Assessment of Stress by Serum Biomarkers in Calves and Their Relationship to Ultimate pH as an Indicator of Meat Quality.

Seventy-eight calves from Asturiana de los Valles, Retinta, and Rubia Gallega breeds, under extensive and intensive farm systems and animal mixing and non-mixing conditions, and during the transport and lairage in slaughterhouses, were studied. This research aimed to study the effect of breed, farm system and mixing conditions on serum biomarkers (cortisol, lactate, glucose, serum amyloid A, haptoglobin, and C-reactive protein) and their relationship with pHu at slaughter time, and to evaluate the response of the serum biomarkers of calves throughout fattening period. Moreover, this study aims to evaluate the response of the biomarkers in each breed during the fattening period. At slaughter time, cortisol and lactate were affected by BreedxFarm; Retinta showed the opposite pattern to the others and revealed the highest glucose in extensive farm systems. Rubia Gallega in mixing revealed the highest Amyloid A and haptoglobin. Extensive calves in mixing conditions showed the highest glucose. There was a relationship among the variables cortisol, lactate, Amyloid A, and pHu. Slaughter time was a major stressor, and the stress response was mainly affected by breed. At slaughter, several biomarkers should be considered.

Assessment of (-) epicatechin as natural additive for improving safety and functionality in fresh "Piel de Sapo" melon juice.

Epicatechin (EC) is a very abundant flavonoid in vegetable tissues that presents high antioxidant activity in living systems. The minimum inhibitory concentration (MIC) of (-)EC was determined in three species of bacteria commonly associated with foodborne illness of plant origin: Listeria (L.) monocytogenes, Escherichia (E.) coli -serogroups O157: H7 and O111- and Bacillus (B.) cereus; two strains of probiotic-type lactic acid bacteria (PT-LAB) and two control strains. All 10 strains were assayed under three temperature conditions (30º, 10º, and 4ºC) and at each temperature under two pH conditions (6.7 and 5.5). Mean EC MIC values were generally lower at refrigeration (4º and 10ºC) temperatures and at standard pH (6.7). By inoculating with each of the strains separately, both melon juice (MJ) and MJ supplemented with EC (ECSMJ), at the accepted maximum sensorial limit, and storing them at 4ºC for 10 days; the final counts (CFU/mL) were lower for ECSMJ than for plain MJ both for pathogenic bacteria and for PT-LAB. The presence of EC during refrigerated storage counteracted the ability of MJ as a growth medium for all the pathogenic bacteria. ECSMJ increased the antioxidant activity of MJ significantly to levels similar to those of EC alone. (-) Epicathechin would be a promising ingredient for increasing the functional properties of "Piel de Sapo" MJ (phenolic compounds and antioxidant ability) while contributing to improving the safety of this type of juice during prolonged refrigerated storage at 4ºC.

A Follow-Up Study of Cognitive Development in Low Risk Preterm Children.

The results of a longitudinal study on the cognitive development of one group of full-term and three groups of low risk preterm children with different gestational ages (GA) are presented. The 181 participants were divided into four GA groups of similar size. The aims were: 1) To check if there are differences in cognitive development (measured through the Batelle scale) among the GA groups. 2) To establish the predictive factors of cognitive development at 22 and 60 months of age, taking into account biomedical, environmental and individual factors. The results of the repeated measures ANOVA performed at 22 and 60 months of age indicated that the cognitive trajectories of the four GA groups were similar. Linear regression analyses showed that the effect of the different predictors changed in relation to the time of measurement of cognitive development. Biological factors and the quality of home environment had a moderate effect on the cognitive development at 22 months of age. Cognitive results obtained at 22 months of age, and, to a lesser extent, working memory had the greatest effect on cognitive development at 60 months. GA does not predict cognitive development. Preterm children do not show cognitive delay if they are healthy.

