Unveiling the challenges of UTUC biopsies and cytology: insights from a global real-world practice study.

PURPOSE: Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology. METHODS: To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC. RESULTS: We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade. CONCLUSION: Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).

The Use of Radiomic Tools in Renal Mass Characterization.

The incidence of renal mass detection has increased during recent decades, with an increased diagnosis of small renal masses, and a final benign diagnosis in some cases. To avoid unnecessary surgeries, there is an increasing interest in using radiomics tools to predict histological results, using radiological features. We performed a narrative review to evaluate the use of radiomics in renal mass characterization. Conventional images, such as computed tomography (CT) and magnetic resonance (MR), are the most common diagnostic tools in renal mass characterization. Distinguishing between benign and malignant tumors in small renal masses can be challenging using conventional methods. To improve subjective evaluation, the interest in using radiomics to obtain quantitative parameters from medical images has increased. Several studies have assessed this novel tool for renal mass characterization, comparing its ability to distinguish benign to malign tumors, the results in differentiating renal cell carcinoma subtypes, or the correlation with prognostic features, with other methods. In several studies, radiomic tools have shown a good accuracy in characterizing renal mass lesions. However, due to the heterogeneity in the radiomic model building, prospective and external validated studies are needed.

Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics.

Cell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria. This is due to dysregulation of the dynamics of interorganelle contacts between lipid droplets, mitochondria, peroxisomes and the endolysosomal system. This process accelerates the biogenesis of multivesicular bodies leading to higher EV production through the dynamic regulation of microtubule-based kinesin motors. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT.

P2X7 receptor inhibition ameliorates ubiquitin-proteasome system dysfunction associated with Alzheimer's disease.

BACKGROUND: Over recent years, increasing evidence suggests a causal relationship between neurofibrillary tangles (NFTs) formation, the main histopathological hallmark of tauopathies, including Alzheimer's disease (AD), and the ubiquitin-proteasome system (UPS) dysfunction detected in these patients. Nevertheless, the mechanisms underlying UPS failure and the factors involved remain poorly understood. Given that AD and tauopathies are associated with chronic neuroinflammation, here, we explore if ATP, one of the danger-associated molecules patterns (DAMPs) associated with neuroinflammation, impacts on AD-associated UPS dysfunction. METHODS: To evaluate if ATP may modulate the UPS via its selective P2X7 receptor, we combined in vitro and in vivo approaches using both pharmacological and genetic tools. We analyze postmortem samples from human AD patients and P301S mice, a mouse model that mimics pathology observed in AD patients, and those from the new transgenic mouse lines generated, such as P301S mice expressing the UPS reporter UbG76V-YFP or P301S deficient of P2X7R. RESULTS: We describe for the first time that extracellular ATP-induced activation of the purinergic P2X7 receptor (P2X7R) downregulates the transcription of ß5 and ß1 proteasomal catalytic subunits via the PI3K/Akt/GSK3/Nfr2 pathway, leading to their deficient assembly into the 20S core proteasomal complex, resulting in a reduced proteasomal chymotrypsin-like and postglutamyl-like activities. Using UPS-reported mice (UbGFP mice), we identified neurons and microglial cells as the most sensitive cell linages to a P2X7R-mediated UPS regulation. In vivo pharmacological or genetic P2X7R blockade reverted the proteasomal impairment developed by P301S mice, which mimics that were detected in AD patients. Finally, the generation of P301S;UbGFP mice allowed us to identify those hippocampal cells more sensitive to UPS impairment and demonstrate that the pharmacological or genetic blockade of P2X7R promotes their survival. CONCLUSIONS: Our work demonstrates the sustained and aberrant activation of P2X7R caused by Tau-induced neuroinflammation contributes to the UPS dysfunction and subsequent neuronal death associated with AD, especially in the hippocampus.

