STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness.

The signal transducer and activator of transcription 3 (STAT3) is a transcription factor mainly activated by phosphorylation in either tyrosine 705 (Y705) or serine 727 (S727) residues that regulates essential processes such as cell differentiation, apoptosis inhibition, or cell survival. Aberrant activation of STAT3 has been related to development of nearly 50% of human cancers including clear cell renal cell carcinoma (ccRCC). In fact, phosho-S727 (pS727) levels correlate with overall survival of ccRCC patients. With the aim to elucidate the contribution of STAT3 phosphorylation in ccRCC development and progression, we have generated human-derived ccRCC cell lines carrying STAT3 Y705 and S727 phosphomutants. Our data show that the phosphomimetic substitution Ser727Asp facilitates a pro-tumoral phenotype in vitro, in a Y705-phosphorylation-independent manner. Moreover, we describe that STAT3 phosphorylation state determines the expression of different subsets of target genes associated with distinct biological processes, being pS727-dependent genes the most related to cellular hallmarks of cancer. In summary, the present study constitutes the first analysis on the role of overall STAT3 phosphorylation state in ccRCC and demonstrates that pS727 promotes the expression of a specific subset of target genes that might be clinically relevant as novel biomarkers and potential therapeutic targets for ccRCC.

A propósito de un caso: servicio de indicación farmacéutica en paciente con edema y varices / Regarding a case: pharmaceutical indication service in a patient with edema and varicose veins

Paciente varón de 69 años acude a la farmacia comunitaria solicitando una crema que le ayude a mejorar la hinchazón que presenta en las piernas. Para la evaluación de este caso clínico se ha seguido el esquema propuesto por Foro de Atención Farmacéutica en FC (Foro AF-FC). Se sospecha que se trata de un problema de salud insuficientemente tratado, dando lugar a un Resultado Negativo asociado a la Medicación (RNM). Se lleva a cabo el servicio de indicación farmacéutica y se registra en SEFAC e_XPERT INDICA+PRO. En la primera intervención se le recomienda una pomada a base de Polisulfato sódico 5 mg/g, así como consejos de salud. A las dos semanas se realiza la primera evaluación y el paciente presenta cierta mejoría, pero continúa con hinchazón en los tobillos. En la segunda visita se le indica unas medias de compresión normal y unas cápsulas a base de extractos naturales que le ayuden a eliminar líquidos, así como continuar con la pomada. En la segunda evaluación, comenta que la combinación propuesta le funciona bien y que el problema de salud está prácticamente resuelto. (AU)

Mean structure of the supercritical turbulent spiral in Taylor-Couette flow.

The large-scale laminar/turbulent spiral patterns that appear in the linearly unstable regime of counter-rotating Taylor-Couette flow are investigated from a statistical perspective by means of direct numerical simulation. Unlike the vast majority of previous numerical studies, we analyse the flow in periodic parallelogram-annular domains, following a coordinate change that aligns one of the parallelogram sides with the spiral pattern. The domain size, shape and spatial resolution have been varied and the results compared with those in a sufficiently large computational orthogonal domain with natural axial and azimuthal periodicity. We find that a minimal parallelogram of the right tilt significantly reduces the computational cost without notably compromising the statistical properties of the supercritical turbulent spiral. Its mean structure, obtained from extremely long time integrations in a co-rotating reference frame using the method of slices, bears remarkable similarity with the turbulent stripes observed in plane Couette flow, the centrifugal instability playing only a secondary role. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical transactions paper (Part 2)'.

