Dysregulated energy metabolism impairs chondrocyte function in osteoarthritis.

OBJECTIVES: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage. METHODS: Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U-13C] isotope with liquid chromatography-mass spectrometry (LC-MS). We further evaluated cellular bioenergetic profiles by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) and investigated the effects of low-dose and short-term effects of 2-deoxyglucose (2DG) on chondrocytes. RESULTS: OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U-13C] glucose labelling revealed that less glucose-derived carbon entered the tricarboxylic acid (TCA) cycle. On the other hand, mitochondrial respiratory rates were markedly decreased in the OA chondrocytes compared to non-OA chondrocytes. These changes were accompanied by decreased cellular ATP production, mitochondrial membrane potential and disrupted mitochondrial morphology. We further demonstrated in vitro that short-term inhibition of glycolysis suppressed matrix degeneration gene expression in chondrocytes and bovine cartilage explants cultured under inflammatory conditions. CONCLUSION: This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.

Advances in biotechnology and informatics to link variation in the genome to phenotypes in plants and animals.

Advances in our understanding of genome structure provide consistent evidence for the existence of a core genome representing species classically defined by phenotype, as well as conditionally dispensable components of the genome that shows extensive variation between individuals of a given species. Generally, conservation of phenotypic features between species reflects conserved features of the genome; however, this is evidently not necessarily always the case as demonstrated by the analysis of the tunicate chordate Oikopleura dioica. In both plants and animals, the methylation activity of DNA and histones continues to present new variables for modifying (eventually) the phenotype of an organism and provides for structural variation that builds on the point mutations, rearrangements, indels, and amplification of retrotransposable elements traditionally considered. The translation of the advances in the structure/function analysis of the genome to industry is facilitated through the capture of research outputs in "toolboxes" that remain accessible in the public domain.

[Role of pediatric urologist in the treatment of congenital adrenal hyperplasia: a study of satisfaction and psychosocial aspects]. / Papel del urólogo pediátrico en el tratamiento de la hiperplasia suprarrenal congénita: estudio de satisfacción y aspectos psicosociales.

OBJECTIVE: Study the role of the pediatric urologist in the treatment of CAH and the satisfaction of families and patients to identify the psychosocial aspects that we can improve. MATERIAL AND METHODS: Retrospective study in girls with CAH treated in our center. We reviewed the medical records, analyzing the variables: place of birth, age at diagnosis, surgery, complications and follow up. Analysis of satisfaction and psychosocial aspects by telephone survey. RESULTS: Between 1975-2011, 25 girls with CAH have been treated in our center. Cystoscopy and vaginoscopy was performed before clitoroplasty in 68% (16 girls), adding vulvovaginoplasty in 40% and vaginal descent in the 20%. The mean age was 8.78 +/- 2.30 months. Vaginal stenosis was the main complication (36%), performing introitus plasty in two girls, vaginal expansion in other 2 and dilation of the rest. 15 surveys were made, all expressed satisfaction with treatment, and only 6.67% reported shortages information. With the aesthetic results of the genitoplasty 20% showed dissatisfaction. The family concern was constant at 60%, and sporadic in the rest. 13.3% required psychological support. Currently 80% have normal psychosocial life. CONCLUSION: The HSC requires a multidisciplinary approach right from birth to allow adequate psychosocial development. The pediatric urologist has an important weight in the multidisciplinary treatment. Realizing early feminizing genitoplasty decreases family impact and increases satisfaction. The prolonged follow-up will allow the detection and treatment of complications.

Advances in biotechnology and linking outputs to variation in complex traits: Plant and Animal Genome meeting January 2012.

The Plant and Animal Genome (PAG, held annually) meeting in January 2012 provided insights into the advances in plant, animal, and microbe genome studies particularly as they impact on our understanding of complex biological systems. The diverse areas of biology covered included the advances in technologies, variation in complex traits, genome change in evolution, and targeting phenotypic changes, across the broad spectrum of life forms. This overview aims to summarize the major advances in research areas presented in the plenary lectures and does not attempt to summarize the diverse research activities covered throughout the PAG in workshops, posters, presentations, and displays by suppliers of cutting-edge technologies.

