Hepatitis C Virus positivity prediction from serum samples using NIRS and L1-penalized classification.

AIMS: The hepatitis C virus (HCV) has developed a strategy to coexist with its host resulting in varying degrees of tissue and cell damage, which generate different pathological phenotypes, such as varying degrees of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, there is no integrated information that can predict the evolutionary course of the infection. We propose to combine Near-infrared spectroscopy (NIRS) and machine learning techniques to provide a predictive model. In this work, we propose to discriminate HCV positivity in biobank patient serum samples. METHODS: 126 serum samples from 38 HCV patients in different stages of the disease were obtained from the Biobank of Hospital Universitario Fundación Alcorcon. NIRS spectrum was captured by a FT-NIRS Spectrum 100 (Perkin Elmer) device in reflectance mode. For each patient, the HCV positivity was identified (PCR) and labeled as detectable =1 and undetectable =0. We propose an L1-penalized logistic regression model to classify each spectrum as positive (1) or negative (0) for HCV presence (x). The regularization parameter is selected using 5- fold cross-validation. The penalized model will induce sparsity in the solution so that only a few relevant wavelengths will be different from zero. RESULTS: L1-penalized logistic regression model provided 167 wavelengths different from zero. The accuracy on an independent test set was 0.78. CONCLUSIONS: We present a straightforward promising approach to detect HCV positivity from patient serum samples combining NIRS and machine learning techniques. This result is encouraging to predict HCV progression, among other applications. Clinical relevance- We presented a simple while promising approach to use machine learning and NIRS to analyze viral presence on sample serums.

Predictive modeling of hypophosphatasia based on a case series of adult patients with persistent hypophosphatasemia.

Approximately half of individuals with hypophosphatasemia (low levels of serum alkaline phosphatase) have hypophosphatasia, a rare genetic disease in which patients may have stress fractures, bone and joint pain, or premature tooth loss. We developed a predictive model based on specific biomarkers of this disease to better diagnose this condition. INTRODUCTION: Hypophosphatasemia is a condition in which low levels of alkaline phosphatase (ALP) are detected in the serum. Some individuals presenting with this condition may have a rare genetic disease called hypophosphatasia (HPP), which involves mineralization of the bone and teeth. Lack of awareness of HPP and its nonspecific symptoms make this genetic disease difficult to diagnose. We developed a predictive model based on biomarkers of HPP such as ALP and pyridoxal 5'-phosphate (PLP), because clinical manifestations sometimes are not recognized as symptoms of HPP. METHODS: We assessed 325,000 ALP results between 2010 and 2015 to identify individuals suspected of having HPP. We performed univariate and multivariate analyses to characterize the relationship between hypophosphatasemia and HPP. Using several machine learning algorithms, we developed several models based on biomarkers and compared their performance to determine the best model. RESULTS: The final cohort included 45 patients who underwent a genetic test. Half (23 patients) showed a mutation of the ALPL gene that encodes the tissue-nonspecific ALP enzyme. ALP (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.3-0.8, p = 0.01) and PLP (OR 1.06, 95% CI 1.01-1.15, p = 0.04) were the only variables significantly associated with the presence of HPP. Support vector machines and logistic regression were the machine learning algorithms that provided the best predictive models in terms of classification (area under the curve 0.936 and 0.844, respectively). CONCLUSIONS: Given the high probability of a misdiagnosis, its nonspecific symptoms, and a lack of awareness of serum ALP levels, it is difficult to make a clinical diagnosis of HPP. Predictive models based on biomarkers are necessary to achieve a proper diagnosis. Our proposed machine learning approaches achieved reasonable performance compared to traditional statistical methods used in biomedicine, increasing the likelihood of properly diagnosing such a rare disease as HPP.

Respuesta hipertensiva al ejercicio: ¿tiene implicaciones pronósticas? / Hypertensive response to exercise: Does it has prognostic implications?

