Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury.

BACKGROUND AND AIMS: Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. APPROACH AND RESULTS: Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. CONCLUSIONS: We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia.

BACKGROUND AND AIMS: Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 ( Prom1 )-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1 -expressing HPC proliferation leading to profibrogenic ductular reactions in BA. APPROACH AND RESULTS: The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1 -expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1 , FN14 , and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression. CONCLUSION: TWEAK/FN14 signaling activation in Prom1 -expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.

GreenLight Laser Enucleation of the Prostate (GreenLEP): Initial Experience with a Simplified Technique.

OBJECTIVE: To present outcomes of a simplified GreenLight laser enucleation of the prostate (GreenLEP) technique and to inform urologists considering incorporation of enucleation into their practice. METHODS: We reviewed all consecutive GreenLEPs by a single surgeon from 2015 to 2018. Baseline patient characteristics, pre-enucleation prostate volume, enucleated adenoma weight, blood loss, lasering time, and energy utilized were recorded. Primary outcomes were urinary flow rate (uroflow) and postvoid residual. Secondary outcomes included International Prostate Symptom Score (IPSS) and prostate-specific antigen change. Primary and secondary outcomes were measured up to 3 years and compared using Student's t test. Adverse event and complication rates were recorded. RESULTS: One hundred and eight patients underwent GreenLEP with mean follow up of 10.2 months. Statistically significant improvements were noted at 3 months in Qmax (237%, P <.01) and Qavg (227%, P <.01), with changes remaining durable through 2 years. Statistically significant improvements were noted at 3 months in International Prostate Symptom Score (-64%, P <.01), postvoid residual (-83%, P <.01), and prostate-specific antigen change (-77%, P <.01). Adverse event and complication rates were comparable to other published enucleation studies. Sexual activity was reported in 36% of patients, all of whom reported retrograde ejaculation. Patients experienced dysuria (6%), stress urinary incontinence (6%), urge urinary incontinence (16%), urethral stricture (6%), bladder perforation (n = 2), prostatic capsular perforation (n = 1), and ureteral injury (n = 1). CONCLUSION: Simplified GreenLEP shows effective and durable results with an acceptable adverse event and complication profile. This technique is optimal for novice enucleators familiar with photoselective vaporization.

A Simplified Technique for GreenLight Laser Enucleation of the Prostate.

OBJECTIVE: To present a simplified technique for GreenLight laser enucleation of the prostate (GreenLEP), designed to reduce the learning curve commonly associated with endoscopic prostate enucleation. MATERIALS AND METHODS: GreenLEP is a novel endoscopic treatment for BPH which allows for durable resection of large glands with minimal energy use, minimal bleeding and has been shown to be non-inferior to holmium laser enucleation of the prostate (HoLEP). Furthermore, GreenLEP has been shown to be superior to GreenLight PVP For glands >80 g with respect to operative time, unplanned hospital readmission and decrease in post treatment PSA and prostate size. Unfortunately, a steep learning curve has remained a roadblock for adaptation by many urologists. Our technique for lobe-by-lobe GreenLEP is described and shown. RESULTS: GreenLEP allows for removal of the entire transition zone in patients with large glands traditionally best treated with staged TURP or simple prostatectomy. A lobe-by-lobe approach allows the urologist to learn the procedure in a stepwise fashion as they become increasingly comfortable with the technique. During the learning process, some lobes may be addressed by enucleation while others by vaporization. CONCLUSION: This simplified technique allows novice enucleators with GreenLight experience to feel more comfortable with GreenLEP, simplifying the learning curve.

[Anxiety and depression in daily clinical practice]. / Ansiedad y depresión en la práctica clínica diaria.

Anxiety and depression are two important clinical entities associated not only with mental health, but to health and illness in general. However, professionals in most of the non-psychiatric health settings avoid referring to either one. The prime objective of this work is to review publications showing the important correlation between anxiety and depression and various diseases. For the purpose of this study, diseases were divided into specialties, taking into account the bibliographical sources of the articles cited. Based on the information provided by this review, physicians -psychiatry specialists or not- should permanently consider anxiety and depression as important factors when dealing with patients in their daily consultation. Their therapeutic proposal after adopting this approach may lead to a radical change in results, noticeably improving patients' quality of life with the benefcial effects derived from the treatments implemented. This review was conducted with the contributions of scientifc psychosomatics and psychoneuroimmunoendocrinology (PNIE).

[Association between anxiety and depression in allergic illnesses]. / Asociación entre ansiedad y depresión en la enfermedad alérgica.

