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1.
Glycobiology ; 34(10)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39214076

RESUMEN

Carbohydrate binding modules (CBMs) are protein domains that typically reside near catalytic domains, increasing substrate-protein proximity by constraining the conformational space of carbohydrates. Due to the flexibility and variability of glycans, the molecular details of how these protein regions recognize their target molecules are not always fully understood. Computational methods, including molecular docking and molecular dynamics simulations, have been employed to investigate lectin-carbohydrate interactions. In this study, we introduce a novel approach that integrates multiple computational techniques to identify the critical amino acids involved in the interaction between a CBM located at the tip of bacteriophage J-1's tail and its carbohydrate counterparts. Our results highlight three amino acids that play a significant role in binding, a finding we confirmed through in vitro experiments. By presenting this approach, we offer an intriguing alternative for pinpointing amino acids that contribute to protein-sugar interactions, leading to a more thorough comprehension of the molecular determinants of protein-carbohydrate interactions.


Asunto(s)
Aminoácidos , Biología Computacional , Aminoácidos/química , Aminoácidos/metabolismo , Simulación de Dinámica Molecular , Carbohidratos/química , Simulación del Acoplamiento Molecular , Unión Proteica , Sitios de Unión , Proteínas Virales/química , Proteínas Virales/metabolismo , Proteínas Virales/genética
2.
Community Dent Health ; 41(2): 128-133, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38682571

RESUMEN

OBJECTIVE: Social media is a platform for sharing views on aspects of life, including oral health. This study aimed to characterize Facebook posts related to toothache information. METHODS: Two independent investigators retrieved 500 English-language posts with the highest level of interaction using CrowdTangleTM and analyzed their facticity, motivation, author's profile, content, sentiment, and type of post. Data were analysed descriptively and using Pearson's Chi-square and Mann-Whitney U tests and multiple logistic regression models. RESULTS: Most posts were produced by regular users and were not financially motivated, although commercial posts had significantly higher total interaction among users. While link- or video-containing posts (OR = 1.66) and posts with positive sentiments (OR = 1.53) were associated with users' total interaction, older (OR = 1.81) and link- or video-containing posts (OR = 2.04) were associated with overperforming scores. Misinformation was positively associated with financial motivation (OR = 2.03) and positive sentiments (OR = 3.79). CONCLUSION: This study highlights the importance of addressing the spread of misinformation related to oral health on social media and taking steps to ensure that accurate and reliable information is readily available. Toothache-related misinformation was associated with positive sentiments and financial motivation. Links, videos, and positive sentiments awakened greater user engagements with toothache-related posts.


Asunto(s)
Comunicación , Medios de Comunicación Sociales , Odontalgia , Humanos , Odontalgia/psicología , Motivación
3.
Phys Rev Lett ; 130(16): 166402, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37154653

RESUMEN

In the quest for efficient thermoelectrics, semiconducting behavior is a targeted property. Yet, this is often difficult to achieve due to the complex interplay between electronic structure, temperature, and disorder. We find this to be the case for the thermoelectric clathrate Ba_{8}Al_{16}Si_{30}: Although this material exhibits a band gap in its ground state, a temperature-driven partial order-disorder transition leads to its effective closing. This finding is enabled by a novel approach to calculate the temperature-dependent effective band structure of alloys. Our method fully accounts for the effects of short-range order and can be applied to complex alloys with many atoms in the primitive cell, without relying on effective medium approximations.

4.
Pacing Clin Electrophysiol ; 46(6): 454-458, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36585766

RESUMEN

BACKGROUND: Twiddler's syndrome is a poorly understood clinical phenomenon when patients either consciously or subconsciously rotate their cardiac device resulting in lead dislodgement. We aimed to determine the true prevalence and risk factors associated with Twiddler's syndrome in a real-world population. METHODS: A retrospective chart review was performed on all patients who underwent cardiac device implantation from January 1st 2017 until Jan 1st 2022. We specifically searched for the terms "Twiddler" or "Twiddler's" imbedded within the text of the medical chart. Demographic and clinical variables were collected from the electronic medical record system. We utilized multivariable logistic regression analysis as well as Kaplan-Meier prediction models to determine independent clinical predictors of Twiddler's syndrome as well as associated mortality, respectively. RESULTS: Twenty one out of 1793 patients (1.2%) were identified as having Twiddler's syndrome after chart review. Independent variables associated with Twiddler's syndrome were female sex (OR 3.76; 95% CI 1.29-10.95), antidepressant medications (OR 3.58; 95% CI 1.07-11.99), and BMI (OR 1.08; 95% CI 1.03-1.31). There was no increased six-month mortality via Kaplan-Meier analysis. CONCLUSION: Our study shows that 1.2% of patients in our real-world population had evidence of Twiddler's syndrome. Independent predictors of Twiddler's syndrome include female sex, antidepressant medications as well as BMI.