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Prevalencia y características clínicas de la esteatohepatitis no alcohólica en una población con hipertensión arterial esencial / Prevalence and clinical features of non-alcoholic steatohepatitis in a hypertensive population

Objetivo: El hígado graso no alcohólico es una enfermedad hepática crónica caracterizada por el depósito de grasa en los hepatocitos. En su evolución puede generar inflamación, denominada esteatohepatitis no alcohólica (EHNA), y fibrosis. La EHNA se ha asociado con el síndrome metabólico (SM) y con otros factores de riesgo cardiovascular. Nuestro objetivo ha sido analizar las características epidemiológicas de la EHNA en una población hipertensa, con alta prevalencia de SM, y valorar cuáles son los posibles factores que se asocian con la EHNA. Métodos: Se han utilizado los datos de 3.473 pacientes de la Unidad de Hipertensión del Hospital Universitario de Móstoles en un estudio retrospectivo, observacional y transversal. La EHNA se definió como la presencia de esteatosis hepática determinada mediante ecografía abdominal, junto con el aumento de alanina aminotransferasa y/o aspartato aminotransferasa mayor o igual a 1,5 veces el valor superior de la normalidad, en ausencia de otras causas de hepatopatía: consumo de alcohol, hepatitis autoinmune, farmacológica, vírica o hemocromatosis. Se realizaron análisis univariantes para evaluar la relación de cada variable con la variable dependiente, un estudio multivariante mediante regresión logística y un análisis de la varianza para estudiar la relación del número de factores de SM con la presencia de EHNA. Resultados: La cohorte final incluyó 2.242 pacientes (51,3% varones), de los cuales 255 (11,4%) presentaban criterios de EHNA (71% varones). El 52,6% presentaba SM (69,4% en el grupo de EHNA frente al 50,5% sin EHNA, p=0,001). La prevalencia de diabetes mellitus tipo 2 fue de 11,5% (16,5% en el grupo con EHNA frente al 10,8% de los pacientes sin EHNA, p=0,01). En el análisis multivariado, el perímetro abdominal, la presencia de SM (como variable categórica), el índice de masa corporal, la diabetes mellitus tipo 2, la edad, la insulina plasmática basal y la ferritinemia se asociaron de forma independiente con la presencia de EHNA. El análisis de la varianza reveló que la EHNA y los niveles de transaminasas se correlacionaron también de forma significativa con el número de factores de SM. Conclusiones: En nuestra población, tanto el SM como la diabetes mellitus tipo 2 y varios factores relacionados con el SM se asociaron de manera independiente con la presencia de EHNA. La EHNA puede así representar también la manifestación hepática del SM en los pacientes con hipertensión arterial esencial

Objective: Non-alcoholic fatty liver is a chronic liver disease in which fat is deposited in the liver, causing an inflammation called non-alcoholic steatohepatitis (NASH), and fibrosis. NASH is associated with metabolic syndrome (MS) and other cardiovascular risk factors. The aim of this study was to analyse the epidemiological features of NASH within a hypertensive population, with a high prevalence of MS, and to determine the features related to NASH. Methods: The computerised records were collected from 3,473 patients from Mostoles University Hospital's Hypertension Unit in order to perform a retrospective, cross-sectional study. NASH was considered as ultrasound-detected fatty liver disease along with serum levels of alanine aminotransferase or aspartate aminotransferase 1.5 times above normal values, having ruled out other causes of liver disease: alcohol abuse, autoimmune hepatitis, drug toxicity, virus and hemochromatosis. A univariate, multivariate, and ANOVA analysis were performed to assess the effect of the studied features on the response of interest. Results: The cohort included 2,242 patients (51.3% men). NASH was present in 255 patients (11.4%) of whom 71% were men. MS was detected in 52.6% of patients (69.4% in the NASH group, and 50.5% in the non-NASH group, P=.001). Prevalence of type 2 diabetes mellitus was 11.5% (16.5% in the NASH group, and 10.8% in the non-NASH group, P=.01). In a multivariate analysis, waist circumference, MS, body mass index, type 2 diabetes mellitus, age, fasting serum insulin, and serum ferritin were associated with NASH. ANOVA revealed that NASH and transaminases were also significantly associated with components of metabolic syndrome. Conclusions: In the population studied, MS, type 2 diabetes mellitus, and several components of MS were independently associated with NASH. Therefore, NASH can be considered as the liver manifestation of MS in patients with arterial hypertension

[Prevalence and clinical features of non-alcoholic steatohepatitis in a hypertensive population]. / Prevalencia y características clínicas de la esteatohepatitis no alcohólica en una población con hipertensión arterial esencial.

