Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts.

RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.

Evaluation of Free Online ADMET Tools for Academic or Small Biotech Environments.

For a new molecular entity (NME) to become a drug, it is not only essential to have the right biological activity also be safe and efficient, but it is also required to have a favorable pharmacokinetic profile including toxicity (ADMET). Consequently, there is a need to predict, during the early stages of development, the ADMET properties to increase the success rate of compounds reaching the lead optimization process. Since Lipinski's rule of five, the prediction of pharmacokinetic parameters has evolved towards the current in silico tools based on empirical approaches or molecular modeling. The commercial specialized software for performing such predictions, which is usually costly, is, in many cases, not among the possibilities for research laboratories in academia or at small biotech companies. Nevertheless, in recent years, many free online tools have become available, allowing, more or less accurately, for the prediction of the most relevant pharmacokinetic parameters. This paper studies 18 free web servers capable of predicting ADMET properties and analyzed their advantages and disadvantages, their model-based calculations, and their degree of accuracy by considering the experimental data reported for a set of 24 FDA-approved tyrosine kinase inhibitors (TKIs) as a model of a research project.

Recent advances in the nucleolar responses to DNA double-strand breaks.

DNA damage poses a serious threat to human health and cells therefore continuously monitor and repair DNA lesions across the genome. Ribosomal DNA is a genomic domain that represents a particular challenge due to repetitive sequences, high transcriptional activity and its localization in the nucleolus, where the accessibility of DNA repair factors is limited. Recent discoveries have significantly extended our understanding of how cells respond to DNA double-strand breaks (DSBs) in the nucleolus, and new kinases and multiple down-stream targets have been identified. Restructuring of the nucleolus can occur as a consequence of DSBs and new data point to an active regulation of this process, challenging previous views. Furthermore, new insights into coordination of cell cycle phases and ribosomal DNA repair argue against existing concepts. In addition, the importance of nucleolar-DNA damage response (n-DDR) mechanisms for maintenance of genome stability and the potential of such factors as anti-cancer targets is becoming apparent. This review will provide a detailed discussion of recent findings and their implications for our understanding of the n-DDR. The n-DDR shares features with the DNA damage response (DDR) elsewhere in the genome but is also emerging as an independent response unique to ribosomal DNA and the nucleolus.

Efficient fractionation and analysis of ribosome assembly intermediates in human cells.

Biochemical studies of the human ribosome synthesis pathway have been hindered by technical difficulties in obtaining intact preribosomal complexes from internal regions of the nucleolus. Here we provide a detailed description of an extraction method that enables efficient detection, isolation, and characterization of nucleolar preribosomes containing large pre-rRNA species. The three-step Preribosome Sequential Extraction (PSE) protocol preserves the integrity of early preribosomal complexes and yields preparations amenable to biochemical analyses from low amounts of starting material. We validate this procedure through the detection of specific trans-acting factors and pre-rRNAs in the extracted preribosomes using affinity matrix pull-downs and sedimentation assays. In addition, we describe the application of the PSE method for monitoring cellular levels of ribosome-free 5S RNP complexes as an indicator of ribosome biogenesis stress. Our optimized experimental procedures will facilitate studies of human ribosome biogenesis in normal, mutant and stressed-cell scenarios, including the characterization of candidate ribosome biogenesis factors, preribosome interactors under specific physiological conditions or effects of drugs on ribosome maturation.

Focal accumulation of preribosomes outside the nucleolus during metaphase-anaphase in budding yeast.