Prevalencia y factores asociados a incontinencia urinaria en el área de salud este de Valladolid / Prevalence and factors associated with urinary incontinence in the east area of health of Valladolid

INTRODUCCIÓN: La incontinencia urinaria (IU) es la pérdida involuntaria de orina que constituye un problema social o higiénico importante y es demostrable de forma objetiva. Es un síntoma común que aparece en muchas enfermedades, afectando a todos los grupos de edad y a ambos sexos. En España se estima una prevalencia global de 24% en la mujer y 7% en el hombre, aumentando con la edad hasta el 50% y 29% respectivamente. A pesar de su repercusión en la calidad de vida se encuentra infradiagnosticada por diversos motivos. OBJETIVO: Determinar la prevalencia de la IU y sus factores asociados. MATERIAL Y MÉTODO: En este estudio epidemiológico observacional retrospectivo se recogieron datos de las historias clínicas de pacientes con IU de la Unidad de Suelo Pélvico del Área de Salud Este de Valladolid. RESULTADOS: Los tipos de incontinencia más frecuentes fueron: de esfuerzo (43,13%) y mixta (39,21%). Los factores de riesgo y patología asociada más importantes fueron episiotomía (57,1%) y cistocele (32,6%) en las mujeres y adenocarcinoma de próstata (60%) en los hombres. Tras tratamiento rehabilitador en un intervalo de 2 a 3 meses mejoraron las respuestas en los cuestionarios de incontinencia urinaria (ICIQ-SF). CONCLUSIONES: Los datos recopilados están en consonancia con estudios revisados, y viendo los avances en prevención y tratamiento de IU resulta coherente su abordaje multidisciplinar

INTRODUCTION: Urinary incontinence (UI) is the involuntary loss of urine that is a major social or hygienic problem and is objectively provable. It is a common symptom that appears in many diseases, affecting all age groups and both sexes. In Spain it is estimated a prevalence of 24% in women and 7% in men, increasing with age up to 50% and 29% respectively. Despite its impact on quality of life, it is under-diagnosed for various reasons. OBJECTIVE: To determine the prevalence of UI and its associated factors. MATERIAL AND METHOD: In this retrospective longitudinal epidemiological study data were collected from the medical histories of patients with UI belonging to the Pelvic Floor Unit of the East Health Area in Valladolid. RESULTS: The most frequent types of incontinence were: effort (43,13%) and mixed (39,21%). The most important risk factors and associated diseases were episiotomy (57.1%) and cystocele (32.6%) in women and adenocarcinoma of prostate (60%) in men. Responses in the questionnaires of urinary incontinence (ICIQ-SF) improved after 2-3 months of rehabilitation treatment. CONCLUSIONS: The collected data are consistent with studies reviewed, and seeing the progress in prevention and treatment of UI, multidisciplinary approach is coherent

Annexins A2 and A6 interact with the extreme N terminus of tau and thereby contribute to tau's axonal localization.

During neuronal development, the microtubule-associated protein tau becomes enriched in the axon, where it remains concentrated in the healthy brain. In tauopathies such as Alzheimer's disease, tau redistributes from the axon to the somatodendritic compartment. However, the cellular mechanism that regulates tau's localization remains unclear. We report here that tau interacts with the Ca2+-regulated plasma membrane-binding protein annexin A2 (AnxA2) via tau's extreme N terminus encoded by the first exon (E1). Bioinformatics analysis identified two conserved eight-amino-acids-long motifs within E1 in mammals. Using a heterologous yeast system, we found that disease-related mutations and pseudophosphorylation of Tyr-18, located within E1 but outside of the two conserved regions, do not influence tau's interaction with AnxA2. We further observed that tau interacts with the core domain of AnxA2 in a Ca2+-induced open conformation and interacts also with AnxA6. Moreover, lack of E1 moderately increased tau's association rate to microtubules, consistent with the supposition that the presence of the tau-annexin interaction reduces the availability of tau to interact with microtubules. Of note, intracellular competition through overexpression of E1-containing constructs reduced tau's axonal enrichment in primary neurons. Our results suggest that the E1-mediated tau-annexin interaction contributes to the enrichment of tau in the axon and is involved in its redistribution in pathological conditions.

