Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression.

BACKGROUND: DNA replication progression can be affected by the presence of physical barriers like the RNA polymerases, leading to replication stress and DNA damage. Nonetheless, we do not know how transcription influences overall DNA replication progression. RESULTS: To characterize sites where DNA replication forks stall and pause, we establish a genome-wide approach to identify them. This approach uses multiple timepoints during S-phase to identify replication fork/stalling hotspots as replication progresses through the genome. These sites are typically associated with increased DNA damage, overlapped with fragile sites and with breakpoints of rearrangements identified in cancers but do not overlap with replication origins. Overlaying these sites with a genome-wide analysis of RNA polymerase II transcription, we find that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. Indeed, we find that slowing down transcription elongation slows down directly replication progression through genes. This indicates that transcription and replication can coexist over the same regions. Importantly, rearrangements found in cancers overlapping transcription-replication collision sites are detected in non-transformed cells and increase following treatment with ATM and ATR inhibitors. At the same time, we find instances where transcription activity favors replication progression because it reduces histone density. CONCLUSIONS: Altogether, our findings highlight how transcription and replication overlap during S-phase, with both positive and negative consequences for replication fork progression and genome stability by the coexistence of these two processes.

Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer.

PURPOSE: Detection of circulating tumor DNA (ctDNA) in patients who have completed treatment for early-stage breast cancer is associated with a high risk of relapse, yet the optimal assay for ctDNA detection is unknown. EXPERIMENTAL DESIGN: The cTRAK-TN clinical trial prospectively used tumor-informed digital PCR (dPCR) assays for ctDNA molecular residual disease (MRD) detection in early-stage triple-negative breast cancer. We compared tumor-informed dPCR assays with tumor-informed personalized multimutation sequencing assays in 141 patients from cTRAK-TN. RESULTS: MRD was first detected by personalized sequencing in 47.9% of patients, 0% first detected by dPCR, and 52.1% with both assays simultaneously (P < 0.001; Fisher exact test). The median lead time from ctDNA detection to relapse was 6.1 months with personalized sequencing and 3.9 months with dPCR (P = 0.004, mixed-effects Cox model). Detection of MRD at the first time point was associated with a shorter time to relapse compared with detection at subsequent time points (median lead time 4.2 vs. 7.1 months; P = 0.02). CONCLUSIONS: Personalized multimutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.

Human Health Risk Assessment of Arsenic and Other Metals in Herbal Products Containing St. John's Wort in the Metropolitan Area of Mexico City.

Consumption of St. John's wort plant is high worldwide due to its various medicinal properties. However, herbal products containing St. John's wort may be contaminated with toxic metals. This is often related to contamination of both water and the atmosphere, lack of proper cultivation methods, and inadequate plant storage conditions, as well as a lack of stricter sanitary supervision. A safety assessment of copper (Cu), lead (Pb), cadmium (Cd) and arsenic (As) content in 23 products containing St. John's wort (pharmaceutical herbal products, food supplements and traditional herbal remedies) sold in the metropolitan area of Mexico City was conducted. The analysis of metals was determined using a graphite-furnace atomic absorption spectrometer. All herbal products were contaminated with Cu, Pb, Cd and As. The pharmaceutical herbal items showed less contamination by metals. The daily human intake (DHI) values for Pb exceeded the permissible limits in the group of traditional herbal remedies. The DHI calculation for As exceeded the permitted intake values for all items in the group of traditional herbal remedies, five food supplements and one pharmaceutical herbal product. The hazard indicator calculation of the non-carcinogenic cumulative risk values for traditional herbal remedies was greater than 1, suggesting a risk to human health.

TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells.

Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts.

Adrenal incidentalomas, cortisol secretion and cancer: is there a real crosstalk?

