Expresión de Anhidrasa Carbónica IX en Carcinoma de Células Renales. Implicaciones Diagnósticas y pronosticas

INTRODUCCION. El carcinoma de células renales (CCR) es la tercera neoplasia urológica más frecuente. La mayoría de los pacientes (60-70%) se presentan con enfermedad localizada, pero aproximadamente un tercio de estos pacientes, recidivarán y fallecerán de su enfermedad. Actualmente no existe ningún marcador tisular o plasmático de diagnóstico ni de pronóstico de la enfermedad. La anhidrasa carbónica (CA), es un enzima cuya función es acelerar de forma reversible la conversión de dióxido de carbono (CO2) y agua (H2O) en ácido carbónico (H2CO3). Este a su vez se convierte en bicarbonato (HCO3-) y un hidrogenión (H+). Existen 6 familias de CA, y cada una tiene varias isoenzimas, la anhidrasa carbónica IX (CAIX) participa en la vía de la hipoxia-inducible, jugando un papel esencial en la angiogénesis de los tumores. CAIX está ausente en la mayoría de los tejidos humanos normales mientras que se expresa en el CCR de células claras (CCRcc). CAIX Regula el pH celular en respuesta a la hipoxia tumoral y al metabolismo anaerobio. La pérdida de función de VHL puede llevar a un acúmulo de HIF- 1α, con el consiguiente aumento de CAIX.HIPÓTESIS. Los niveles de CAIX en suero de pacientes con CCR, presentan variaciones tras la nefrectomía radical, existiendo diferencias en los valores de expresión de dicha molécula, que pueden llegar o no a desaparecer según desarrollen los pacientes o no recidiva tumoral.OBJETIVOS. Determinar la expresión de CAIX en tejido y suero de pacientes diagnosticados de CCR. Valorar si la expresión de CAIX está relacionada con el grado nuclear, la presencia de necrosis y el estadio tumoral. PACIENTES MATERIAL Y METODOS. Se analizaron 234 casos de CCR, de los cuales 168 eran CCRcc. Se extrajo muestra de sangre periférica de antes de la nefrectomía, a las 24 horas de esta y en el seguimiento, así como muestra de tejido tumoral y de tejido renal sano. Se utilizaron técnicas inmunohistoquímicas para evaluar la expresión de CAIX en tejido así como la técnica de ELISA para cuantificar la expresión en plasma.RESULTADOS. En los pacientes con CCRcc la CAIX se expresa en el análisis inmunohistoquímico en el 91,74% de los casos. No hubo expresión de CAIX en las muestras de tejido renal sano analizadas. La probabilidad de que la expresión de CAIX en tejido tumoral sea negativa aumenta cuanto más grande sea el tumor (T>10cm) (p=0,004). No se encontraron relaciones estadísticamente significativas entre la expresión inmunohistoquímica de CAIX en tejido tumoral en función de la T, la N, la M, el estadio tumoral, el Fuhrman, la presencia de necrosis, la progresión o el éxitus por CCRcc. Tampoco hubo diferencias estadísticamente significativas en los análisis de supervivencia, pero se aprecia una tendencia a supervivencias más cortas en los pacientes con CAIX negativa. Existe una relación estadísticamente significativa entre el tamaño tumoral y la CAIX en suero prequirúrgico y postquirúrgico, de modo que a más tamaño aumentan los valores de CAIX (p Existe una relación entre la progresión y el éxitus por CCRcc en función de la CAIX, de modo que hay más probabilidad de éxitus en pacientes con más cantidad de CAIX en suero prequirúrgico. La supervivencia global (SG), supervivencia libre de enfermedad (SLE), y la supervivencia cáncer específica (SCE) son menores cuanto más valor de CAIX hay en suero prequirúrgico, de forma estadísticamente significativa (p Tras la cirugía, los valores de CAIX en suero postquirúrgico disminuyen, sin embargo no hemos podido determinar si estos valores llegan a desaparecer hasta límites de normalidad de individuos sanos.CONCLUSIONES. La cuantificación de los niveles de CAIX en suero en pacientes con masas renales ofrece una gran cantidad de estrategias en el diagnóstico y pronóstico de la enfermedad. La CAIX podría ser una herramienta de apoyo de diagnóstico de CCRcc antes de la nefrectomía, en pacientes con masas renales pequeñas, así como ayudarnos en la estimación del estadio tumoral junto con las pruebas de imagen. La CAIX permite una estimación de la progresión y el riesgo de muerte por CCRcc, por lo que podría emplearse para identificar a pacientes con alto riesgo de recaída y muerte, independientemente de su estadio tumoral y proponer en este grupo de pacientes estrategias de seguimiento intensivo o tratamiento precoz.<br /