Asunto(s)
Corazón , Humanos , Femenino , Masculino , Falla de Equipo , Estudios Retrospectivos , Prevalencia , Síndrome
5.
An Acad Bras Cienc ; 95(suppl 1): e20230179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37585972

RESUMEN

Notosuchian crocodyliforms were major components of the South American Cretaceous biota and, for over 125 years, paleontological fieldwork in this continent recovered several well-preserved fossils of these animals. They are largely recognized for terrestrial life and specialized feeding habits, frequently presenting bizarre taxa such as Comahuesuchus. A new species, Comahuesuchus bonapartei n. sp. (MUCPv 597; cast MN), is described from geological strata of Sierra Barrosa Formation (Upper Turonian) and Portezuelo Formation (Lower Coniacian) of Lake Barreales, Patagonia, Argentina. The new fossil comprises a right dentary bone that shares important and unique anatomical features with specimens of Comahuesuchus brachybuccalis, such as the presence of a well-marked shelf on the lateral surface of the bone; a flat, low, and wide mandibular symphysis; an enlarged, labiolingually compressed caniniform tooth at caudal position in the dentary; the presence of serrated mesial and distal carinae in the caniniform with a faceted labial surface, and the absence or extremely reduction in number of the postcaniniform dentition. C. bonapartei differs from C. brachybuccalis in having individual dentary alveoli, rather a dentition set in groove. Phylogenetic analyses support a sister-relationship between both species, which are well nested within notosuchians.


Asunto(s)
Dinosaurios , Lagos , Animales , Filogenia , Argentina , Mandíbula/anatomía & histología , Paleontología , Fósiles , Dinosaurios/anatomía & histología
6.
Bull Environ Contam Toxicol ; 112(1): 6, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38063862

RESUMEN

The aim of this study is to assess and identify the most suitable geospatial interpolation algorithm for environmental sciences. The research focuses on evaluating six different interpolation methods using annual average PM10 concentrations as a reference dataset. The dataset includes measurements obtained from a target air quality network (scenery 1) and a sub-dataset derived from a partitive clustering technique (scenery 2). By comparing the performance of each interpolation algorithm using various indicators, the study aims to determine the most reliable method. The findings reveal that the kriging method demonstrates the highest performance within environmental sciences, with a spatial similarity of approximately 70% between the two scenery datasets. The performance indicators for the kriging method, including RMSE (root mean square error), MAE (mean absolute error), and MAPE (mean absolute percentage error), are measured at 3.2 µg/m3, 10.2 µg/m3, and 7.3%, respectively.This study addresses the existing gap in scientific knowledge regarding the comparison of geospatial interpolation techniques. The findings provide valuable insights for environmental managers and decision-makers, enabling them to implement effective control and mitigation strategies based on reliable geospatial information and data. In summary, this research evaluates and identifies the most suitable geospatial interpolation algorithm for environmental sciences, with the kriging method emerging as the most reliable option. The study's findings contribute to the advancement of knowledge in the field and offer practical implications for environmental management and planning.


Asunto(s)
Contaminación del Aire , Ciencia Ambiental , Monitoreo del Ambiente/métodos , Algoritmos , Análisis Espacial
7.
Vertex ; 34(160, abr.-jun.): 7-19, 2023 07 10.
Artículo en Español | MEDLINE | ID: mdl-37562390

RESUMEN

Objectives: The study was aimed at measuring the impact of training on forensic case formulation in mental health and to provide more evidence on the reliability of the TEC-F. Method: Nine psychiatrists and six psychologists from various Latin American countries participated in a quasi-pedagogical experiment. The quality of formulations was independently and blindly measured pre- and post-intervention with the TEC-F and the assignment of two standard vignettes was also randomly manipulated. Quality mean differences and instrument reliability indicators were calculated. Results: The values of intraclass correlation coefficients were 0.92; 0.94; 0.83; 0.93 and 0.95 and the values of Cronbach's alpha coefficient were 0.83; 0.94; 0.63; 0.77 and 0.93, for the dimensions transparency, specificity, communication, reasoning and for the total TEC-F respectively. The results of the 19-day test-retest were excellent. The mean TEC-F total quality pre-course was 31.4 and the mean post-course, 38.4 (p = 0.003 and p = 0.001 for group test and paired test respectively). Conclusions: The pedagogical intervention produced a significant improvement in the quality of the expert's formulations. The study added evidence supporting the TEC-F reliability.