Background: Cortisol has immunomodulatory effects that increase the risk and evolution of several diseases. Cancer is characterized by a proinflammatory state in which cells exert impaired function and proliferation. The relation between cortisol secretion and increased risk of malignant neoplasm, or their behavior, has not been fully elucidated. Aim: To determine the relation between cortisol secretion and the prevalence and clinical outcome of malignant neoplasms in patients with adrenal incidentalomas (AIs). Methods: Multicenter retrospective study that included 935 patients with AIs. Cortisol secretion was defined by a cortisol post-dexamethasone suppression test > 1.8 µg/dL, and nonfunctioning AIs (NFAIs) as a value ≤ 1.8 µg/dL. Results: Cortisol secretion was evident in 30.8% of the patients and cancer in 23.6% (especially breast, colorectal, prostate and thyroid cancer). No differences in the cancer prevalence were found between patients with cortisol secretion and NFAIs (63.6% vs. 63.4%, p=0.10). After adjusting by age, cortisol secretion was not associated with the presence of cancer (OR 1.29, CI 0.93-1.78). However, cortisol secretion was significantly associated with stage IV of cancer at diagnosis (OR 2.68, CI 1.19- 6.00) and mortality (OR 3.2, CI 1.28- 7.97). Patients with NFAI and breast cancer required treatment with chemo- and radio-therapy more frequently that patients with cortisol secreting AI (90% vs 10% and 92.9% vs 7.1% respectively, p<0.05), similarly patients with prostate cancer required radiotherapy more frequently (90.9% vs 9.1%, p=0.05); also, patients with colorectal cancer and NFAI, tended to require chemotherapy more frequently(76.5% vs 23.5%, p=0.06). Conclusion: Cortisol secretion does not increase the risk of malignant neoplasm, but it affects its clinical course, treatment requirements and mortality, leading to a worst prognosis and higher mortality when compared with patients with NFAIs.

Análisis no-lineal de la onda gamma del electroencefalograma en una prueba de atención e inhibición / Non-linear analysis of the electroencephalogram gamma wave in an attention and inhibition test

Introducción: Durante las últimas décadas se ha estudiado la señal del electroencefalograma desde una perspectiva de matemática no-lineal. Esto permite entender la actividad eléctrica cerebral como un sistema dinámico complejo. Objetivo: Evaluar los exponentes de Hurst y sus correlaciones en la onda gamma durante una tarea de atención alternante e inhibición de la interferencia en estudiantes universitarios. Métodos: La muestra se constituyó por 14 alumnos de educación física. Para evaluar la actividad eléctrica cerebral se utilizó el dispositivo cerebro-interfaz Emotiv Epoc®. La atención alternante se estimó con el test de símbolos y dígitos, mientras que para la inhibición de la interferencia se empleó la prueba de palabras y colores de Stroop. Resultados: En la prueba de atención alternante, cuatro individuos revelaron mayor propensión al caos en el hemisferio derecho, uno presentó más tendencia en el hemisferio izquierdo y dos no tuvieron una predisposición definida. Por otra parte, durante la prueba de inhibición de la interferencia, cinco presentaron variaciones de las medias de Hurst entre las tres láminas del efecto Stroop, sobre todo de la región temporal. Los exponentes Hurst en ambas pruebas fueron inferiores a 0,5. Conclusiones: Durante la prueba de atención se observó un mayor caos de la actividad eléctrica cerebral, sin existir correlaciones entre las regiones estudiadas. Durante la prueba de inhibición las modificaciones de los exponentes de Hurst no presentaron patrones definidos hacia el orden o caos(AU)

Introduction: During the last decades the electroencephalogram signal has been studied from a nonlinear mathematical perspective. This allows understanding brain electrical activity as a complex dynamical system. Objective: To evaluate Hurst exponents and their correlations in the gamma wave during an alternating attention and interference inhibition task in university students. Methods: The sample consisted of 14 physical education students. The Emotiv Epoc® brain-interface device was used to evaluate brain electrical activity. Alternating attention was estimated with the symbols and digits test, while the Stroop words and colors test was used for interference inhibition. Results: In the alternating attention test, four individuals revealed a greater propensity to chaos in the right hemisphere, one showed a greater tendency in the left hemisphere and two had no defined predisposition. On the other hand, during interference inhibition, variations of Hurst average values between the three Stroop effect slices were determined in five subjects, especially in the temporal region. Hurst exponents in both tests were found to be less than 0.5. Conclusions: During the attention test, a greater chaos of brain electrical activity is observed, with no correlations between the regions studied. During the inhibition test, the modifications of the Hurst exponents do not present defined patterns towards order or chaos(AU)

Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer.