Diseño y validación de contenido de la escala "ECOEnf" para la evaluación de competencias enfermeras / Design and content validation of the "ecoenf" scale to assess nursing competencies

Justificación: La evaluación de competencias es un proceso esencial en la educación superior y en el desarrollo profesional continuo; y requiere disponer de instrumentos validados. Objetivo: Diseñar y validar el contenido de un instrumento de evaluación para competencias enfermeras. Método: Mediante técnicas de consenso de expertos y aplicando criterios estadísticos, se establecen las unidades competenciales y resultados de aprendizaje que componen la escala. Resultados: Escala de evaluación con 7 unidades de competencia, 72 resultados de aprendizaje y un Índice de Validación de Contenido (CVI) total de 0.85 (mínimo de 0.53 y un máximo de 0.93 en las diferentes UC). La puntuación total del índice de Kappa para la herramienta es de 0.83. Conclusiones: se obtiene una escala con alta validez de contenido para la evaluación de competencias enfermeras. El método para su diseño puede utilizarse para diseñar otros instrumentos de evaluación

Background: Competency assessment is an essential process in higher education and in continuous professional development, and needs to have reliable tools. Aim: To design and validate the content of an assessment tool for nursing competencies. Methods: Using expert consensus techniques and applying statistical criteria established the competency units and learning outcomes of the assessment tool. Results: Assessment scale consisting of 7 competency units, 72 learning outcomes and a total Content Validation Index (CVI) of 0.85 (minimum 0.53 and maximum 0.93 for different UCs). The total score of Kappa Index of the tool was 0.83. Conclusions: A high content validity scale was developed to assess nursing competencies. The method for its design can be used to design other assessment tools

Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis.

The fundamental cellular role and molecular interactions of annexins in vesicle trafficking and membrane remodeling remain to be further clarified in order to better understand and exploit their contributions to health and disease. We focused on distinctive features of atypical annexins from all domains of life using phylogenomic, molecular systematic and experimental approaches, to extend the current paradigm and better account for annexin diversity of structure, function and mechanistic role in membrane homeostasis. The analysis of gene duplications, organization of domain architectures and profile hidden Markov models of subfamily orthologs defined conserved structural features relevant to molecular interactions and functional divergence of seven family clades ANXA-G. Single domain annexins of bacteria, including cyanobacteria, were frequently coupled to enzymatic units conceivably related to membrane metabolism and remodeling. Multiple ANX domains (up to 20) and various distinct functional domains were observed in unique annexins. Canonical type 2 calcium binding ligands were well-preserved in roughly half of all ANX domains, but alternative structural motifs comprised of 'KGD', cysteine or tryptophan residues were prominently conserved in the same strategic interhelical loops. Selective evolutionary constraint, site-specific location and co-occurrence in all kingdoms identify alternative modes of fundamental binding interactions for annexins.

An evolutionary roadmap to the microtubule-associated protein MAP Tau.

