Síndrome metabólico en los cálculos de oxalato cálcico: ¿es tan importante en este tipo de litiasis? / Metabolic syndrome in calcium oxalate stones: Is it so important in this type of lithiasis?

introducción y objetivo Se ha descrito la asociación del síndrome metabólico con la litogénesis, especialmente en cálculos de ácido úrico. El objetivo de este trabajo es analizar la importancia del síndrome metabólico en la litogénesis oxalocálcica. Materiales y métodos Evaluación metabólica de 151 pacientes: parámetros bioquímicos, hormonales y orina de 24horas; características asociadas al síndrome metabólico. Se evaluó la relación entre las características asociadas con el síndrome metabólico y las relacionadas con la litogénesis mediante el coeficiente de correlación de Spearman (CCS), «t» de Student y prueba exacta de Fisher. Resultados El índice de masa corporal promedio (IMC) fue 25,9 (DE 3,7). La mediana de edad fue de 51 años (18,6-84,8) y el 64,9% eran hombres. No hubo diferencias estadísticamente significativas entre hipertensión y estradiol, testosterona, triglicéridos o colesterol (p>0,05). Referente a la glucosa la media fue 114,5 y 93,5mg/dl en pacientes con y sin hipertensión (p=0,000). Los niveles de glucosa, estradiol, testosterona o colesterol no variaron con la proteinuria (p>0,05). La media de triglicéridos fue 185,6 y 108.2mg/dl en pacientes con y sin proteinuria (p=0,001). La hipertensión y la proteinuria no se asociaron (p=0,586). El IMC se correlacionó con el ácido úrico sérico y urinario y la creatinina urinaria. Conclusiones Existen pocas asociaciones entre las características del síndrome metabólico y las anomalías relacionadas con la litogénesis. El síndrome metabólico no parece tener un papel relevante en el desarrollo de cálculos oxalocálcicos (AU)

Introduction and objective The association of metabolic syndrome with lithogenesis has been described, especially in uric acid stones. The aim of the work was to analyze the role of the metabolic syndrome in oxalocalcic lithogenesis. Materials and methods Metabolic evaluation of 151 patients including biochemical, hormonal and 24-urine urine parameters, as well as characteristics associated with metabolic syndrome. The relationship between characteristics associated with metabolic syndrome and those related to lithogenesis was evaluated using Spearman's correlation coefficient (SCC), Student's t test and Fisher's exact test. Results The average body mass index (BMI) was 25.9 (SD 3.7). The median age was 51 years (18.6-84.8) and 64.9% were men. There were no statistically significant differences between hypertension and estradiol, testosterone, triglycerides, or cholesterol (P=.191, .969, .454, .345, respectively). Regarding glucose, mean value was 114.5 and 93.5mg/dl in patients with and without hypertension (P=.000). Glucose, estradiol, testosterone, or cholesterol levels did not vary with proteinuria (P=.518, P=.227, P=.095, P=.218, respectively). Mean triglycerides were 185.6 and 108.2mg/dl in patients with and without proteinuria (P=.001). Hypertension and proteinuria were not associated (P=.586). BMI correlated with serum and urinary uric acid and urinary creatinine. Conclusions There are few associations between the characteristics of metabolic syndrome and abnormalities related to lithogenesis. Metabolic syndrome does not seem to have a relevant role in the development of oxalocalcic stones (AU)

Metabolic syndrome in calcium oxalate stones: Is it so important in this type of lithiasis?

INTRODUCTION AND OBJECTIVE: The association of the metabolic syndrome with lithogenesis has been described, especially in uric acid stones. The aim of the work was to analyze the role of the metabolic syndrome in oxalocalcic lithogenesis. MATERIALS AND METHODS: Metabolic evaluation of 151 patients including biochemical, hormonal and 24-urine urine parameters, as well as characteristics associated with metabolic syndrome. The relationship between the characteristics associated with the metabolic syndrome and those related to lithogenesis was evaluated using Spearman's correlation coefficient (SCC), Student's t test and Fisher's exact test. RESULTS: The average body mass index (BMI) was 25.9 (SD 3.7). The median age was 51 years (18.6-84.8) and 64.9% were men. There were no statistically significant differences between hypertension and estradiol, testosterone, triglycerides or cholesterol (P=.191, .969, .454, .345, respectively). Regarding glucose, the mean was 114.5 and 93.5mg/dl in patients with and without hypertension (P=.000). The levels of glucose, estradiol, testosterone or cholesterol did not vary with proteinuria (P=.518, P=.227, P=.095, P=.218, respectively). The mean triglycerides were 185.6 and 108.2mg/dl in patients with and without proteinuria (P=.001). Hypertension and proteinuria were not associated (P=.586). BMI correlated with serum and urinary uric acid and urinary creatinine. CONCLUSIONS: There are few associations between the characteristics of the metabolic syndrome and the anomalies related to lithogenesis. Metabolic syndrome does not seem to have a relevant role in the development of oxalocalcic stones.