BACKGROUND: Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions. METHODS: This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms. RESULTS: Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity. CONCLUSIONS: Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.

Impacto de la pandemia por SARS-CoV-2 en la formación de los alumnos de la Carrera de Médico Especialista en Reumatología / Impact of the SARS-CoV-2 pandemic on a group of Rheumatology trainees of Argentina

Introducción: en 2020, la rápida evolución de la pandemia por SARS-CoV-2 desencadenó una emergencia sanitaria que generó una importante reorganización del sistema de salud, lo que llevó a la discontinuación y posterior adecuación de los sistemas de formación. El objetivo de este estudio fue describir el impacto de la pandemia en un grupo de reumatólogos en formación en la Ciudad Autónoma de Buenos Aires. Materiales y métodos: se envió una encuesta online por correo electrónico a los alumnos de la Carrera de Especialista en Reumatología de la Sociedad Argentina de Reumatología y de la Universidad de Buenos Aires. Incluyó 24 preguntas relacionadas con el impacto de la pandemia en diferentes aspectos de la formación y las nuevas estrategias educativas implementadas. Resultados: de 114 alumnos contactados, respondieron 79 (69,3%). Aproximadamente el 90% indicó que su formación se afectó. Un 46% consideró que la práctica médica y la actividad académica se comprometieron por igual y el 45% solo la práctica médica. Un 50% realizó tareas no relacionadas con su formación. El 57% suspendió temporalmente la asistencia a su centro. También informaron una reducción del 55% (DE 18,6) de las actividades relacionadas con la consulta. Conclusiones: la pandemia por SARS-CoV-2 afectó a los estudiantes de Reumatología al limitar sus actividades prácticas y académicas, y por deber realizar tareas ajenas a su formación en más de la mitad de los casos.

Introduction: in 2020, the rapid evolution of the SARS-CoV-2 pandemic triggered a health emergency, generating an important heath system reorganization which led to the discontinuation and subsequent adaptation of training systems. The objective was to describe the pandemic impact on a group of rheumatology trainees in Buenos Aires, Argentina. Materials and methods: an online survey was sent through e-mail to rheumatology specialist course trainees of Argentine Society of Rheumatology and University of Buenos Aires. It included 24 close-ended questions about the pandemic impact on different aspects of rheumatology training and the new implemented educational response strategies. Results: from 114 trainees contacted, 79 (69.3%) responded. Approximately 90% indicated that their rheumatology training was affected. Forty-six percent thought that medical practice and academic activity were equally affected and 45% that only medical practice was compromised. About 50% reported that they had to perform tasks unrelated to their training. Fifty-seven percent discontinued temporarily the training site attendance. Participants reported a mean reduction of 55% (SD 18.6) of activities related to patient care. Conclusions: the SARS-CoV-2 pandemic affected rheumatology trainees, by limiting their practical and academics activities, and having to perform tasks unrelated to their training in more than a half.

Nefroureterectomía radical lumboscópica con rodete vesical endoscópico, en cáncer urotelial de tracto urinario superior / Lumboscopic radical nephroureterectomy with endoscopic bladder cuff excision in an upper urinary tract urothelial tumor

Los carcinomas uroteliales son el 4to tumor más común. Pueden ubicarse en el tracto urinario inferior (vejiga y uretra) o en el tracto urinario superior (cavidades renales, pelvis renal y uréter). Presentamos una serie de 3 casos, con cuadro de hematuria macroscópica, documentando tumores uroteliales, realizándose en estos casos un abordaje lumboscópico de riñón y una resección endoscópica del rodete vesical. Se realiza nefroureterectomía lumboscópica con resección de rodete vesical endoscópica transuretral. Los 3 pacientes fueron egresados al segundo día posquirúrgico sin complicaciones y en los tres casos el rodete vesical sin evidencia de actividad tumoral, y actualmente en vigilancia con excelente resultados oncológicos. La nefroureterectomía lumboscópica con resección endoscópica del rodete vesical es una técnica reproducible en manos experimentadas, con iguales resultados oncológicos que el abordaje abierto.