BACKGROUND: The microtubule associated protein Tau (MAPT) promotes assembly and interaction of microtubules with the cytoskeleton, impinging on axonal transport and synaptic plasticity. Its neuronal expression and intrinsic disorder implicate it in some 30 tauopathies such as Alzheimer's disease and frontotemporal dementia. These pathophysiological studies have yet to be complemented by computational analyses of its molecular evolution and structural models of all its functional domains to explain the molecular basis for its conservation profile, its site-specific interactions and the propensity to conformational disorder and aggregate formation. RESULTS: We systematically annotated public sequence data to reconstruct unspliced MAPT, MAP2 and MAP4 transcripts spanning all represented genomes. Bayesian and maximum likelihood phylogenetic analyses, genetic linkage maps and domain architectures distinguished a nonvertebrate outgroup from the emergence of MAP4 and its subsequent ancestral duplication to MAP2 and MAPT. These events were coupled to other linked genes such as KANSL1L and KANSL and may thus be consequent to large-scale chromosomal duplications originating in the extant vertebrate genomes of hagfish and lamprey. Profile hidden Markov models (pHMMs), clustered subalignments and 3D structural predictions defined potential interaction motifs and specificity determining sites to reveal distinct signatures between the four homologous microtubule binding domains and independent divergence of the amino terminus. CONCLUSION: These analyses clarified ambiguities of MAPT nomenclature, defined the order, timing and pattern of its molecular evolution and identified key residues and motifs relevant to its protein interaction properties and pathogenic role. Additional unexpected findings included the expansion of cysteine-containing, microtubule binding domains of MAPT in cold adapted Antarctic icefish and the emergence of a novel multiexonic saitohin (STH) gene from repetitive elements in MAPT intron 11 of certain primate genomes.

Breakthroughs spotlighting roles for extracellular nucleotides and apyrases in stress responses and growth and development.

Animal and plant cells release nucleotides into their extracellular matrix when touched, wounded, and when their plasma membranes are stretched during delivery of secretory vesicles and growth. These released nucleotides then function as signaling agents that induce rapid increases in the concentration of cytosolic calcium, nitric oxide and superoxide. These, in turn, are transduced into downstream physiological changes. These changes in plants include changes in the growth of diverse tissues, in gravitropism, and in the opening and closing of stomates. The concentration of extracellular nucleotides is controlled by various phosphatases, prominent among which are apyrases EC 3.6.1.5 (nucleoside triphosphate diphosphohydrolases, NTPDases). This review provides phylogenetic and pHMM analyses of plant apyrases as well as analysis of predicted post-translational modifications for Arabidopsis apyrases. This review also summarizes and discusses recent advances in research on the roles of apyrases and extracellular nucleotides in controlling plant growth and development. These include new findings that document how apyrases and extracellular nucleotides control auxin transport, modulate stomatal aperture, and mediate biotic and abiotic stress responses, and on how apyrase suppression leads to growth inhibition.

Particle repositioning maneuver versus Brandt-Daroff exercise for treatment of unilateral idiopathic BPPV of the posterior semicircular canal: a randomized prospective clinical trial with short- and long-term outcome.

OBJECTIVE: To compare the outcome and probability of recurrence in a series of patients with unilateral idiopathic benign paroxysmal positional vertigo of the posterior canal (PC-BPPV) that were randomly treated by Brandt-Daroff exercise (B-D exercise) or by particle repositioning maneuver (PRM). STUDY DESIGN: Randomized prospective clinical trial. SETTING: Tertiary referral center. PATIENTS: Patients were included in this study if they complained of vertigo and had been diagnosed as having unilateral idiopathic PC-BPPV for at least 1 week before Dix-Hallpike maneuver (DHM), remained for 30 days in the randomly assigned treatment, and had at least 48 months' follow-up. INTERVENTION: Forty-one patients were treated with a single PRM and 40 patients by B-D exercise. MAIN OUTCOME MEASURE: Resolution of benign paroxysmal positional nystagmus on the DHM. The probability of recurrence was also studied. RESULTS: At Day 7, DHM was negative in 80.5% of the PRM-treated patients and in 25% of those treated by B-D exercise (p < 0.001). At Month 1, the differences between both treatment groups remained statistically significant (92.7% in PRM versus 42.5% in the B-D exercise had a negative DHM; p < 0.001). The variable that influenced that DHM became negative was the PRM (RR = 4.8; 95% confidence interval, 2.5-9.2; p < 0.001). The number of recurrences in PRM and B-D exercise were 0.56 ± 0.8 and 0.48 ± 0.8, respectively (p = 0.48). The recurrence rate at 48 months was 35.5% (15/41) in B-D exercise and 36.6% (9/31) in the PRM group (p = 0.62). Although the time interval until the first recurrence was similar (p = 0.44), patients included in the PRM group showed a significantly longer time interval between the first and second recurrence (p = 0.04). CONCLUSION: PRM is more effective treatment and as safe as B-D exercise in the short term for unilateral and idiopathic PC-BPPV, and although it does not reduce the probability of recurrence in the 4-year follow-up period compared with B-D exercise, it may delay the second recurrence's onset in those patients who had already experienced a single recurrence. Our study supports the use of PRM as the treatment of choice in unilateral and idiopathic PC-BPPV, although exercise may be also considered as an alternative treatment in selected cases.