Saccharomyces cerevisiae contains one nucleolus that remains intact in the mother-cell side of the nucleus throughout most of mitosis. Based on this, it is assumed that the bulk of ribosome production during cell division occurs in the mother cell. Here, we show that the ribosome synthesis machinery localizes not only in the nucleolus but also at a center that is present in the bud side of the nucleus after the initiation of mitosis. This center can be visualized by live microscopy as a punctate body located in close proximity to the nuclear envelope and opposite to the nucleolus. It contains ribosomal DNA (rDNA) and precursors of both 40S and 60S ribosomal subunits. Proteins that actively participate in ribosome synthesis, but not functionally defective variants, accumulate in that site. The formation of this body occurs in the metaphase-to-anaphase transition when discrete regions of rDNA occasionally exit the nucleolus and move into the bud. Collectively, our data unveil the existence of a previously unknown mechanism for preribosome accumulation at the nuclear periphery in budding yeast. We propose that this might be a strategy to expedite the delivery of ribosomes to the growing bud.

Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

During the biogenesis of small ribosomal subunits in eukaryotes, the pre-40S particles formed in the nucleolus are rapidly transported to the cytoplasm. The mechanisms underlying the nuclear export of these particles and its coordination with other biogenesis steps are mostly unknown. Here we show that yeast Rrp12 is required for the exit of pre-40S particles to the cytoplasm and for proper maturation dynamics of upstream 90S pre-ribosomes. Due to this, in vivo elimination of Rrp12 leads to an accumulation of nucleoplasmic 90S to pre-40S transitional particles, abnormal 35S pre-rRNA processing, delayed elimination of processing byproducts, and no export of intermediate pre-40S complexes. The exportin Crm1 is also required for the same pre-ribosome maturation events that involve Rrp12. Thus, in addition to their implication in nuclear export, Rrp12 and Crm1 participate in earlier biosynthetic steps that take place in the nucleolus. Our results indicate that, in the 40S subunit synthesis pathway, the completion of early pre-40S particle assembly, the initiation of byproduct degradation and the priming for nuclear export occur in an integrated manner in late 90S pre-ribosomes.

Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors.

The R-RAS2 GTP hydrolase (GTPase) (also known as TC21) has been traditionally considered quite similar to classical RAS proteins at the regulatory and signaling levels. Recently, a long-tail hotspot mutation targeting the R-RAS2/TC21 Gln72 residue (Q72L) was identified as a potent oncogenic driver. Additional point mutations were also found in other tumors at low frequencies. Despite this, little information is available regarding the transforming role of these mutant versions and their relevance for the tumorigenic properties of already-transformed cancer cells. Here, we report that many of the RRAS2 mutations found in human cancers are highly transforming when expressed in immortalized cell lines. Moreover, the expression of endogenous R-RAS2Q72L is important for maintaining optimal levels of PI3K and ERK activities as well as for the adhesion, invasiveness, proliferation, and mitochondrial respiration of ovarian and breast cancer cell lines. Endogenous R-RAS2Q72L also regulates gene expression programs linked to both cell adhesion and inflammatory/immune-related responses. Endogenous R-RAS2Q72L is also quite relevant for the in vivo tumorigenic activity of these cells. This dependency is observed even though these cancer cell lines bear concurrent gain-of-function mutations in genes encoding RAS signaling elements. Finally, we show that endogenous R-RAS2, unlike the case of classical RAS proteins, specifically localizes in focal adhesions. Collectively, these results indicate that gain-of-function mutations of R-RAS2/TC21 play roles in tumor initiation and maintenance that are not fully redundant with those regulated by classical RAS oncoproteins.

Needs Assessment in Parents of Children Affected by Cancer: A Qualitative Perspective.

BACKGROUND: Childhood cancer is a "stressful experience" for parents in their role as caregivers. The aim of this study is to analyze the needs of a group of parents who have children diagnosed with cancer. The assessment looks at all areas of their daily life using a qualitative content analysis approach. METHODS: This study uses open questions designed to investigate the main problems faced by the parents of children with cancer. All the answers were analyzed using MAXQDA 20 software. The study was conducted according to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: The content analysis of the answers from 13 mothers and 7 fathers is presented. The main themes as priority areas of need were: "informal social support", "coping", "stressors/imbalances" and "health problems". Dissatisfaction with the support provided from the informal network was detected. Although the participants expressed active coping, they also exhibited helplessness, as well as concerns regarding possible sequelae and the impact of this situation on the family's economic/work context. Conciliation problems were a source of stress. All this is consistent with the participants suffering from a variety of health issues. CONCLUSIONS: the results show the effect of childhood cancer on different aspects of family life. They provide essential information for designing psychosocial interventions.