Urothelial carcinomas are the 4th most common tumor. They can be located in the lower urinary tract (bladder and urethra) or in the upper urinary tract (renal cavities, renal pelvis, and ureter). We present a series of 3 cases, with a picture of macroscopic hematuria, documenting urothelial tumors, performing in these cases a lumboscopic approach to the kidney and an endoscopic resection of the bladder rim. Lumboscopic nephroureterectomy was performed with transurethral endoscopic bladder rump resection. The 3 patients were discharged on the second postoperative day without complications and in the three cases the bladder rim without evidence of tumor activity, and currently under surveillance with excellent oncological results. Lumboscopic nephroureterectomy with endoscopic resection of the bladder rim is a reproducible technique in experienced hands, with the same oncological results as the open approach.

The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma.

The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.

Experiencia en Nefrectomía Parcial y Enucleación de Tumor Renal Laparoscópico "Zero Isquemia", en Cochabamba, Bolivia

Resumen El manejo quirúrgico de los tumores renales pequeños es la cirugía conservadora de nefronas, este tipo de manejo se reservaba para pacientes seleccionados, con riñón solitario, enfermedad renal crónica o tumores bilaterales. La evidencia sugiere que la nefrectomía parcial laparoscópica es equivalente en términos de resultados oncológicos y superior en las mediciones de calidad de vida comparada al abordaje abierto. Objetivos: determinar los resultados oncológicos en cuanto a bordes libres del tumor y complicaciones quirúrgicas en pacientes sometidos a nefrectomía parcial y enucleación de tumor renal laparoscópico "Zero isquemia". Metodología: estudio retrospectivo, observacional, y comparativo, universo pacientes de la Clínica privada Los Ángeles y de la Caja Nacional de Salud, Hospital Obrero Nº2, Cochabamba, Bolivia, que fueron sometidos a nefrectomía parcial laparoscópica, se agruparon en dos grupos: Grupo I: nefrectomía parcial y Grupo II: enucleación, se analizaron: tamaño y localización del tumor, RENAL score, tiempo quirúrgico, sangrado, días de estancia, complicaciones y reporte histopatológico. Se utilizó el SPSS versión 20 (IBM, Chicago, IL). Resultados: se evaluaron 17 pacientes, 3 fueron excluidos por terminar en cirugía radical, 6 parciales (Grupo I) y 8 enucleaciones (Grupo II). Edad promedio de 45,7 (± 8,6) vs 51,2 (± 6,3) años. Tamaño del tumor 7,8 (2,5-10) vs 3,2 (1-5,7) cm, El RENAL score en global de todos los pacientes fue de baja a moderada, se realizó un análisis por separado, en el grupo I, la distribución fue complejidad baja n=2 (33,3%), moderada n= 1 (16,7%) y alta n= 3 (50%), en el grupo II, baja complejidad n=5 (62,5%), moderada n=2 (25%), alta complejidad n= 1 (12,5%). Hubo diferencias a favor del grupo II (enucleación) en cuanto a tiempo quirúrgico y sangrado transoperatorio, presentando solo 1 caso con fuga urinaria, resuelta con colocación de catéter JJ, se evidencia iguales tiempos de estancia intrahospitalaria, en cuanto a los bordes quirúrgicos, se tuvo 2 (14,2%) casos con bordes positivos 1 para cada abordaje, los cuales se mantienen en vigilancia estrecha. Conclusiones: el abordaje laparoscópico es una opción equiparable al abierto, se obtuvieron iguales resultados en cuanto a control oncológico en relación a bordes libres y con menos complicaciones, aunque se requiere experiencia en cirugía laparoscópica y aumentar el seguimiento en tiempo y mayor número de casos.