Evolutionary adaptation of plant annexins has diversified their molecular structures, interactions and functional roles.

Annexins are an homologous, structurally related superfamily of proteins known to associate with membrane lipid and cytoskeletal components. Their involvement in membrane organization, vesicle trafficking and signaling is fundamental to cellular processes such as growth, differentiation, secretion and repair. Annexins exist in some prokaryotes and all eukaryotic phyla within which plant annexins represent a monophyletic clade of homologs descended from green algae. Genomic, proteomic and transcriptomic approaches have provided data on the diversity, cellular localization and expression patterns of different plant annexins. The availability of 35 complete plant genomes has enabled systematic comparative analysis to determine phylogenetic relationships, characterize structures and observe functional specificity between and within individual subfamilies. Short amino termini and selective erosion of the canonical type 2 calcium coordinating sites in domains 2 and 3 are typical of plant annexins. The convergent evolution of alternate functional motifs such as 'KGD', redox-sensitive Cys and hydrophobic Trp/Phe residues argues for their functional relevance and contribution to mechanistic diversity in plant annexins. This review examines recent findings and advances in plant annexin research with special focus on their structural diversity, cellular and molecular interactions and their potential integrated functions in the broader context of physiological responses.

Phosphorylation of CRN2 by CK2 regulates F-actin and Arp2/3 interaction and inhibits cell migration.

CRN2 (synonyms: coronin 1C, coronin 3) functions in the re-organization of the actin network and is implicated in cellular processes like protrusion formation, secretion, migration and invasion. We demonstrate that CRN2 is a binding partner and substrate of protein kinase CK2, which phosphorylates CRN2 at S463 in its C-terminal coiled coil domain. Phosphomimetic S463D CRN2 loses the wild-type CRN2 ability to inhibit actin polymerization, to bundle F-actin, and to bind to the Arp2/3 complex. As a consequence, S463D mutant CRN2 changes the morphology of the F-actin network in the front of lamellipodia. Our data imply that CK2-dependent phosphorylation of CRN2 is involved in the modulation of the local morphology of complex actin structures and thereby inhibits cell migration.

[Abuse in the elderly]. / Maltrato en el anciano.

Reflections on the UN decree of June 15 as International Day of No Abuse of the Elderly which have been enhanced by the celebration in Madrid, Hospital Clinico San Carlos, a day devoted to this topic with the aim of raising awareness among professionals working in health centers and other interest groups, groups of retirees and social services, health problems and abuse in the elderly

Estudio de la determinación de la hemoglobina glucosilada en pacientes con diabetes mellitus 2 en sangre capilar en un centro de atención primaria / Capillary HbA1c determination on type 2 diabetes patients in a primary health centre