Prevalencia de la miocardiopatía hipertrófica en una amplia muestra de la población laboral española / Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population

Antecedentes y objetivo En España no existen estudios que hayan evaluado la prevalencia de la miocardiopatía hipertrófica en la población general. El objetivo de este trabajo fue evaluar la prevalencia de la miocardiopatía hipertrófica en una muestra amplia de la población laboral española. Materiales y métodos Se incluyó a 13.179 trabajadores (73% varones, con una edad media de 40 años) de 5 regiones españolas a los que, entre mayo de 2008 y noviembre de 2010, se les realizó un reconocimiento médico con un electrocardiograma. Se derivó a los trabajadores con alteraciones sugestivas en el electrocardiograma o con antecedentes médicos predisponentes (síncope de esfuerzo o muerte súbita en familiar menor de 50 años) para una evaluación ecocardiográfica. Se definió miocardiopatía hipertrófica a la presencia de un grosor parietal igual o mayor a 13mm en cualquier segmento del ventrículo izquierdo. Se estimó la prevalencia de la miocardiopatía hipertrófica en toda la muestra y en los trabajadores no hipertensos. Resultados Se seleccionó a 1.008 trabajadores para el ecocardiograma, aunque solo 496 (49,2% de los seleccionados) acudieron a la prueba. Tras el ecocardiograma se detectaron 16 casos de miocardiopatía hipertrófica y se estimó una prevalencia del 0,24% en el total de la muestra. En el subgrupo de trabajadores no hipertensos se objetivaron 10 casos de miocardiopatía hipertrófica, que se corresponden con una prevalencia estimada del 0,19%. Conclusiones En nuestra muestra de la población laboral española la prevalencia estimada de miocardiopatía hipertrófica fue del 0,24%. En el subgrupo de pacientes no hipertensos la prevalencia estimada fue del 0,19% (AU)

Background and objectives To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. Materials and methods The study included 13,179 workers (73% men; mean age, 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. Results A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. Conclusions In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19% (AU)

Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age: 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population. / Prevalencia de la miocardiopatía hipertrófica en una amplia muestra de la población laboral española.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age, 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Análisis de la expresión nuclear de pSer727-STAT3 como factor pronóstico en pacientes con carcinoma renal de células claras / Analysis of the nuclear expression of pSer727-STAT3 as a prognostic factor in patients with clear cell renal carcinoma

INTRODUCCIÓN: Actualmente no existe ningún marcador pronóstico para el carcinoma renal de células claras (CRCC). La proteína STAT3 (Signal Transducer and Activator of Transcription 3) está implicada en la carcinogénesis del CRCC. Su activación se produce mediante fosforilación del residuo serina 727, translocándose al núcleo donde participa en la carcinogénesis y progresión tumoral. El objetivo primario del estudio fue evaluar la supervivencia cáncer-específica en una serie de 166 pacientes afectos de CRCC, y su posterior correlación con la expresión de pSer727-STAT3 como marcador pronóstico de CRCC. MATERIAL Y MÉTODOS: Realizamos un estudio retrospectivo en 166 pacientes con CRCC intervenidos mediante nefrectomía parcial o radical entre 2000 y 2010. Se construyó un microarray de tejido tumoral y se analizó la expresión inmunohistoquímica de pSer727-STAT3. La variable principal del estudio fue la supervivencia cáncer-específica. RESULTADOS: El grupo de riesgo según la UICC fue en 78 pacientes (47%) bajo, en 52 (31,3%) intermedio y en 36 (21,7%) alto; 11 pacientes (6,7%) debutaron con enfermedad metastásica. Durante un seguimiento medio de 97,2 meses (1-208), 37 pacientes (22,3%) desarrollaron recurrencia local y/o a distancia. La mortalidad cáncer-específica fue del 28,3% y la mortalidad global del 67,5%. La expresión media de pSer727-STAT3 fue de 92,9 (IC 95%:84,6-101,1) sin observarse relación con grupos de riesgo u otros factores pronósticos. En un análisis de regresión logística de Cox, pSer727-STAT3 no se comportó como un predictor independiente de mortalidad cáncer-específica. Sin embargo, en pacientes de alto riesgo y metastásicos, la supervivencia cáncer-específica fue significativamente mayor cuando la expresión de pSer727-STAT3 fue inferior a 110, HR: 5,4 (IC 96%:1,8-16,4) y HR: 2,3 (IC 95%: 1,1-4,6) respectivamente, p > 0,001. CONCLUSIONES: pSer727-STAT3 no es un marcador de supervivencia en los pacientes con CRCC. Sin embargo, en pacientes de alto riesgo, es un marcador de supervivencia cáncer-específica, incluso en pacientes metastásicos que reciben tratamiento con antiangiogénicos

