Near-Infrared Light Activated Formulation for the Spatially Controlled Release of CRISPR-Cas9 Ribonucleoprotein for Brain Gene Editing.

The CRISPR/Cas9 system has emerged as a promising platform for gene editing; however, the lack of an efficient and safe delivery system to introduce it into cells continues to hinder clinical translation. Here, we report a rationally designed gene-editing nanoparticle (NP) formulation for brain applications: an sgRNA:Cas9 ribonucleoprotein complex is immobilized on the NP surface by oligonucleotides that are complementary to the sgRNA. Irradiation of the formulation with a near-infrared (NIR) laser generates heat in the NP, leading to the release of the ribonucleoprotein complex. The gene-editing potential of the formulation was demonstrated in vitro at the single-cell level. The safety and gene editing of the formulation were also demonstrated in the brains of reporter mice, specifically in the subventricular zone after intracerebral administration and in the olfactory bulb after intranasal administration. The formulation presented here offers a new strategy for the spatially controlled delivery of the CRISPR system to the brain.

Mondor's penile disease requiring thrombectomy: A case report and literature review.

The thrombophlebitis of the superficial dorsal vein of the penis, called Mondor's penile disease (PMD), is a condition with a low incidence worldwide. In general, it is considered a self-limited disease that usually resolves with conservative management and very rarely requires surgical intervention. We report the case of a 41-year-old patient, who presented PMD which persists after medical treatment with nonsteroidal antiinflammatory drug and low molecular weight heparin. Surgery was decided and thrombectomy plus resection of the superficial penile vein was performed with satisfactory results. A review of the literature is presented, focusing on the limited available evidence of surgical management.

[Videourodynamics: Current indications, technique and considerations.] / Videourodinamia: indicaciones actuales, técnicas y consideraciones.

OBJECTIVES: Describe the technique, indications and the correct interpretation given the findings in different clinical entities, and to serve as a guide for urologists, urology residents and even medical students. MATERIAL AND METHODS: A literature search was performed using Pubmed, Cochrane and Scopus database for articles and guidelines published between January 1970 and June 2020. RESULTS: Videourodynamics is a diagnostic procedure that combines the urodynamic study with simultaneous images of the lower urinary tract to assess the anatomy and function during the different phases of micturition.This study provides important information that can modify therapeutic behavior and therefore clinical outcomes of patients. CONCLUSION: The role of videourodynamics becomes more relevant nowadays in the assessment of the pathophysiology of voiding dysfunction, being the gold standard for the workup of neurogenic bladder and voiding dysfunction in young people and women and, possibly in persistent/recurrent incontinence in both men and women.

OBJETIVO: Describir la técnica, las indicaciones y la correcta interpretación dados los hallazgos en diferentes entidades clínicas, y servir como guía para urólogos, residentes de urología e incluso estudiantes de medicina.MATERIAL Y MÉTODO: Se realizó una revisión bibliográfica internacional de artículos o guías en las bases de datos PubMed, Cochrane y Scopus entre enero de 1970 y junio de 2020. RESULTADOS: La videourodinamia es un procedimiento diagnóstico que integra el estudio urodinámico con imágenes simultáneas del tracto urinario inferior para evaluar la anatomía y la función durante las diferentes fases de micción. Este estudio aporta información relevante que puede modificar la conducta terapéutica y por ende los desenlaces clínicos de los pacientes.CONCLUSIÓN: El papel de la videourodinamia cada vez toma más relevancia en la evaluación de la fisiopatología de la disfunción miccional, siendo incluso el patrón de oro para el estudio de disfunción vesical neurogénica y trastornos del vaciado en jóvenes y mujeres y, posiblemente la incontinencia recidivada tanto en hombres como en mujeres.

Engineered extracellular vesicles as brain therapeutics.

Extracellular vesicles (EVs) are communication channels between different cell types in the brain, between the brain and the periphery and vice-versa, playing a fundamental role in physiology and pathology. The evidence that EVs might be able to cross the blood-brain barrier (BBB) make them very promising candidates as nanocarriers to treat brain pathologies. EVs contain a cocktail of bioactive factors, yet their content and surface can be further engineered to enhance their biological activity, stability and targeting ability. Native and engineered EVs have been reported for the treatment of different brain pathologies, although issues related to their modest accumulation and limited local therapeutic effect in the brain still need to be addressed. In this review, we cover the therapeutic applications of native and bioengineered EVs for brain diseases. We also review recent data about the interaction between EVs and the BBB and discuss the challenges and opportunities in clinical translation of EVs as brain therapeutics.