Genome studies at the PAG 2011 conference.

The contents of the plenary lectures presented at the Plant and Animal Genome (PAG) meeting in January 2011 are summarized in order to provide some insights into the advances in plant, animal and microbe genome studies as they impact on our understanding of complex biological systems. The areas of biology covered include the dynamics of genome change, biological recognition processes and the new processes that underpin investment in science. This overview does not attempt to summarize the diversity of activities that are covered during the PAG through workshops, posters and the suppliers of cutting-edge technologies, but reviews major advances in specific research areas.

[Evaluation of urodynamics and continence in bladder augmentations with sigmoids]. / Evaluación urodinámica y de la continencia en las ampliaciones vesicales con sigmoides.

AIM: To evaluate our experience in sigmoid augmentation to manage renal upper tract dilatation and urinary incontinence. MATERIAL AND METHODS: Retrospective descriptive study of the augmentation cystoplasties with sigmoid patch. We analyze clinical, urodinamic and surgical parameters. RESULTS: We have make 30 cistoplasties with a mean age of 10.24 years (3-15 years) with a mean follow up of 8 years (9 months-15 years). The main diagnosis was neurogenic bladder (63,3%) being the main indication for the augmentation the progressive dilatation of the renal upper tract (43,3%). We associate to the procedure the collocation of an artificial sphinter (30%), Mitrofanoff or ureteral reimplantation. There was no major complication. In the urodinamics, the bladders had low capacity, high pression and low compliance. After surgery, urodinamic parameters improve. During follow up, continence improve with more intermittent clean catheterism (median 4/day). Vesical lithiasis was more common late complication with nor acute abdominal surgical illness nor malignancy; 2 patients finished in renal transplantation. Evolution was positive in 66%, and negative in 18,5%. CONCLUSIONS: Sigmoid augmentation cystoplasty is a good technique, that allows urodinamic and continence improvement. The conscience in the importance of intermittent catheterisms reduces the incidence of complications.

[Recent changes in prostate cancer mortality in Spain. Trends analysis from 1991 to 2005]. / Cambios recientes en la mortalidad por cáncer de próstata en España: estudio de tendencias en el período 1991-2005.

OBJECTIVE: [corrected] To describe the evolution of prostate cancer mortality in Spain during the period 1991-2005. SUBJECTS AND METHODS: A trend analysis for age standardized mortality rates (European standard population) was performed, using joinpoint regression analysis, which allows estimation of the annual percent change of rates and to find significant changes in such trend. RESULTS: Age standardized mortality rates in Spain reached their peak value in 1996. The joinpoint analysis identified two different periods in the trend of the age standardized rates: a first one of increase in rates between 1991 and 1996 (2.1% annual increase) and a second period starting in 1996, in which rates decline at an annual rate of 2.7%. CONCLUSION: The tendency of prostate cancer seen in Spain resembles that of industrialized areas, with an increase in its age standardized death rates that suffers a downturn by the end of the past decade. Mortality declines for prostate cancer are now evident in 14 out of the 17 Autonomous Communities. Increases in PSA screening and better treatment of early-stage disease, possibly acting in combination, remain plausible hypotheses.

Diagnóstico microbiológico de la COVID-19 / Microbiological diagnosis of COVID-19

El diagnóstico microbiológico de la infección por SARS-CoV-2 es de gran importancia por su repercusión clínica a nivel individual y para la elaboración de estrategias de salud pública para intentar frenar su propagación. Actualmente la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) es la técnica de elección para el diagnóstico microbiológico del paciente sintomático por COVID-19, detectando material genético del virus en el organismo. Requiere un adecuado manejo de las muestras y un laboratorio bien equipado. Otros métodos diagnósticos utilizados son la detección de anticuerpos generados por el individuo en contacto con el virus, son útiles para el estudio de infección pasada, estudios de vacunas o estrategias epidemiológicas; y la detección de antígenos del SARS-CoV-2 en muestras biológicas, de mayor rentabilidad, menor coste y gran especificidad, pero con altas tasas de falsos negativos en pacientes con baja carga viral. Es fundamental una correcta indicación e interpretación de las pruebas diagnósticas para su mayor rentabilidad