Laparoscopic simple prostatectomy vs bipolar plasma enucleation of the prostate in large benign prostatic hyperplasia. a two-center 3-year comparison

Purpose: To compare surgery outcomes and safety of button bipolar enucleation of the prostate vs laparoscopic simple prostatectomy in patients with large prostates (&gt; 80&nbsp;g) in a two-center cohort study. Methods: All patients with lower urinary tract symptoms due to benign prostatic enlargement (Prostate volume &gt; 80&nbsp;cc) undergoing button bipolar enucleation of the prostate (BTUEP) or laparoscopic simple prostatectomy (LSP) in two centers were enrolled. Data on clinical history, physical examination, urinary symptoms, uroflowmetry and prostate volume were collected at 0, 1, 3 6, 12, 24 and 36&nbsp;months. Early and long-term complications were recorded. Results: Overall, 296 patients were enrolled. Out of them, 167/296 (56%) performed a LSP and 129/296 (44%) performed a BTUEP. In terms of efficacy both procedures showed durable results at three years with a reintervention rate of 8% in the LSP group and of 5% in the BTUEP group. In terms of safety, BTUEP and LSP presented similar safety profiles with a 9% of transfusion rate and no major complications. Conclusion: LSP and BTUEP are safe and effective in treating large-volume adenomas with durable results at three years when performed in experienced centers

Hyperphosphatemia Promotes Senescence of Myoblasts by Impairing Autophagy Through Ilk Overexpression, A Possible Mechanism Involved in Sarcopenia

In mammalians, advancing age is associated with sarcopenia, the progressive and involuntary loss of muscle mass and strength. Hyperphosphatemia is an aging-related condition involved in several pathologies. The aim of this work was to assess whether hyperphosphatemia plays a role in the age-related loss of mass muscle and strength by inducing cellular senescence in murine myoblasts and to explore the intracellular mechanism involved in this effect. Cultured mouse C2C12 cells were treated with 10 mM beta-glycerophosphate (BGP] at different periods of time to induce hyperphosphatemia. BGP promoted cellular senescence after 24 h of treatment, assessed by the increased expression of p53, acetylated-p53 and p21 and senescence associated beta-galactosidase activity. In parallel, BGP increased ILK expression and activity, followed by mTOR activation and autophagy reduction. Knocking-down ILK expression increased autophagy and protected cells from senescence induced by hyperphosphatemia. BGP also reduced the proliferative capacity of cultured myoblasts. Old mice (24months-old] presented higher serum phosphate concentration, lower forelimb strength, higher expression of p53 and ILK and less autophagy in vastus muscle than young mice (5-months-old]. In conclusion, we propose that hyperphosphatemia induces senescence in cultured myoblasts through ILK overexpression, reducing their proliferative capacity, which could be a mechanism involved in the development of sarcopenia, since old mice showed loss of muscular strength correlated with high serum phosphate concentration and increased levels of ILK and p53

Disponibilidad y promoción de alcohol según la tipología de los locales y las condiciones socioeconómicas del área