Treacle Sticks the Nucleolar Responses to DNA Damage Together.

The importance of chromatin environment for DNA repair has gained increasing recognition in recent years. The nucleolus is the largest sub-compartment within the nucleus: it has distinct biophysical properties, selective protein retention, and houses the specialized ribosomal RNA genes (collectively referred to as rDNA) with a unique chromatin composition. These genes have high transcriptional activity and a repetitive nature, making them susceptible to DNA damage and resulting in the highest frequency of rearrangements across the genome. A distinct DNA damage response (DDR) secures the fidelity of this genomic region, the so-called nucleolar DDR (n-DDR). The composition of the n-DDR reflects the characteristics of nucleolar chromatin with the nucleolar protein Treacle (also referred to as TCOF1) as a central coordinator retaining several well-characterized DDR proteins in the nucleolus. In this review, we bring together data on the structure of Treacle, its known functions in ribosome biogenesis, and its involvement in multiple branches of the n-DDR to discuss their interconnection. Furthermore, we discuss how the functions of Treacle in ribosome biogenesis and in the n-DDR may contribute to Treacher Collins Syndrome, a disease caused by mutations in Treacle. Finally, we outline outstanding questions that need to be addressed for a more comprehensive understanding of Treacle, the n-DDR, and the coordination of ribosome biogenesis and DNA repair.

A hotspot mutation targeting the R-RAS2 GTPase acts as a potent oncogenic driver in a wide spectrum of tumors.

A missense change in RRAS2 (Gln72 to Leu), analogous to the Gln61-to-Leu mutation of RAS oncoproteins, has been identified as a long-tail hotspot mutation in cancer and Noonan syndrome. However, the relevance of this mutation for in vivo tumorigenesis remains understudied. Here we show, using an inducible knockin mouse model, that R-Ras2Q72L triggers rapid development of a wide spectrum of tumors when somatically expressed in adult tissues. These tumors show limited overlap with those originated by classical Ras oncogenes. R-Ras2Q72L-driven tumors can be classified into different subtypes according to therapeutic susceptibility. Importantly, the most relevant R-Ras2Q72L-driven tumors are dependent on mTORC1 but independent of phosphatidylinositol 3-kinase-, MEK-, and Ral guanosine diphosphate (GDP) dissociation stimulator. This pharmacological vulnerability is due to the extensive rewiring by R-Ras2Q72L of pathways that orthogonally stimulate mTORC1 signaling. These findings demonstrate that RRAS2Q72L is a bona fide oncogenic driver and unveil therapeutic strategies for patients with cancer and Noonan syndrome bearing RRAS2 mutations.

When Your Child Has Cancer: A Path-Analysis Model to Show the Relationships between Flourishing and Health in Parents of Children with Cancer.

BACKGROUND: Childhood cancer is a disease with a psychosocial impact on parents who experience health problems and distress. Their reactions depend on the relationship of multiple factors. The objective of this paper is to evaluate the interrelationships between flourishing and the variables linked to the health and wellbeing of parents of children with cancer. METHODS: Mothers/fathers of children with cancer participated in an exploratory study in response to a series of questionnaires. Likert-type scales were used to measure perceived health, wellbeing, flourishing, stress, coping, and social support. RESULTS: Out of a total of 94 children, 138 parents (60 men/78 women) are represented. Participants show physical symptoms and an unstable coping pattern. A path analysis model is presented. As to the goodness of adjustment of the statistics used, good results were obtained. Flourishing tends to coexist with wellbeing, while flourishing coexists negatively with symptoms. There is an indirect relationship between flourishing and poor health. There is a positive relationship between flourishing and coping, as well as between flourishing and satisfaction with the support received (especially from sons/daughters). This support was negatively related to the subjective health report. CONCLUSIONS: Flourishing is shown as a healthy coping strategy. The results can enrich the development of psychosocial interventions aimed at promoting adequate adaptation.

Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis.

Technical problems intrinsic to the purification of preribosome intermediates have limited our understanding of ribosome biosynthesis in humans. Addressing this issue is important given the implication of this biological process in human disease. Here we report a preribosome purification and tagging strategy that overcomes some of the existing technical difficulties. Using these tools, we find that the pre-40S precursors go through two distinct maturation phases inside the nucleolus and follow a regulatory step that precedes late maturation in the cytoplasm. This regulatory step entails the intertwined actions of both PARN (a metazoan-specific ribonuclease) and RRP12 (a phylogenetically conserved 40S biogenesis factor that has acquired additional functional features in higher eukaryotes). Together, these results demonstrate the usefulness of this purification method for the dissection of ribosome biogenesis in human cells. They also identify distinct maturation stages and metazoan-specific regulatory mechanisms involved in the generation of the human 40S ribosomal subunit.

Spanish Version of the Flourishing Scale (FS) on the Parents of Children With Cancer: A Validation Through Rasch Analysis.

The interest in the study of flourishing is due to the fact that it has been proven that it contributes to a good adjustment to the demands of the environment, relating to indicators of health and well-being. There are many researches that have tried to find out what dimensions make it up. The goal of this study is to validate the Spanish Version of The Flourishing Scale (FS), being the first time it is applied to Spanish parents of children with cancer. A total of 138 parents of children with cancer participated in a semi-structured interview. Through IBM SPSS and Winsteps descriptive analyzes and the internal consistency of the FS were calculated. Rasch analysis was used to study the dimensionality of the scale, the adjustment of each one of the items, the reliability values for the items and for the people, the validity of the construct, the functioning of the response categories, and the differential item functioning (DIF). The external construct validity of the FS was examined with associated measures. Results found that parents indicated a flourishing attitude (M = 3.85; sd = 0.63). We confirm that the FS maintains an adequate internal consistency and a unidimensional structure. We observed a good alignment between the question and the person's abilities as soon as a high reliability for the items. Although the sample is large enough to corroborate the difficulty hierarchy of the items, the construct validity could be improved by introducing items of moderate and high difficulty. On the other hand, the answer category 3 overlaps with the 2 and 4, so we propose possible solutions. Regarding a possible DIF, this exists in relation to "gender," "level of education" and "by the situation with respect to treatment." Finally, the convergent validity of the FS is demonstrated, there being a significant correlation with well-being, satisfaction with social support and coping. In general, the results show adequate psychometric properties of the Spanish version of the FS, so we recommend integrating it in psychosocial interventions aimed at parents of children with cancer, in order to provide them with resources to deal with the disease.

[Dental health: relationship between dental caries and food consumption]. / Salud dental: relación entre la caries dental y el consumo de alimentos.

Although the reduction and prevalence of dental caries in many countries has been largely associated with the use of fluorine and improving dental hygiene, eating habits also play a role in the development of caries. Fermentable carbohydrates characteristics of the food, rate of consumption, food protectors, the quality and quantity of saliva indices that determine the remineralization of teeth are factors to be considered. All these elements are analyzed through the sociodemographic, behavioral, physical and biological environment directly or indirectly with diet and caries.

