Tumours in the pineal region in the paediatric age: Reports of 23 cases and a review of the literature

Introducción. Los tumores de la región pineal se localizan en una encrucijada de estructuras neurovasculares de difícil acceso quirúrgico y limitadas posibilidades de resección; por ello, el manejo de estas lesiones habitualmente requiere la asociación de tratamiento adyuvante radioterápico y/o quimioterápico. Pacientes y métodos. Análisis retrospectivo de las características epidemiológicas, clínicas, neurorradiológicas y anatomopatológicas de 23 pacientes con tumores de la región pineal tratados entre los años 1997 y 2010 en el Hospital Infantil Niño Jesús. Se discuten los factores implicados en el pronóstico de esta cohorte tras el tratamiento quirúrgico o adyuvante. Resultados. El estudio incluyó 6 niñas y 17 niños con edades comprendidas entre los 4 meses y 18 años. El 95% de los pacientes comenzó con signos de hidrocefalia aguda o subaguda, que precisaron la implantación de una derivación ventriculoperitoneal (82%). Se obtuvo una muestra histológica tumoral en todos los casos. Cinco pacientes fueron biopsiados y 18 fueron intervenidos mediante craneotomía. El germinoma (ocho casos) y el teratoma maduro (un caso) fueron los tumores con mayor supervivencia; los tumores no germinomatosos (tres casos), del parénquima pineal (cuatro casos) y gliomas (cinco casos) presentaron mayor tasa de recidiva y un peor pronóstico. Conclusión. El estudio de marcadores tumorales permite orientar el diagnóstico de determinados tumores de la región pineal. Actualmente, se recomienda realizar una toma histológica tumoral para establecer un diagnóstico preciso y un tratamiento oncológico específicoIntroduction. Tumours in the pineal region are located at a meeting point of several neurovascular structures that are difficult to reach surgically and for which the possibility of resection is limited; as a result the management of these lesions usually requires associated adjunctive treatment with radiotherapy and/or chemotherapy. Patients and methods. This study is a retrospective analysis of the epidemiological, clinical, neuroimaging and pathological characteristics of 23 patients with tumours in the pineal region who were treated between the years 1997 and 2010 in the Hospital Infantil Niño Jesús. The factors involved in the prognosis of this cohort following surgical or adjunctive treatment are also discussed. Results. Subjects included in the study were 6 girls and 17 boys with ages ranging from 4 months to 18 years. It was found that the initial symptoms in 95% of the patients were signs of acute or subacute hydrocephalus, which required the placement of a ventriculoperitoneal shunt (82%). A histological sample of the tumour tissue was collected in all cases. Biopsy samples were taken in the case of five patients and 18 underwent surgery involving a craniotomy. Germinoma (eight cases) and mature teratoma (one case) were the tumours with the longest survival times; non-germinomatous tumours (three cases), those of the pineal parenchyma (four cases) and gliomas (five cases) presented the highest rates of recurrence and a poorer prognosis. Conclusions. The study of tumour markers can be used to guide the diagnosis of certain tumours of the pineal region. At present, the recommended procedure involves taking a histological sample of the tumour in order to establish an accurate diagnosis and a specific oncological treatmen

Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement

Mutations in LRRK2 increase its kinase activity and cause Parkinson's disease. LRRK2 phosphorylates a subset of Rab proteins which allows for their binding to RILPL1. The phospho-Rab/RILPL1 interaction causes deficits in ciliogenesis and interferes with the cohesion of duplicated centrosomes. We show here that centrosomal deficits mediated by pathogenic LRRK2 can also be observed in patient-derived iPS cells, and we have used transiently transfected cell lines to identify the underlying mechanism. The LRRK2-mediated centrosomal cohesion deficits are dependent on both the GTP conformation and phosphorylation status of the Rab proteins. Pathogenic LRRK2 does not displace proteinaceous linker proteins which hold duplicated centrosomes together, but causes the centrosomal displacement of CDK5RAP2, a protein critical for centrosome cohesion. The LRRK2-mediated centrosomal displacement of CDK5RAP2 requires RILPL1 and phospho-Rab proteins, which stably associate with centrosomes. These data provide fundamental information as to how pathogenic LRRK2 alters the normal physiology of a cell.We are grateful to Erich Nigg and Francis Barr for providing a variety of constructs and antibodies, and to Dario Alessi for providing various A549 cell lines and MEF cells. We thank LauraMontosa for excellent technical assistance with confocal microscopy. This work was supported by The Michael J. Fox Foundation for Parkinson's research (to S.H.), intramural funding from Rutgers University (to S.H.), the Spanish Ministry of Economy and Competitiveness (SAF2017-89402-R to S.H.), the BBVA Foundation (to S.H., S.A.C., and R.W. M.), the Spanish Ministry of Education, Culture and Sport (FPU12/04367 to J.M. P., FPU15/05233 to A.J. L.O.), and the Spanish Ministry of Science, Innovation and Universities (EST18/00412 to A.J.L. O.)

Focusing on Comorbidity A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders

Background: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. Objectives: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. Methods: The novel approach consists of a modification of Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. Discussion: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Profile of a group of university audience in Mexico according to their citizen participation, trust in institutions and civic interaction in the media in 2017.

The present quantitative study shows the singularities of the university audience in Mexico in 2017, measured according to their civic participation, how they assess national institutions, and how they interact with the media regarding social and political issues. The surveyed population consisted of 1,195 young adults of 23 years of average age and who are part of private universities located in Jalisco, Mexico City and Aguascalientes. The results indicate that the offline participation in social capital is more significant than online participation of this university audience. The only institutions that have an approval index for this audience are religious institutions, universities, and the media. Finally, the university audience in Mexico has features of being passive and conservative regarding its consumption of information and its political participation in media. This population reflects apathy in expressing their opinion in media regarding social and political issues in the country

RAB8, RAB10 and RILPL1 contribute to both LRRK2 kinase-mediated centrosomal cohesion and ciliogenesis deficits

Mutations in the LRRK2 kinase are the most common cause of familial Parkinson's disease, and variants increase risk for the sporadic form of the disease. LRRK2 phosphorylates multiple RAB GTPases including RAB8A and RAB10. Phosphorylated RAB10 is recruited to centrosome-localized RILPL1, which may interfere with ciliogenesis in a disease-relevant context. Our previous studies indicate that the centrosomal accumulation of phosphorylated RAB8A causes centrosomal cohesion deficits in dividing cells, including in peripheral patient-derived cells. Here, we show that both RAB8 and RAB10 contribute to the centrosomal cohesion deficits. Pathogenic LRRK2 causes the centrosomal accumulation not only of phosho-RAB8 but also of phospho-RAB10, and the effects on centrosomal cohesion are dependent on RAB8, RAB10 and RILPL1. Conversely, the pathogenic LRRK2-mediated ciliogenesis defects correlate with the centrosomal accumulation of both phospho-RAB8 and phospho-RAB10. LRRK2-mediated centrosomal cohesion and ciliogenesis alterations are observed in patient-derived peripheral cells, as well as in primary astrocytes from mutant LRRK2 mice, and are reverted upon LRRK2 kinase inhibition. These data suggest that the LRRK2-mediated centrosomal cohesion and ciliogenesis defects are distinct cellular readouts of the same underlying phospho-RAB8/RAB10/RILPL1 nexus and highlight the possibility that either centrosomal cohesion and/or ciliogenesis alterations may serve as cellular biomarkers for LRRK2-related PD.Michael J. Fox Foundation for Parkinson’s research (to S.H.); European Regional Development Fund; Spanish Ministry of Economy and Competitiveness (SAF2017-89402-R to S.H.); Spanish Ministry of Education, Culture and Sport (FPU15/05233 to A.J.L.O.)