Optimización cardiopulmonar y de la calidad de vida en la fase de recuperación de la infección por COVID-19 a través de un programa de rehabilitación / Cardiopulmonary optimization and quality of life in the recovery phase of COVID-19 infection through a rehabilitation program

Introducción: la enfermedad por COVID-19 puede provocar una gran variedad de problemas de salud a largo plazo, como deterioro de la función pulmonar, reducción del rendimiento del ejercicio y disminución de la calidad de vida. Nuestro estudio tuvo como objetivo investigar la eficacia, viabilidad y seguridad de la rehabilitación pulmonar en pacientes con COVID-19 y comparar los resultados entre pacientes con un curso leve/moderado y grave/crítico de la enfermedad. Material y métodos: los pacientes en la fase posaguda de un curso leve a crítico de COVID-19 ingresados en un programa integral de rehabilitación pulmonar, se incluyeron en este estudio de cohorte prospectivo y observacional. Se evaluaron antes y después varias medidas de rendimiento del ejercicio, distancia de caminata de 6 minutos, función pulmonar (capacidad vital forzada (CVF)) y calidad de vida (encuesta de salud de formato corto de 36 preguntas (SF-36)). Se incluyeron 43 pacientes en el estudio (20 con COVID leve/moderado y 23 con COVID grave/crítico). Resultados: al ingreso los pacientes tenían una distancia de caminata reducida (leve: mediana 401 m, rango intercuartílico (IQR) 335-467 m; severo: 108 m, 84-132 m); una CVF deteriorada (leve: 72 %, severo: 35 %), y una puntuación baja de salud mental SF-36 (leve: 52 puntos, severo: 32 puntos. Los pacientes recibieron sesiones ajustadas a sus capacidades físicas y en ambos subgrupos mejoraron en la prueba de caminata de 6 minutos (leve/moderada: +54 m, severo/crítico: +117 m, ambos p <0.002), en CVF (leve/moderada: + 8.9 % , p = 0.004; severo/crítico: + 12.4 %, p <0.003) y en el componente mental SF-36 (leve / moderado: +6.8 puntos, p = 0.062; severo/crítico: +16.7 puntos, -p <0,005). Discusión y conclusiones: un programa de ejercicio bien estructurado resulta en un beneficio en las esferas de capacidad aeróbica, volúmenes pulmonares y calidad de vida; en tal sentido, se recomienda ampliar las muestras poblacionales para poder aplicar nuestro protocolo a otros centros encargados de la rehabilitación de pacientes con COVID-19.

Introduction: COVID-19 disease can cause a wide variety of long-term health problems, such as impaired lung function, reduced exercise performance, and decreased quality of life. Our study aimed to investigate the efficacy, feasibility, and safety of pulmonary rehabilitation in patients with COVID-19 and to compare the results between patients with a mild/moderate and severe/critical course of the disease. Materials and Methods: Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive pulmonary rehabilitation program were included in this prospective, observational cohort study. Various measures of exercise performance, 6-minute walk distance, lung function (forced vital capacity (FVC)), and quality of life (36-question short-form health survey (SF-36)) were assessed before and after. We include 43 patients in this study (20 with mild/moderate COVID and 23 with severe/critical COVID-19). Results: At admission, patients had reduced walking distance (mild: median 401 m, interquartile range (IQR) 335-467 m; severe: 108 m, 84-132 m), impaired FVC (mild: 72%, severe: 35%,) and a low SF-36 mental health score (mild: 52 points, severe: 32 points). This patients received sessions adjusted to their physical abilities, and in both subgroups the patients improved on the walking test of 6 min (mild/moderate: +54m, severe/critical: +117m, both p < 0.002), FVC (mild/moderate: +8.9%, p=0.004; severe/critical: +12.4%, p <0.003) and mental component SF-36 (mild / moderate: +6.8 points, p = 0.062; severe / critical: +16.7 points, -p <0.005). Discussion and Conclusions: A well-structured exercise program results in a benefit in the patients' spheres of aerobic capacity, lung volumes and quality of life, in this sense it is recommended to expand population samples to be able to apply our protocol to other centers in charge of the rehabilitation of COVID 19 patients.

Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study.