Microbiological diagnosis of SARS-CoV-2 infection is crucial due to its clinical repercussion at the individual level and for the development of public health strategies to try to stop its spread. Currently, reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard for microbiological diagnosis of symptomatic COVID-19 patients, detecting genetic material of the virus in the body. It requires proper sample handling and a well-equipped laboratory. Other diagnostic methods used are the detection of antibodies generated by the individual in contact with the virus, useful for the study of past infection, vaccine studies or epidemiological strategies; and the detection of SARS-CoV-2 antigens in biological samples, with greater profitability, lower cost and high specificity, but with high rates of false negatives in patients with low viral load. Correct indication and interpretation of diagnostic tests is essential for greater profitability

Gene expression evidence for off-target effects caused by RNA interference-mediated gene silencing of Ubiquitin-63E in the cattle tick Rhipicephalus microplus.

Knowledge of cattle tick (Rhipicephalus (Boophilus) microplus; Acari: Ixodidae) molecular and cellular pathways has been hampered by the lack of an annotated genome. In addition, most of the tick expressed sequence tags (ESTs) available to date consist of ∼50% unassigned sequences without predicted functions. The most common approach to address this has been the application of RNA interference (RNAi) methods to investigate genes and their pathways. This approach has been widely adopted in tick research despite minimal knowledge of the tick RNAi pathway and double-stranded RNA (dsRNA) uptake mechanisms. A strong knockdown phenotype of adult female ticks had previously been observed using a 594 bp dsRNA targeting the cattle tick homologue for the Drosophila Ubiquitin-63E gene leading to nil or deformed eggs. A NimbleGen cattle tick custom microarray based on the BmiGI.V2 database of R. microplus ESTs was used to evaluate the expression of mRNAs harvested from ticks treated with the tick Ubiquitin-63E 594 bp dsRNA compared with controls. A total of 144 ESTs including TC6372 (Ubiquitin-63E) were down-regulated with 136 ESTs up-regulated following treatment. The results obtained substantiated the knockdown phenotype with ESTs identified as being associated with ubiquitin proteolysis as well as oogenesis, embryogenesis, fatty acid synthesis and stress responses. A bioinformatics analysis was undertaken to predict off-target effects (OTE) resulting from the in silico dicing of the 594 bp Ubiquitin-63E dsRNA which identified 10 down-regulated ESTs (including TC6372) within the list of differentially expressed probes on the microarrays. Subsequent knockdown experiments utilising 196 and 109 bp dsRNAs, and a cocktail of short hairpin RNAs (shRNA) targeting Ubiquitin-63E, demonstrated similar phenotypes for the dsRNAs but nil effect following shRNA treatment. Quantitative reverse transcriptase PCR analysis confirmed differential expression of TC6372 and selected ESTs. Our study demonstrated the minimisation of predicted OTEs in the shorter dsRNA treatments (∼100-200 bp) and the usefulness of microarrays to study knockdown phenotypes.

Síndrome de Allen Master: causa excepcional de abdomen agudo en el embarazo / Allen Master syndrome: exceptional cause of acute abdomen in pregnancy

Se presenta un caso de abdomen agudo en una gestante de 20 semanas, por una torsión anexial. Ante la ausencia de signos ecográficos compatibles con patología en los primeros momentos y el empeoramiento clínico, se solicitó una RMN que permitió la aproximación diagnóstica y facilitó la indicación urgente de cirugía abdominal. En el curso de la laparotomía se diagnosticó una hernia interna del anexo, con marcado componente vascular a través de un defecto del ligamento ancho, que obligó a la anexectomía. Tras el diagnóstico y el tratamiento realizado, la gestación continúa con buenos resultados materno-fetal. Estos orificios han sido presentados excepcionalmente como causa de hernias internas digestivas, urológicas y anexiales, siendo controvertido su origen, congénito, inflamatorio o traumático. Se repasan las pruebas complementarias indicadas en el manejo diagnóstico del dolor abdominal en el embarazo, incluyendo las últimas recomendaciones de la European Society of Urogenital Radiology-ESUR.