Hepatitis C virus infection and the role of a pharmaceutical care program.

PURPOSE: The design, implementation, and assessment of a comprehensive pharmaceutical care program (CPCP) for hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAA) are described. SUMMARY: The advent of DAA regimens has caused the evolution of the role of hospital pharmacists, leading to the development of more specialized models of pharmaceutical care. Three clinical pharmacists were incorporated into the pharmacy department of a general tertiary teaching hospital in Madrid, Spain, with the aim of developing and implementing a CPCP for HCV-infected patients. Pharmacists were responsible for proposing standards and local guidelines to physicians, monitoring adherence to guidelines, managing drug interactions and adverse drug events (ADEs), providing patient education, and evaluating health outcomes and costs. Implementation steps included (1) estimation of the healthcare demand and pharmacy resources, (2) definition of the workflow of the CPCP, (3) definition of the treatment care plan, for which tools were developed to support pharmaceutical validation, detection, and management of ADEs and drug-drug interactions, and (4) program assessment in terms of safety and cost-effectiveness. The pharmacists' interventions performed, severity of errors intercepted, and patients' satisfaction with the CPCP were also assessed. This CPCP demonstrates that the involvement of the pharmacist throughout the care plan prevents harmful medication errors in this population (0.1 per patient) and prompts significant cost savings (€1.2 million for 1,930 treated patients). CONCLUSION: The implementation of a CPCP developed by hospital pharmacists for patients treated with DAA for HCV infection is an effective approach for preventing harmful medication errors and improving cost- effectiveness.

Faecal Transplantation, Pro- and Prebiotics in Parkinson's Disease; Hope or Hype?

Faecal microbiome transplantation (FMT) is an attractive technique, because the administration is relatively simple and in general has a mild adverse effect pattern. Moreover, FMT consists of a broad mixture, which could be beneficial, because at this moment it is not known what type of changes in the microbiome are needed. However, except from a few cases no clinical data in Parkinson's disease (PD) is available yet. There is some indication that FMT might be beneficial in severe constipated PD patients, but the clinical data to support this are very scarce. So, actually there are no good data in the public domain to support FMT at this moment in PD patients. FMT at this moment is a black box with too many unanswered questions, also with respect to safety concerns. Only the administration of species of Lactobacillus and Bifidobacterium over a time period of four to twelve weeks has repeatedly proven to be effective in treating constipation in PD. Also, no solid clinical data are available about the possible effects of probiotic treatment on motor symptoms or progression of PD. Therefore, also probiotic treatments in PD should wait until better clinical data become available, in order to select the right target populations and to have good estimates of the clinical effects to be expected.

Tendinitis del tendón largo del cuello: un imitador inusual del ictus isquémico / Longus colli tendinitis: An unusual stroke mimic

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Direct costs of a home parenteral nutrition programme.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a lifesaving treatment for people with chronic intestinal failure and its cost has been reported to be very high. The purpose of the present paper was to study the direct healthcare and non-healthcare costs associated with the HPN programme managed by a tertiary hospital. METHODS: Observational, retrospective study of all adult patients on HPN from 11.1.2014 to 10.31.2015 treated at Gregorio Marañón University Hospital (Madrid, Spain). An economic evaluation was undertaken to calculate the direct healthcare (HPN provision, outpatient monitoring and management of complications) and non-healthcare costs (transportation process) of the HPN programme. The variables were collected from medical records, the dispensary and the hospital's financial services. The unit costs were taken from official price lists. RESULTS: Thirty-two patients met the inclusion criteria. Total direct healthcare and non-healthcare costs amounted to €13,363.53 per patient (€124.02 per patient per day). The direct healthcare costs accounted for 98.32% of overall costs, while the non-healthcare costs accounted for the remaining 1.68%. HPN provision accounted for the majority of the costs (74.25%), followed by management of complications (21.85%) and outpatient monitoring (2.23%). CONCLUSIONS: The direct healthcare costs accounted for the majority of HPN expenditure, specifically HPN provision was the category with the highest percentage.

Reaction time and rhythm of movement in Huntington's disease.

