¿Estamos de acuerdo con la calidad técnica de nuestras radiografías de tórax? Un radiólogo, un técnico especialista en radiodiagnóstico y un médico de familia intentan corroborarlo

ObjetivoValorar el grado de concordancia en la interpretación de la calidad técnica de las radiografías de tórax de un centro de salud entre el técnico especialista en radiodiagnóstico (TER), el médico de familia y el radiólogo.DiseñoEstudio transversal.EmplazamientoAtención primaria. Centro de Salud de Cartuja en Granada.ParticipantesPacientes del Centro de Salud de Cartuja con estudio radiológico simple de tórax durante 2002. Mediante muestreo aleatorio simple se seleccionaron 150 estudios. Se rechazaron 2 por tratarse de exploraciones repetidas del mismo paciente y 7 porque no presentaban una calidad mínima. La muestra final fue de 141 exploraciones.Mediciones principalesLos observadores cumplimentaron independientemente, para cada exploración, un protocolo de 11 ítems sobre calidad técnica de la imagen. Para cada ítem se calculó el índice kappa entre parejas de observadores, así como el índice kappa global.ResultadosEl 96% de las exploraciones fuerealizado con placas radiográficas de gran tamaño (35×43). Sólo en 2 preguntas hubo una concordancia aceptable o buena entre los 3 observadores (kappa=0,559-0,858). En 5 preguntas, la concordancia fue homogéneamente baja (kappa=0,034-0,375). En algunas preguntas se apreció una fuerte discrepancia entre la valoración del TER y la realizada por los otros 2 observadores.ConclusionesLa concordancia general puede considerarse baja, aunque algo mayor entre el radiólogo y el médico de familia que entre cada uno de éstos y el TER. Esto plantea la necesidad de mejorar la formación de los profesionales en cuanto a la valoración de la calidad técnica de las imágenes. Además, se detecta un gasto innecesario de placas radiográficas de gran tamaño.ObjectiveTo appraise the degree of concordance in the interpretation of the technical quality of chest x-rays at a health centre between an expert in x-ray diagnosis, a family doctor, and a radiologist.DesignTransversal study.SettingPrimary care. Cartuja Health Centre, Granada, Spain.ParticipantsPatients at the Cartuja Health Centre who had a simple chest x-ray in 2002. 150 studies were chosen by simple randomised sampling.Two were rejected because they dealt with a repeat examination of the same patient and seven because they did not reach minimum quality. The final sample was 141 x-rays.Main measurementsThe observers filled in independently, for each examination, an 11- item protocol on the technical quality of the images. The kappa index between pairs of observers was calculated for each item, as was the overall kappa index.Results96% of the examinations were conducted with large x-ray plates (35×43). There was only acceptable or good concordance between the 3 observers in 2 questions (kappa, 0.559-0.858). In 5 questions concordance was homogeneously low (kappa, 0.034-0.375). In some questions there was a strong discrepancy between the appraisal of the expert and that of the 2 other observers.ConclusionsGeneral concordance can be considered low, although it is somewhat greater between the radiologist and the family doctor than between either of these and the expert. This poses the need to improve professional training in evaluation of the technical quality of images. In addition, there was unnecessary expense in large-size x-ray plates

Utilización de la densidad de incidencia, en la valoración de faciores de riesgo de la infección nosocomial