A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6-7 weeks to 13-14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.

Púrpura trombocitopénica posterior a vacunación contra COVID-19 / Thrombocytopenic purpura following COVID-19 vaccination

Resumen Introducción: la pandemia por COVID-19 ha generado un costo inexorable a los gobiernos y una mortalidad elevada en términos generales, el proceso de vacunación es la única estrategia efectiva en disminuir la morbimortalidad en general, sin embargo, dicha administración no está exenta de riesgos. Presentación del caso: presentamos el caso clínico de una paciente de género femenino de la séptima década, quien es vacunada contra el COVID-19 y tras cuatro días posteriores a la segunda dosis de vacuna anti COVID-19, comienza a presentar lesiones purpúricas que inician en miembros inferiores y ascienden progresivamente hasta el tronco asociado a artralgias intensas, dolor abdominal y náuseas. Es ingresada encontrándose recuentos plaquetarios menores a 10 mil plaquetas y se hace el diagnóstico de una púrpura trombocitopénica inmune asociada a la vacuna de AstraZeneca contra COVID-19, iniciándose terapia inmunosupresora específica. Discusión: el presente caso constituye la aparición de una púrpura trombocitopénica idiopática, patología poco frecuente con un amplio repertorio de eventos desencadenantes encontrándose las infecciones y reacciones vacunales dentro de los principales detonantes. La presente reacción vacunal es poco frecuente siendo lo anecdótico en específico la presencia de púrpura trombocitopénica inmune, hasta el momento son muy escasas las descripciones en la literatura sobre este tipo de reacción vacunal razón por la cual se decide recopilar y publicar el mismo mencionando la evidencia científica disponible más reciente sobre el tema. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2268).

Abstract Introduction: the COVID-19 pandemic has generated an inexorable cost for governments and an elevated mortality overall. Vaccination is the only effective strategy for decreasing overall morbidity and mortality; however, this vaccination is not without risks. Case presentation: we present the clinical case of a female patient in her seventies who was vaccinated against COVID-19 and four days after the second dose of the COVID-19 vaccine developed purpuric lesions beginning on her lower limbs and ascending progressively towards the trunk, associated with intense arthralgias, abdominal pain and nausea. She was admitted with platelet counts of less than 10,000, was diagnosed with immune thrombocytopenic purpura associated with the AstraZeneca COVID-19 vaccine, and was started on specific immunosuppressive therapy. Discussion: this is a case of idiopathic thrombocytopenic purpura, a rare pathology with a broad repertoire of triggering events, with infections and vaccine reactions among the main triggers. This vaccine reaction is rare, with the specific anecdotal point being the presence of immune thrombocytopenic purpura. To date, there are very few descriptions of this type of vaccine reaction in the literature, which is why we chose to compile and publish it, mentioning the most recent scientific evidence available on the subject. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2268).

Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection.

All healthy humans have high levels of natural anti-α-galactosyl (α-Gal) antibodies (elicited by yet uncharacterized glycotopes), which may play important roles in immunoglycomics: (a) potential protection against certain parasitic and viral zoonotic infections; (b) targeting of α-Gal-engineered cancer cells; (c) aiding in tissue repair; and (d) serving as adjuvants in α-Gal-based vaccines. Patients with certain protozoan infections have specific anti-α-Gal antibodies, elicited against parasite-derived α-Gal-bearing glycotopes. These glycotopes, however, remain elusive except for the well-characterized glycotope Galα1,3Galß1,4GlcNAcα, expressed by Trypanosoma cruzi. The discovery of new parasitic glycotopes is greatly hindered by the enormous structural diversity of cell-surface glycans and the technical challenges of classical immunoglycomics, a top-down approach from cultivated parasites to isolated glycans. Here, we demonstrate that reversed immunoglycomics, a bottom-up approach, can identify parasite species-specific α-Gal-bearing glycotopes by probing synthetic oligosaccharides on neoglycoproteins. This method was tested here seeking to identify as-yet unknown glycotopes specific for Leishmania major, the causative agent of Old-World cutaneous leishmaniasis (OWCL). Neoglycoproteins decorated with synthetic α-Gal-containing oligosaccharides derived from L. major glycoinositolphospholipids served as antigens in a chemiluminescent enzyme-linked immunosorbent assay using sera from OWCL patients and noninfected individuals. Receiver-operating characteristic analysis identified Galpα1,3Galfß and Galpα1,3Galfß1,3Manpα glycotopes as diagnostic biomarkers for L. major-caused OWCL, which can distinguish with 100% specificity from heterologous diseases and L. tropica-caused OWCL. These glycotopes could prove useful in the development of rapid α-Gal-based diagnostics and vaccines for OWCL. Furthermore, this method could help unravel cryptic α-Gal-glycotopes of other protozoan parasites and enterobacteria that elicit the natural human anti-α-Gal antibodies.