Huntington disease (HD) is characterized by several hyperkinesias though motor slowness is also another cardinal in this disease. In addition, self-paced timing movements are also disturbed in HD, which may also affect several rhythmic voluntary movements such as gait. Motor slowness can be measured with clinical scales such as the Unified Huntington's Disease Rating Scale (UHDRS) and timed tests, but also with the reaction time (RT) paradigm. We evaluated RT as a measure of motor slowness in 30 patients with genetically confirmed Huntington's disease and 24 control subjects. We also evaluated self-paced timing precision (SPTP) by applying a simple software program devised by our group. Clinical assessment was performed according to the UHDRS, including motor section, total functional capacity (TFC) and cognitive section (verbal fluency test, symbol digit, and Stroop test) The mean values obtained for RT and SPTP were statistically different in HD as compared with those from controls (p<0.0005). We observed a statistically significant correlation between RT and TFC scores (rs=-0.57, p<0.005 Spearman's correlation) and also between SPTP values and TFC scores (rs=-0.40, p<0.05 Spearman's correlation). In addition, RT and SPTP significantly correlated with cognitive scores (including digit symbol, verbal fluency and Stroop tests). Simple tests such as RT and SPTP provide an objective evaluation of motor impairment in HD yielding measures that correlate with clinical assessment and functional disability.

Recurrence of stroke amongst women of reproductive age: impact of and on subsequent pregnancies.

BACKGROUND AND PURPOSE: The risk of recurrence of stroke after pregnancy is poorly known. METHODS: This was an observational study of women younger than 45 years of age with transient ischaemic attack (TIA), cerebral infarction (CI), cerebral venous thrombosis (CVT) or intracerebral hemorrhage (ICH) treated in a stroke unit (January 1996-2011). The clinical data were prospectively collected in a database. Information on reproductive history after stroke was obtained using telephone surveys (2011). The variables were demographic data, vascular risk factors, stroke type, outcomes, medical advice concerning pregnancies after stroke, number of pregnancies after stroke, neurological assessment during pregnancy, antithrombotic treatments during pregnancy/puerperium, fertility treatments administered and information about hemorrhagic/ischaemic stroke recurrence. RESULTS: Overall, 102 women were included: 24 TIA, 64 CI (four large vessel disease, 14 cardioembolic, 12 small vessel disease, 17 undetermined etiology, 17 uncommon etiology), 12 CVT and two ICH. Mean age at the time of first stroke was 35 (±7.5) years. Median follow-up was 7.4 years (range 1-17). Thirty-two pregnancies occurred in 27 patients (previous diagnosis: four TIA, 17 CI, five CVT and one ICH). One woman became pregnant using in vitro fertilization. Only eight pregnancies were followed up by a neurologist. Of 26 pregnancies without previous history of ICH, 18 (62%) underwent preventive antithrombotic treatment. No recurrence of stroke was observed during pregnancy/puerperium. Of the women without pregnancies after the first cerebrovascular event, four CIs and three TIAs were observed. CONCLUSION: The recurrence of stroke after pregnancy is very low, which should be considered when counseling these patients.

Optimal excitation and emission wavelengths to analyze amino acids and optimize neurotransmitters quantification using precolumn OPA-derivatization by HPLC.

We describe an analytical methodology to obtain high sensitivity and better resolution through the study of fluorometric excitation (λex) and emission (λem) spectrum wavelengths of OPA-amino acids. The spectrum emission study revealed a maximum signal peak at 450 nm for aspartate and glutamine. For glycine, taurine, and GABA, the maximum signal peak was at 448 and for glutamate at 452 nm. The remaining amino acids analyzed showed a maximum emission around 450 nm. The best signal obtained within the spectrum excitation experiments was using 229- to 450-nm λex-λem. The drawbacks observed at these wavelengths were a baseline drift and negative peaks occurrence. Thus, the excitation wavelength of 240 nm was chosen (240- to 450-nm λex-λem) as a compromise between a very good signal response and a baseline stability to resolve the 18 amino acids studied. Furthermore, this protocol was properly validated. On the other hand, the elution gradient program used for neuroactive amino acids (aspartate, glutamate, glycine, taurine and GABA) showed separation to the baseline, in a 15-min run in all of them. Other amino acids, up to 18, also exhibited a very good separation in a 25-min run. In conclusion, we propose the use of 240- to 450-nm λex-λem wavelengths, in OPA-amino acids analysis, as the most suitable protocol to obtain the best signal response, maintaining an optimum chromatographic resolution.

RNA aptamer-mediated interference of HCV replication by targeting the CRE-5BSL3.2 domain.