Abstract Surgical management of small renal tumors involves nephron-sparing surgery, which used to be reserved for selected patients with a solitary kidney, chronic kidney disease or bilateral tumors. Evidence suggests that laparoscopic partial nephrectomy is equivalent to the open approach in terms of oncologic outcomes and superior in quality of life measures. Objectives: to determine oncologic outcomes regarding tumor free edges and surgical complications in patients undergoing laparoscopic "Zero ischemia" partial nephrectomy and enucleation of renal tumor. Methodology: retrospective, observational, and comparative study, with a universe of patients from Los Angeles private clinic and Caja Nacional de Salud, Hospital Obrero Nº2, Cochabamba, Bolivia, who underwent laparoscopic partial nephrectomy, were grouped in two groups: Group I: partial nephrectomy and Group II: enucleation. The following were analyzed: tumor size and location, RENAL score, surgical time, bleeding, days of stay, complications and histopathological report. SPSS version 20 (IBM, Chicago, IL) was used for statistical analysis. Results: seventeen patients were evaluated, 3 were excluded due to completion of radical surgery, 6 partial nephrectomies (Group I) and 8 enucleations (Group II). Mean age 45.7 (± 8.6) vs 51.2 (± 6.3) years. Tumor size 7.8 (2.5-10) vs 3.2 (1-5.7) cm, The overall RENAL score of all patients was low to moderate, a separate analysis was performed, in group I, the distribution was low complexity 2 (33.3%), moderate n=1 (16.7%) and high n=3 (50%), in group II, low complexity n=5 (62.5%), moderate n=2 (25%), high complexity n=1 (12.5%). There were differences in favor of group II (enucleation) in terms of surgical time and transoperative bleeding, presenting only 1 case with urinary leakage, resolved with placement of a JJ catheter. In terms of surgical edges, there were 2 (14.2%) cases with positive edges, 1 for each approach, which are kept under close surveillance. Conclusions: laparoscopic approach is an option comparable to the open one, equal results were obtained with respect to oncologic control in relation to free edges and with fewer complications, although experience in laparoscopic surgery is required, as well as an increase in follow-up time and a greater number of cases.

Strengthen "the sustainable farm" concept via efficacious conversion of farm wastes into methane.

With escalating global demand for renewable energy, exploitation of farm wastes (i.e., agriculture straw wastes (ASWs), livestock wastewater (LW) and sewage sludge (SS)) has been considered to attain maximum methane yield (MY) via anaerobic digestion (AD). Results pointed that mixture of SS and LW as anaerobes' source with 20 g of ASWs/300 mL of working volume achieved maximum MY and volatile solid (VS) removal efficiency of 0.44 (±0.05) L/gVS and 51.4 (±4.1)%, respectively. This was mainly because of emerging heavy duty bacterial species (i.e., Syntrophorhabdaceae and Synergistaceae) and archaeal community (i.e, Methanosarcina and Methanoculleus) after 70 days of anaerobic incubation. This was acquired along with boosting enzymatic activity, especially xylanase, cellulase and protease up to 71.5(±7.9), 179.3(±14.3) and 207.2(±16.2) U/100 mL, respectively. Furthermore, the digestate contained high concentrations of NH4+ (960.1±(76.8) mg/L), phosphorus (126.3±(10.1) mg/L) and trace metals, making it a good candidate as organic fertilizer.

A Health Risk Assessment of Lead and Other Metals in Pharmaceutical Herbal Products and Dietary Supplements Containing Ginkgo biloba in the Mexico City Metropolitan Area.