[Circumferential calcifications in cromophobe renal cell carcinoma: Description of a clinical case and review of the literature.] / Calcificaciones anormales en tumor renal de células cromófobas: descripción de un caso clínico y revisión de la literatura.

We present a clinical case of an asymptomatic 61-year-old man was found to have a left kidney mass. Ultrasound and CT showed a 6 x 5 cms mass with calcifications. Histologic examination of the radical nephrectomy specimen revealed a chromophobe renal cell carcinoma. The unique feature of this case is the type of calcifications present in a tumor of this category. To our knowledge, were port the first case of chromophobe renal cell carcinoma with peripheral linear calcifications. A literature review onchromophobe renal cell carcinoma with calcifications is performed.

Presentamos el caso de un varón de 61 años diagnosticado de forma incidental de una tumoración renal izquierda. Las imágenes radiológicas obtenidas mediante ecografía y TAC muestran una masa de 6 x 5 cms con calcificaciones circunferenciales y periféricas. El estudio anatomopatológico de la pieza de nefrectomía radical evidencia un carcinoma renal de células cromófobas. La peculiaridad de este caso reside en el tipo de calcificaciones presentes en un tumor de este tipo no habiéndose descrito previamente, en nuestro conocimiento, calcificaciones lineales periféricas como éstas, en carcinoma renal de células cromófobas. Realizamos una revisión de la literatura acerca de las calcificaciones en carcinoma renal de células cromófobas.

[Usefulness of laser Holmium Lumenis Pulse 120 H® in the treatment of renal lithiasis through RIRS: Preliminary experience.] / Utilidad del láser Holmium Lumenis Pulse 120 H® en el tratamiento de las litiasis renales mediante RIRS: experiencia preliminar.

INTRODUCTION: The Holmium laser is the most used energy source in flexible ureterrenoscopy (URSf). The Lumenis Pulse 120H® laser has a higher system energy, a higher energy per pulse and a higher repetition frequency in relation to other types of lasers, which offers advantages in the treatment of lithiasis. OBJECTIVE: To analyze the results that we have obtained with the use of the Lumenis Pulse120H® laser in patients treated by intrarenal retrograde surgery (RIRS). As secondary objectives there are: the study of the demographic variables of the patients, the characteristics of the stones and the complications associated with the procedure. MATERIAL AND METHODS: An observational, retrospective study of the first 26 patients treated by RIRS and Lumenis Pulse 120H® laser has been performed in our Service between August 2018 and February 2019. The size of the lithiasis was measured on the simple radiography and the CT, in addition, the volume of the lithiasis was calculated. For the realization of RIRS, 8.5Fr digital flexible ureterorenoscope (Olympus®) and the Holmium Lumenis 120H® laser with 200 micron laser fibers from Lumenis® were used. Statistical analysis was performed with the SPSSv21 system. RESULTS: A total of 26 patients with renal lithiasis have been analyzed. The median age was 55.15 years (40.67-67.05). 57.7% of the patients had prior surgical treatment of lithiasis. Thirteen patients presented the litiasis in the renal pelvis, ten in the Upper Calicial Group (GCS), fifteen in the Middle Calicial Group (GCM) and eighteen in the Lower Calicial Group (GCI). The median of the lithiasic volume was 1826.41 mm3. Our overall success rate was 80.8% (100% success in lithiasis less than 2 cm and 85.7% in lithiasis between 2-3 cm). Five patients presented complications, of which 4 were ClavienII and 1 Clavien IIIb. No significant results were found between the lithiasic size and the presence of complications (p = 0.128). CONCLUSIONS: The use of the Lumenis Pulse 120H®laser is an useful tool for the treatment of kidney stones by RIRS, due to his efficiency in the fragmentation and dusting, taking into account that very large lithiasic masses require, in a high percentage of cases, more than one treatment session.