[Predictors of biochemical recurrence after radical prostatectomy at an oncology reference center in Colombia.] / Factores predictores de recaída bioquímica después de prostatectomía radical en un centro oncológico colombiano.

OBJECTIVE: To determine predictors of BCR in patients with localized PCa undergoing RP at an oncology reference center in Colombia. MATERIALS AND METHODS: A retrospective analytical study was conducted on patients with localized PCa undergoing RP and who at least had one adverse pathological factor for BCR. We consider BCR as two consecutive elevations of PSA after RP, greater than 0.2 ng/ml. For the bivariate analysis we used Kaplan-Meier, and Cox proportional risk analysis to estimate the hazard ratio as well as to determine variables independently associated with the outcome. RESULTS: 280 patients were included. The medianage was 65.3 years, with a median follow up of 52.2 months. BCR occurred in 39% of patients, with a median BCR time of 24.8 months. In the multivariate analysis, high risk [HR 2.07 (95% CI 1.11 - 3.86)], positive surgical margins [HR 2.79 (95% CI 1.66 - 4.69)] and tertiary Gleason pattern [HR 2.16 (95% CI 1.16 - 4.01)] were identified as independent variables associated significantly with BCR. Limitations include retrospective design and sample size. CONCLUSIONS: High risk, positive surgical margins and the presence of tertiary Gleason pattern are the predictive factors of BCR after RP in the Colombian population.

OBJETIVO: Determinar los predictores de recaída bioquímica en pacientes con cáncer de próstata localizado llevados a prostatectomía radical en un centro oncológico de referencia en Colombia.MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo analítico en pacientes con cáncer de próstata localizado que fueron llevados a prostatectomía radical y que tuvieran al menos un factor patológico adverso para recaída bioquímica. Las variables analizadas fueron la edad, el riesgo, el estadio pT, el estadio pN, la densidad ganglionar, los márgenes quirúrgicos, el grupo grado de Gleason y el patrón terciario del Gleason. Consideramos recaída bioquímica como 2 elevaciones consecutivas del PSA después de la prostatectomía radical, mayor a 0,2 ng/ml. Para el análisis bivariado usamos Kaplan-Meier y el análisis de riesgo proporcional de Cox para estimar el HR así como para determinarlas variables independientemente asociadas con el desenlace. RESULTADOS: Se incluyeron 280 pacientes. La edad promedio fue de 65,3 años, con una media de seguimiento de 52,2 meses. La recaída bioquímica ocurrió en el 39% de los pacientes, con una media de tiempo hasta la recaída bioquímica de 24,8 meses. En el análisis multivariado, el riesgo alto [HR 2,07 (IC95% 1,11­ 3,86)], los márgenes quirúrgicos positivos [HR 2,79 (IC95% 1,66 ­ 4,69)] y el patrón terciario del Gleason [HR 2,16 (IC 95% 1,16 ­ 4,01)] fueron identificados como variables independientes asociadas significativamente con recaída bioquímica. Las limitaciones incluyen el diseño retrospectivo del estudio y el tamaño de la muestra. CONCLUSIONES: El riesgo alto, los márgenes quirúrgicos positivos y la presencia de patrón terciario de Gleason son las variables predictoras de recaída bioquímica después de prostatectomía radical en la población colombiana.

Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability.

BACKGROUND: Sympathetic renal denervation (SRD) has been proposed as a therapeutic alternative for patients with resistant hypertension not controlled on pharmacological therapy. Two studies have suggested an effect of SRD in reducing short-term blood pressure variability (BPV). However, this has not been addressed in a randomized comparative trial. We aimed to compare the effects of spironolactone and SRD on circadian BP and BPV. METHODS: This is a post-hoc analysis of a randomized trial in 24 true resistant hypertensive patients (15 men, 9 women; mean age 64 years) comparing 50mg of spironolactone (n = 13) vs. SRD (n = 11) on 24-hour BP. We report here the comparative effects on daytime (8 am-10 pm) and nighttime (0 am-6 am) BP, night-to-day ratios and BP and heart rate variabilities (SD and coefficient of variation of 24-hour, day and night, as well as weighted SD and average real variability (ARV)). RESULTS: Spironolactone was more effective than SRD in reducing daytime systolic (P = 0.006), daytime diastolic (P = 0.006), and nighttime systolic (P = 0.050) BP. No differences were observed in the night-to-day ratios. In contrast, SRD-reduced diastolic BPV (24 hours, daytime, nighttime, weighted, and ARV; all P < 0.05) with respect to spironolactone, without significant differences in systolic BPV. CONCLUSION: Spironolactone is more effective than SRD in reducing ambulatory BP. However, BPV is significantly more reduced with SRD. This effect could be important in terms of potential prevention beyond BP reduction and deserves further investigation.