A pesar de que la reducción de la incidencia y prevalencia de la caries dental en muchos países se relaciona en gran medida con el uso sistemático del flúor en las pastas dentífricas y la mejora de la higiene dental, se debe tener presente la importancia de los hábitos alimentarios en la prevención primaria y secundaria de la caries dental. En este sentido, destacan los carbohidratos fermentables, determinadas características de los alimentos, la frecuencia de consumo, distintos tipos de alimentos, algunos como factores protectores, la cantidad y la calidad de la saliva, en tanto que ello determina el índice de remineralización de los dientes etc. Todos estos elementos son analizados a través de los factores sociodemográficos, de comportamiento, físico-ambientales y biológicos relacionados directa o indirectamente con dieta y caries.

[Factors linked to adhesion to treatment in patients with refractory and non-refractory epilepsy]. / Factores vinculados a la adhesión al tratamiento en pacientes con epilepsia refractaria y no refractaria.

INTRODUCTION: Non-compliance with therapy is a problem in clinical practice in chronic diseases. Nevertheless, there are important gaps in our knowledge on this subject and its associated factors in patients with epilepsy. Moreover, failure to comply could lead to poor classification of the patients according to the definition of refractory epilepsy. AIMS: To examine the behaviour in terms of therapy compliance and the clinical, psychosocial and developmental factors involved in a group of patients with epilepsy, and also to analyse the differences in the psychosocial variables depending on the degree of resistance. PATIENTS AND METHODS: The study involved 112 epileptic patients recruited consecutively in the epilepsy unit of a tertiary health care centre. Patients were administered a questionnaire designed to collect sociodemographic and clinical variables, together with data about treatment, adhesion, reasons for non-compliance, social support, health, welfare and degree of response to treatment. RESULTS: The levels of non-compliance with therapy agreed with those found in previous studies. No significant differences in the level of adhesion were found between patients with refractory epilepsy and pharmacologically-controlled epilepsy, although significant differences were observed in the level of health, welfare, social support and other associated variables. CONCLUSIONS: The level of compliance of epileptic patients is rather poor. Patients with refractory epilepsy are more aware of the severity of their disease, they are more critical with the health care system and with their social setting, and they tend to comply better with their treatment. Hence, there are no reasons to believe that therapy non-compliance can explain a high proportion of the resistance that exists in epilepsy.

Repercusiones psicosociales del cáncer infantil: apoyo social y salud en familias afectadas / Psychosocial consequences of childhood cancer, social support and health in families affected

El propósito de esta investigación es analizar las repercusiones psicosociales que genera el cáncer infantil en los progenitores. Para ello, se han estudiado variables ligadas a síntomas físicos y psicológicos y el papel del apoyo social percibido sobre la salud. La muestra está compuesta por 51 padres pertenecientes a una asociación de familias afectadas de Almería (España), que respondieron a un cuestionario semiestructurado enviado por correo postal. Aunque los progenitores manifiestan fundamentalmente síntomas de cansancio, dolores de cabeza y nerviosismo, no se observan valores especialmente negativos respecto a su salud percibida y su satisfacción con la vida. Existen relaciones significativas entre el estrés ante situaciones asociadas a la enfermedad y la salud y el bienestar de los participantes. El apoyo social percibido del núcleo familiar incide significativa-mente en la salud. Los análisis de regresión permiten contrastar la relevancia de las variables asociadas al estrés y el apoyo de la pareja y de los hijos sobre la percepción de síntomas y bienestar. Estos resultados destacan la importancia de seguir analizando los factores psicosociales que afectan a las familias afectadas con la finalidad de favorecer su adaptación a la enfermedad y minimizar el impacto que esta puede tener en la salud. © 2015, Fundación Universitaria Konrad Lorenz.

The purpose of this study is to analyze the psychosocial impact on parents generated by childhood cancer. An evaluation was carried out in variables related to physical and psychological symptoms, and the role of perceived social support in their health. The sample consisted of 51 parents that belonged to an association of affected families from Almeria (Spain), who answered a semi-structured questionnaire sent by post. Although these parents showed fatigue, headaches and nervousness, they did not particularly give negative scores for perceived health and satisfaction with life. There are significant differences between stressful situations related to this illness and health and well-being of participants. Perceived social support of the family unit has a significant impact on health. Regression analyses allow contrasting the relevance of the variables associated with stress and social support of the parents and children on the perception of symptoms and well-being. These results indicate the importance of continuing to analyze in depth the psychosocial factors that have an impact on the families affected, in order to facilitate their adaptation to the disease and minimize the impact it may have on health. © 2015, Konrad Lorenz University Foundation.