Smoking and substance use during pregnancy are major preventable causes of mortality and morbidity, having a bidirectional and deleterious relationship with the mental health of the mother and child. As part of the WOMAP (Woman Mental Health and Addictions on Pregnancy) initiative, our study aimed to describe the prevalence of co-occurring mental illness and substance use problems, diagnoses and severity of those considered at risk and rates of treatment.A screening of 2,014 pregnant women was done using the AC-OK scale and they were asked about their smoking habits and services use for mental health/substance abuse. Of these, 170 women were considered at risk of co-occurring mental illness and substance use problems (≥ 2 positive responses to the AC-OK-Mental Health subscale, ≥ 1 positive response to the AC-OK-Substance Abuse subscale and/or smoking more than once a month and no use of specialized services) and were assessed with a more extensive battery of measures (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Posttraumatic stress disorder [PTSD] Checklist for DSM-5 [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] and Fagerström).In the last year, 614 women (30.5%) smoked tobacco (42.5% daily) and 9.8% were positive for both substance use and mental illness per the AC-OK. Only 11.1% of them received specific treatment in the previous three months while another 13.6% were scheduled to attend services in the following month. From the subsample assessed in depth, 62(36.5%) endorsed at least moderate depression, 35(20.6%) endorsed at least moderate anxiety, 32(18.8%) endorsed PTSD on the PCL, and 37 out of 88 alcohol users scored above the threshold in AUDIT (≥ 3).In conclusion, high prevalence and low treatment rates suggest that effective detection mechanisms should be integrated into usual care, allowing for early interventions. ------------------------------------------------------------------ El tabaquismo y el consumo de sustancias durante el embarazo son importantes causas prevenibles de morbimortalidad, teniendo una relación bidireccional y deletérea con la salud mental de la madre y el niño. Como parte de la iniciativa WOMAP (Woman Mental Health and Addictions on Pregnancy), se estudiaron 2014 embarazadas buscando describir la prevalencia de trastornos mentales y por uso de sustancias concurrentes, las tasas de tratamiento y los diagnósticos y la gravedad. Las participantes fueron evaluadas con la escala AC-OK y se les preguntó sobre sus hábitos tabáquicos y uso de servicios de salud mental/sustancias. De las participantes, 170 mujeres resultaron positivas para un trastorno mental y por uso de sustancias concurrentes (≥ 2 positivos a la subescala AC-OK-Salud Mental, ≥ 1 positivos a la subescala AC-OK-Sustancias y/o fumar más de una vez al mes y no estar en tratamiento) y fueron evaluadas en profundidad mediante una batería de escalas (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Post-traumatic stress disorder Checklist [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] y Fagerström). En el último año, 614 mujeres (30,5 %) fumaron tabaco (42,5 % diariamente) y el 9,8 % fueron positivas para problemas por uso de sustancias y salud mental según la AC-OK. Solo el 11,1 % había recibido tratamiento en los tres meses previos y solo un 13,6 % tenía una cita en el siguiente mes. De las 170 pacientes evaluadas secundariamente, 62(36,5 %) presentaron al menos depresión moderada, 35(20,6 %) al menos ansiedad moderada, 32(18,8 %) fueron positivas a la PCL-5, y 37 de las 88 que reconocieron uso de alcohol puntuaron por encima del umbral en AUDIT (≥ 3). En conclusión, la combinación de una prevalencia significativa junto con bajas tasas de tratamiento, remarcan la necesidad de mecanismos de detección efectivos en la atención habitual, permitiendo una intervención temprana.2020-2

Universidad y sociedad: comunicación e integración en empresas e instituciones públicas y organizaciones no lucrativas. Nuevos avances

Depto. de Teorías y Análisis de la ComunicaciónFac. de Ciencias de la InformaciónFALSEsubmitte

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Physical therapy in unilateral and bilateral vestibular hypofunction

[ES] Introducción: La rehabilitación vestibular (RV) basada en la terapia física, tiene el objetivo, en el caso de patología vestibular, de inducir la compensación del sistema nervioso central (SNC) a nivel de núcleos vestibulares y de otros niveles del SNC. Incluye ejercicios de habituación, adaptación y sustitución vestibular, ejercicios para mejorar el equilibrio y el control postural dinámico y ejercicios para el acondicionamiento general. En este capítulo discutimos los recientes avances sobre el adiestramiento del equilibrio y de la marcha, la estabilidad de la mirada y la habituación, en el contexto de los trastornos vestibulares uni y bilaterales. Método: Revisión narrativa. Resultados: Los ejercicios se prescriben para mejorar la función; fortaleciendo, y favoreciendo la flexibilidad y la resistencia, a través de la adaptación del RVO, la habituación, la sustitución sensorial, la marcha y el equilibrio postural. Son más eficaces los programas personalizados que los genéricos. El cumplimiento mejora con la personalización y las visitas de seguimiento a un fisioterapeuta. Discusión/Conclusiones: La RV permite mejorar el déficit funcional y los síntomas subjetivos derivados de la hipofunción vestibular periférica uni y bilateral, así como las alteraciones del equilibrio de origen central. Los objetivos de la RV consisten en reducir los síntomas para mejorar la estabilidad postural y de la mirada (particularmente durante los movimientos de la cabeza) y devolver al individuo a sus actividades normales, incluyendo la actividad física, la conducción y el trabajo habitual. Los médicos deben ofrecer la RV a quienes muestren limitaciones funcionales relacionadas con un déficit vestibular, pues actualmente se considera el tratamiento estándar en la disfunción vestibular periférica

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field