INTRODUCCIÓN: El láser de Holmium es la fuente de energía más utilizada en la ureterrenoscopia flexible (URSf). El láser Lumenis Pulse 120H® tiene una mayor energía del sistema, una mayor energía por pulso y una frecuencia de repetición más elevada en relación a otros tipos de láser, lo que ofrece ventajas en el tratamiento de las litiasis. OBJETIVO: Analizar los resultados que hemos obtenido con la utilización del láser Lumenis Pulse120H® en pacientes tratados mediante RIRS. Como objetivos secundarios se encuentra el estudio de las variables demográficas de los pacientes, de las características del cálculo y de las complicaciones asociadas al procedimiento.MATERIAL Y MÉTODOS: Se ha realizado un estudio observacional, retrospectivo, de los primeros 26 pacientes tratados mediante RIRS y láser Lumenis Pulse 120H® en nuestro Servicio entre agosto 2018 y febrero 2019. El tamaño de la litiasis fue medido en la radiografía simple y el TC (tomografía computarizada) y, aparte, se calculó el volumen de la litiasis. El análisis estadístico se realizó con el sistema SPSSv21. RESULTADOS: Se han analizado un total de 26 pacientes con litiasis renales. Un 57,7% de los pacientes tenían tratamiento quirúrgico previo de litiasis. Presentaban litiasis en la pelvis renal 13 pacientes, en Grupo Calicial Superior (GCS) 10, en Grupo Calicial Medio (GCM) 15 y en Grupo Calicial Inferior (GCI) 18. La mediana del volumen litiásico fue de 1.826,41 mm3. Nuestra tasa global de éxito fue del 80,8% (100% éxito en litiasis menores de 2 cm y 85,7% en litiasis entre 2-3cm). Cinco pacientes presentaron complicaciones, de ellos 4 fueron Clavien II y 1 Clavien IIIb. No se hallaron resultados significativos al relacionar el tamaño litiásico con las complicaciones (p=0,128). CONCLUSIONES: La utilización del láser Lumenis Pulse120H® es una herramienta útil y segura para el tratamiento de los cálculos renales mediante RIRS, debido a la eficacia en la fragmentación y pulverización de los mismos, teniendo en cuenta que las masas litiásicas muy grandes requieren, en un alto porcentaje de casos, más de una sesión de tratamiento.

Trypanosoma brucei colonizes the tsetse gut via an immature peritrophic matrix in the proventriculus.

The peritrophic matrix of blood-feeding insects is a chitinous structure that forms a protective barrier against oral pathogens and abrasive particles1. Tsetse flies transmit Trypanosoma brucei, which is the parasite that causes human sleeping sickness and is also partially responsible for animal trypanosomiasis in Sub-Saharan Africa. For this parasite to establish an infection in flies, it must first colonize the area between the peritrophic matrix and gut epithelium called the ectoperitrophic space. Although unproven, it is generally accepted that trypanosomes reach the ectoperitrophic space by penetrating the peritrophic matrix in the anterior midgut2-4. Here, we revisited this event using fluorescence- and electron-microscopy methodologies. We show that trypanosomes penetrate the ectoperitrophic space in which the newly made peritrophic matrix is synthesized by the proventriculus. Our model describes how these proventriculus-colonizing parasites can either migrate to the ectoperitrophic space or become trapped within peritrophic matrix layers to form cyst-like bodies that are passively pushed along the gut as the matrix gets remodelled. Furthermore, early proventricular colonization seems to be promoted by factors in trypanosome-infected blood that cause higher salivary gland infections and potentially increase parasite transmission.