INTRODUCTION: Currently, clear cell renal carcinoma (CCRCC) has no prognostic markers. STAT3 protein (Signal Transducer and Activator of Transcription 3) is involved in the carcinogenesis of CCRCC. Its activation is produced by phosphorylation of the serine 727 residue, translocating to the nucleus where it is involved in carcinogenesis and tumor progression. The primary objective of the study was to evaluate cancer-specific survival rates in a series of 166 patients with CCRCC, and its subsequent correlation with the expression of pSer727-STAT3 as a prognostic marker of CCRCC. MATERIAL AND METHODS: We conducted a retrospective study on 166 patients with CCRCC undergoing partial or radical nephrectomy between 2000 and 2010. A tumor tissue microarray was constructed for immunohistochemical analysis of pSer727-STAT3 expression. The main variable of the study was cancer-specific survival. RESULTS: Patients were classified according to the UICC risk groups as follows: low in 78 patients (47%), intermediate in 52 (31.3%) and high 36 (21.7%); 11 patients (6.7%) were diagnosed with metastatic disease. During a mean follow-up of 97.2 months (1-208), 37 patients (22.3%) developed local and/or distant recurrence. Cancer-specific and overall mortality rates were 28.3% and 67.5%, respectively. The mean expression of pSer727-STAT3 was 92.9 (95% CI: 84.6-101.1) without showing any relationship with risk groups or other prognostic factors. In a Cox logistic regression analysis, pSer727-STAT3 did not behave as an independent predictor of cancer-specific mortality. However, in high-risk and metastatic patients, cancer-specific survival was significantly higher when the expression of pSer727-STAT3 was lower than 110, HR: 5.4 (96% CI: 1.8-16.4) and HR: 2.3 (95% CI: 1.1-4.6) respectively, P<.001. CONCLUSIONS: pSer727-STAT3 is not a survival marker in patients with CCRCC. However, it is a cancer-specific survival marker in high-risk patients, even in metastatic patients undergoing treatment with antiangiogenic agents

Analysis of the nuclear expression of pSer727-STAT3 as a prognostic factor in patients with clear cell renal carcinoma. / Análisis de la expresión nuclear de pSer727-STAT3 como factor pronóstico en pacientes con carcinoma renal de células claras.

INTRODUCTION: Currently, clear cell renal carcinoma (CCRCC) has no prognostic markers. STAT3 protein (Signal Transducer and Activator of Transcription 3) is involved in the carcinogenesis of CCRCC. Its activation is produced by phosphorylation of the serine 727 residue, translocating to the nucleus where it is involved in carcinogenesis and tumor progression. The primary objective of the study was to evaluate cancer-specific survival rates in a series of 166 patients with CCRCC, and its subsequent correlation with the expression of pSer727-STAT3 as a prognostic marker of CCRCC. MATERIAL AND METHODS: We conducted a retrospective study on 166 patients with CCRCC undergoing partial or radical nephrectomy between 2000 and 2010. A tumor tissue microarray was constructed for immunohistochemical analysis of pSer727-STAT3 expression. The main variable of the study was cancer-specific survival. RESULTS: Patients were classified according to the UICC risk groups as follows: low in 78 patients (47%), intermediate in 52 (31.3%) and high 36 (21.7%); 11 patients (6.7%) were diagnosed with metastatic disease. During a mean follow-up of 97.2 months (1-208), 37 patients (22.3%) developed local and/or distant recurrence. Cancer-specific and overall mortality rates were 28.3% and 67.5%, respectively. The mean expression of pSer727-STAT3 was 92.9 (95% CI: 84.6-101.1) without showing any relationship with risk groups or other prognostic factors. In a Cox logistic regression analysis, pSer727-STAT3 did not behave as an independent predictor of cancer-specific mortality. However, in high-risk and metastatic patients, cancer-specific survival was significantly higher when the expression of pSer727-STAT3 was lower than 110, HR: 5.4 (96% CI: 1.8-16.4) and HR: 2.3 (95% CI: 1.1-4.6) respectively, P<.001. CONCLUSIONS: pSer727-STAT3 is not a survival marker in patients with CCRCC. However, it is a cancer-specific survival marker in high-risk patients, even in metastatic patients undergoing treatment with antiangiogenic agents.