The use of the medicinal plant Ginkgo biloba has increased worldwide. However, G. biloba is capable of assimilating both essential and toxic metals, and the ingestion of contaminated products can cause damage to health. The aim of this study was to investigate the safety of manganese (Mn), copper (Cu), lead (Pb), arsenic (As), and cadmium (Cd) in 26 items containing Ginkgo biloba (pharmaceutical herbal products, dietary supplements, and traditional herbal remedies) purchased in the metropolitan area of Mexico City. Metal analysis was performed using a graphite furnace atomic absorption spectrometer. All of the products were contaminated with Pb, 54% of them with As, and 81% with Cd. The lowest values of Pb, As, and Cd were detected in pharmaceutical herbal products > dietary supplements > traditional herbal remedies. The daily intake dose (DID) of pharmaceutical herbal products was within the established limits for the five metals. Dietary supplements and traditional herbal remedies exceeded the DID limits for Pb. The hazard quotients estimation and non-carcinogenic cumulative hazard estimation index for Mn, As, and Cd indicated no human health risk. Our results suggest that products containing G. biloba for sale in Mexico are not a health risk.

Resección laparoscópica de mielolipoma suprarrenal gigante / Laparoscopic resection of giant adrenal myelolipoma

Los mielolipomas suprarrenales son neoplasias suprarrenales benignas compuestas como su nombre lo indica, por tejido adiposo y tejido hematopoyético. Comprenden entre 6 - 16% de los incidentalomas suprarrenales, El tamaño de estos tumores es variable, desde unos pocos milímetros hasta > 10 cm, es entonces cuando se denominan adrenomielolipomas gigantes. Los síntomas de presentación más comunes son: Dolor abdominal: 22,5%, dolor en hipocondrio: 13,9%, dolor en el flanco: 13,9%, masa abdominal: 5,2%, y en raras ocasiones, disnea, dolor en espalda, fiebre, pérdida de peso y virilización. Presentación del caso: paciente masculino de 61 años de edad, con presencia de tumor de 15 x 12 cm, dependiente de glándula suprarrenal derecha, que comprime polo superior de riñón derecho, de -20 UH, compatible con mielolipoma suprarrenal derecho gigante, hallazgos incidentales, durante protocolo de estudio por crecimiento prostático, se realiza procedimiento de resección de tumor suprarrenal por abordaje laparoscópico, con excelentes resultados clínicos, sangrado mínimo y recuperación inmediata. Conclusión: el mielolipoma suprarrenal es un tumor benigno que se diagnostica en la mayoría de los casos de manera incidental, se sabe que clínicamente es no funcional, aunque siempre se deben de hacer estudios hormonales preoperatorios. El tratamiento de los mielolipomas suprarrenales, depende de cada caso clínico, siendo una recomendación el tratamiento quirúrgico de los tumores grandes >5 cm, sugerimos que se pueda optar por el abordaje laparoscópico, por ser el menos invasivo y con menor tasa de complicaciones, además de la recuperación pronta del paciente.

Adrenal myelolipomas are benign adrenal neoplasms composed, as the name implies, of adipose tissue and myeloid (hematopoietic) tissue. They comprise between 6 and 16% of adrenal incidentalomas. The size of these tumors is variable and can vary from a few millimeters to more than 10 cm when they are called giant adrenomyelolipomas. The most common clinical presenting symptoms of adrenal myelolipomas are as follows: Abdominal pain: 22.5%, hypochondrial pain: 13.9%, flank pain: 13.9%, abdominal mass: 5.2%, and rarely, dyspnea, back pain, fever, weight loss and virilization. Presentation of the case: 61-year-old male, with the presence of a 15 x 12 cm tumor, dependent on the right adrenal gland, compressing the upper pole of the right kidney, -20 HU, compatible with giant right adrenal myelolipoma, incidental findings, during study protocol due to prostatic growth, a laparoscopic adrenal tumor resection procedure is performed, with excellent clinical results, minimal bleeding and immediate recovery. Conclusion: adrenal myelolipoma is a benign tumor that is diagnosed incidentally in most cases, it is known to be non-functional clinically, although preoperative hormonal studies should always be done. The treatment of adrenal myelolipomas depends on each clinical case, being a recommendation the surgical treatment of large tumors> 5 cm, we suggest that the laparoscopic approach be chosen, as it is the least invasive and with the lowest rate of complications, in addition of the prompt recovery of the patient.