Experimental Assessment of New Generation of Ureteral Stents: Biodegradable and Antireflux Properties.

Objective: The aim was to assess a new biodegradable and antireflux intraureteral stent (BraidStent®) design in a swine model after ureteral laparoscopic operation. Materials and Methods: A total of 24 female pigs underwent initial endoscopic, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Afterward, unilateral ureteropelvic junction obstruction was performed by laparoscopic approach. Six weeks later, the animals underwent laparoscopic Anderson-Hynes pyeloplasty, and were randomly assigned to Group-I, in which a double-pigtail ureteral stent was inserted for 6 weeks, or Group-II, in which a BraidStent®, a biodegradable intraureteral stent design, was placed. Follow-up assessments were performed at 3 and 6 weeks and 5 months. Results: In terms of therapeutic success, complete resolution was observed in 91.6% of Group-I animals and 88.8% in Group-II. No evidence of vesicoureteral reflux (VUR) was observed in Group-II animals and statistical significance in VUR and ureteral orifice damage were observed between groups. BraidStent® degradation occurred in a controlled manner between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6% and 83.3% in Group-II at 3 and 6 weeks of follow-up, respectively. In Group-II, the positive bacteriuria rate was 41.6% and the migration rate 25%. Pathological assessment showed a significant improvement in ureteral healing in Group-II vs Group-I. Conclusions: The results of this comparative study in a porcine model indicate that the intraureteral BraidStent performed similarly to conventional ureteral stents. It avoids complete ureteral length intubation, the adverse effects associated with conventional ureteral stents, and maintains a high level of distal ureteral peristalsis. Moreover, the BraidStent® exhibited a predictable and controlled degradation rate and did not cause any obstructive fragments. However, further studies are needed to improve the anchoring system and reduce the risk of bacterial colonization.

ATP Measurement in Cerebrospinal Fluid Using a Microplate Reader.

Imbalance in extracellular ATP levels in brain tissue has been suggested as a triggering factor for several neurological disorders. Here, we describe the most sensitive and reliable technique for monitoring the ATP levels in mice cerebrospinal samples collected by cisterna magna puncture technique and quantified using a microplate reader.

[Laparoscopic renal cyst excision: Large simple renal cyst treatment with renal cell carcinoma cells in its wall. Histogenetic considerations and bibliographic review.] / Quistectomía laparoscópica: tratamiento de un quiste simple de gran tamaño con carcinoma de células renales en su pared. Consideraciones histogenéticas y revisión de la literatura.

OBJECTIVE: The incidence of simple renal cysts is very high, especially in elderly people. However, malignant transformation of a simple renal cyst is exceptional. Likewise, the treatment to be carried out, in these rare cases, is controversial, with respect to opting for radical renal surgery. METHODS: We present the case of a patient with a solid nodule in a large cyst. Complete removal of the cyst was performed by transperitoneal laparoscopic technique. The histopathological study of the surgical piece revealed the existence of a cyst with clear renal cell carcinoma with nucleolar grade 2. The clinical evolution has been satisfactory, performing a minimally invasive surgery (laparoscopic cyst excision). DISCUSSION: Although it is considered that surgical treatment of choice is radical surgery in these cases, we believe that nephron sparing surgery may represent a therapeutic option, taking into account the young age of our patient. A histogenetic hypothesis is discussed to explain the appearance of a clear cell tumor in a simple renal cyst. CONCLUSION: The development of a renal cell carcinoma in simple renal cysts is a very infrequent pathology.Laparoscopic total cystectomy is a minimally invasive therapeutic option for the treatment of renal cell carcinoma originating in a simple renal cyst, although it is of an important size. We establish the hypothesis of migration of the cells of the renal collecting tubes into the cyst wall to explain the malignant transformation of the renal simple cyst.