A case of acute abdomen in a pregnant 20 weeks is presented with an adnexal torsion. In the absence of pathologic ultrasound signs with in the early stages and clinical worsening, was requested an MRI that allowed the diagnostic approach and the indication for urgent abdominal surgery. During laparotomy was observed an internal adnexal hernia through a defect in the broad ligament, with marked vascular component which forced the adnexectomy. After the diagnosis and treatment performed, the pregnancy continues with good maternal and fetal outcomes. These defects were presented exceptionally as a cause of digestive, urological and adnexal internal hernias. The origin remains controversial, congenital, inflammatory or traumatic. Complementary tests in the diagnostic management of abdominal pain in pregnancy are reviewed, including the latest recommendations of the European Society of Urogenital Radiology-ESUR.

[Urinary symptoms and urodynamic findings in Parkinson's disease]. / Sintomatología miccional y alteraciones urodinámicas en la enfermedad de Parkinson.

INTRODUCTION: Urinary symptoms in Parkinson's disease (PD) are minor but disabling. We have analyzed correlation of urinary symptoms with motor symptoms, duration and severity of PD and urodynamic abnormalities observed. Response to treatment with tolterodine was also assessed. METHODS: PD male patients with a score in IPSS questionnaire over 7 and female patients with a score in IU-4 scale over 5 were included in the study. Intensity of neurological symptoms (UPDRS score), seriousness of PD (Hohen-Yahr stage), urodynamic parameters, and urinary sediment were analyzed in each patient. Abdominal ultrasonography and rectal examination were performed in males to exclude obstructive prostatic pathology. Patients without evidence of urinary flow obstruction were treated with tolterodine. RESULTS: Three out of the 19 patients were excluded because of abnormal urinary sediment and the rest (n = 16) were included. Urinary symptoms correlated with rigidity severity (p < 0.01) and years of evolution of PD (p < 0.01). Rigidity (p < 0.01) was the neurological sign with the highest UPDRS motor scale score. Overactive bladder was present in 13 cases (81.2%) and 4 of them had urinary flow obstruction. Clinical improvement in nine patients treated with tolterodine was mild (33%). CONCLUSIONS: Urinary symptoms correlate with rigidity severity and with years of evolution of PD. The use of both the urinary questionnaire and urodynamic study allow us to identify the type of bladder dysfunction and select the patients who would benefit the most from anticholinergics. Tolterodine reduced miccional urgency and frequency in PD, but was ineffective on urinary incontinence.

[Malignant Brenner tumor of the ovary]. / Tumor de Brenner maligno del ovário.

One case of Malignant Brenner Tumor is presented. Clinical and Anatomo Pathological aspects are review.

[Exceptional variety of endometrial cancer]. / Variedad excepcional de cáncer de endometrio.

We present a clinical case and histology of rare endometrial neoplasm: Giant cell carcinoma of the endometrium.

Papel del urólogo pediátrico en el tratamiento de la hiperplasia suprarrenal congénita: estudio de satisfacción y aspectos psicosociales / Role of pediatric urologist in the treatment of Congenital adrenal hyperplasia: a Study of satisfaction and psychosocial aspects

