Cognitive and Neuropsychiatric Features of Orthostatic Tremor: A Case-Control Comparison.

Introduction Evidence suggests that the cerebellum could play a role in the pathophysiology of orthostatic tremor. The link between orthostatic tremor and the cerebellum is of interest, especially in light of the role the cerebellum plays in cognition, and it raises the possibility that orthostatic tremor patients could have cognitive deficits consistent with cerebellar dysfunction. Our aim was to examine whether orthostatic tremor patients had cognitive deficits and distinct personality profiles when compared with matched controls. Methods Sixteen consecutive orthostatic tremor patients (65.7 ± 13.3 years) and 32 healthy matched controls underwent a neuropsychological battery and the Personality Assessment Inventory. In linear regression models, the dependent variable was each one of the neuropsychological test scores or the Personality Assessment Inventory subscales and the independent variable was orthostatic tremor vs. control. Results Adjusted for age in years, sex, years of education, comorbidity index, current smoker, and depressive symptoms, diagnosis (orthostatic tremor vs. healthy control) was associated with poor performance on tests of executive function, visuospatial ability, verbal memory, visual memory, and language tests, and on a number of the Personality Assessment Inventory subscales (somatic concerns, anxiety related disorders, depression, and antisocial features). Older-onset OT (> 60 years) patients had poorer scores on cognitive and personality testing compared with their younger-onset OT counterparts. Conclusion Orthostatic tremor patients have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits. Cognitive impairment and personality disturbances could be disease-associated nonmotor manifestations of orthostatic tremor.pre-print426 K

Identification of Androgen Receptor Metabolic Correlome Reveals the Repression of Ceramide Kinase by Androgens

Prostate cancer (PCa) is one of the most prevalent cancers in men. Androgen receptor signaling plays a major role in this disease, and androgen deprivation therapy is a common therapeutic strategy in recurrent disease. Sphingolipid metabolism plays a central role in cell death, survival, and therapy resistance in cancer. Ceramide kinase (CERK) catalyzes the phosphorylation of ceramide to ceramide 1-phosphate, which regulates various cellular functions including cell growth and migration. Here we show that activated androgen receptor (AR) is a repressor of CERK expression. We undertook a bioinformatics strategy using PCa transcriptomics datasets to ascertain the metabolic alterations associated with AR activity. CERK was among the most prominent negatively correlated genes in our analysis. Interestingly, we demonstrated through various experimental approaches that activated AR reduces the mRNA expression of CERK: (i) expression of CERK is predominant in cell lines with low or negative AR activity; (ii) AR agonist and antagonist repress and induce CERK mRNA expression, respectively; (iii) orchiectomy in wildtype mice or mice with PCa (harboring prostate-specific Pten deletion) results in elevated Cerk mRNA levels in prostate tissue. Mechanistically, we found that AR represses CERK through interaction with its regulatory elements and that the transcriptional repressor EZH2 contributes to this process. In summary, we identify a repressive mode of AR that influences the expression of CERK in PCa.A.G.-M. is funded by the MINECO (SAF2016-79695-R) and the department of education (IKERTALDE IT1106-16). V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia and the Basque Department of Health (2016111109) and the MINECO RTI2018-097267-B-I00. The work of A. Carracedo is supported by the Basque Department of Industry, Tourism and Trade (Elkartek), the department of education (IKERTALDE IT1106-16) and health (RIS3), the MICINN (PID2019-108787RB-I00 (FEDER/EU); Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks RED2018-102769-T), the AECC (GCTRA18006CARR), La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/ and the European Research Council (Consolidator Grant 819242). CIBERONC was co-funded with FEDER funds and funded by ISCIII

Adverse clinical events in the hospital: characterization from the point of view of the health worker.