The RNA genome of hepatitis C virus (HCV) contains multiple conserved structural RNA domains that play key roles in essential viral processes. A conserved structural component within the 3' end of the region coding for viral RNA-dependent RNA polymerase (NS5B) has been characterized as a functional cis-acting replication element (CRE). This study reports the ability of two RNA aptamers, P-58 and P-78, to interfere with HCV replication by targeting the essential 5BSL3.2 domain within this CRE. Structure-probing assays showed the binding of the aptamers to the CRE results in a structural reorganization of the apical portion of the 5BSL3.2 stem-loop domain. This interfered with the binding of the NS5B protein to the CRE and induced a significant reduction in HCV replication (≈50%) in an autonomous subgenomic HCV replication system. These results highlight the potential of this CRE as a target for the development of anti-HCV therapies and underscore the potential of antiviral agents based on RNA aptamer molecules.

Efectos letales y subletales de nanopartículas y material soluble de oro en el desarrollo de embriones de pez cebra / The lethal and sub-lethal effects of nanoparticulated and soluble gold on the development of zebrafish embryos

La toxicidad de las nanopartículas de oro (AuNP) en el desarrollo de pez cebra resulta un tanto controvertida, ya que algunos autores demuestran su inocuidad, mientras que otros autores advierten de la presencia de efectos tóxicos. Por otro lado, la toxicidad del material base de la AuNP en solución aún no se ha investigado, aunque generalmente se requiera. Por consiguiente, el objetivo de este estudio fue investigar los efectos de la exposición de AuNP y el oro soluble en embriones de pez cebra, aportando reflexiones sobre la toxicidad de AuNP. Para ello, se llevaron a cabo ensayos toxicológicos en embriones de pez cebra con AuNP sin recubrimiento y recubiertas con ácido hialurónico (12,8 ± 1,6 nm, TEM), así como el material base (HAuCl4) de dichas AuNP. Los resultados demuestran que las AuNP no fueron tóxicas durante las primeras fases del desarrollo de los embriones (0-48 h). Por otro lado, el HAuCl4 resultó ser letal a concentraciones > 64,1 mg/L. A concentraciones subletales (48,1-0,7 mg/L), el HAuCl4 no alteró el desarrollo ni la actividad motora o cardiaca, aunque redujo notablemente la capacidad de eclosión a > 5.7 mg/L, situándose el NOAEC en 2,7 mg/L. Teniendo en cuenta nuestros resultados y los encontrados por otros autores, se puede concluir que la superficie de carga y en menor medida el tamaño de las AuNP resultaron ser los factores clave para explicar la toxicidad de la AuNP. Nuestros resultados también confirmaron que este modelo, con embriones de pez cebra, es adecuado para el estudio de toxicidad de las nanopartículas, siempre y cuando éstas estén completamente caracterizadas antes y durante el ensayo de toxicidad (AU)

Toxicity of gold nanoparticles (AuNPs) on zebrafish development is a rather controversial aspect in literature, and the investigation of the bulk material has not been considered yet, even though it is generally required. Therefore, we investigated the potential adverse effects of AuNPs and soluble gold on zebrafish embryos, while trying to find a rationale for gold nanoparticle toxicity. For such a purpose, uncoated and coated with hyaluronic acid AuNPs (12.8 ± 1.6 nm, TEM) and the bulk material (HAuCl4) were tested for their toxicity in zebrafish embryos. Results showed that the AuNPs were non-toxic for the zebrafish development during exposure (0-48h). Soluble gold (HAuCl4) was lethal at > 64.1 mg/L. At sublethal concentrations (48.1-0.7 mg/L) HAuCl4 did not alter embryo development, spontaneous movements or heartbeat rate, but the hatching ability was affected at > 5.7 mg/L, resulting in a NOAEC of 2.7 mg/L. According to our data and others found in scientific literature, it can be concluded that surface charge and, to a lesser extent, the size of the gold nanoparticles are key factors to explain toxicity of gold nanoparticles. Our results also confirmed that this model is suitable for studying nanoparticle toxicity, although the nanoparticles themselves should be fully characterised before and during the toxicity test (AU)

Inhibition of hepatitis C virus internal ribosome entry site-mediated translation by an RNA targeting the conserved IIIf domain.