Factores de riesgo de parto pretérmino en Bogotá D. C., Colombia / Risk factors for preterm birth in Bogota D. C., Colombia

Resumen Introducción. El parto pretérmino es aquel que ocurre antes de la semana 37 de gestación. Este tipo de parto se asocia a múltiples factores de riesgo, algunos de los cuales pueden ser prevenidos. En Colombia son escasos los estudios sobre los factores de riesgo asociados al parto pretérmino, de ahí la importancia de su análisis. Objetivo. Identificar los factores de riesgo para parto pretérmino en un grupo de gestantes de Bogotá D.C., Colombia. Materiales y métodos. Estudio de cohorte retrospectivo. La muestra estuvo compuesta por 452 pacientes que habían participado en un estudio primario y que ya habían dado a luz. Resultados. La incidencia de parto pretérmino fue de 10.40% (IC95%: 7.60-13.20) y los factores de riesgo asociados fueron los siguientes: ser diagnosticada con preeclampsia severa, con un riesgo relativo (RR) de 7.47 (IC95%: 4.59-11.95); tener preeclampsia (severa y no severa), con un RR=5.05 (IC95%: 3.0-8.51), y ocurrencia de restricción del crecimiento intrauterino (RCIU), con un RR=4.40 (IC95%: 2.44-7.98). Conclusiones. De acuerdo con los hallazgos reportados en el presente estudio, es necesario planear e implementar estrategias y políticas públicas en Bogotá D.C. que promuevan mejores prácticas de atención prenatal que, a su vez, permitan la detección temprana de condiciones como la preeclampsia y la RCIU, lo que hará posible reducir la incidencia de partos pretérmino en la ciudad y utilizar la experiencia y resultados obtenidos en el resto del país.

Abstract Introduction: A preterm birth occurs before the 37th week of pregnancy. It is associated with multiple risk factors, some of which can be prevented. In Colombia, few studies have addressed the risks factors associated with preterm birth, hence the importance of analyzing them. Objective: To identify risk factors for preterm birth in a population of pregnant women in Bogotá D.C., Colombia. Materials and methods: Retrospective cohort study. The sample was composed of 452 patients who had participated in a primary study and had already given birth. Results: The incidence of preterm birth was 10.40% (95%CI: 7.60-13.20). The following risk factors associated with preterm delivery were found: being diagnosed with severe preeclampsia, with a relative risk (RR)=7.47 (95%CI: 4.59-11.95); having preeclampsia (severe and non-severe), with a RR=5.05 (95%CI: 3.0-8.51); and occurrence of intrauterine growth restriction (IUGR), with a RR=4.40 (95%CI: 2.44-7.98). Conclusions: According to the findings reported in this study, it is necessary to plan and implement strategies and public policies in Bogotá D.C. that promote better prenatal care practices that, in turn, allow the early detection of conditions such as preeclampsia and IUGR. This will reduce the incidence of preterm birth in the city and will allow using the experience and results obtained here in the rest of the country.

Plasmacytoid Urothelial Carcinoma of the Bladder: Case Report and Review of the Literature / Carcinoma urotelial de vejiga, variante plasmocitoide: Reporte de un caso y revisión de la literatura

Introduction Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histological variant, accounting for 1 to 3% of the invasive urothelial carcinomas, and it is typically aggressive. So far, it has not been well characterized, and the literature is based on reports and case series. Case Report A 70-year-old male patient presenting with 4 months of constitutional and urinary symptoms, with an ultrasound finding of bilateral hydronephrosis and diffuse thickening of the bladder walls. In the cystoscopy, trigone of infiltrated appearance, a biopsy wass performed, whose immunohistochemistry revealed a PUC. The abdominopelvic image showed an infiltrative lesion that compromised the muscle of the bladder and extended to the perivesical fat, without adequate plane of cleavage with the prostate and a single hypogastric adenopathy suspected of malignancy. It was classified as cT3b vs cT4aN1M0 (chest computed tomography [CT] negative for malignancy), and the patient was submitted to a radical cystoprostatectomy, extended pelvic lymphadenectomy and non-continent urinary diversion with ileal conduit. The pathology revealed a diffuse PUC with prostatic stromal involvement and 22 of 39 lymph nodes positive for malignancy. Finally, the patient presented a series of postoperative complications and died. Conclusion Plasmacytoid urothelial carcinoma of the bladder is a rare entity, characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis. Currently, an aggressive approach is recommended due to its high invasive potential.