ObjetivoDeterminar la fiabilidad analítica y practicabilidad del analizador de pruebas a la cabecera del paciente (POCT) Afinion para la HbA1c, y las ventajas de implantarlo para los controles intraanuales de los pacientes con diabetes mellitus 2 (DM2).DiseñoEstudio descriptivo transversal. Validación de un instrumento de medida.EmplazamientoAtención Primaria: Centro de Atención Primaria (CAP) Carmel y Laboratorio Clínico Bon Pastor.Participantes94 personas con DM2 seleccionados, según resultado previo de HbA1c.MétodoEn la consulta se realizaron las mediciones en sangre capilar con Afinion y se evaluó su practicabilidad mediante cuestionario de 11 preguntas. En la misma visita se efectuó una extracción de sangre venosa que se remitió al laboratorio para la medida de HbA1c por Afinion y por cromatografía líquida de alta presión (HPLC). Finalmente se valoró la eficiencia en términos de tiempo.ResultadosEl coeficiente de variación (CV) intraserial fue inferior al 1% y el interserial inferior al 3%.La comparación de los resultados obtuvo la siguiente recta de regresión: Afinion capilar=0,95 Afinion venosa+0,21. En el IC 95% no se detecta error sistemático ni proporcional. Cuando se compararon los resultados con HPLC venosa: Afinion capilar=0,80 HPLC+1,14, con un IC 95% que muestra una diferencia estadísticamente significativa en ambos valores. En la practicabilidad, se obtiene una puntuación entre 7 y 9,2 (profesionales) y entre 7,7 y 9,2 (pacientes).La implantación supondría un ahorro de tiempo en el control de diabetes entre 600 y 900h/año.ConclusionesAfinion puede ser una buena opción para las determinaciones analíticas de HbA1c intraanuales por su accesibilidad y eficiencia en la utilización de recursos, pero que es imprescindible que los profesionales sanitarios conozcan sus limitaciones para valorar adecuadamente los resultados(AU)

ObjectiveTo determine the reliability and practicability of the point-of-care- test (POCT) analyzer, Afinion, for capillary HbA1c testing. To assess the benefits of its implementation on the intra-annual follow up of type 2 diabetic patients.DesignDescriptive cross-sectional study. Analytical validation of the Afinion reader.SettingPrimary Health Care (CAP Carmel and Bon Pastor Clinic Laboratory).ParticipantsA total of 94 type 2 diabetic patients selected according to their previous HbA1c value.MethodsWe performed one capillary puncture and one venous extraction on each visit. The capillary sample was assessed in real time on the Afinion in the Primary Health Care Centre and the venous sample was sent to Bon Pastor Clinic Laboratory for assessment on an Afinion analyzer and by a high performance liquid chromatrography (HPLC) reference method. Practicability was assesses by both by the operators of the Afinion and the patients using an 11 question questionnaire. The efficiency in terms of process timings was also evaluated.ResultsIntra-serial coefficient of variation (CV) was lower than 1% and inter-serial lower than 3%. The regression analysis showed: Afinion capillary sample=0.95 Afinion venous+0.21. No systematic or proportional error was detected in the 95% confidence interval (95% CI). The comparison between venous HPLC and Afinion showed: Afinion capillary sample=0.80 HPLC+1.14. A statistically significant difference was shown for these values at the 95% CI. Practicability was valued by users from 7 to 9.2 (professionals) and from 7.7 to 9.2 (patients). Implementation of the Afinion capillary method for intra-annual testing in follow up of diabetic patients could result in the saving of 600-900 professional hours/year(AU)

ConclusionsAfinion seems to be a good choice for the intra-annual determination of HbA1c when compared to the traditional process due to its accessibility, practicability and efficiency. Professionals should know the limitations of the POCT method in order to consider the validity of the result(AU)

Maltrato en el anciano / Abuse in the elderly

Reflexiones en torno a la decisión de la ONU de declarar el 15 de junio como Día Internacional del No Maltrato al Adulto Mayor, que se vieron potenciadas por la celebración en Madrid, por el Hospital Clínico San Carlos, de una jornada dedicada a este tema, con el objetivo de sensibilizar a los profesionales que trabajan en centros sanitarios y a otros grupos de interés, grupos de jubilados y servicios sociales, sobre problemas de salud, abuso y maltrato en las personas mayores(AU)

Reflections on the UN decree of June 15 as International Day of No Abuse of the Elderly, which have been enhanced by the celebration in Madrid, Hospital Clínico San Carlos, a day devoted to this topic with the aim of raising awareness among professionals working in health centers and other interest groups, groups of retirees and social services, health problems and abuse in the elderly(AU)

[Capillary HbA1c determination on type 2 diabetes patients in a primary health centre]. / Estudio de la determinación de la hemoglobina glucosilada en pacientes con diabetes mellitus 2 en sangre capilar en un centro de atención primaria.