Introducción: un evento adverso es un incidente que ha producido daño en un paciente y que puede o no estar asociado a un error clínico. Un porcentaje elevado de profesionales de la salud se encuentran implicados en este tipo de eventos anualmente. Gran parte de los profesionales desconocen la existencia de los sistemas implantados en sus centros de trabajo para una comunicación correcta de los eventos adversos. Objetivos: identificar las características de los profesionales hospitalarios afectados por algún evento adverso y evaluar su conocimiento de los sistemas de notificación. Metodología: estudio observacional descriptivo transversal. Se evaluaron variables demográficas, laborales y relacionadas con los eventos adversos y los sistemas de notificación. Resultados: participaron 207, 45,4% enfermeros y 54,6% médicos, de 39,24±10,07 años y con una experiencia de 14,43±9,9 años.  El 71,8% resultaron afectados por algún evento adverso.  El primer evento adverso ocurrió a los 6,45±6,18 años. El 42,1% conocía algún sistema de notificación; pero sólo el 24,61% de éstos, afectados por un evento adverso, lo notificaron. Los médicos fueron más afectados por un evento adverso, además, más precozmente (p < 0,001); y también conocían los sistemas de notificación (p= 0,001). Discusión: muchos sanitarios, con escasa experiencia, fueron afectados por eventos adversos. Pocos conocían los sistemas de notificación y muchos menos los utilizaban. Los médicos resultaron más afectados, y más precozmente, por los eventos adversos y conocían mejor los sistemas de notificación.Introduction: an adverse event is an incident that has caused harm to a patient and that may or may not be associated with a clinical error. A high percentage of health professionals are involved in this type of event annually. A large part of the professionals are unaware of the existence of the systems implemented in their work centers for a correct communication of adverse events. Objectives: to identify the characteristics of hospital professionals affected by an adverse event and to evaluate their knowledge of the notification systems. Methods: cross-sectional descriptive observational study. Demographic, labor and related variables with adverse events and notification systems were evaluated. Results: 207, 45.4% nurses and 54.6% doctors, participated, 39.24 ± 10.07 years and with an experience of 14.43 ± 9.9 years. 71.8% were affected by some adverse event. The first adverse event occurred at 6.45 ± 6.18 years. 42.1% knew of some notification system; but only 24.61% of these, affected by an adverse event, reported it. Physicians were more affected by an adverse event, moreover earlier (p <0.001) and they were also more aware of notification systems (p = 0.001). Discussion: many health workers, with little experience, were affected by adverse events. Few knew notification systems and far fewer used them. Doctors were more affected, and earlier, by adverse events and were better acquainted with notification systems

Melting and transverse depinning of driven vortex lattices in the periodic pinning of Josephson junction arrays

We study the non-equilibrium dynamical regimes of a moving vortex lattice in the periodic pinning of a Josephson junction array (JJA) for {\it finite temperatures} in the case of a fractional or submatching field. We obtain a phase diagram for the current driven JJA as a function of the driving current I and temperature T. We find that when the vortex lattice is driven by a current, the depinning transition at $T_p(I)$ and the melting transition at $T_M(I)$ become separated even for a field for which they coincide in equilibrium. We also distinguish between the depinning of the vortex lattice in the direction of the current drive, and the {\it transverse depinning} in the direction perpendicular to the drive. The transverse depinning corresponds to the onset of transverse resistance in a moving vortex lattice at a given temperature $T_{tr}$. For driving currents above the critical current we find that the moving vortex lattice has first a transverse depinning transition at low T, and later a melting transition at a higher temperature, $T_{M}>T_{tr}$.Comment: 17 pages, 19 figure

Conflictos sociales y mediación universitaria en el Espacio Europeo de Educación Superior