OBJETIVO: La incidencia de los quistes renales simples es muy frecuente, sobre todo en personas de edad avanzada. Sin embargo, la transformación maligna de un quiste renal simple es excepcional. Así mismo, el tratamiento a realizar, en estos casos raros, es un motivo de controversia, con respecto a optar por una cirugía radical renal.MÉTODOS: Presentamos el caso de un paciente con nódulo sólido en un quiste de gran tamaño. Se realiza extirpación completa del quiste mediante técnica de laparoscopia vía transperitoneal. El estudio histopatológico de la pieza quirúrgica revela la existencia un quiste con un carcinoma renal de células claras con grado nucleolar 2. La evolución clínica ha sido satisfactoria, realizando una cirugía de mínima invasión (quistectomía laparoscópica). DISCUSIÓN: Aunque se considera que el tratamiento quirúrgico es la cirugía radical en estos casos, nosotros consideramos que la cirugía preservadora de nefronas puede representar una opción terapéutica, teniendo en cuenta la edad de nuestro paciente. Se comenta una hipótesis histogenética para explicar la aparición de un tumor de células claras en un quiste renal simple. CONCLUSIONES: El desarrollo de un carcinoma de células renales en quistes renales simples es una patología muy infrecuente. La quistectomía total laparoscópica es una opción terapéutica mínimamente invasiva, para el tratamiento del carcinoma de células renales originado en un quiste renal simple, aunque éste sea de un tamaño importante. Proponemos la hipótesis de una migración de las células de los túbulos renales en la pared del quiste para explicar la transformación maligna del quiste simple renal.

Antireflux ureteral stent proof of concept assessment after minimally invasive treatment of obstructive uropathy in animal model.

OBJECTIVES: To assess the efficacy of a new anti-reflux intraureteral stent design in a swine model after minimally invasive treatment of ureteral stricture to reduce ureteral stent morbidity, previous to manufacture this design in a biodegradable fashion. METHODS: Twenty-eight female pigs were included. The study began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment. Afterwards, obstructive uropathy model in right ureter was created. Obstruction was confirmed 6 weeks later and animals were randomly distributed into 2 groups. Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the aforementioned diagnostic methods and pathological study. RESULTS: None of the study animals showed any vesicoureteral reflux signs or ureteral orifice injury. There were no urinomas or ureteric fistulas. The dislodgement rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral peristalsis below the stent, and 100% at the final follow-up. After pathological assessment, no differences were shown at UPJ and healing in the incised area was correct in both groups. CONCLUSIONS: The new stent design avoids vesicoureteral reflux and bladder trigone irritation, consequently might reduce morbidity associated with double pigtail ureteral stents. This study also shows that it is only necessary temporary scaffolding the incised ureteral segment and not the entire length of the ureter after minimally invasive surgery. It is also necessary to manufacture this design in a biodegradable material, thus avoiding its removal.

Haploinsufficient TNAP Mice Display Decreased Extracellular ATP Levels and Expression of Pannexin-1 Channels.

Hypophosphatasia (HPP) is a rare heritable metabolic bone disease caused by hypomorphic mutations in the ALPL (in human) or Akp2 (in mouse) gene, encoding the tissue-nonspecific alkaline phosphatase (TNAP) enzyme. In addition to skeletal and dental malformations, severe forms of HPP are also characterized by the presence of spontaneous seizures. Initially, these seizures were attributed to an impairment of GABAergic neurotransmission caused by altered vitamin B6 metabolism. However, recent work by our group using knockout mice null for TNAP (TNAP-/-), a well-described model of infantile HPP, has revealed a deregulation of purinergic signaling contributing to the seizure phenotype. In the present study, we report that adult heterozygous (TNAP+/-) transgenic mice with decreased TNAP activity in the brain are more susceptible to adenosine 5'-triphosphate (ATP)-induced seizures. Interestingly, when we analyzed the extracellular levels of ATP in the cerebrospinal fluid, we found that TNAP+/- mice present lower levels than control mice. To elucidate the underlying mechanism, we evaluated the expression levels of other ectonucleotidases, as well as different proteins involved in ATP release, such as pannexin, connexins, and vesicular nucleotide transporter. Among these, Pannexin-1 (Panx1) was the only one showing diminished levels in the brains of TNAP+/- mice. Altogether, these findings suggest that a physiological regulation of extracellular ATP levels and Panx1 changes may compensate for the reduced TNAP activity in this model of HPP.