Genetic parameters related to environmental variability of weight traits in a selection experiment for weight gain in mice; signs of correlated canalised response.

Data from an experimental mice population selected from 18 generations to increase weight gain were used to estimate the genetic parameters associated with environmental variability. The analysis involved three traits: weight at 21 days, weight at 42 days and weight gain between 21 and 42 days. A dataset of 5273 records for males was studied. Data were analysed using Bayesian procedures by comparing the Deviance Information Criterion (DIC) value of two different models: one assuming homogeneous environmental variances and another assuming them as heterogeneous. The model assuming heterogeneity was better in all cases and also showed higher additive genetic variances and lower common environmental variances. The heterogeneity of residual variance was associated with systematic and additive genetic effects thus making reduction by selection possible. Genetic correlations between the additive genetic effects on mean and environmental variance of the traits analysed were always negative, ranging from -0.19 to -0.38. An increase in the heritability of the traits was found when considering the genetic determination of the environmental variability. A suggested correlated canalised response was found in terms of coefficient of variation but it could be insufficient to compensate for the scale effect associated with an increase of the mean.

Monitoring of Official Degree Qualifications: The Key Role of Academic Quality Assurance Systems (AQAS) / El proceso de seguimiento de los títulos oficiales: El papel "clave" de los Sistemas de Garantía de Calidad

The purpose of this article is focused on the development of a protocol designed to facilitate the monitoring process of the official degrees of a Spanish university. In response to the criteria and guidelines established in the Royal Decree 1393/2007, this proposal seeks to make available to the focus groups a useful and flexible tool, tailored to the different existing regulations, which assesses progress in the development of the curriculum, ensures the effective implementation of the degrees, and publishes the information available, relevant and appropriate. It also helps to identify weaknesses, potential improvements and best practices for dissemination. All this, with the ultimate aim of assuring the accreditation of Official Degrees. The monitoring protocol articulates the assessment, as a Check-List, in fulfillment of an annual series of indicators set out in the Academic Quality Assurance Systems (AQAS) included in the Proceedings of Degrees. Finally, the monitoring of new degrees comes up as a result of adaptation to the requirements of the European Higher Education Area.

El propósito de este artículo se centra en el desarrollo de un protocolo diseñado para facilitar el proceso de seguimiento de las titulaciones oficiales en las Universidades Españolas. En respuesta a los criterios y directrices establecidos en el Real Decreto 1393/2007, la presente propuesta tiene por objeto poner a disposición de los grupos de interés una herramienta útil y flexible, adaptada a las diferentes regulaciones existentes, que evalúa el progreso en el desarrollo del plan de estudios, asegura la aplicación efectiva de los grados, y publica la información disponible, relevante y apropiada. También ayuda a identificar los puntos débiles, las posibles mejoras y las prácticas más adecuadas para su difusión. Todo esto, con el fin último de garantizar la acreditación de los Títulos Oficiales. El protocolo de seguimiento articula la evaluación, así como una lista de control, en cumplimiento de una serie de indicadores establecidos en los Sistemas de Garantía de Calidad (SGC) incluidos en los Procedimientos de Grado. Por último, el seguimiento de los nuevos Títulos de Grado surge como resultado de la adaptación a los requerimientos del Espacio Europeo de Educación Superior.