Hepatitis C virus (HCV) translation initiation depends on an internal ribosome entry site (IRES). We previously identified an RNA molecule (HH363-10) able to bind and cleave the HCV IRES region. This paper characterizes its capacity to interfere with IRES function. Inhibition assays showed that it blocks IRES activity both in vitro and in a human hepatoma cell line. Although nucleotides involved in binding and cleavage reside in separate regions of the inhibitor HH363-10, further analysis demonstrated the strongest effect to be an intrinsic feature of the entire molecule; the abolishment of either of the two activities resulted in a reduction in its function. Probing assays demonstrate that HH363-10 specifically interacts with the conserved IIIf domain of the pseudoknot structure in the IRES, leading to the inhibition of the formation of translationally competent 80S particles. The combination of two inhibitory activities targeting different sequences in a chimeric molecule may be a good strategy to avoid the emergence of resistant viral variants.

Estudio sobre el conocimiento de factores de riesgo cardiovascular en estudiantes de medicina / Medical students’ knowledge of cardiovascular risk factors

Objetivos: Valorar el conocimiento de los estudiantes de Medicina de la Universidad de Navarra sobre la enfermedad cardiovascular y susfactores de riesgo.Material y métodos: Estudio descriptivo transversal en una muestra de 334 alumnos de 1º, 4º y 6º curso, autocumplimentando un cuestionario anónimo. Se utilizó el programa estadístico SPSS 11.0Resultados: La mayoría de los alumnos de 4º y 6º identifi caron correctamente los factores de riesgo cardiovascular (FRCV). Los de 4º identifi canmejor los valores lipídicos y los de 6º reconocen mejor la hipertensión arterial y el aumento del índice de masa corporal como FRCV. Un 97,8% considera la dieta mediterránea como factor protector. Conclusión: Existe un buen conocimiento de los FRCV entre los estudiantes de Medicina de la Universidad de Navarra y va aumentando a lo largo de la carrera

Objectives: To evaluate cardiovascular risk factor awareness among medical students at the University of Navarra.Material and Methods: A descriptive cross-sectional study including 334 students of the 1st, 4th and 6th year. They answered an anonymous structuredquestionnaire, and the results were analyzed using SPSS 11.0.Results: Most 4th and 6th year students correctly identifi ed the cardiovascular risk factors (CVRF). The 4th year students obtained better results on lipid values while the 6th year students performed better on body mass index and arterial hypertension. 97.8% of the sample considered the Mediterranean diet to be a protective factor.Conclusion: University of Navarra’s medical students are well informed about CVRF and their knowledge increases along the degree course

[Medical students' knowledge of cardiovascular risk factors]. / Estudio sobre el conocimiento de factores de riesgo cardiovascular en estudiantes de medicina.

OBJECTIVES: To evaluate cardiovascular risk factor awareness among medical students at the University of Navarra. MATERIAL AND METHODS: A descriptive cross-sectional study including 334 students of the 1st, 4th and 6th year. They answered an anonymous structured questionnaire, and the results were analyzed using SPSS 11.0. RESULTS: Most 4th and 6th year students correctly identified the cardiovascular risk factors (CVRF). The 4th year students obtained better results on lipid values while the 6th year students performed better on body mass index and arterial hypertension. 97.8% of the sample considered the Mediterranean diet to be a protective factor. CONCLUSION: University of Navarra's medical students are well informed about CVRF and their knowledge increases along the degree course.

[Acute tryptophan depletion in eating disorders]. / Depleción aguda de triptófano en trastornos de la conducta alimentaria.

INTRODUCTION: This work describes the rational bases justifying the use of acute tryptophan depletion technique in eating disorders (ED) and the methods and design used in our studies. Tryptophan depletion technique has been described and used in previous studies safely and makes it possible to evaluate the brain serotonin activity. Therefore it is used in the investigation of hypotheses on serotonergic deficiency in eating disorders. Furthermore, and given the relationship of the dysfunctions of serotonin activity with impulsive symptoms, the technique may be useful in biological differentiation of different subtypes, that is restrictive and bulimic, of ED. METHODS: 57 female patients with DSM-IV eating disorders and 20 female controls were investigated with the tryptophan depletion test. A tryptophan-free amino acid solution was administered orally after a two-day low tryptophan diet to patients and controls. Free plasma tryptophan was measured at two and five hours following administration of the drink. Eating and emotional responses were measured with specific scales for five hours following the depletion. A study of the basic characteristics of the personality and impulsivity traits was also done. Relationship of the response to the test with the different clinical subtypes and with the temperamental and impulsive characteristics of the patients was studied. RESULTS: The test was effective in considerably reducing plasma tryptophan in five hours from baseline levels (76%) in the global sample. The test was well tolerated and no severe adverse effects were reported. Two patients withdrew from the test due to gastric intolerance. CONCLUSIONS: The tryptophan depletion test could be of value to study involvement of serotonin deficits in the symptomatology and pathophysiology of eating disorders.