OBJETIVOS: El estudio se propuso medir el impacto de un entrenamiento sobre formulación pericial del caso forense en salud mental y extender evidencias relacionadas con la confiabilidad de la TEC-F. MÉTODO: Nueve psiquiatras y seis psicólogos de diversos países latinoamericanos participaron de un cuasi-experimento pedagógico. Se midió independientemente y a ciegas la calidad de las formulaciones con la TEC-F pre y post intervención y también se manipuló aleatoriamente la asignación de dos viñetas estándares. Se calcularon diferencias de medias e indicadores de confiabilidad del instrumento. RESULTADOS: Los valores de coeficientes de correlación intraclase fueron 0,92; 0,94; 0,83; 0,93 y 0,95 y los valores del coeficiente Alfa de Cronbach fueron 0,83; 0,94; 0,63; 0,77 y 0,93, para las dimensiones transparencia, especificidad, comunicación, fundamentación y para el total TEC-F respectivamente. Los resultados del test-retest a 19 días fueron excelentes. La media de calidad total TEC-F precurso fue 31,4 y la media post curso, 38,4 (p = 0,003 y p = 0,001 para prueba grupal y para prueba apareada respectivamente). CONCLUSIONES: La intervención pedagógica produjo una significativa mejoría en la calidad de las formulaciones periciales. El estudio adicionó evidencias sosteniendo la confiabilidad de la TEC-F.


Asunto(s)
Salud Mental , Violencia , Estudios Retrospectivos
8.
PLoS Med ; 19(7): e1004033, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35797409

RESUMEN

BACKGROUND: Pay-for-performance (P4P) programmes to incentivise health providers to improve quality of care have been widely implemented globally. Despite intuitive appeal, evidence on the effectiveness of P4P is mixed, potentially due to differences in how schemes are designed. We exploited municipality variation in the design features of Brazil's National Programme for Improving Primary Care Access and Quality (PMAQ) to examine whether performance bonuses given to family health team workers were associated with changes in the quality of care and whether the size of bonus mattered. METHODS AND FINDINGS: For this quasi-experimental study, we used a difference-in-differences approach combined with matching. We compared changes over time in the quality of care delivered by family health teams between (bonus) municipalities that chose to use some or all of the PMAQ money to provide performance-related bonuses to team workers with (nonbonus) municipalities that invested the funds using traditional input-based budgets. The primary outcome was the PMAQ score, a quality of care index on a scale of 0 to 100, based on several hundred indicators (ranging from 598 to 660) of health care delivery. We did one-to-one matching of bonus municipalities to nonbonus municipalities based on baseline demographic and economic characteristics. On the matched sample, we used ordinary least squares regression to estimate the association of any bonus and size of bonus with the prepost change over time (between November 2011 and October 2015) in the PMAQ score. We performed subgroup analyses with respect to the local area income of the family health team. The matched analytical sample comprised 2,346 municipalities (1,173 nonbonus municipalities; 1,173 bonus municipalities), containing 10,275 family health teams that participated in PMAQ from the outset. Bonus municipalities were associated with a 4.6 (95% CI: 2.7 to 6.4; p < 0.001) percentage point increase in the PMAQ score compared with nonbonus municipalities. The association with quality of care increased with the size of bonus: the largest bonus group saw an improvement of 8.2 percentage points (95% CI: 6.2 to 10.2; p < 0.001) compared with the control. The subgroup analysis showed that the observed improvement in performance was most pronounced in the poorest two-fifths of localities. The limitations of the study include the potential for bias from unmeasured time-varying confounding and the fact that the PMAQ score has not been validated as a measure of quality of care. CONCLUSIONS: Performance bonuses to family health team workers compared with traditional input-based budgets were associated with an improvement in the quality of care.