Distorsión clínica y simulación en la incapacidad temporal: un estudio preliminar

Various studies show the high frequency of malingering when applying for temporary incapacity, and poor training to detect it. Using a descriptive and retrospective study, this work aims to basically address the phenomenon of distortion in medical assessment of disability by reviewing the first 100 medical discharges issued by a medical assessor of the Instituto Nacional de la Seguridad Social [National Social Security Institute] (INSS). Following the analysis of the data, the description of the sample shows that that directly paid and "white collar” workers have a higher frequency of moderate and marked distortion. However, the Special Agricultural Scheme revealed the presence of the highest marked distortion, with 10 out of 14 cases (71%, p < .001 with Fisher's F), but this did not occur in the unemployed workers, who present only 22% of marked distortion, and its distribution is no different from that of the group as a whole. The need for training for the medical evaluation of disability in malingering and distortion of symptoms are discussed and recommended.Distintos trabajos muestran la alta frecuencia de la simulación en la solicitud de incapacidades temporales (IT), así como la escasa formación en la detección de la misma. Este trabajo tiene por finalidad abordar de manera básica, mediante un estudio descriptivo y retrospectivo, el fenómeno de la distorsión en la valoración médica de la incapacidad mediante la revisión de las primeras 100 altas médicas emitidas por un médico evaluador del INSS. De la descripción de la muestra destaca, tras los análisis de los datos, que los grupos de trabajadores en pago directo y de “cuello blanco” presentan una mayor frecuencia de distorsión moderada y marcada. No obstante, la mayor presencia de distorsión marcada se encuentra en el Régimen Especial Agrario, con 10 de los 14 casos (71%, p<0,001 en la F de Fisher) y, sin embargo, no ocurre así en los trabajadores desempleados, que sólo presentan un 22% de distorsión marcada y su distribución no es diferente a la del grupo en su conjunto. La necesidad de formación para la valoración médica de incapacidad (VMI) en simulación y distorsión de síntomas es discutida y recomendada

Equity in the access to mammography in Spain

The purpose of this study is to measure the access to mammography of women aged 40-70 in Spain and to analyze the factors related to access to the test. Women were considered to have access to mammography if they had received at least one mammogram in the preceding 2 years. Numerous studies have shown that breast cancer mortality is reduced in women receiving periodic mammography, although experts disagree about the most appropriate age range for screening. An equitable health care system should provide access to effective procedures to all persons who need them. A number of factors influencing the access to mammography have been described. We conducted a cross-sectional population-based survey of 3218 women residing in Spain who were between 40 and 70 years of age. The sample was selected using a multi-stage stratified cluster technique, with proportional assignment to each stratum. Data collection took place between March and May 1994 by means of individual oral interviews using a standardized questionnaire. The questionnaire included information on the dependent variable (mammography use) and the independent variables (those potentially associated with access to the test). Information on other independent variables was collected in official institutions or from existing publications. Data analysis consisted of univariate and multivariate analyses. Only about 28% of all women had received a mammogram in the last 2 years. According to the univariate analysis, access to mammography is most strongly associated with number of gynaecologist visits, residence in the autonomous community of Navarre, and physician referral for mammography. In the multivariate analysis, the factors most strongly associated with access to mammography are gynaecologist visits at least once in the last 2 years (OR = 8.71; CI = 6.84-11.10), existence of a breast cancer screening programme (OR = 7.64; CI = 5.24-11.10), and physician referral for testing (OR = 4.78; CI = 3.83-5.96). The multivariate analysis also showed a significant association with place of residence and with women's attitudes about testing. A small proportion of Spanish women who could potentially benefit from mammography have received the test in the last 2 years. Establishing breast cancer screening programs equitably throughout the nation, and carrying out educational interventions aimed at women and especially at physicians, will help to reduce inequalities and increase the access to mammography in Spain.mammography access equity Spain