Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive ...oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro‐oxidant enzymes. In addition to these well‐described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber–Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria‐targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment‐resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age‐related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high‐safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet‐to‐be identified basic action(s) of this ancient molecule.
Pedagogies employing critical traditions have increasingly been used to ameliorate achievement disparities and centralize issues of power in the education of Students of Color. In this study, I trace ...a teacher’s journey—new to critical pedagogies—as she learned about community cultural wealth and incorporated family histories as counterstorytelling curricula with her sixth-grade class of immigrant students in California’s Central Valley. I examine the pedagogical implementation with examples of students’ meaning making. The teacher and students demonstrated what I am advancing as migration capital—or knowledges, sensibilities, and skills cultivated through the array of migration/immigration experiences to the United States or its borderlands. This study highlights the potential of community cultural wealth pedagogies and as pedagogical tools to counter deficit narratives with Latina/o immigrant youth.
Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. ...We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.
Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy.
To ...measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations.
We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions.
Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16).
Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.
Introduction
Robotic-assisted rectal cancer surgery offers multiple advantages for surgeons, and it seems to yield the same clinical outcomes as regards the short-time follow-up of patients compared ...to conventional laparoscopy. This surgical approach emerges as a technique aiming at overcoming the limitations posed by rectal cancer and other surgical fields of difficult access, in order to obtain better outcomes and a shorter learning curve.
Material and methods
A systematic review of the literature of robot-assisted rectal surgery was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in October 2015 in PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials, for articles published in the last 10 years and pertaining the learning curve of robotic surgery for colorectal cancer. It consisted of the following key words: “rectal cancer/learning curve/robotic-assisted laparoscopic surgery”.
Results
A total of 34 references were identified, but only 9 full texts specifically addressed the analysis of the learning curve in robot-assisted rectal cancer surgery, 7 were case series and 2 were non-randomised case-comparison series. Eight papers used the cumulative sum (CUSUM) method, and only one author divided the series into two groups to compare both. The mean number of cases for phase I of the learning curve was calculated to be 29.7 patients; phase II corresponds to a mean number 37.4 patients. The mean number of cases required for the surgeon to be classed as an expert in robotic surgery was calculated to be 39 patients.
Conclusion
Robotic advantages could have an impact on learning curve for rectal cancer and lower the number of cases that are necessary for rectal resections.
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•Semi-crystalline Fe-BTC MOF material is an efficient support for enzymes.•It can be used by either in-situ or post-synthesis approaches.•The in-situ (one-step) biocatalysts are more ...active and have lower enzyme leaching.•This enzyme support improves the benefits given by some other MOF-based supports.
Metal-organic frameworks (MOFs) have revolutionized the potential applications of nanoporous materials. One of the most recent and promising applications of these materials is their use as supports for enzyme immobilization. In this context, the in-situ (one-step) methodologies, which do not require the use of MOFs with pores larger than the enzyme to be immobilized, seem to be particularly encouraging. This work presents a systematic study of the semi-crystalline Fe-BTC MOF material (commercialized as Basolite F300) employed as support of the enzymes laccase and lipase through either in-situ or post-synthesis methodology. The presence of the enzyme in the resultant solid biocatalysts was proved by CHNS chemical analysis, thermogravimetric analysis, Bradford assays and by SDS-PAGE electrophoresis. The enzymatic activity of the resultant Fe-BTC-based biocatalysts was also tested. The in-situ approach is particularly relevant due to various reasons: (i) the enzyme immobilization is given in one step; (ii) it is rapid (10min); (iii) it is very efficient in terms of encapsulation capacity (≥98% for laccase and ≥87% for lipase); (iv) the enzymes are fully retained and no leaching is observed after an initial release of only around 10% of the enzyme molecules weakly immobilized; and (v) the activity of the retained enzyme can be substantially maintained (97% with respect to the free enzyme in the case of lipase). Any of these parameters systematically improves these given by the post-synthesis (two-step) approach. Moreover, Fe-BTC widely surpasses the benefits given by other MOF-based supports either by in-situ or post-synthesis approaches.
Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy.
This study aimed ...to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait.
This study is a retrospective analysis of data from prospectively maintained databases.
This study was conducted at a comprehensive cancer center.
Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included.
Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision.
Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group.
A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group.
Generalizability, sample size, and follow-up duration were limitations of this study.
Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team. See Video Abstract at http://links.lww.com/DCR/B688.