Valor de la proteína STAT3 como factor pronóstico en el carcinoma renal de célula clara. Revisión sistemática / The role of STAT3 protein as a prognostic factor in the clear cell renal carcinoma. Systematic review

Contexto y objetivo: En los últimos años se han producido avances significativos en el conocimiento de la carcinogénesis renal. Hoy en día los tumores renales se clasifican en función de su perfil genético, y además se han desarrollado tratamientos específicos basados en la identificación de dianas terapéuticas. Sin embargo, todavía no se han identificado marcadores pronósticos. El objetivo de esta revisión es analizar la literatura que ha evaluado la expresión de la proteína STAT3 como marcador molecular en el carcinoma renal de célula clara (ccRCC). Adquisición de evidencia: En enero de 2018 se realizó una búsqueda sistemática de la literatura en Pubmed, Cochrane Library y Sciencedirect de las publicaciones realizadas desde 1990. Los términos de búsqueda fueron renal cell carcinoma and STAT3 or STAT-3 and prognostic factor. Se siguieron los principios de la declaración PRISMA y la estrategia de selección PICO, seleccionándose los artículos originales con series de pacientes diagnosticados de ccRCC localizado o metastásico, donde se analiza la actividad de STAT3 como marcador pronóstico. Se identificaron 132 publicaciones de las que finalmente se han revisado 10 por cumplir los criterios de inclusión. Síntesis de evidencia: La activación (fosforilación) de STAT3 (pSTAT3) en el residuo Ser727 es importante en el desarrollo y progresión de ccRCC. La expresión de pSTAT3 parece ser un marcador pronóstico y predictor de resistencia a algunos tratamientos en pacientes con enfermedad diseminada. Existe poca evidencia de su utilidad como un marcador pronóstico en pacientes con enfermedad localizada. Conclusiones: La expresión de pSTAT3(Ser727) en el núcleo de las células del ccRCC puede ser un marcador pronóstico y de respuesta al tratamiento en pacientes con ccRCC. La evidencia científica actual es limitada y son necesarios más estudios que demuestren su utilidad

Context and objective: There have been significant advances in the knowledge of renal carcinogenesis in the last years. Nowadays, renal tumours are classified according to their genetic profile and specific treatments based on the identification of therapeutic targets have also been developed. However, no prognostic markers have yet been identified. The aim of this review is to analyze literature that has evaluated the expression of the STAT3 protein as a molecular marker in clear cell renal carcinoma (ccRCC). Evidence acquisition: In January 2018 a systematic review was conducted in Pubmed, Cochrane library and Sciencedirect databases, from papers published from 1990. Search terms were "renal cell carcinoma" and "STAT3" or "STAT-3" and prognostic factor. Following the principles of the PRISMA declaration and the PICO selection strategy, original articles with series of patients diagnosed with localized or metastatic ccRCC, and where the activity of STAT3 is analyzed as a prognostic marker, were selected. A total of 132 publications were identified, of which 10 were finally revised, for they met the inclusion criteria. Evidence synthesis: STAT3 activation (phosphorylation) through Ser727 is important during ccRCC development and progression. PSTAT3 expression seems to be a prognostic marker and an antiangiogenic-resistance marker in metastatic patients. There is little evidence as prognostic marker in patients with localized disease. Conclusions: STAT3 (Ser 727) expression in the nucleus of the ccRCC cells can be a prognostic marker and an antiangiogenic-resistance marker. Current scientific evidence is limited and more studies are needed to demonstrate its usefulness

The role of STAT3 protein as a prognostic factor in the clear cell renal carcinoma. Systematic review. / Valor de la proteína STAT3 como factor pronóstico en el carcinoma renal de célula clara. Revisión sistemática.