ResumenEn la literatura se han propuesto las medidas de densidad de incidencia para la valoración de la infección nosocomial. A través de una cohorte retrospectiva de 843 pacientes se realiza una comparación entre la razón de densidades de incidencia (RDI) y el cociente de incidencias acumuladas o riesgo relativo (RR) en la cuantificación de factores de riesgo de la infección hospitalaria. Las variables que se analizaron fueron la intervención quirúrgica, su duración, el tipo de cirugía, la gravedad de la enfermedad subyacente y la edad. En todas las situaciones la RDI fue inferior al RR, al eliminar la prolongación de estancia producida por los distintos factores de riesgo. Ejemplos de ello fueron el que la RDI para la operación fue de 2,78, mientras que el RR ofreció valores de 6,46, o en la edad, donde los mayores de 60 años presentaron un RR significativo de 1,67, mientras que la RDI fue de 0,96. Esto sugiere que el empleo de la RDI facilitaría la comparabilidad de los resultados entre diferentes centros en la cuantificación de factores de riesgo para la infección nosocomial, aparte de cuantificar con más exactitud los distintos factores de riesgo, lo que tiene importancia a la hora de establecer las medidas de control.SummarySeveral authors have suggested that incidence density should be used in studying nosocomial infection. We assess several risk factors for hospital infection by two ratios, the incidence density ratio (IDR) and the relative risk (RR), in an historical cohort of 843 patients. The variables analyzed were: operation, its length, type of surgical wound, severity of underlying disease, and age. The IDR figures were always lower than those yielded by the RR. For example, the IDR for operated patients was 2.78, whereas RR yielded a figure of 6.46, or the IDR for patients >60 years old was 0.96, whereas the RR achieved a significant value of 1.67. This suggests that the use of IDR lo analyze risk factors for nosocomial infection improves comparability of results obtained in different hospital settings. Also, it may allow a more exact quantification of an effect. These facts influence implementation of nosocomial infection control measures

Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Abstract Aim This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m 2 24-h intravenous (i.v.) infusion every 3weeks (q3wk) ( Arm A ), or doxorubicin 75mg/m 2 i.v. q3wk, or doxorubicin 60mg/m 2 i.v. plus ifosfamide (range, 6–9g/m 2 ) i.v. q3wk ( Arm B ). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p =0.9573; hazard ratio=0.86, p =0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma

Timing of molt of barn swallows is delayed in a rare Clock genotype

Photoperiodic responses are major factors entraining circannual life-cycles, functioning to adaptively synchronize annual routines to seasonal fluctuations in ecological conditions. Photoperiodism in physiology and behaviour is enforced by genes, including the vertebrate Clock orthologues, which are associated, for example, with phenology of migration in fish and breeding in birds. However, the role of Clock in photoperiodic plumage molt processes is unknown. We analyzed variation in molt schedules in relation to Clock genotype, using the long-distance migratory barn swallow (Hirundo rustica) as a model and by identifying males and females using molecular sexing techniques. Consistently with previous studies, we found one very common (Q7) and two rare (Q6, Q8) variants of a functionally significant Clock polyglutamine repeat.Molt schedules of primary wing feathers of swallows during their wintering period in Nigeria differed among Clock genotypes: rare (1.1%) Q7=Q8 heterozygotes had significantly delayed molt compared to the other genotypes. Molt schedules did not differ between males and females, and no differential association between molt and Clock in relation to sex emerged. The same rare Clock genotype that exhibited delayed breeding in Europe was here found to delay molt in Africa. Though based on a limited number of Q7=Q8 individuals from an otherwise very large sample, these novel results suggest that Clock is involved in the photoperiodic control of both molt and breeding, potentially also via reciprocal carry-over effects. If confirmed in species with higher Clock polymorphism, present results may have far-reaching consequences for the study of photoperiodic control of molt and expression of annual routines