ANTECEDENTES:Estudios retrospectivos sugieren que observar y esperar es una alternativa segura a la escisión mesorrectal total en pacientes seleccionados con una respuesta clínica completa después de la quimiorradioterapia.OBJETIVO:Determinar la proporción de pacientes con cáncer de recto que pueden beneficiarse de observar y esperar.DISEÑO:Análisis retrospectivo de datos de bases de datos mantenidas de forma prospectiva.ESCENARIO:Centro Oncológico Integral.PACIENTES:Pacientes consecutivos con adenocarcinoma de recto en estadio II o III tratados con TNT utilizando quimioterapia de inducción entre 2012 y 2019 bajo el cuidado del mismo cirujano.INTERVENCIÓN:La terapia neoadyuvante total de tipo inducción consistió en ocho ciclos de leucovorín-fluorouracilo-oxaliplatino o cinco ciclos de capecitabina-oxaliplatino antes de la quimiorradioterapia. A los pacientes con una respuesta clínica completa se les ofreció observar y esperar, y a los pacientes con tumor residual se les ofreció la escisión mesorrectal total.PRINCIPALES RESULTADOS Y MEDIDAS:La respuesta del tumor se evaluó con un tacto rectal, endoscopia y resonancia magnética. Se compararon las características de los pacientes y la supervivencia libre de recurrencia entre el grupo de observación y espera y el grupo de escisión mesorrectal total.RESULTADOS:Se incluyó en el análisis a un total de 88 pacientes. Uno (1%) murió durante la terapia neoadyuvante. Cincuenta y cinco pacientes (62.5%) tuvieron una respuesta clínica incompleta y se sometieron a cirugía; 10 (18%) de los 55 desarrollaron metástasis a distancia y 3 (5%) desarrollaron recidiva local. Los 32 pacientes restantes (36.3%) tuvieron una cCR (respuesta clínica completa) y se sometieron a observar y esperar. En promedio, los pacientes del grupo de observación y espera eran mayores y tenían tumores más pequeños y distales en comparación con el grupo de cirugía. La dosis mediana de radiación, el número de ciclos de quimioterapia, la tasa de eventos adversos y la duración del seguimiento no difirieron sustancialmente entre el grupo de escisión mesorrectal total y el grupo de observación y espera. En el grupo de observación y espera, 2 (6%) pacientes desarrollaron recrecimiento del tumor y uno de ellos tuvo metástasis a distancia. La supervivencia libre de recurrencia fue significativamente mayor en el grupo de observación y espera.LIMITACIONES:Generalizabilidad, tamaño de la muestra, duración del seguimiento.CONCLUSIONES:Aproximadamente un tercio de los pacientes con cáncer de recto en estadio II o III pueden beneficiarse de un abordaje de observación y espera con el objetivo de preservar el recto si se tratan con terapia neoadyuvante total de tipo inducción y son seguidos por un equipo multidisciplinario experimentado. Consulte Video Resumen en http://links.lww.com/DCR/B688.
A barrier to the widespread adoption of watch-and-wait management for locally advanced rectal cancer is the inaccuracy and variability of identifying tumor response endoscopically in patients who ...have completed total neoadjuvant therapy (chemoradiotherapy and systemic chemotherapy).
This study aimed to develop a novel method of identifying the presence or absence of a tumor in endoscopic images using deep convolutional neural network-based automatic classification and to assess the accuracy of the method.
In this prospective pilot study, endoscopic images obtained before, during, and after total neoadjuvant therapy were grouped on the basis of tumor presence. A convolutional neural network was modified for probabilistic classification of tumor versus no tumor and trained with an endoscopic image set. After training, a testing endoscopic imaging set was applied to the network.
The study was conducted at a comprehensive cancer center.
Images were analyzed from 109 patients who were diagnosed with locally advanced rectal cancer between December 2012 and July 2017 and who underwent total neoadjuvant therapy.
The main outcomes were accuracy of identifying tumor presence or absence in endoscopic images measured as area under the receiver operating characteristic for the training and testing image sets.
A total of 1392 images were included; 1099 images (468 of no tumor and 631 of tumor) were for training and 293 images (151 of no tumor and 142 of tumor) for testing. The area under the receiver operating characteristic for training and testing was 0.83.
The study had a limited number of images in each set and was conducted at a single institution.
The convolutional neural network method is moderately accurate in distinguishing tumor from no tumor. Further research should focus on validating the convolutional neural network on a large image set. See Video Abstract at http://links.lww.com/DCR/B959 .
ANTECEDENTES:Una barrera para la aceptación generalizada del tratamiento de Observar y Esperar para el cáncer de recto localmente avanzado, es la imprecisión y la variabilidad en la identificación de la respuesta tumoral endoscópica, en pacientes que completaron la terapia neoadyuvante total (quimiorradioterapia y quimioterapia sistémica).OBJETIVO:Desarrollar un método novedoso para identificar la presencia o ausencia de un tumor en imágenes endoscópicas utilizando una clasificación automática basada en redes neuronales convolucionales profundas y evaluar la precisión del método.DISEÑO:Las imágenes endoscópicas obtenidas antes, durante y después de la terapia neoadyuvante total se agruparon en base de la presencia del tumor. Se modificó una red neuronal convolucional para la clasificación probabilística de tumor versus no tumor y se entrenó con un conjunto de imágenes endoscópicas. Después del entrenamiento, se aplicó a la red un conjunto de imágenes endoscópicas de prueba.ENTORNO CLINICO:El estudio se realizó en un centro oncológico integral.PACIENTES:Analizamos imágenes de 109 pacientes que fueron diagnosticados de cáncer de recto localmente avanzado entre diciembre de 2012 y julio de 2017 y que se sometieron a terapia neoadyuvante total.PRINCIPALES MEDIDAS DE VALORACION:La precisión en la identificación de la presencia o ausencia de tumores en imágenes endoscópicas medidas como el área bajo la curva de funcionamiento del receptor para los conjuntos de imágenes de entrenamiento y prueba.RESULTADOS:Se incluyeron mil trescientas noventa y dos imágenes: 1099 (468 sin tumor y 631 con tumor) para entrenamiento y 293 (151 sin tumor y 142 con tumor) para prueba. El área bajo la curva operativa del receptor para entrenamiento y prueba fue de 0,83.LIMITACIONES:El estudio tuvo un número limitado de imágenes en cada conjunto y se realizó en una sola institución.CONCLUSIÓN:El método de la red neuronal convolucional es moderadamente preciso para distinguir el tumor de ningún tumor. La investigación adicional debería centrarse en validar la red neuronal convolucional en un conjunto de imágenes mayor. Consulte Video Resumen en http://links.lww.com/DCR/B959 . (Traducción -Dr. Fidel Ruiz Healy ).
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