OBJETIVO: Estudiar el papel del urólogo en el tratamiento de la hiperplasia suprarrenal congénita (HSC) y la satisfacción de familiares y pacientes, para identificar los aspectos psicosociales que podemos mejorar.Material y métodos. Estudio retrospectivo de niñas con HSC tra-tadas en nuestro centro. Revisamos las historias clínicas, analizando las variables: lugar de nacimiento, edad de diagnóstico, cirugía, complica-ciones y seguimiento posterior. Análisis de la satisfacción y psicosocial mediante encuesta telefónica.Resultados. Entre 1975-2011, 25 niñas con HSC han sido tratadas en nuestro centro. Se realizó cistoscopia/vaginoscopia previa clitoro-plastia en el 68% (16 niñas), añadiendo vulvovaginoplastia al 40% y descenso vaginal al 20%. La edad media fue de 8,78±2,30 meses. La estenosis vaginal fue la principal complicación (36%), realizándose introitoplastia en dos niñas, ampliación vaginal en otras 2 y dilataciones en el resto. Se hicieron 15 encuestas, todos manifestaron satisfacción con el tratamiento, sólo el 6,67% refirió escasez de información. Con los resultados estéticos de la genitoplastia un 20% mostraron insatisfacción. La preocupación familiar fue constante en el 60%, siendo esporádica en el resto. El 13,3% requirió apoyo psicológico. Actualmente el 80% llevan una vida psicosocial normal. CONCLUSIÓN: La HSC requiere de un correcto tratamiento multi-disciplinar desde el nacimiento para permitir un adecuado desarrollo psicosocial. El urólogo pediátrico tiene un importante peso en el trata-miento multidisciplinar. Realizando la genitoplastia feminizante precoz disminuye el impacto familiar y aumenta la satisfacción. El seguimiento prolongado permitirá la detección y tratamiento de las complicaciones

OBJECTIVE: Study the role of the pediatric urologist in the treatment of CAH and the satisfaction of families and patients to identify the psychosocial aspects that we can improve. MATERIAL AND METHODS: Retrospective study in girls with CAH treated in our center. We reviewed the medical records, analyzing the variables: place of birth, age at diagnosis, surgery, complications and follow up. Analysis of satisfaction and psychosocial aspects by tel-ephone survey. RESULTS: Between 1975-2011, 25 girls with CAH have been treated in our center. Cystoscopy and vaginoscopy was performed before clito-roplasty in 68% (16 girls), adding vulvovaginoplasty in 40% and vaginal descent in the 20%. The mean age was 8.78 ± 2.30 months. Vaginal stenosis was the main complication (36%), performing introitus plasty in two girls, vaginal expansion in other 2 and dilation of the rest. 15 surveys were made, all expressed satisfaction with treatment, and only 6.67% reported shortages information. With the aesthetic results of the genitoplasty 20% showed dissatisfaction. The family concern was con-stant at 60%, and sporadic in the rest. 13.3% required psychological support. Currently 80% have normal psychosocial life. CONCLUSION: The HSC requires a multidisciplinary approach right from birth to allow adequate psychosocial development. The pediatric urologist has an important weight in the multidisciplinary treatment. Realizing early feminizing genitoplasty decreases family impact and increases satisfaction. The prolonged follow-up will allow the detection and treatment of complications

Evaluación urodinámica y de la continencia en las ampliaciones vesicales con sigmoides / Evaluation of urodynamics and continence in bladder augmentations with sigmoids

Objetivo. Queremos evaluar nuestra experiencia en las cistoplastias con sigmoides en el manejo de la dilatación del tracto urinario superior y la incontinencia urinaria. Material y métodos. Realizamos un estudio descriptivo retrospectivo de las ampliaciones realizadas con sigmoides (1994-2009). Analizamos parámetros clínicos, quirúrgicos y especialmente urodinámicos, pre/postcistoplastia. Resultados. Hemos realizado 30 cistoplastias con una edad de 10,24años (3-15 años), siguiéndose 8 años (9 meses-15 años). El diagnóstico de base era la vejiga neurógena (63,3%), siendo la indicación principal para la ampliación la afectación del tracto urinario superior 43,3%)y la incontinencia. El procedimiento se asoció a la colocación de esfínter artificial (30%), estoma tipo Mitrofan off (30%) o reimplante ureteral(30%), No existiendo ninguna complicación (..) (AU)