OBJECTIVE: Non-alcoholic fatty liver is a chronic liver disease in which fat is deposited in the liver, causing an inflammation called non-alcoholic steatohepatitis (NASH), and fibrosis. NASH is associated with metabolic syndrome (MS) and other cardiovascular risk factors. The aim of this study was to analyse the epidemiological features of NASH within a hypertensive population, with a high prevalence of MS, and to determine the features related to NASH. METHODS: The computerised records were collected from 3,473 patients from Mostoles University Hospital's Hypertension Unit in order to perform a retrospective, cross-sectional study. NASH was considered as ultrasound-detected fatty liver disease along with serum levels of alanine aminotransferase or aspartate aminotransferase 1.5 times above normal values, having ruled out other causes of liver disease: alcohol abuse, autoimmune hepatitis, drug toxicity, virus and hemochromatosis. A univariate, multivariate, and ANOVA analysis were performed to assess the effect of the studied features on the response of interest. RESULTS: The cohort included 2,242 patients (51.3% men). NASH was present in 255 patients (11.4%) of whom 71% were men. MS was detected in 52.6% of patients (69.4% in the NASH group, and 50.5% in the non-NASH group, P=.001). Prevalence of type 2 diabetes mellitus was 11.5% (16.5% in the NASH group, and 10.8% in the non-NASH group, P=.01). In a multivariate analysis, waist circumference, MS, body mass index, type 2 diabetes mellitus, age, fasting serum insulin, and serum ferritin were associated with NASH. ANOVA revealed that NASH and transaminases were also significantly associated with components of metabolic syndrome. CONCLUSIONS: In the population studied, MS, type 2 diabetes mellitus, and several components of MS were independently associated with NASH. Therefore, NASH can be considered as the liver manifestation of MS in patients with arterial hypertension.

Cystatin C as a predictor of cardiovascular outcomes in a hypertensive population.

Calculating the estimated glomerular filtration rate (eGFR) using creatinine-based equations may underestimate cardiovascular risk. Cystatin C-based eGFR may be a stronger prognostic biomarker than creatinine-based eGFR when assessing cardiovascular outcomes and mortality. Our aim was to determine whether levels of serum cystatin C, as an estimator of GFR, had a higher predictive value than creatinine-based eGFR for incident cardiovascular disease among hypertensive patients. We retrospectively analyzed the records of 2016 hypertensive patients from the Hypertension Unit at Mostoles University Hospital between 2006 and 2016. We calculated the eGFR using 3 CKD-EPI equations. The outcomes we included in our study were cardiovascular death, non-cardiovascular death, stroke, incident heart failure, and myocardial infarction. We used the Cox regression hazard model to estimate the hazard ratio. Our analysis found that, in terms of cardiovascular morbidity and mortality, both cystatin C-based eGFR (HR 2.88, 95% CI 1.86-4.47, P<0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.83, 95% CI 1.73-4.63, P<0.0001). In terms of all-cause mortality, cystatin C-based eGFR (HR 4.24, 95% CI 2.38-7.53, P<0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.77, 95% CI 1.43-5.36, P<0.0001). Our findings suggest that both cystatin C-based eGFRs may be stronger predictors of all-cause mortality and cardiovascular events in our hypertensive cohort when compared to creatinine-based eGFR, and may improve the risk assessment in certain populations.

Implicación de las moléculas HLA de clase I en el escape inmunitario de tumores urológicos / Involvement of HLA Class I Molecules in the Immune Escape of Urologic Tumors

Contexto y objetivo: Analizar la influencia de las distintas alteraciones de las moléculas del antígeno leucocitario humano de clase i (HLA I ) en la promoción del cáncer renal, vesical y prostático. También estudiaremos la correlación entre la expresión de estas moléculas y la progresión de la enfermedad neoplásica, además de la respuesta al tratamiento. Adquisición de evidencias: Se ha podido constatar, experimentalmente, que el sistema inmunitario puede reconocer y destruir células tumorales. Mediante el análisis de la expresión de las moléculas HLA I, en la superficie de células tumorales, hemos podido estudiar este mecanismo de escape tumoral frente al sistema inmunitario. Síntesis de evidencias: Una alteración o daño irreversible en las moléculas HLA de clase i es utilizado por las células cancerígenas como mecanismo de escape frente al sistema inmunitario. La función de estas moléculas es reconocer péptidos endógenos y presentarlos a los linfocitos T del sistema inmunitario. Existe una clara relación entre alteraciones reversibles de HLA I y el éxito de la terapia, mientras que las lesiones irreversibles implican una falta de respuesta al tratamiento. La activación del sistema inmunitario puede revertir la expresión de moléculas HLA I en aquellos tumores con lesiones reversibles, mientras que los tumores con lesiones irreversibles no responden a dicha activación. Determinar el tipo de alteración HLA I en los tumores es de vital importancia a la hora de elegir el tipo de tratamiento a seguir buscando el éxito terapéutico. Aquellos tumores con lesiones reversibles pueden ser tratados con inmunoterapias clásicas, sin embargo, los tumores con alteraciones irreversibles deberían seguir protocolos alternativos, como el uso de vectores virales que trasporten los genes HLA dañados para conseguir la reexpresión de la proteína. Conclusión: A partir de los estudios realizados, en tumores urológicos, podemos concluir que las moléculas HLA de clase i tienen un papel fundamental en el escape de estos tumores frente al sistema inmunitario