Asunto(s)
Salud de la Familia , Reembolso de Incentivo , Brasil , Humanos , Atención Primaria de Salud , Calidad de la Atención de Salud
9.
Health Res Policy Syst ; 20(1): 13, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-35073897

RESUMEN

BACKGROUND: As a source of readily available evidence, rigorously synthesized and interpreted by expert clinicians and methodologists, clinical guidelines are part of an evidence-based practice toolkit, which, transformed into practice recommendations, have the potential to improve both the process of care and patient outcomes. In Brazil, the process of development and updating of the clinical guidelines for the Brazilian Unified Health System (Sistema Único de Saúde, SUS) is already well systematized by the Ministry of Health. However, the implementation process of those guidelines has not yet been discussed and well structured. Therefore, the first step of this project and the primary objective of this study was to summarize the evidence on the effectiveness of strategies used to promote clinical practice guideline implementation and dissemination. METHODS: This overview used systematic review methodology to locate and evaluate published systematic reviews regarding strategies for clinical practice guideline implementation and adhered to the PRISMA guidelines for systematic review (PRISMA). RESULTS: This overview identified 36 systematic reviews regarding 30 strategies targeting healthcare organizations, healthcare providers and patients to promote guideline implementation. The most reported interventions were educational materials, educational meetings, reminders, academic detailing and audit and feedback. Care pathways-single intervention, educational meeting-single intervention, organizational culture, and audit and feedback-both strategies implemented in combination with others-were strategies categorized as generally effective from the systematic reviews. In the meta-analyses, when used alone, organizational culture, educational intervention and reminders proved to be effective in promoting physicians' adherence to the guidelines. When used in conjunction with other strategies, organizational culture also proved to be effective. For patient-related outcomes, education intervention showed effective results for disease target results at a short and long term. CONCLUSION: This overview provides a broad summary of the best evidence on guideline implementation. Even if the included literature highlights the various limitations related to the lack of standardization, the methodological quality of the studies, and especially the lack of conclusion about the superiority of one strategy over another, the summary of the results provided by this study provides information on strategies that have been most widely studied in the last few years and their effectiveness in the context in which they were applied. Therefore, this panorama can support strategy decision-making adequate for SUS and other health systems, seeking to positively impact on the appropriate use of guidelines, healthcare outcomes and the sustainability of the SUS.


Asunto(s)
Práctica Clínica Basada en la Evidencia , Salud Pública , Atención a la Salud , Personal de Salud , Humanos , Cultura Organizacional , Guías de Práctica Clínica como Asunto , Revisiones Sistemáticas como Asunto
10.
Int J Mol Sci ; 23(15)2022 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-35955755

RESUMEN

Human intestinal organoids (HIOs) generated from human pluripotent stem cells hold great promise for modeling human development and as a possible source of tissue for transplantation. HIOs generate all of the main epithelial and mesenchymal cell types found in the developing human intestine and mature into intestinal tissue with crypts and villi following transplantation into immunocompromised mice. However, incomplete in vitro patterning and the presence of contaminating neurons could hinder their use for regenerative medicine in humans. Based on studies in model organisms, we hypothesized that the treatment of HIOs with all trans retinoic acid (ATRA) would improve their in vitro growth and patterning. We found that ATRA not only improved the patterning of HIOs, ATRA also increased organoid forming efficiency, improved epithelial growth, enriched intestinal subepithelial myofibroblasts (ISEMFs) and reduced neuronal contamination in HIOs. Taken together, our studies demonstrate how the manipulation of a single developmental signaling pathway can be used to improve the survival, patterning and cellular composition of HIOs.


Asunto(s)
Organoides , Células Madre Pluripotentes , Animales , Diferenciación Celular , Humanos , Mucosa Intestinal/metabolismo , Intestinos , Ratones , Tretinoina/metabolismo , Tretinoina/farmacología
11.
Vertex ; 33(156): 25-34, 2022 Jun.
Artículo en Español | MEDLINE | ID: mdl-35856780