Prevalencia y factores de riesgo de colelitiasis en pacientes menores de 18 años en un hospital de segundo nivel / Prevalence and risk factors for cholelithiasis in patients under 18 years of age at a second level health care hospital

Objetivo: Observar la prevalencia de litiasis vesicular y factores de riesgo en menores de 18 años, en un hospital de segundo nivel. Sede: Hospital General de Matamoros ''Dr. Alfredo Pumarejo Lafaurie'', Tamaulipas. Diseño: Estudio retrospectivo, transversal, observacional, descriptivo. Análisis estadístico: Porcentajes como medida de resumen para variables cualitativas. Pacientes y métodos: Se revisaron 706 expedientes clínicos de pacientes con diagnóstico de colelitiasis en un periodo comprendido entre enero de 2003 a diciembre de 2008. Las variables estudiadas fueron: edad menor de 18 años, sexo, antecedentes familiares de litiasis vesicular, enfermedades hemolíticas, uso de hormonales, embarazos, índice de masa corporal, síntoma predominante, complicaciones (coledocolitiasis y pancreatitis), tiempo de estancia hospitalaria y estudio histopatológico vesicular. Resultados: Se identificaron 26 casos con edad promedio de 12.8 años, todas mujeres, 16 pacientes (61.5%) con antecedente de embarazo. Sólo una paciente presentó peso normal, sobrepeso en siete pacientes, obesidad grado l en ocho pacientes, grado II en seis pacientes, grado III en cuatro pacientes, el 100% con antecedentes de litiasis vesicular materna. Conclusión: La prevalencia de colelitiasis en menores de 18 años fue de 3.6%. Los factores de riesgo asociados a pacientes mayores de 18 años fueron similares en la población estudiada menor de 18 años.

Objective: To observe the prevalence of gallbladder lithiasis and risk factors in patients under 18 years in a second level health care hospital. Setting: General Hospital of Matamoros ''Dr. Alfredo Pumarejo Lafaurie'', Tamaulipas. Mexico. Design: Retrospective, cross-sectional, descriptive, observational study. Statistical analysis: Percentages as summary measure for qualitative variables. Patients and methods: We reviewed 706 clinical files of patients with choledocholithiasis diagnosed between January 2003 and December 2008. Studied variables were: age below 18 years, sex, familial antecedents of gallbladder lithiasis, hemolytic diseases, use of hormones, pregnancies, body mass index, predominating symptom, length of in-hospital stay, and histopathological study of the gallbladder. Results: We identified 26 cases with an average age of 12.8 years; all were women, 16 patients (61.5%) with antecedents of pregnancy. Only one patient had a normal weight, seven patients were overweight, eight patients coursed with obesity grade I, six with grade II, and four with grade III. All (100%) had antecedents of maternal gallbladder lithiasis. Conclusion: Prevalence of choledocholithiasis in patients under 18 years of age was of 3.6%. Associated risk factors for patients below 18 years of age are similar to those encountered over 18 years of age.

Genetic parameters for canalisation analysis of litter size and litter weight traits at birth in mice.

The aim of this research was to explore the genetic parameters associated with environmental variability for litter size (LS), litter weight (LW) and mean individual birth weight (IW) in mice before canalisation. The analyses were conducted on an experimental mice population designed to reduce environmental variability for LS. The analysed database included 1,976 records for LW and IW and 4,129 records for LS. The total number of individuals included in the analysed pedigree was 3,997. Heritabilities estimated for the traits under an initial exploratory approach varied from 0.099 to 0.101 for LS, from 0.112 to 0.148 for LW and from 0.028 to 0.033 for IW. The means of the posterior distribution of the heritability under a Bayesian approach were the following: 0.10 (LS), 0.13 (LW) and 0.03 (IW). In general, the heritabilities estimated under the initial exploratory approach for the environmental variability of the analysed traits were low. Genetic correlations estimated between the trait and its variability reached values of -0.929 (LS), -0.815 (LW) and 0.969 (IW). The results presented here for the first time in mice may suggest a genetic basis for variability of the evaluated traits, thus opening the possibility to be implemented in selection schemes.