OBJECTIVE: To determine the reliability and practicability of the point-of-care- test (POCT) analyzer, Afinion, for capillary HbA1c testing. To assess the benefits of its implementation on the intra-annual follow up of type 2 diabetic patients. DESIGN: Descriptive cross-sectional study. Analytical validation of the Afinion reader. SETTING: Primary Health Care (CAP Carmel and Bon Pastor Clinic Laboratory). PARTICIPANTS: A total of 94 type 2 diabetic patients selected according to their previous HbA1c value. METHODS: We performed one capillary puncture and one venous extraction on each visit. The capillary sample was assessed in real time on the Afinion in the Primary Health Care Centre and the venous sample was sent to Bon Pastor Clinic Laboratory for assessment on an Afinion analyzer and by a high performance liquid chromatrography (HPLC) reference method. Practicability was assesses by both by the operators of the Afinion and the patients using an 11 question questionnaire. The efficiency in terms of process timings was also evaluated. RESULTS: Intra-serial coefficient of variation (CV) was lower than 1% and inter-serial lower than 3%. The regression analysis showed: Afinion capillary sample=0.95 Afinion venous+0.21. No systematic or proportional error was detected in the 95% confidence interval (95% CI). The comparison between venous HPLC and Afinion showed: Afinion capillary sample=0.80 HPLC+1.14. A statistically significant difference was shown for these values at the 95% CI. Practicability was valued by users from 7 to 9.2 (professionals) and from 7.7 to 9.2 (patients). Implementation of the Afinion capillary method for intra-annual testing in follow up of diabetic patients could result in the saving of 600-900 professional hours/year. CONCLUSIONS: Afinion seems to be a good choice for the intra-annual determination of HbA1c when compared to the traditional process due to its accessibility, practicability and efficiency. Professionals should know the limitations of the POCT method in order to consider the validity of the results.

Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.

Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. We identified strumpellin as a novel valosin-containing protein binding partner. Strumpellin mutations have been shown to cause hereditary spastic paraplegia. We demonstrate that strumpellin is a ubiquitously expressed protein present in cytosolic and endoplasmic reticulum cell fractions. Overexpression or ablation of wild-type strumpellin caused significantly reduced wound closure velocities in wound healing assays, whereas overexpression of the disease-causing strumpellin N471D mutant showed no functional effect. Strumpellin knockdown experiments in human neuroblastoma cells resulted in a dramatic reduction of axonal outgrowth. Knockdown studies in zebrafish revealed severe cardiac contractile dysfunction, tail curvature and impaired motility. The latter phenotype is due to a loss of central and peripheral motoneuron formation. These data imply a strumpellin loss-of-function pathogenesis in hereditary spastic paraplegia. In the human central nervous system strumpellin shows a presynaptic localization. We further identified strumpellin in pathological protein aggregates in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, various myofibrillar myopathies and in cortical neurons of a Huntington's disease mouse model. Beyond hereditary spastic paraplegia, our findings imply that mutant forms of strumpellin and valosin-containing protein may have a concerted pathogenic role in various protein aggregate diseases.