Introducción El carcinoma urotelial plasmocitoide (CUP) de la vejiga es una variante histológica poco frecuente; representa el 1 al 3% de los carcinomas uroteliales invasivos y es típicamente agresiva. Hasta el momento no ha sido bien caracterizada, y la literatura se basa en reportes y series de casos. Reporte de Caso Paciente masculino de 70 años presentando por 4 meses síntomas constitucionales y urinarios, con hallazgo ecográfico de hidronefrosis bilateral y engrosamiento difuso de las paredes vesicales. En la cistoscopia, trígono de apariencia infiltrada, se realizó biopsia cuya inmunohistoquímica reveló un CUP. En imagen abdominopélvica, se evidenció lesión infiltrativa que comprometía la muscular de la vejiga y se extendía a la grasa perivesical, sin adecuado plano de clivaje con la próstata y un único ganglio hipogástrico sospechoso de malignidad. Se clasificó como cT3b vs cT4aN1M0 (TAC tórax negativo para malignidad) y fue llevado a cistoprostatectomía radical, linfadenectomía pélvica extendida y derivación urinaria no continente con conducto ileal. La patología reveló un carcinoma urotelial variante difusa plasmocitoide con compromiso de estroma prostático y 22 de 39 ganglios positivos para malignidad. Finalmente, el paciente presentó una serie de complicaciones posoperatorias y falleció. Conclusión El carcinoma urotelial de vejiga variante plasmocitoide es una entidad poco frecuente, caracterizada por alta agresividad, un estadio avanzado al momento del diagnóstico, y un pobre pronóstico. En la actualidad, se recomienda un enfoque agresivo dado su alto potencial invasivo.

Orinoterapia para el control de las manifestaciones clínicas del asma bronquial en niños: intervención realizada en un centro holístico / Urinotherapy for the control of the clinical manifestations of bronchial asthma in children: intervention conducted in a holistic center

La orinoterapia, parte de la medicina tradicional, se basa en la práctica de estilos de vida saludables y el uso de la propia orina para mejorar el estado de salud. Objetivo: determinar el efecto de la orinoterapia en el control de las manifestaciones clínicas del asma bronquial en niños de 4 a 11 años que asistieron al Centro de Retiro Holístico Anna Margottini (CRHAM) entre octubre de 2008 a enero de 2009. Material y métodos: enfoque cuantitativo, diseño ex post facto, basado en la recolección y descripción de datos obtenidos de 30 niños a los que se les aplicó el Child Asthma Control Test, antes y después de haber recibido orinoterapia. Resultados: antes de recibir orinoterapia, 19 de 30 niños (63,3 por ciento) no controlaban el asma bronquial y once controlaban el asma parcialmente. Contrario a esto, luego de recibir orinoterapia 24 de los 30 niños (80 por ciento) controlan su asma adecuadamente; seis de los niños (20 por ciento) controlan el asma parcialmente no quedando ningún niño en el nivel no controlado. Conclusión: al comparar el grado de control de las manifestaciones clínicas del asma bronquial antes y despues de recibir orinoterapia, se observa que el nivel de control del asma de los niños se ha incrementado con la aplicación del tratamiento. Sin embargo, la orinoterapia no radica en el uso exclusivo de la propia orina, sino también en la practica de estilos de vida saludables como el consumo de fitos, los cuales ya han demostrado su beneficio en el tratamiento del asma.

The urinotherapy part of traditional medicine is based on the practice of the healthy lifestyles and use their own urine to improve health status. Objective: To determine the effect of urinotherapy to control the clinical manifestations of bronchial asthma in children 4 to 11 years who attended the Center for Holistic Retreat Margottini Anna (CRHAM) between October 2008 and January 2009. Material and methods: Experimental design is not ex post facto, of a quantitative approach, since it was based on the collection and description of the data obtained from 30 children who were interviewed with the Child Asthma Control Test before and after receiving urinotherapy. Results: Before receiving urinotherapy 19 of 30 children (63.3 per cent) did not control the asthma and 11 partially controlled asthma. Contrary to this, it was noted that after receiving urinotherapy 24 of the 30 children (80 per cent) adequately control their asthma, 6 of all children (20 per cent) partially controlled asthma is not leaving any child in the uncontrolled level. Conclusion: By comparing the degree of control of the clinical manifestations of bronchial asthma before and after receiving urinotherapy is observed that the level of asthma control of children in this study increased with the treatment. However urinotherapy not only lies in the exclusive use of one's own urine, but also in the practice of healthy lifestyles such as consumption of phytosanitary of which has already demonstrated its benefit in the treatment of asthma.