CONTEXT AND OBJECTIVE: There have been significant advances in the knowledge of renal carcinogenesis n the last years. Nowadays, renal tumors are classified according to their genetic profile and specific treatments based on the identification of therapeutic targets have also been developed. However, no prognostic markers have yet been identified. The aim of this review is to analyse literature that has evaluated the expression of the STAT3 protein as a molecular marker in clear cell renal carcinoma (ccRCC). EVIDENCE ACQUISITION: In January 2018 a systematic review was conducted in Pubmed, Cochrane library and Sciencedirect databases, from papers published from 1990. Search terms were"renal cell carcinoma"and"STAT3"or"STAT-3"and"prognostic factor. Following the principles of the PRISMA declaration and the PICO selection strategy, original articles with series of patients diagnosed with localized or metastatic ccRCC, and where the activity of STAT3 is analysed as a prognostic marker, were selected. A total of 132 publications were identified, of which 10 were finally revised, for they met the inclusion criteria. EVIDENCE SYNTHESIS: STAT3 activation (phosphorylation) through Ser727 is important during ccRCC development and progression. PSTAT3 expression seems to be a prognostic marker and an antiangiogenic-resistance marker in metastatic patients. There is little evidence as prognostic marker in patients with localized disease. CONCLUSIONS: STAT3 (Ser 727) expression in the nucleus of the ccRCC cells can be a prognostic marker and an antiangiogenic-resistance marker. Current scientific evidence is limited and more studies are needed to demonstrate its usefulness.

Establishment of urinary exosome-like vesicles isolation protocol for FHHNC patients and evaluation of different exosomal RNA extraction methods.

BACKGROUND: Molecular and cellular pathophysiological events occurring in the majority of rare kidney diseases remain to be elucidated. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder caused by mutations in either CLDN16 or CLDN19 genes. This disease is characterized by massive urinary wasting of magnesium and calcium, osmosis deregulation and polyuria. Patients with p.G20D homozygous mutation in CLDN19 gene exhibit different progression to kidney failure suggesting that beyond the pathogenic mutation itself, other molecular events are favoring disease progression. Due to the fact that biopsy is not clinically indicated in these patients, urinary exosome-like vesicles (uEVs) can be envisioned as a valuable non-invasive source of information of events occurring in the kidney. Exosome research has increased notably to identify novel disease biomarkers but there is no consensus standardized protocols for uEVs isolation in patients with polyuria. For this reason, this work was aimed to evaluate and refine different uEVs isolation methods based on differential centrifugation, the gold standard method. RESULTS: Characterization by NTA, cryo-TEM and immunoblotting techniques identified the most appropriate protocol to obtain the highest yield and purest uEVs enriched fraction possible from urine control samples and FHHNC patients. Moreover, we tested five different RNA extraction methods and evaluated the miRNA expression pattern by qRT-PCR. CONCLUSIONS: In summary, we have standardized the conditions to proceed with the identification of differentially expressed miRNAs in uEVs of FHHNC patients, or other renal diseases characterized by polyuria.

Root caries analysis in working population of 35-44 years of age (Spain).

BACKGROUND: The aim of this study was to analyse the influence of socio-demographic variables, toothbrushing frequency, frequency of snacking between meals, and tobacco and alcohol consumption, in root caries in the Spanish working population of Valencia and Murcia regions. MATERIAL AND METHODS: Cross sectional study of 458 workers 35-44 years of age, who underwent a routine work-related check-up, from June 2009 to April 2010, and were also examined, following the WHO methodology, by a calibrated dentist. Stratified random sampling. Participants fulfilled a questionnaire comprising demographic data, toothbrushing frequency, snacking frequency and tobacco and alcohol consumption. RESULTS: The DFS index (root caries) in the employed population of 35-44 years was 0.45 ± 1.3, with a root caries prevalence of 18.6% and an active root caries prevalence of 13.5%. Higher root caries prevalence and active root caries prevalence were associated with male gender, manual occupations, foreign country of origin, lower levels of education and income, lower brushing frequency and higher frequency of snacking between meals. The DFS index was associated with all studied socio-demographic variables, but gender, and it was also associated with brushing frequency. The mean number of root decayed teeth was associated with all socio-demographic variables, but country of origin, and it was also associated with brushing frequency. CONCLUSIONS: Adult workers 35-44 years of age showed worse root condition in regard to caries than general population of this age cohort. In this study, the frequency of toothbrushing and snacking between meals were the variables that influenced more in root caries.