This study aims at determining whether there was an association among anxiety, depression and allergic illnesses. It suggests the proper therapeutic treatment. During a year, our research work team worked with a group of 82 female and male patients (from 13 to 76 years old) who suffered from various types of allergies. Two psychometric scales were used to carry out this study: Hamilton's scale for anxiety whereas Beck Depression Inventory (BDI-II) and Zung's for depression. The association and its percentage were analyzed in patients who reported typical symptoms during their first check-up. They were free of psychopharmacologic drugs and psychotherapies. The presence of anxiety and depression was interpreted as another factor in the development of allergic symptoms. The following results were achieved as regards: for anxiety, an association positive 95 %. For depression, the results showed that there was a positive tendency for the association with an allergic illness. The conclusions showed that there is a positive association between anxiety and allergies. As regards depression and allergic illness, there is only a positive tendency. These final results would raise awareness of how to deal with anxiety and depression in allergic patients, both psychopharmacologically and psychotherapeutically.

Asociación entre ansiedad y depresión en la enfermedad alérgica / [Association between anxiety and depression in allergic illnesses].

This study aims at determining whether there was an association among anxiety, depression and allergic illnesses. It suggests the proper therapeutic treatment. During a year, our research work team worked with a group of 82 female and male patients (from 13 to 76 years old) who suffered from various types of allergies. Two psychometric scales were used to carry out this study: Hamilton’s scale for anxiety whereas Beck Depression Inventory (BDI-II) and Zung’s for depression. The association and its percentage were analyzed in patients who reported typical symptoms during their first check-up. They were free of psychopharmacologic drugs and psychotherapies. The presence of anxiety and depression was interpreted as another factor in the development of allergic symptoms. The following results were achieved as regards: for anxiety, an association positive 95

. For depression, the results showed that there was a positive tendency for the association with an allergic illness. The conclusions showed that there is a positive association between anxiety and allergies. As regards depression and allergic illness, there is only a positive tendency. These final results would raise awareness of how to deal with anxiety and depression in allergic patients, both psychopharmacologically and psychotherapeutically.

Asociación entre ansiedad y depresión en la enfermedad alérgica. / [Association between anxiety and depression in allergic illnesses].

This study aims at determining whether there was an association among anxiety, depression and allergic illnesses. It suggests the proper therapeutic treatment. During a year, our research work team worked with a group of 82 female and male patients (from 13 to 76 years old) who suffered from various types of allergies. Two psychometric scales were used to carry out this study: Hamiltons scale for anxiety whereas Beck Depression Inventory (BDI-II) and Zungs for depression. The association and its percentage were analyzed in patients who reported typical symptoms during their first check-up. They were free of psychopharmacologic drugs and psychotherapies. The presence of anxiety and depression was interpreted as another factor in the development of allergic symptoms. The following results were achieved as regards: for anxiety, an association positive 95

. For depression, the results showed that there was a positive tendency for the association with an allergic illness. The conclusions showed that there is a positive association between anxiety and allergies. As regards depression and allergic illness, there is only a positive tendency. These final results would raise awareness of how to deal with anxiety and depression in allergic patients, both psychopharmacologically and psychotherapeutically.

Daño neurológico por preeclampsia-eclampsia: fisiopatología, prevención y tratamiento / Neurologic damage due to preeclampsia-eclampsia: physiolopathology, prevention and treatment

La preeclampsia-eclampsia se complica a menudo con alteraciones cerebrovasculares. Las manifestaciones clínicas son variables y el vasoespasmo es un problema habitual. Se presenta edema, trombosis, hemorragias, cambios fibrinoides transmurales, se pierde la autorregulación cerebral en las regiones dañadas y los trastornos iónicos transmembrana pueden ser la causa de convulsiones. El tratamiento preventivo de la preeclamsia-eclampsia consiste en el control de la presión arterial y del volumen intravascular, protección de las lesiones edoteliales e interrupción del embarazo. Las medidas específicas incluyen el empleo de glucocorticoides, clacioantagonistas, fenobarbital, flunitrazepan, clonazepan, difenilhidantoína y sulfato de magnesio intravenoso. El seguimiento de la enfermedad se hace mediante la evaluación frecuente del estado físico de la enferma, EEG, tomografía computada y resonancia magnética. Las emergencias quirúrgicas requieren de la presencia de un neurocirujano. En este artículo revisamos la fisiopatología, prevención y tratamiento del daño neurológico debido a la preeclampsia-eclampsia