CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases

Nivel de funcionalidad de los enfermos crónicos y su relación con la calidad de vida de los cuidadores informales, Villavicencio, Colombia, 2011

Objective: To examine the relationship between chronic patients’ functionality level and the quality of life of their informal caregivers.Method: An observational cross-sectional descriptive study was carried out. The sample (n=180) was collected from patients caregivers volunteers registered in the Program of Chronic Illnesses of six local health units at the municipality of Villavicencio. Functionality level was measured using PULSES profile, Gardner version. Quality of life was measured by Ferrell’s Quality of Life family version.Results: An association OR=1,23) between decreased functionality level among the patients and decreased quality of life among the caregivers was found, although did not reach statistical significance. A significant association was identified between upper limbs function deterioration (OR 2,25), excretory functions deterioration (OR 2,31) and of the support factors (OR=2,13) and decreased in the psychological dimension of caregivers’ quality of life.Conclusions: Caregivers’ quality of life is affected by deterioration on functionality level of those chronic patients who are taken care for. Evaluation and follow-up of quality of life level among caregivers’ would improve self-care awareness and ability for informal care.Objetivo: Examinar la relación que existe entre el nivel de funcionalidad de los enfermos crónicos y el nivel de calidad de vida de sus cuidadores informales.  Método: Se desarrolló un estudio cuantitativo descriptivo observacional en cuidadores informales de enfermos con entidades crónicas.  La muestra (n=180) se recolectó de los cuidadores voluntarios mayores de edad que cuidaban a pacientes registrados en el Programa de Enfermedades Crónicas de seis unidades locales de salud del municipio de Villavicencio.  Las mediciones de nivel de funcionalidad y calidad de vida de los cuidadores se realizaron aplicando los instrumentos PULSES versión de Gardner e instrumento de Calidad de Vida versión familiar de B. Ferrell respectivamente. Resultados: Se encontró asociación que no alcanzó niveles de significancia entre limitación en el nivel de funcionalidad del enfermo crónico y calidad de vida del cuidador informal (OR: 1,23).  Se halló asociación significativa entre deterioro de la función de miembros superiores (OR 2,25), de la función excretora (OR 2,31) y de los factores de apoyo (OR=2,13) y deterioro de la dimensión psicológica de la calidad de vida de los cuidadores informales. Conclusiones: El cuidador informal se ve afectado por la condición de dependencia de la persona enferma a quien cuida y puede deteriorar su calidad de vida.  La valoración y seguimiento de la calidad de vida del cuidador permitirá mejorar su autocuidado y su habilidad para cuidar al enfermo crónico

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Cognitive impairment and magnetic resonance imaging correlates in primary progressive multiple sclerosis

Objectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=−.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction

Fungal Adenylyl Cyclase Acts As a Signal Sensor and Integrator and Plays a Central Role in Interaction with Bacteria

10.1371/journal.ppat.1003612PLoS Pathogens910