Context and objective: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. Evidences acquisition: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Evidences synthesis: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. Conclusion: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system

Effect of extender and amino acid supplementation on sperm quality of cooled-preserved Andalusian donkey (Equus asinus) spermatozoa.

The main aim of this study was to evaluate the efficacy of two commercially available liquid stallion semen extenders for the preservation of Andalusian donkey semen at 5°C for up to 72h, and to evaluate the effect of amino acid addition on sperm quality of cooled donkey semen. In addition, this study investigated the effect of seasons on semen characteristics of Andalusian jackasses. Throughout a year, 50 ejaculates were collected from ten adult donkeys and a complete semen evaluation was performed immediately after collection. In Experiment 1, semen samples (n=32) were pooled, divided into two aliquots, and cooled in either Gent(®) A or INRA 96(®). In Experiment 2, pooled semen samples (n=9) were cooled in Gent A(®) supplemented with 0 (as control), 20, 40, or 60mM for each glutamine, proline, or taurine. Fresh semen and chilled samples were assessed for sperm motility, morphology, acrosome integrity, and plasma membrane integrity. Sperm motility variables were greater (P<0.05) in Gent(®) A than in INRA 96(®). The presence of glutamine, proline, or taurine in Gent(®) A improved (P<0.001) the motility of Andalusian donkey spermatozoa. Differences (P<0.05) in some sperm variables were observed among seasons. In conclusion, Gent(®) A maintained sperm motility characteristics after 72h of cold storage to a greater extent than INRA 96(®). Moreover, motility was greater when Gent(®) A supplemented at different concentrations of amino acids than Gent(®) A with no supplementation. An effect of seasons on the semen quality of the Andalusian donkey was demonstrated.

Effect of single layer centrifugation using Androcoll-E-Large on the sperm quality parameters of cooled-stored donkey semen doses.

The aim of this study was to determine the effect of single layer centrifugation (SLC) using Androcoll-E-Large on donkey sperm quality parameters after 24 h of cool-storage. Ejaculates were collected from Andalusian donkeys and then cooled at 5°C. SLC was carried out after 24 h of cool-storage using Androcoll-E-Large. In the first experiment, all sperm parameters assessed (total and progressive sperm motility, viability, sperm morphology and sperm kinematics VCL, VSL, VAP, LIN, STR, WOB, ALH and BCF) were statistically compared between semen samples processed or not with Androcoll-E-Large. Significant differences (P<0.05) were found between SLC-selected and unselected semen samples for all parameters assessed, obtaining better results after SLC. In the second experiment, semen samples were classified in two groups according to their sperm progressive motility (PM) before SLC. Then, the increments obtained in semen quality parameters after SLC were compared between groups. No significant differences were found between groups, indicating that SLC improved the sperm quality parameters of entire set of semen samples processed with independence to their original PM. In conclusion, SLC with Androcoll-E-Large can be used in donkeys, increasing the sperm quality of cooled-stored donkey semen doses after 24 h of cool storage.

Involvement of HLA class I molecules in the immune escape of urologic tumors.

CONTEXT AND OBJECTIVE: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. EVIDENCES ACQUISITION: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. EVIDENCES SYNTHESIS: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. CONCLUSION: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system.

Relationship between conventional semen characteristics, sperm motility patterns and fertility of Andalusian donkeys (Equus asinus).