Tumor de Células de Sertoli Esclerosante Testicular

Resumen Actualmente el tumor de células de Sertoli de tipo esclerosante, se encuentra clasificado como una variante de los tumores de células de Sertoli NOS (sin otra especificación), ya que ambos tumores presentan mutación del gen CTNNB1, codificador de b-catenina, la relevancia de su identificación radica en que esta variante se correlaciona, aunque en un bajo porcentaje, con potencial metastásico.Masculino de 56 años de edad, con cuadro de 7 años de evolución, caracterizado por presentar dolor testicular izquierdo con leve aumento de consistencia en polo inferior de testículo izquierdo, se realiza ecografía testicular, en la que se evidencia lesión heterogénea de 2 cm de diámetro máximo, dependiente de polo inferior de testículo izquierdo; se realiza orquiectomía radical izquierda, con reporte histopatológico: tumor de células de sertoli testicular. Cursando posteriormente con evolución satisfactoria, con cicatrización completa de la herida, y actualmente en vigilancia, sin necesidad de tratamiento adyuvante. Conociendo su relativa rareza y los pocos casos notificados, los tumores testiculares de células de Sertoli siguen siendo un misterio relativo y en la actualidad, continúan siendo un desafío para su diagnóstico. Con este caso, pretendemos apoyar en el conocimiento y fomentar la investigación adicional de estos tumores, con el objetivo de optimizar el diagnóstico, dar un adecuado tratamiento.

Abstract Currently, the sclerosing-type Sertoli cell tumor is classified as a variant of the NOS Sertoli cell tumors (without other specification), because it has been shown that both tumors present mutation in the CTNNB1 gene, which encodes the b-catenin (19), the relevance of its identification lies in the fact that this variant is correlated, although in a low percentage, with metastatic potential. A 56-year-old male, with a 7-year evolution, characterized by presenting left testicular pain with a slight increase in consistency in the lower pole of the left testicle, a testicular ultrasound was performed, which revealed a heterogeneous lesion of 2 cm in diameter maximum, dependent on the lower pole of the left testis; Left radical orchiectomy was performed, with histopathological report: testicular sertoli cell tumor. Later, with satisfactory evolution, with complete wound healing, and currently under surveillance, without the need for adjuvant treatment.Knowing their relative rarity and the few reported cases, testicular Sertoli cell tumors remain a relative mystery and today, they continue to be a challenge for diagnosis. With this case, we intend to support the knowledge and promote additional research on these tumors, with the aim of optimizing the diagnosis and providing adequate treatment.

Fetal and Postnatal Nicotine Exposure Modifies Maturation of Gonocytes to Spermatogonia in Mice.

Studies in laboratory animals have shown that male offspring from dams, exposed to nicotine during pregnancy and postnatal periods, show alterations in fertility, although the origin of this is still uncertain. In this study, we examined in a mouse model if the process of gonocyte maturation to spermatogonia was affected in male offspring from dams with nicotine administration during pregnancy and postnatal periods. BALB/C mice, with and without nicotine administrations in pregnancy and postnatal periods, were studied. The animals were euthanized at 3, 7, 10, 16, and 35 days postpartum (dpp). Testicular tissue samples were processed for histological, ultrastructural, and immunohistochemical studies; and testicular lipoperoxidation was determined. It was observed that in the nicotine-exposed animals, there was increased apoptosis and a reduction in the number of gonocytes that matured to spermatogonia. This gonocyte-spermatogonia maturation reduction was associated with a greater immunoreactivity to nicotinic acetylcholine receptors in the germ cells. Lipoperoxidation was similar in both groups until 16 dpp, with significant reduction at 35 dpp. Our findings suggest that nicotine intake during pregnancy and postnatal periods can affect the process of maturation of gonocytes to spermatogonia and the pool of available spermatogonia for spermatogenesis.