Aim. To evaluate our experience in sigmoid augmentation to manage renal upper tract dilatation and urinary incontinence. Material and methods. Retrospective descriptive study of the augmentation cystoplasties with sigmoid patch. We analyze clinical, urodynamic and surgical parameters. Results. We have make 30 cistoplasties with a mean age of 10.24years (3-15 years) with a mean follow up of 8 years (9 months-15 years).The main diagnosis was neurogenic bladder (63,3%) being the main indication for the augmentation the progressive dilatation of the renal upper tract (43,3%). We associate to the procedure the collocation of an artificial sphinter (30%), Mitrofan off or ureteral reimplantation. There was no major complication. In the urodinamics, the bladders had low (..) (AU)

Sintomatología miccional y alteraciones urodinámicas en la enfermedad de Parkinson / Urinary symptoms and urodynamic findings in Parkinson's disease

Introducción. Los síntomas urinarios en la enfermedad de Parkinson (EP) son síntomas menores, pero invalidantes. Analizamos su correlación con síntomas motores, duración y gravedad de la EP y con las alteraciones urodinámicas observadas. También estudiamos la respuesta al tratamiento con tolterodina. Métodos. Se incluyeron pacientes con EP y puntuaciones en los cuestionarios de síntomas urinarios superiores a 7 en varones (IPSS) y a 5 en mujeres (IU-4). Se analizó intensidad de los síntomas neurológicos (escala UPDRS), gravedad de la EP (escala Hohen-Yahr), parámetros del estudio urodinámico y sedimento urinario. En varones además se realizó tacto rectal y ecografía abdominal para valorar patología prostática obstructiva. Los pacientes sin obstrucción al flujo urinario recibieron tratamiento con tolterodina. Resultados. Diecinueve pacientes fueron seleccionados, excluyéndose 3 por sedimento patológico. En los 16 restantes se observó una correlación positiva de la intensidad de los síntomas urinarios con los años de evolución de la EP (p<0,01) y con la rigidez (p<0,01), que fue el síntoma más intenso. En 13 casos (81,2 %) se detectó hiperactividad de detrusor, de los que 4 presentaron datos urodinámicos de obstrucción. El porcentaje de mejoría de los síntomas urinarios en los 9 casos tratados con tolterodina fue bajo (33 %). Conclusiones. La gravedad de los síntomas urinarios se correlaciona con el grado de rigidez y con los años de evolución de la EP. La combinación de los cuestionarios y el estudio urodinámico permiten identificar el tipo de disfunción vesical y seleccionar a los pacientes tributarios de tratamiento anticolinérgico. La tolterodina redujo los síntomas de urgencia y frecuencia miccional en la EP, pero fue ineficaz sobre la incontinencia urinaria

Introduction. Urinary symptoms in Parkinson's disease (PD) are minor but disabling. We have analyzed correlation of urinary symptoms with motor symptoms, duration and severity of PD and urodynamic abnormalities observed. Response to treatment with tolterodine was also assessed. Methods. PD male patients with a score in IPSS questionnaire over 7 and female patients with a score in IU-4 scale over 5 were included in the study. Intensity of neurological symptoms (UPDRS score), seriousness of PD (Hohen-Yahr stage), urodynamic parameters, and urinary sediment were analyzed in each patient. Abdominal ultrasonography and rectal examination were performed in males to exclude obstructive prosthatic pathology. Patients without evidence of urinary flow obstruction were treated with tolterodine. Results. Three out of the 19 patients were excluded because of abnormal urinary sediment and the rest (n = 16) were included. Urinary symptoms correlated with rigidity severity (p < 0.01) and years of evolution of PD (p<0.01). Rigidity (p<0.01) was the neurological sign with the highest UPDRS motor scale score. Overactive bladder was present in 13 cases (81.2 %) and 4 of them had urinary flow obstruction. Clinical improvement in nine patients treated with tolterodine was mild (33 %). Conclusions. Urinary symptoms correlate with rigidity severity and with years of evolution of PD. The use of both the urinary questionnaire and urodynamic study allow us to identify the type of bladder dysfunction and select the patients who would benefit the most from anticholinergics. Tolterodine reduced miccional urgency and frequency in PD, but was ineffective on urinary incontinence