Sperm quality has an important role in determining fertility. The aims of this study were to compare the conventional sperm parameters, plus the characteristics of the motility patterns of the different sperm subpopulations, of donkey donors with different fertility level, and to determine their relationships to fertility. Thirty ejaculates from 6 Andalusian donkeys were assessed for gel-free volume, pH, sperm concentration, motility and morphology. The fertility of donkeys was classified on the basis of pregnancy rates per cycle, where donkeys with a per cycle pregnancy rate ≥60% were considered to be "fertile" (n=3) and those with a per cycle pregnancy rate <40% were categorized to be "sub-fertile" (n=3). Significant differences (P<0.001) between the "fertile" and the "sub-fertile" group were found for total and progressive motility, and for straight line velocity. Sperm variables associated (P<0.05) with an increase in percent pregnant per cycle included total motility (r=0.37), progressive motility (r=0.53), curvilinear velocity (r=0.44), straightness (r=0.39), beat cross frequency (r=0.44), and gel-free volume (r=0.53). Four sperm subpopulations (sP) were identified in fresh semen: sP1 (slow and non-progressive spermatozoa, 20%), sP2 (moderately slow but progressive spermatozoa, 71.2%), sP3 (highly active but non-progressive spermatozoa, 2.9%), and sP4 (highly active and progressive spermatozoa, 5.9%). The lowest percentage (3.1%; P<0.001) of sP4 spermatozoa was observed in the "sub-fertile" group. Three of the sperm subpopulations were related (P<0.05) to fertility (sP2, r=0.54; sP3, r=0.45; sP4, r=0.56). In conclusion, we were able to relate the fertility of donkeys with in vitro measures of sperm motility using computer-assisted sperm analysis techniques.

Arteritis de Takayasu como causa de hipertensión secundaria / Takayasu arteritis: cause of secondary hypertension

Describimos un caso, en una mujer de mediana edad, de hipertensión arterial con diferencias de tensión arterial entre ambos brazos, secundaria a secuelas de arteritis de Takayasu, con afectación de troncos supraaórticos y aorta abdominal y estenosis ligera de ambas arterias renales e infartos corticales renales bilaterales. Del total de los pacientes con esta entidad, 80-90% son del género femenino, con inicio de la enfermedad entre los 10 y los 40 años de edad. Se caracteriza por la aparición de estenosis y aneurismas localizados o segmentarios de los vasos afectos (AU)

We present the case of a middle aged woman with arterial hypertension in whom the blood pressure was different in both arms. This condition was secondary to sequels of Takayasu arteritis, with involvement of the supraaortic trunk and abdominal aorta and mild stenosis of both renal arteries and bilateral ischemic lesions in both kidneys. Of the total patients affected by this condition, 80-90% are women, aged 10 to 40 years. Takayasu arteritis is characterized by the appearance of stenosis and localized or segmental aneurysms of the affected vessels (AU)

Sperm motility patterns in Andalusian donkey (Equus asinus) semen: effects of body weight, age, and semen quality.

The aims of this study were to (1) identify sperm subpopulations with specific motion characteristics in fresh Andalusian donkey ejaculates; (2) evaluate the effects of individual donkey and ejaculates within the same donkey on the distribution of the subpopulations found; and (3) explore the relationship between the age and the body weight of donkey donors, the sperm quality parameters, and the sperm subpopulations structure. Sixty ejaculates from 12 Andalusian donkeys (five ejaculates per donkey), ranging in age from 4 to 15 years, were collected. Immediately after collection, sperm characteristics (volume, sperm concentration, objective sperm motility, and sperm morphology) were assessed. Donkeys were evaluated for body weight. Significant (P < 0.05) correlations were established between the body weight of the donkeys and the pH (r = -0.52), sperm motility (percentage of motile spermatozoa: r = -0.31; percentage of progressive motile spermatozoa: r = -0.34), and total sperm abnormalities (r = 0.38). The correlations of the age with the measures of semen quality were low and not significant (P > 0.05). A multivariate clustering procedure separated 65,342 motile spermatozoa into four subpopulations: subpopulation 1, consisting of slow and nonprogressive spermatozoa (15.4%), subpopulation 2, consisting of moderately slow but progressive spermatozoa (35.9%), subpopulation 3, consisting of highly active but nonprogressive spermatozoa (18.5%), and subpopulation 4, consisting of highly active and progressive spermatozoa (30.2%). The distribution of these subpopulations varied significantly (P < 0.05) according to several parameters such as the individual donkey, the ejaculate of the same donkey, the total motility, and the overall sperm concentration. Our results show the existence of four well-defined motile sperm subpopulations in Andalusian donkey ejaculates, and suggest a high heterogeneity in the ejaculate structure in donkey. The relationship between the distribution of the sperm subpopulations and individual donkey, total motility, and sperm concentration shows that the spermatozoa of each have different motility patterns. However, the proportions of sperm subpopulations in the ejaculates did not vary with age and body weight. Finally, the study of discrete subpopulations of motile spermatozoa could lead to a substantial increase in information acquired during donkey semen analysis.

