , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/química , Receptores Virales/metabolismo , Receptores Virales/química , Receptores Virales/genética , Envoltura Viral/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/químicaRESUMEN
Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Micobacterias no Tuberculosas , Reacción en Cadena de la Polimerasa , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/clasificación , Sensibilidad y Especificidad , ARN Ribosómico 16S/genética , Tuberculosis/diagnóstico , Tuberculosis/microbiología , ADN Bacteriano/genética , Técnicas Biosensibles/métodosRESUMEN
Spider venoms are composed of hundreds of proteins and peptides. Several of these venom toxins are cysteine-rich peptides in the mass range of 3-9 kDa. Small peptides (<3 kDa) can be fully characterized by mass spectrometry analysis, while proteins are generally identified by the bottom-up approach in which proteins are first digested with trypsin to generate shorter peptides for MS/MS characterization. In general, it is sufficient for protein identification to sequence two or more peptides, but for venom peptidomics it is desirable to completely elucidate peptide sequences and the number of disulfide bonds in the molecules. In this chapter, we describe a methodology to completely sequence and determine the number of disulfide bonds of spider venom peptides in the mass range of 3-9 kDa by multiple enzyme digestion, mass spectrometry of native and digested peptides, de novo analysis, and sequence overlap alignment.
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Venenos de Araña , Arañas , Animales , Espectrometría de Masas en Tándem , Venenos de Araña/química , Péptidos/química , Secuencia de Aminoácidos , Disulfuros/análisis , Arañas/metabolismoRESUMEN
Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood. Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Mathematical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly alter the effect of codon usage. This new mode of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.
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Codón , Metabolismo Energético , Estabilidad del ARN , ARN Mensajero , Humanos , Metabolismo Energético/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Codón/genética , Uso de Codones , Biosíntesis de Proteínas , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Adenosina Trifosfato/metabolismo , Regulación de la Expresión GénicaRESUMEN
INTRODUCTION: Delays in prehospital care attributable to the call-taking process can often be traced back to miscommunication, including uncertainty around the call location. Geolocation applications have the potential to streamline the call-taking process by accurately identifying the caller's location. OBJECTIVE: To develop and validate an application to geolocate emergency calls and compare the response time of calls made via the application with those of conventional calls made to the Brazilian Medical Emergency System (Serviço de Atendimento Médico de Urgência-SAMU). METHODS: This study was conducted in two stages. First, a geolocating application for SAMU emergency calls (CHAMU192) was developed using a mixed methods approach based on design thinking and subsequently validated using the System Usability Scale (SUS). In the second stage, sending time of the geolocation information of the app was compared with the time taken to process information through conventional calls. For this, a hypothetical case control study was conducted with SAMU in the Maringá, Paraná, Brazil. A control group of 350 audio recordings of emergency calls from 2019 was compared to a set of test calls made through the CHAMU192 app. The CHAMU192 group consisted of 201 test calls in Maringá. In test calls, the location was obtained by GPS and sent to the SAMU communication system. Comparative analysis between groups was performed using the Mann-Whitney test. RESULTS: CHAMU192 had a SUS score of 90, corresponding to a "best imaginable" usability rating. The control group had a median response time of 35.67 seconds (26.00-48.12). The response time of the CHAMU192 group was 0.20 (0.15-0.24). CONCLUSION: The use of the CHAMU192 app by emergency medical services could significantly reduce response time. The results demonstrate the potential of app improving the quality and patient outcomes related to the prehospital emergency care services.
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Servicios Médicos de Urgencia , Aplicaciones Móviles , Humanos , Estudios de Casos y Controles , Tiempo de Reacción , ComunicaciónRESUMEN
Although Covid-19 was not the first pandemic, it was unique in the scale and intensity with which societies responded. Countries reacted differently to the threat posed by the new virus. The public health crisis affected European societies in many ways. It also influenced the way the media portrayed vaccines and discussed factors related to vaccine hesitancy. Europeans differed in their risk perceptions, attitudes towards vaccines and vaccine uptake. In European countries, Covid-19-related discourses were at the centre of media attention for many months. This paper reports on a media analysis which revealed significant differences as well as some similarities in the media debates in different countries. The study focused on seven European countries and considered two dimensions of comparison: between the pre-Covid period and the beginning of the Covid pandemic period, and between countries. The rich methodological approach, including linguistics, semantic field analysis and discourse analysis of mainstream news media, allowed the authors to explore the set of meanings related to vaccination that might influence actors' agency. This approach led the authors to redefine vaccine hesitancy in terms of characteristics of the "society in the situation" rather than the psychological profile of individuals. We argue that vaccine hesitancy can be understood in terms of agency and temporality. This dilemma of choice that transforms the present into an irreversible past and must be taken in relation to an uncertain future, is particularly acute under the pressure of urgency and when someone's health is at stake. As such, it is linked to how vaccine meaning is co-produced within public discourses.
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COVID-19 , Medios de Comunicación Sociales , Vacunas , Humanos , Incertidumbre , Vacunación , Vacunas/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Europa (Continente)/epidemiologíaRESUMEN
The aim of this study was to evaluate the physiology of 13 yeast strains by assessing their kinetic parameters under anaerobic conditions. They included Saccharomyces cerevisiae CAT-1 and 12 isolated yeasts from different regions in Brazil. The study aimed to enhance understanding of the metabolism of these strains for more effective applications. Measurements included quantification of sugars, ethanol, glycerol, and organic acids. Various kinetic parameters were analyzed, such as specific substrate utilization rate (qS), maximum specific growth rate (µmax), doubling time, biomass yield, product yield, maximum cell concentration, ethanol productivity (PEth), biomass productivity, and CO2 concentration. S. cerevisiae CAT-1 exhibited the highest values in glucose for µmax (0.35 h-1), qS (3.06 h-1), and PEth (0.69 gEth L-1 h-1). Candida parapsilosis Recol 37 did not fully consume the substrate. In fructose, S. cerevisiae CAT-1 stood out with higher values for µmax (0.25 h-1), qS (2.24 h-1), and PEth (0.60 gEth L-1 h-1). Meyerozyma guilliermondii Recol 09 and C. parapsilosis Recol 37 had prolonged fermentation times and residual substrate. In sucrose, only S. cerevisiae CAT-1, S. cerevisiae BB9, and Pichia kudriavzevii Recol 39 consumed all the substrate, displaying higher PEth (0.72, 0.51, and 0.44 gEth L-1 h-1, respectively) compared to other carbon sources.