Resección laparoscópica de adenocarcinoma de uraco / Laparoscopic resection of uraco adenocarcinoma

El adenocarcinoma de uraco es una enfermedad neoplásica rara, con una incidencia de 1 por 5 millones de habitantes. Clínicamente se manifiesta con hematuria (73%), dolor abdominal (14%), disuria (13%), mucosuria (10%), síntomas irritativos (40%), masa palpable en la parte baja del abdomen (17%), bacteriuria (8%), flujo mucoso umbilical (2%). Presentamos el caso de paciente de 45 años, con diagnóstico de adenocarcinoma de uraco, que recibió múltiples tratamientos sin respuesta, realizándose, cirugía radical con resección en bloque de ombligo, uraco, peritoneo, fascia posterior del musculo recto del abdomen y cistectomía parcial, por abordaje laparoscópico, con excelentes resultados oncológicos y estéticos, con recuperación rápida, y sin complicaciones. El papel de la quimioterapia y radioterapia y su beneficio para el paciente aún no está claro. Con este caso queremos aportar con un nuevo caso a la literatura, además de poder mostrar que el manejo con mínima invasión puede ser adecuada en manos expertas, con resultados iguales a la cirugía abierta, con el beneficio ya conocido del abordaje laparoscópico.

Urachal adenocarcinoma is a rare tumor entity, an average incidence of 1 case per 5 million inhabitants is described. Clinically it manifests with hematuria (73%), abdominal pain (14%), dysuria (13%), mucosuria (10%), irritative symptoms (40%), palpable mass in the lower abdomen (17% ), bacteriuria (8%), umbilical mucosal flow (2%). We present the case of a 45-year-old patient with a diagnosis of urachal adenocarcinoma, who received multiple treatments without response, performing radical surgery with en bloc resection of the umbilicus, urachus, peritoneum, posterior fascia of the rectus abdominis muscle and partial cystectomy. by laparoscopic approach, with excellent oncological and aesthetic results, with fast recovery, and without complications. The role of chemotherapy and radiation therapy and their benefit to the patient is still unclear. With this case we want to contribute a new case to the literature, in addition to being able to show that minimally invasive management can be adequate in expert hands, with results equal to open surgery, with the already known benefit of the laparoscopic approach.

1,3-Propanediol production from glycerol in polyurethane foam containing anaerobic reactors: performance and biomass cultivation and retention.

The use of batch and upflow anaerobic reactors filled with polyurethane foam for pure glycerol fermentation was evaluated. The best reactor operational conditions to obtain high yield and productivity of 1,3-propanediol (1,3-PDO) as the main product and the role of the polyurethane foam in the growth and retention of suspended and attached biomass in the reactors were investigated. In the experiment at 30 °C with a batch reactor (700 mL), biomass growth was mostly as immobilized attached cells, and the achieved 1,3-PDO yield was up to 0.58 mol mol-gly-1. In the experiment (30 °C) with an upflow anaerobic reactor (717 mL), glycerol loading rates (gly-LR) ranging from 6.94 to 15.47 g gly L-1 day-1 were applied during a 102-day period. During the operation, average 1,3-PDO yield was 0.47 mol mol-gly-1, reaching a maximum of 0.51 mol mol-gly-1 at gly-LR of 13.57 g gly L-1 day-1. High 1,3-PDO productivity (5.35 to 5.44 g L-1 day-1) was obtained when gly-LR was 13.57 to 15.47 g gly L-1 day-1. Comparing the close yield values in both batch and continuous reactors and based on microbial evaluation, it is concluded that most of the 1,3-PDO generated in the continuous reactor was due to the suspended biomass retained by the foam cubes. The Clostridium genus was the predominant 1,3-PDO producer. Good yields and productivities with packed reactors were attributed to polyurethane foam used for mixed culture growth and retention. Consequently, they are worth considering for 1,3-PDO production from pure glycerol.

S-allyl Cysteine, a Garlic Compound, Produces an Antidepressant-Like Effect and Exhibits Antioxidant Properties in Mice.

Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.