Embryonic cerebrospinal fluid activates neurogenesis of neural precursors within the subventricular zone of the adult mouse brain.

INTRODUCTION: There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. RESULTS: Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. CONCLUSIONS: Embryonic CSF is a powerful neurogenesis inductor in homologous neuronal precursors in the adult brain. This property of embryonic CSF could be a useful tool in neuroregeneration strategies.

Uricemia y síndrome metabólico en pacientes con hipertensión arterial / Uricemia and metabolic syndrome in patients with arterial hypertension

Objetivo. Los niveles de uricemia se han asociado con el síndrome metabólico (SM). Sin embargo, la relación entre estas 2 variables en pacientes con hipertensión arterial (HTA) esencial no ha sido estudiada. Pacientes y métodos. Estudio observacional, transversal, de 592 pacientes con HTA esencial. Para la definición de SM se emplearon >=3 criterios de la ATP-III. Se excluyeron a los pacientes con tratamiento hipouricemiante. Resultados. La prevalencia de SM fue del 52% (IC del 95%: 48-56%) y aumentó gradualmente a medida que se incrementaba la uricemia (uricemia: <=4,7mg/dl, 36%; uricemia >=6,8mg/dl, 70%; p<0,001). Los enfermos hipertensos con SM mostraron una uricemia media más elevada que los que no tenían esta comorbilidad (6,1±1,5mg/dl vs 5,4±1,3mg/dl; p<0,0001). La prevalencia de hiperuricemia (varones: >=7,0mg/dl; mujeres: >=6,0mg/dl) en los pacientes hipertensos que no recibían tratamiento diurético fue del 24,3% (en aquellos con SM, 40,5% frente a un 11,4% en los que no tenían SM; p<0,001). En el análisis multivariante los triglicéridos (OR: 1,008; IC del 95%: 1,004-1,012; p<0,001) y el índice de masa corporal (IMC) (OR: 1,118; IC del 95%: 1,059-1,181; p<0,001) fueron predictores independientes de la uricemia. Conclusiones. En los pacientes con HTA esencial, aproximadamente la mitad padecen SM y uno de cada 4 presenta hiperuricemia. El determinante más relevante del incremento de la concentración sérica de uratos es el aumento del IMC(AU)

Objective. Serum urate levels have been associated with metabolic syndrome (MS). However, the relationship between these two variables in patients with essential arterial hypertension has not been studied. Patients and methods. A Cross-sectional study in 592 patients with essential hypertension. The MS was defined according to the ATP-III criteria. We excluded patients with hypouricemic treatment. Results. The prevalence of MS was 52% (95% CI, 48-56%) and there was a graded increase with increasing serum urate (uricemia <=.7 mg/dl, 36%; uricemia >=6.8 mg/dl, 70%, P < 0.001). Hypertensive patients with MS showed a higher mean uricemia than those without this comorbidity (6.1 ± 1.5 mg/dl versus 5.4 ± 1.3 mg/dl, P <0.0001). The prevalence of hyperuricemia (men, > 7.0 mg/dL; women, >6.0 mg/dL) in hypertensive patients without diuretic treatment, was 24% (in those with MS 40% versus 11% without MS). In multivariate analysis, triglycerides (OR = 1.008, CI 95%: 1.004-1.012, P < 0.001) and body mass index (BMI) (OR = 1.118, CI 95%: 1.059-1.181, P < 0.001), were independent predictors of serum uric acid levels. Conclusions. In patients with essential hypertension, about half have MS and one out of four has hyperuricemia. The most important determinant of hyperuricemia is BMI(AU)

[Uricemia and metabolic syndrome in patients with arterial hypertension]. / Uricemia y síndrome metabólico en pacientes con hipertensión arterial.