[Training program in endourological surgery. Future perspectives.] / Programa formativo en cirugía endoscópica. Perspectivas de futuro.

Current training in urological endoscopy lacks a specific training program. However, there is a clear need for a specific and uniform program, which will ensure the training, regardless of the unit where it is carried out. So, the goal is to first evaluate the current model and then bring improvements for update. The hospital training accreditation programme are only the adjustment of the official program of the urology specialty to the specific circumstances of each center, which causes variability in training of residents. After reviewing 19 training programs belonging to 12 Spanish regions. The current outlook shows that scarcely 10% of hospitals quantify the number of procedures/ year, although the Spanish program emphasizes that the achievement of the residents should be quantified. Urology residents, sense their training as inadequate and therefore their level of satisfaction is moderate. The three main problems detected by residents as an obstacle on their training are: the lack of supervision, tutors completing their own learning. Finally, the lack of quantification in surgical activities is described as a threat. This has no easy solution, since the learning curve of the most common techniques in endourology is not correctly established. Regarding aspects that can improve the current model, they highlight the need to design a specific program. The need to customize the training, the ineludible accreditation of tutors and obviously dignify the tutor's teaching activity. Another basic aspect is the inclusion of new technologies as training tools, e-learning. As well as the implementation of an adequate competency assessment plan and the possibility of relying on simulation systems. Finally, they highlight the need to attend monographic meetings and external clinic rotations to promote critical training.

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1.

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders.

Neuronal P2X7 Receptor: Involvement in Neuronal Physiology and Pathology.

The proposed presence of P2X7 receptor (P2X7R) in neurons has been the source of some contention. Initial studies suggested an absence of P2X7R mRNA in neurons, and the apparent nonspecificity of the antibodies used to identify P2X7R raised further doubts. However, subsequent studies using new pharmacological and biomolecular tools provided conclusive evidence supporting the existence of functional P2X7Rs in neurons. The P2X7 receptor has since been shown to play a leading role in multiple aspects of neuronal physiology, including axonal elongation and branching and neurotransmitter release. P2X7R has also been implicated in neuronal pathologies, in which it may influence neuronal survival. Together, this body of research suggests that P2X7R may constitute an important therapeutic target for a variety of neurological disorders.

Identification of potential protein partners that bind to the variant surface glycoprotein in Trypanosoma equiperdum.

Trypanosoma equiperdum possesses a dense coat of a variant surface glycoprotein (VSG) that is used to evade the host immune response by a process known as antigenic variation. Soluble and membrane forms of the predominant VSG from the Venezuelan T. equiperdum TeAp-N/D1 strain (sVSG and mVSG, respectively) were purified to homogeneity; and antibodies against sVSG and mVSG were raised, isolated, and employed to produce anti-idiotypic antibodies that structurally mimic the VSG surface. Prospective VSG-binding partners were initially detected by far-Western blots, and then by immunoblots using the generated anti-idiotypic antibodies. Polypeptides of ~80 and 55 kDa were isolated when anti-idiotypic antibodies-Sepharose affinity matrixes were used as baits. Mass spectrometry sequencing yielded hits with various proteins from Trypanosoma brucei such as heat-shock protein 70, tryparedoxin peroxidase, VSG variants, expression site associated gene product 6, and two hypothetical proteins. In addition, a possible interaction with a protein homologous to the glutamic acid/alanine-rich protein from Trypanosoma congolense was also found. These results indicate that the corresponding orthologous gene products are candidates for VSG-interacting proteins in T. equiperdum.