Revisión sistemática de los factores pronósticos del carcinoma renal / Systematic review of renal carcinoma prognostic factors

Contexto y objetivo: La evolución natural del carcinoma renal es heterogénea, encontrando diversos escenarios en cuanto a la presentación clínica, evolución y tipo de recidiva (local/metastásica). El objetivo de esta publicación es revisar la literatura existente con relación a los principales factores pronósticos del carcinoma renal. Adquisición de evidencia Se realiza una revisión sistemática mediante Pubmed de los artículos publicados, de acuerdo con los principios de la declaración PRISMA, desde 1999 (primera publicación de la clasificación de Motzer) hasta 2015. Los términos utilizados en la búsqueda han sido «kidney neoplasms», «kidney cancer», «renal cell carcinoma», «prognostic factors», «mortality», «survival» y «disease progression». Síntesis de evidencia: El mejor conocimiento de las vías moleculares implicadas en la oncogénesis renal junto con la aparición de tratamientos dirigidos con nuevas moléculas están provocando que los antiguos modelos pronósticos queden obsoletos, requiriendo de una revisión continua para la actualización de los nomogramas disponibles adaptados a los nuevos escenarios. Conclusiones: Es importante una correcta validación externa de los factores pronósticos existentes mediante estudios prospectivos y multicéntricos, para poder así incorporarlos a la práctica clínica habitual del urólogo

Context and objectives: The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. Evidence acquisition: A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. Evidence synthesis: The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. Conclusions: Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice

Metabolic syndrome or glucose challenge in first episode of psychosis?

Patients with schizophrenia exhibit a reduced life expectancy. Although unhealthy lifestyle or suicide risk plays a role, the main causes are diverse medical conditions such as cardiovascular diseases, type 2 diabetes mellitus and metabolic syndrome. Albeit pharmacological secondary side effects might also trigger previous conditions, studies in naïve patients reflect diverse anomalies at the onset. Patients with a first episode of psychosis, display a wide scope of metabolic abnormalities, ranging from normality till pathological values depending on the parameters studied. We attempted to evaluate the metabolic syndrome and glycemic homeostasis in a subset of antipsychotic-naïve patients with a first episode of non-affective psychosis. Patients (n=84) showed a similar prevalence of metabolic syndrome compared with a matched control sample (n=98) (6% vs 4%, P=0.562), while glucose homeostasis values differed significantly (14% vs. 5%, P=0.034). Our results suggest that metabolic syndrome is not a useful clinical condition to be evaluated in patients before pharmacological treatment. Abnormal glycemic homeostasis at the onset of the disease requires specific diagnostic tools and preventive measures in order to avoid future cardiovascular events. New strategies must be implemented in order to evaluate the cardiovascular risk and subsequent morbidity in patients at the onset of the disease.

Systematic review of renal carcinoma prognostic factors. / Revisión sistemática de los factores pronósticos del carcinoma renal.

CONTEXT AND OBJECTIVES: The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. EVIDENCE ACQUISITION: A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. EVIDENCE SYNTHESIS: The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. CONCLUSIONS: Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice.

Buchnera has changed flatmate but the repeated replacement of co-obligate symbionts is not associated with the ecological expansions of their aphid hosts.