RESUMEN

OBJECTIVES: The "Guide to understand and assess the quality of the case formulation in forensic mental health - TECF" is tested in order to contribute to the development of the forensic reports. METHOD: Twelve mental health professionals of different Latin American traditions assessed with the TECF the quality of ten international forensic reports, both psychological and psychiatric. The guide includes the manual that describes the dimensions, criteria and guidelines to assess the quality of the forensic case formulation. RESULTS: Internal consistency indicators were in a rank of 0.34- 0.81 for the dimensions and 0.85 for the total TECF. The absolute agreement intraclass correlation coefficient among evaluators with similar tradition reached values of 0.72; 0.52; 0.76 and 0.77 for the dimensions and 0.84 for the total. The agreement among evaluators with different traditions was less. CONCLUSIONS: The TECF is a promising instrument to guide the assessment of quality and to stimulate improvement of the forensic reports. Caution is recommended in light of the traditional rating scale method due to the effect that can be produced by the different practices.


Asunto(s)
Psiquiatría Forense , Trastornos Mentales , Humanos , Salud Mental
12.
Development ; 145(19)2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-30143540

RESUMEN

Enteroendocrine cells (EECs) are a minor cell population in the intestine yet they play a major role in digestion, satiety and nutrient homeostasis. Recently developed human intestinal organoid models include EECs, but their rarity makes it difficult to study their formation and function. Here, we used the EEC-inducing property of the transcription factor NEUROG3 in human pluripotent stem cell-derived human intestinal organoids and colonic organoids to promote EEC development in vitro An 8-h pulse of NEUROG3 expression induced expression of known target transcription factors and after 7 days organoids contained up to 25% EECs in the epithelium. EECs expressed a broad array of human hormones at the mRNA and/or protein level, including motilin, somatostatin, neurotensin, secretin, substance P, serotonin, vasoactive intestinal peptide, oxyntomodulin, GLP-1 and INSL5. EECs secreted several hormones including gastric inhibitory polypeptide (GIP), ghrelin, GLP-1 and oxyntomodulin. Injection of glucose into the lumen of organoids caused an increase in both GIP secretion and K-cell number. Lastly, we observed formation of all known small intestinal EEC subtypes following transplantation and growth of human intestinal organoids in mice.


Asunto(s)
Células Enteroendocrinas/citología , Células Enteroendocrinas/metabolismo , Células Madre Pluripotentes/citología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Recuento de Células , Diferenciación Celular , Hormonas/metabolismo , Humanos , Intestinos/citología , Proteínas del Tejido Nervioso/metabolismo , Organoides/citología , Células Madre Pluripotentes/metabolismo , Factores de Tiempo , Factores de Transcripción/metabolismo
13.
An Acad Bras Cienc ; 93(suppl 2): e20200762, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533794

RESUMEN

CT scans of the type braincase of Limaysaurus tessonei (MUCPv-205) allowed the first study of the endocranial cavities (brain and inner ear) for this South American taxon. Comparisons of the cranial endocast of L. tessonei with other sauropods indicate that 1) South American rebbachisaurids are more similar to each other than to Nigersaurus, and 2) certain association of traits are present in all known rebbachisaurid cranial endocasts, such as lack of an enlarged dorsal expansion, poorly laterally projected cerebral hemispheres, presence of a small flocculus of the cerebellum, markedly long passage for the facial nerve (CN VII), markedly inclined pituitary, and presence of a passage for the basilar artery communicating the floor of the endocranial cavity and the pituitary fossa. The relatively enlarged olfactory region indicates that smell was an important sense for this group of dinosaurs, suggesting different olfactory capabilities when compared to coeval titanosaurs.


Asunto(s)
Dinosaurios , Fósiles , Animales , Evolución Biológica , Encéfalo/diagnóstico por imagen , Dinosaurios/anatomía & histología , Cráneo/anatomía & histología , Cráneo/diagnóstico por imagen , Tomografía Computarizada por Rayos X
14.
Gastroenterology ; 157(6): 1556-1571.e5, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31442438