Factores de riesgo de criptorquidia

ResumenObjetivosIdentificar los principales factores de riesgo de criptorquidia en nuestro ámbito geográfico y la posible asociación de ésta con factores ambientales.MétodosSe realizó un estudio retrospectivo de casos y controles. La población diana estuvo constituida por los varones nacidos en el Hospital Universitario San Cecilio de Granada entre el 1 de enero de 1992 y el 31 de diciembre de 1999. Se seleccionaron todos los casos (n = 70) diagnosticados de criptorquidia a partir del primer año de vida en las historias clínicas de urología y endocrinología pediátrica del hospital, así como una muestra de 144 controles sin esta enfermedad, ni ninguna otra genitourinaria relacionada. A partir de la historia obstétrica materna se recogió información sobre los potenciales factores de riesgo considerados: factores previos al embarazo (p. ej., lugar de residencia, profesión de los padres); factores del embarazo (p.ej., enfermedades y tratamiento hormonal durante la gestación); y factores del parto y neonatales (p. ej., tipo de parto, edad gestacional y peso del neonato). Para cada uno de ellos se calculó su odds ratio cruda (ORc) y ajustada (ORa) mediante regresión logística no condicionada.ResultadosLa baja edad gestacional (igual o menor de 37 semanas) y el parto por cesárea se asociaron significativamente con la frecuencia de criptorquidia (respectivamente, ORc= 3,50 y ORc 2,47). También se apreció una asociación con la residencia materna en el Distrito Sanitario Costa-Alpujarra (ORc = 4,04), si bien ésta disminuyó al considerar la profesión del padre en tareas agrícolas. Esta última variable también pareció presentar una asociación, no significativa, con la frecuencia de criptorquidia (ORc = 2,26).ConclusionesNuestros resultados son consistentes con los obtenidos en otros estudios, a excepción de la ausencia de asociación para el bajo peso del recién nacido. La variabilidad geográfica detectada sugiere la existencia de factores ambientales, quizá relacionados con la ocupación en tareas agrícolas.Objetivos: Identificar los principales factores de riesgo de criptorquidia en nuestro ámbito geográfico y la posible asociación de ésta con factores ambientales.SummaryObjectivesTo identify the main risk factors for cryptorchidism in southeast Spain, and their possible association with environmental factors.MethodsIn this retrospective case-control study, the target population consisted of babies born in the University of Granada Hospital (UGH) in Granada, Spain, between 1 January 1992 and 31 December 1999, both inclusive. All boys from the target population aged 1 year or more diagnosed at the Pediatric Urology or Endocrinology Services of the UGH as having cryptorchidism (n = 70) were included, and a random sample of 144 baby boys born without cryptorchidism or any other related genitourinary abnormality or disease formed the control group. The mother's hospital record in the obstetrics clinic was checked to record information on potential risk factors, such as residence (specific health care district), parents' occupation, obstetric antecedents, diseases during pregnancy, gestational age at birth, birth weight and type of delivery. To search for associations between cryptorchidism and each of the variables we calculated crude and adjusted odds ratios with unconditional logistic regression analysis.ResultsLow gestational age at birth (≤ 37 weeks) and cesarian section were significantly associated with cryptorchidism. We also found an association with residence of the mother in the Costa-Alpujarra health care district, but its magnitude decreased when the association was adjusted for the father's occupation in agriculture. This last factor was also associated with cryptorchidism, although the association was not statistically significant.ConclusionsOur findings are consistent with those of other studies, except for the absence of association between low birth weight and cryptorchidism. Geographic variations in our study population suggested that environmental factors –possibly related with farm work– are involved in cryptorchidism

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL

Systematic Two-Hybrid and Comparative Proteomic Analyses Reveal Novel Yeast Pre-mRNA Splicing Factors Connected to Prp19

Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1∶1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe) directly interacts with Prp19, and that Dre4 is conditionally required for pre-mRNA splicing in S. pombe. S. pombe Dre4 and S. cerevisiae Urn1 co-purify U2, U5, and U6 snRNAs and multiple splicing factors, and dre4Δ and urn1Δ strains display numerous negative genetic interactions with known splicing mutants. The S. pombe Prp19-containing Dre4 complex co-purifies three previously uncharacterized proteins that participate in pre-mRNA splicing, likely before spliceosome activation. Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold

Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS

The Guinea Pig as a model for sporadic Alzheimer's Disease (AD): the impact of cholesterol intake on expression of AD-related genes

Extent: 12p.We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.Mathew J. Sharman, Seyyed H. Moussavi Nik, Mengqi M. Chen, Daniel Ong, Linda Wijaya, Simon M. Laws, Kevin Taddei, Morgan Newman, Michael Lardelli, Ralph N. Martins, Giuseppe Verdil