Poliquistosis renal infantil autosómica recesiva con disgenesia biliar. A propósito de un caso / Autosomal recessive polycystic kidney disease. A case report

IntroducciónLa poliquistosis renal autosómica recesiva (PQRAR) es una enfermedad producida por mutaciones del gen PKDH1 que codifica una proteína llamada fibroquisina en el cromosoma 6p13.3. Se caracteriza por la asociación constante de túbulos colectores renales dilatados que forman quistes y por una fibrosis hepática congénita secundaria a una disgenesia biliar.Caso clínicoPresentamos un caso de estudio de autopsia de un recién nacido hembra pretérmino de 35 semanas de edad gestacional, de 2 horas de vida con oligoamnios severo de un embarazo no controlado. En el primer trimestre de embarazo se constató nefromegalia en una ecografía. Los hallazgos macroscópicos más significativos fueron riñones de aspecto esponjoso compuestos con múltiples pequeños quistes y una fibrosis hepática focal. Tras el estudio microscópico se llegó al diagnóstico de enfermedad poliquística renal infantil autosómica recesiva con disgenesia biliar.DiscusiónLa PQRAR plantea el diagnóstico diferencial histológico con: la displasia quística fibrosa y la enfermedad poliquística renal autosómica dominante. Es la alteración en el locus gen denominado PKDH1 del ADN, independientemente de la severidad de la afectación la que confirma el diagnóstico(AU)

IntroductionAutosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder caused by a mutation in the PKD1 gene, which codes for protein polycystin 1, mapped on chromosome 6p13.3. ARPKD is characterised by the formation of cysts from coalescing dilated renal collecting ducts coexisting with congenital hepatic fibrosis secondary to biliar dysgenesis.Case reportWe report the autopsy findings in a 2h old, term female infant with severe oligohydramnios. The pregnancy had not been monitored, although a previous ultrasonography revealed foetal kidney enlargement. The most significant macroscopic findings were sponge kidneys composed of multiple small cysts and focal hepatic fibrosis. Microscopically a diagnosis of autosomal recessive polycystic kidney disease with biliary dysgenesis was made.DiscussionThe clinical and pathological findings are correlated and the most important necropsy findings are described. The relevant literature is reviewed and recent advances in the pathology, genetics, diagnosis, ultrasonography, prevention and treatment of ARPKD are discussed(AU)

Gestación triple tubárica de origen espontáneo / Triple spontaneous tubal pregnancy

A continuación, presentamos el caso de una gestación ectópica de localización tubárica triple, de origen espontáneo y diagnóstico ecográfico tras consulta por dolor abdominal. Se realizó tratamiento quirúrgico por un cuadro de inestabilidad hemodinámica tras la rotura tubárica. La reducida frecuencia del embarazo triple, especialmente de forma espontánea, y la poco frecuente localización ectópica hacen de esta paciente un caso extremadamente inusual (AU)

The aim of this case report is to present a triplet ectopic pregnancy of spontaneous origin and tubal situation diagnosticated by ultrasonography after query for abdominal pain. Surgical treatment was performed due to an haemodynamic shock caused by tubarian hole. The reduced frequence of triplet pregnancy, specially from spontaneous origin and the ectopian location, makes this patient an extremely inusual case (AU)

Structural and functional diversity of novel coronin 1C (CRN2) isoforms in muscle.

Coronin 1C (synonyms: coronin-3, CRN2), a WD40 repeat-containing protein involved in cellular actin dynamics, is ubiquitously expressed in human tissues. Here, we report on the identification and functional characterization of two novel coronin 1C isoforms, referred to as CRN2i2 and CRN2i3, which also associate with F-actin. Analyses of the coronin 1C gene disclosed a single promoter containing binding sites for myogenic regulatory factors and an alternative first exon 1b present in intron 1, which give rise to the novel isoforms. Chromatin immunoprecipitation studies demonstrate MyoD binding to a region of the CRN2 gene, which contains a highly conserved E-box element in exon 1a. Gel-filtration assays suggest that the largest isoform 3 exists as a monomer, in contrast to isoform 1 and isoform 2 appearing as trimers. CRN2i3, which can be induced by MyoD, is exclusively expressed in well-differentiated myoblasts as well as in mature skeletal muscle tissue. In human skeletal muscle, CRN2i3 is a novel component of postsynaptic neuromuscular junctions and thin filaments of myofibrils. Together, our findings postulate a role for CRN2 isoforms in the structural and functional organization of F-actin in highly ordered protein complexes.