RESUMEN

BACKGROUND & AIMS: It has been a challenge to develop fully functioning cells from human pluripotent stem cells (hPSCs). We investigated how activation of hedgehog signaling regulates derivation of enteric neural crest (NC) cells from hPSCs. METHODS: We analyzed transcriptomes of mouse and hPSC-derived enteric NCs using single-cell RNA sequencing (scRNA-seq) to identify the changes in expression associated with lineage differentiation. Intestine tissues were collected from Tg(GBS-GFP), Sufuf/f; Wnt1-cre, Ptch1+/-, and Gli3Δ699/Δ699 mice and analyzed by flow cytometry and immunofluorescence for levels of messenger RNAs encoding factors in the hedgehog signaling pathway during differentiation of enteric NCs. Human NC cells (HNK-1+p75NTR+) were derived from IMR90 and UE02302 hPSC lines. hPSCs were incubated with a hedgehog agonist (smoothened agonist [SAG]) and antagonists (cyclopamine) and analyzed for differentiation. hPSC-based innervated colonic organoids were derived from these hPSC lines and analyzed by immunofluorescence and neuromuscular coupling assay for expression of neuronal subtype markers and assessment of the functional maturity of the hPSC-derived neurons, respectively. RESULTS: Single-cell RNA sequencing analysis showed that neural fate acquisition by human and mouse enteric NC cells requires reduced expression of NC- and cell cycle-specific genes and up-regulation of neuronal or glial lineage-specific genes. Activation of the hedgehog pathway was associated with progression of mouse enteric NCs to the more mature state along the neuronal and glial lineage differentiation trajectories. Activation of the hedgehog pathway promoted development of cultured hPSCs into NCs of greater neurogenic potential by activating expression of genes in the neurogenic lineage. The hedgehog agonist increased differentiation of hPSCs into cells of the neuronal lineage by up-regulating expression of GLI2 target genes, including INSM1, NHLH1, and various bHLH family members. The hedgehog agonist increased expression of late neuronal markers and neuronal activities in hPSC-derived neurons. CONCLUSIONS: In enteric NCs from humans and mice, activation of hedgehog signaling promotes differentiation into neurons by promoting cell-state transition, expression of genes in the neurogenic lineage, and functional maturity of enteric neurons.


Asunto(s)
Diferenciación Celular , Proteínas Hedgehog/metabolismo , Células Madre Pluripotentes Inducidas/fisiología , Neuronas/fisiología , Transducción de Señal/fisiología , Animales , Línea Celular , Sistema Nervioso Entérico/citología , Perfilación de la Expresión Génica/métodos , Proteínas Hedgehog/genética , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/inervación , Masculino , Ratones , Ratones Transgénicos , Cresta Neural/citología , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos
15.
Methods ; 168: 35-39, 2019 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-31185273

RESUMEN

The current five-year survival rate of <5% for pancreatic ductal adenocarcinoma (PDAC) is compounded by late diagnosis, a lack of PDAC-specific intraoperative guidance to ensure complete resection, and the ineffectiveness of current therapies. Previously, utilizing compound 1, a fluorophore with inherent PDAC selectivity, PDAC was visualized both in vivo and ex vivo in a murine model. In the current study, human PDAC tissue is targeted. Compound 1 selectively stains ducts of the adenocarcinoma versus the surrounding stroma, enabling the imaging of PDAC in frozen tissue sections with high contrast. To enhance the potential of 1 for intraoperative applications, the ex vivo staining protocol was optimized for rapid margin assessment, with a final staining time of ~15 min. To measure diagnostic performance, the area under a receiver operating characteristic (ROC) curve was measured for the identification of ductal adenocarcinoma vs. stroma. The bright fluorescence contrast enabled quantitative determination of PDAC (or precancerous PanIN lesions) versus healthy pancreas tissue in human tissue array samples.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico por imagen , Imagen Óptica/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Animales , Humanos , Ratones
16.
Angew Chem Int Ed Engl ; 59(35): 15147-15151, 2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32449244

RESUMEN

We report the first diselenide-based probe for the selective detection of thioredoxin reductase (TrxR), an enzyme commonly overexpressed in melanomas. The probe design involves conjugation of a seminaphthorhodafluor dye with a diselenide moiety. TrxR reduces the diselenide bond, triggering a fluorescence turn-on response of the probe. Kinetic studies reveal favorable binding of the probe with TrxR with a Michaelis-Menten constant (Km ) of 15.89 µm. Computational docking simulations predict a greater binding affinity to the TrxR active site in comparison to its disulfide analogue. In vitro imaging studies further confirmed the diselenide probe exhibited improved signaling of TrxR activity compared to the disulfide analogue.