Este artículo expone los principales datos y conclusiones obtenidas en el Workshop realizado en el año 2016 entre la Universidad de Málaga y Leuven (Bélgica). La líneas de investigación se centra en los conflictos sociales que se producen en el ámbito universitario.El presente trabajo, trata de analizar los conflictos que se producen en el ámbito universitario relacionados con la implementación del Espacio Europeo de Educación Superior y la nueva metodología docente derivada del mismo, que provocan disyuntivas sociales específicas. Estos conflictos, se hacen plausibles en la conciliación, el aprendizaje y el desarrollo del proceso educativo. Por un lado, con la asistencia obligatoria y la dedicación de tiempo que requiere al estudiante en la Universidad y de trabajo en casa. Por otro, por la situación devenida de los recortes en becas universitarias y la necesidad que impone esta reforma educativa de acreditación del B1 como lengua extranjera para la obtención del Título de Graduado. Estas circunstancias, construyen realidades relativas a los significados que el ámbito universitario tiene para las personas, e inciden en las oportunidades del alumnado en condiciones de igualdad en función de su situación social y personal. En el estudio, se analizan las causas y se definen los tipos de conflictos, así como su relación con la citada reforma

Flint and Quartzite: Distinguishing Raw Material Through Bone Cut Marks

Since the 1980s, several experimental analyses have been able to differentiate some lithic tool types and some of their raw materials according to the morphology of cut marks imprinted by such tools when used for butchering activities. Thus, metal tool use has been differentiated in contexts with an abundance of lithic tools, or even the use of hand axes has been documented in carcass processing, in contrast with simple unretouched or retouched flakes. As important as this information is, there are still other important aspects to be analysed. Can cut marks produced with different lithic raw material types be differentiated? Can cut marks made with different types of the same raw material type be characterized and differentiated? The objective of this study is to evaluate if cut marks resulting from the use of different flints and different quartzites are distinguishable from each other. In the present work, an experimental analysis of hundreds of cut marks produced by five types of flint and five varieties of quartzite was carried out. Microphotogrammetry and geometric–morphometric techniques were applied to analyse these cut marks. The results show that flint cut marks and quartzite cut marks can be characterized at the assemblage level. Different types of flint produced cut marks that were not significantly different from each other. Cut marks made with Olduvai Gorge quartzite were significantly different from those produced with a set comprising several other types of quartzites. Crystal size, which is larger in Olduvai Gorge quartzites (0.5 mm) than Spanish quartzites (177–250 μm), is discussed as being the main reason for these statistically significant differences. This documented intra-sample and inter-sample variance does not hinder the resolution of the approach to differentiate between these two generic raw material types and opens the door for the application of this method in archaeological contexts

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm3, respectively. CD4+ T nadir cells was 305 cells/mm3. Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.The authors thank all the patients for their participation. Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively).S

Plan de formación inicial en habilidades docentes para el profesorado de la Facultad de Educación

Memoria ID-0088. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients

Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.This work has been supported by grants from Institute of Health Carlos III, [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander [grant number 1.010.932 to AFR] and the Spanish AIDS Research Network (RD16CIII/0002/0002), and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) [CP14/CIII/00010 and CPII20CIII/0001].info:eu-repo/semantics/publishedVersio

FLK West (Lower Bed II, Olduvai Gorge, Tanzania): a new early Acheulean site with evidence for human exploitation of fauna

This paper presents a detailed taphonomic study of the faunal assemblage from FLK West (Olduvai Gorge, Tanzania), a site with an Acheulean component that dates to 1.7 Ma. The faunal sample analysed here is distributed in different archaeological levels and is associated with a significant lithic accumulation including several large format tools and handaxes. The fauna indicates the proliferation of open environments similar to those found in other Bed II and late Bed I sites. Evidence of anthropogenic activity (e.g. defleshing activities and marrow consumption) has been identified in the form of cut and percussion marks. A photogrammetric and morphometric analysis suggests that these marks were produced with quartzite flakes and not with handaxes. Evidence of interaction with carnivores was also noted; tooth marks were observed on some bones. Such interaction indicates the existence of competition between humans and carnivores for the same ecological niche, and might lead us to reflect on the survival strategies of Lower Pleistocene hominins