Symbiotic associations with bacteria have facilitated important evolutionary transitions in insects and resulted in long-term obligate interactions. Recent evidence suggests that these associations are not always evolutionarily stable and that symbiont replacement, and/or supplementation of an obligate symbiosis by an additional bacterium, has occurred during the history of many insect groups. Yet, the factors favouring one symbiont over another in this evolutionary dynamic are not well understood; progress has been hindered by our incomplete understanding of the distribution of symbionts across phylogenetic and ecological contexts. While many aphids are engaged into an obligate symbiosis with a single Gammaproteobacterium, Buchnera aphidicola, in species of the Lachninae subfamily, this relationship has evolved into a 'ménage à trois', in which Buchnera is complemented by a cosymbiont, usually Serratia symbiotica. Using deep sequencing of 16S rRNA bacterial genes from 128 species of Cinara (the most diverse Lachninae genus), we reveal a highly dynamic dual symbiotic system in this aphid lineage. Most species host both Serratia and Buchnera but, in several clades, endosymbionts related to Sodalis, Erwinia or an unnamed member of the Enterobacteriaceae have replaced Serratia. Endosymbiont genome sequences from four aphid species confirm that these coresident symbionts fulfil essential metabolic functions not ensured by Buchnera. We further demonstrate through comparative phylogenetic analyses that cosymbiont replacement is not associated with the adaptation of aphids to new ecological conditions. We propose that symbiont succession was driven by factors intrinsic to the phenomenon of endosymbiosis, such as rapid genome deterioration or competitive interactions between bacteria with similar metabolic capabilities.

Assessment of a 16S rRNA amplicon Illumina sequencing procedure for studying the microbiome of a symbiont-rich aphid genus.

The bacterial communities inhabiting arthropods are generally dominated by a few endosymbionts that play an important role in the ecology of their hosts. Rather than comparing bacterial species richness across samples, ecological studies on arthropod endosymbionts often seek to identify the main bacterial strains associated with each specimen studied. The filtering out of contaminants from the results and the accurate taxonomic assignment of sequences are therefore crucial in arthropod microbiome studies. We aimed here to validate an Illumina 16S rRNA gene sequencing protocol and analytical pipeline for investigating endosymbiotic bacteria associated with aphids. Using replicate DNA samples from 12 species (Aphididae: Lachninae, Cinara) and several controls, we removed individual sequences not meeting a minimum threshold number of reads in each sample and carried out taxonomic assignment for the remaining sequences. With this approach, we show that (i) contaminants accounted for a negligible proportion of the bacteria identified in our samples; (ii) the taxonomic composition of our samples and the relative abundance of reads assigned to a taxon were very similar across PCR and DNA replicates for each aphid sample; in particular, bacterial DNA concentration had no impact on the results. Furthermore, by analysing the distribution of unique sequences across samples rather than aggregating them into operational taxonomic units (OTUs), we gained insight into the specificity of endosymbionts for their hosts. Our results confirm that Serratia symbiotica is often present in Cinara species, in addition to the primary symbiont, Buchnera aphidicola. Furthermore, our findings reveal new symbiotic associations with Erwinia- and Sodalis-related bacteria. We conclude with suggestions for generating and analysing 16S rRNA gene sequences for arthropod-endosymbiont studies.

Fold-pitchfork bifurcation for maps with Z(2) symmetry in pipe flow.

This study aims to provide a better understanding of recently identified transition scenarios exhibited by traveling wave solutions in pipe flow. This particular family of solutions are invariant under certain reflectional symmetry transformations and they emerge from saddle-node bifurcations within a two-dimensional parameter space characterized by the length of the pipe and the Reynolds number. The present work precisely provides a detailed analysis of a codimension-two saddle-node bifurcation arising in discrete dynamical systems (maps) with Z(2) symmetry. Normal form standard techniques are applied in order to obtain the reduced map up to cubic order. All possible bifurcation scenarios exhibited by this normal form are analyzed in detail. Finally, a qualitative comparison of these scenarios with the ones observed in the aforementioned hydrodynamic problem is provided.

Mode competition in cylindrical flows driven by sidewall oscillations.

The transition from a two-dimensional to three-dimensional flow in systems with spatial O(2) symmetry and spatiotemporal Z(2) symmetry happens in many fluid systems, like wakes or periodically forced flows. In most of these systems, the dynamics after the first bifurcation is very complex and involves cascades of bifurcations in a very narrow parameter range. A numerical study of a flow in an enclosed cylindrical cavity driven by axial oscillations of the sidewall, which allows a detailed study of the secondary bifurcations and the corresponding mode interactions, is presented. The study focuses on a codimension-2 point that acts as the organizing center of the dynamics for moderate values of the forcing frequency. The unraveled dynamics is very rich, including slow-fast dynamics and hysteresis, and may help understand the bifurcation cascades in more complex systems.