Asunto(s)
Colorantes Fluorescentes/uso terapéutico , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Humanos
17.
Rev Endocr Metab Disord ; 20(1): 65-75, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30848433

RESUMEN

Cerebral edema and elevated intracranial pressure (ICP) are common complications of acute brain injury. Hypertonic solutions are routinely used in acute brain injury as effective osmotic agents to lower ICP by increasing the extracellular fluid tonicity. Acute kidney injury in a patient with traumatic brain injury and elevated ICP requiring renal replacement therapy represents a significant therapeutic challenge due to an increased risk of cerebral edema associated with intermittent conventional hemodialysis. Therefore, continuous renal replacement therapy (CRRT) has emerged as the preferred modality of therapy in this patient population. We present our current treatment approach, with demonstrative case vignette illustrations, utilizing hypertonic saline protocols (3% sodium-chloride or, with coexisting severe combined metabolic and respiratory acidosis, with 4.2% sodium-bicarbonate) in conjunction with the CRRT platform, to induce controlled hypernatremia of approximately 155 mEq/L in hemodynamically unstable patients with acute kidney injury and elevated ICP due to acute brain injury. Rationale, mechanism of activation, benefits and potential pitfalls of the therapy are reviewed. The impact of hypertonic citrate solution during regional citrate anticoagulation is specifically discussed. Maintaining plasma hypertonicity in the setting of increased ICP and acute kidney injury could prevent the worsening of ICP during renal replacement therapy by minimizing the osmotic gradient across the blood-brain barrier and maximizing cardiovascular stability.


Asunto(s)
Terapia de Reemplazo Renal Continuo/métodos , Hipernatremia/terapia , Lesiones Encefálicas/terapia , Humanos , Hipertensión Intracraneal/fisiopatología , Insuficiencia Respiratoria/terapia , Solución Salina Hipertónica/uso terapéutico
18.
Rev Endocr Metab Disord ; 20(1): 77, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31062251

RESUMEN

The authors would like to report an error in the formula describing the correction factor for the protein content in the serum/plasma.

19.
J Org Chem ; 84(5): 2585-2595, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30719911

RESUMEN

Fluorescent small molecules enable researchers and clinicians to visualize biological events in living cells, tissues, and organs in real time. Herein, the focus is on the structure and properties of the relatively rare benzo[ a]xanthenes that exhibit enhanced steric and electronic interactions due to their annulated structures. Three types of fluorophores were synthesized: (i) pH- and solvent-dependent seminaphthorhodafluors, (ii) pH- and solvent-independent seminaphthorhodafluors, and (iii) pH-independent but solvent-sensitive seminaphthorhodamines. The probes exhibited promising far-red to near-infrared (NIR) emission, large Stoke shifts, broad full width at half-maximum (fwhm), relatively high quantum yields, and utility in immunofluorescence staining. Deviation of the π-system from planarity due to changes in the fluorophore ionization state resulted in fluorescence properties that are atypical of common xanthene dyes.


Asunto(s)
Colorantes Fluorescentes/química , Xantenos/química , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacocinética , Humanos , Concentración de Iones de Hidrógeno , Modelos Moleculares , Conformación Molecular , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Rodaminas/síntesis química , Rodaminas/química , Espectroscopía Infrarroja Corta/métodos , Electricidad Estática , Relación Estructura-Actividad , Xantenos/síntesis química , Xantenos/farmacocinética
20.
An Acad Bras Cienc ; 91Suppl 2(Suppl 2): e20180661, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30569970

RESUMEN

We describe a dentary of a new titanosaur sauropod, Baalsaurus mansillai, gen. et sp. nov. from the Late Cretaceous of Patagonia, Argentina. The material comes from the Portezuelo Formation, Neuquén Group. Titanosaur sauropods lower jaws are scarce and only nine taxa with dentaries have been described. There are two types of morphology in titanosaur dentaries; "L" shaped or "U" shaped based on the shape, without a phylogenetic issue. In this paper; we recognize a new taxa, Baalsaurus mansillai, represented by an "L" shaped dentary with three apomorphic characters that are not present in other taxa: dentary alveoli with 10 teeth in the anterior ramus, a ventrally and anteriorly inclined symphysis and a wide ventral Meckelian groove surrounded by a thin lamina that forms a keel on the ventral border of the dentary.


Asunto(s)
Dinosaurios/anatomía & histología , Fósiles , Maxilares/anatomía & histología , Diente/anatomía & histología , Animales , Argentina , Dinosaurios/clasificación , Paleontología , Filogenia
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