OBJECTIVE: Serum urate levels have been associated with metabolic syndrome (MS). However, the relationship between these two variables in patients with essential arterial hypertension has not been studied. PATIENTS AND METHODS: A Cross-sectional study in 592 patients with essential hypertension. The MS was defined according to the ATP-III criteria. We excluded patients with hypouricemic treatment. RESULTS: The prevalence of MS was 52% (95% CI, 48-56%) and there was a graded increase with increasing serum urate (uricemia ≤ 4.7 mg/dl, 36%; uricemia ≥ 6.8 mg/dl, 70%, P < 0.001). Hypertensive patients with MS showed a higher mean uricemia than those without this comorbidity (6.1 ± 1.5 mg/dl versus 5.4 ± 1.3 mg/dl, P < 0.0001). The prevalence of hyperuricemia (men, > 7.0 mg/dL; women, > 6.0 mg/dL) in hypertensive patients without diuretic treatment, was 24% (in those with MS 40% versus 11% without MS). In multivariate analysis, triglycerides (OR = 1.008, CI 95%: 1.004-1.012, P < 0.001) and body mass index (BMI) (OR = 1.118, CI 95%: 1.059-1.181, P < 0.001), were independent predictors of serum uric acid levels. CONCLUSIONS: In patients with essential hypertension, about half have MS and one out of four has hyperuricemia. The most important determinant of hyperuricemia is BMI.

Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.

Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates.

Recomendaciones específicas para el manejo del paciente con síndrome metabólico / Specific recommendations for the management of patients with metabolic syndrome

El término síndrome metabólico hace referencia a un acúmulo de factores de riesgo cardiovascular en cuya fisiopatología subyace la existencia de resistencia insulínica. Este trastorno metabólico se asocia a la presencia de obesidad. Un estado proinflamatorio y protrombótico contribuye al desarrollo de este cuadro. La consecuencia principal del síndrome es una mayor frecuencia en la incidencia de enfermedades cardiovasculares y en el desarrollo de diabetes mellitus tipo 2. El tratamiento consiste en la disminución de peso con medidas dietéticas y en la realización de ejercicio físico. Sin embargo, resulta también apropiado el empleo de fármacos específicos para cada uno de los factores de riesgo definitorios presentes. Rimonabant, un bloqueante selectivo de los receptores tipo 1 de los cannabinoides, que reduce el peso y mejora los factores de riesgo metabólico en pacientes obesos o con sobrepeso, podría convertirse en el primer tratamiento específico para este cuadro

The term metabolic syndrome refers to a group of cardiovascular disease risk factors whose underlying pathophysiology is thought to be related to insulin resistance. This common metabolic disorder is associated to the presence of obesity. A proinflammatory and prothrombotic state probably contributes to the syndrome. The primary consequence of this syndrome is the increased risk for cardiovascular disease and type 2 diabetes. The fundamental approach is weight reduction with dietary measures and increased physical activity. However, drug treatment is also appropriate for specific risk factors. Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces body weight and improves metabolic risk factors in overweight or obese patients and could become the first specific drug treatment for this disorder (AU)

Effects of pork vs veal consumption on serum lipids in healthy subjects.

AIMS: To analyse the influence of lean pork (P) and veal (V) consumption on the lipid profile of healthy subjects within the framework of a healthy diet comprising low levels of total fat (TF), saturated fatty acids (SFA) and cholesterol. DESIGN: Double-crossover, randomized and controlled trial SUBJECTS: 44 healthy individuals (22 male and 22 female), recruited voluntarily from the University Complutense of Madrid. The weight and lipid profiles of these volunteers were normal and their dietary patterns were typical for people in our area. INTERVENTIONS: The study comprised 4 phases: stabilisation phase (5 weeks), the participants followed their normal diet; second phase (6 weeks), half of the subjects, were randomised to lean pork or veal consumption, 150 g per day, for their main meal of the day; washout period (5 weeks) and final phase, which was the second phase of intervention (6 weeks). During the intervention stages, only the main meal of the day was taken in the Hospital. The rest of the subjects' diets consisted of different fortnightly menus designed in accordance with the recommendations of the Spanish Society of Arteriosclerosis (SEA). RESULTS: After both stages of intervention had been completed, there was a mean reduction of 5.5% in low-density lipoprotein cholesterol. However, after each intervention there were no significant differences between those who had consumed P, 2.62 (0.55) mmol/L and those who had consumed V, 2.71 (0.47) mmol/L. No differences were observed in any of the other parameters between those who had consumed P and those who had consumed V. CONCLUSIONS: Lean pork and veal produces similar effects on the lipid profiles of healthy subjects. Its consumption, as part of the saturated fat and cholesterol-controlled diet, could therefore be included in food guidelines, both for normal and therapeutic diets.