Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias.

INTRODUCTION: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). METHODS: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins. RESULTS: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used. DISCUSSION: Biomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied.

Screening of dementia genes by whole-exome sequencing in Spanish patients with early-onset dementia: likely pathogenic, uncertain significance and risk variants.

Early-onset Alzheimer's disease (EOAD) and frontotemporal dementia (FTD) have a high proportion of genetically determined cases. Next-generation sequencing technologies have triggered the discovery of new mutations and genetic variants in dementia-causal genes. We performed whole-exome sequencing and selective analysis of known genes causative of EOAD and FTD in a well-characterized Spanish cohort of 103 patients (60 EOAD, 43 FTD) to find genetic variants associated to patients' phenotype. In EOAD patients, a new likely pathogenic variant in PSEN1 gene (p.G378R) was found. In FTD patients, 2 likely pathogenic variants were found, one in MAPT gene (p.P397S) and one in VCP gene (p.R159H). In our series, 2% of early-onset dementia without criteria for clinical genetic testing according to current guidelines presented a likely pathogenic mutation. We have also detected 13 additional variants of uncertain significance in causal genes, as well as rare variants in risk genes for dementia (ABCA7, SORL1, SQSTM1, and TREM2). Next-generation technologies in neurodegenerative diseases constitute a powerful tool that significantly contributes to patients' diagnosis.

Thermal Effects in the Ablation of Bovine Cortical Bone with Pulsed Laser Sources.

Lasers have advantages as bone surgical tools over mechanical methods, but two goals should be achieved to assure its use: Similar ablation rates to those obtained with mechanical tools (1 mm3/s at least) and to avoid thermal damage, a condition that can prevent proper bone healing. We present results of cow femoral bone with a 355 nm nanosecond (ns) and a 1064 nm picosecond (ps) pulsed laser sources that allow us to discuss the influence on the process of pulse duration and the selective ablation through high energy absorption (as bone highly absorbs 355 nm radiation). The treated samples were characterized by scanning electron microscopy (SEM) and Raman spectroscopy. The evaluation of the thermal effects produced in the samples shows clear differences between both laser sources: On one hand, the ns laser allows reaching high ablation rates (around 1 mm3/s); Raman spectra show no signal of bone carbonization, but unavoidable thermal effects in the form of melted and solidified material have been observed by electron microscopy in the samples treated with this laser. On the other hand, ablation without any sign of thermal effects is obtained using the ps laser, but with lower ablation rates, (around 0.15 mm3/s).

Hippocampal atrophy has limited usefulness as a diagnostic biomarker on the early onset Alzheimer's disease patients: A comparison between visual and quantitative assessment.

NIA-AA diagnostic criteria include volumetric or visual rating measures of hippocampal atrophy (HA) as a diagnostic biomarker of Alzheimer's disease (AD). We aimed to determine its utility as a diagnostic biomarker for early onset Alzheimer's disease (EOAD) by assessing Medial Temporal Atrophy (MTA) and hippocampal volume (HV) determination. MTA score and HV quantified by FreeSurfer were assessed in 140 (aged ≤65) subjects with biomarker supported diagnosis: 38 amnesic (A-EOAD), 20 non-amnesic (NA-EOAD), 30 late onset AD (LOAD), 20 fronto-temporal dementia (FTD) and 32 healthy controls (HC). The results showed that the proportion of MTA ≥ 1.5 was higher on LOAD and FTD than EOAD and HC but none of the MTA thresholds (≥1, ≥1.5 and ≥ 2) showed acceptable diagnostic accuracy. LOAD had lower HV than the other groups. A-EOAD HV was lower than NA-EOAD and HC but equal to FTD. The 6258 mm3 cut-off showed good diagnostic accuracy between A-EOAD and HC. Both tools showed a moderate inverse correlation. In conclusion, MTA has a limited diagnostic utility as an EOAD biomarker as it does not discriminate AD from FTD or HC in initial symptomatic stages. HV may discriminate A-EOAD from HC but not from FTD.

CSF microRNA Profiling in Alzheimer's Disease: a Screening and Validation Study.

MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression through post-transcriptional repression of target genes. They have been shown to be implicated in the pathophysiology of Alzheimer's disease (AD) and proposed as disease biomarkers. In the present work, we have studied the expression levels of 754 miRNAs in cerebrospinal fluid (CSF) from AD patients and control subjects. We have explored a first screening cohort (N = 20) and selected 12 miRNAs to be further tested in a second independent validation cohort (N = 69). We have found a significant upregulation of miR-222 and miR-125b in AD CSF. Of these, the association of miR-222 with AD is novel and reported here for the first time whereas upregulation of miR-125b has been previously reported in AD brain. Yet we do not find association with other miRNAs which were previously linked to AD. Our results shed light on potential underlying pathophysiological processes of AD and also point out the need for consensus procedures in CSF miRNA detection and data analysis.

Altered Blood Gene Expression of Tumor-Related Genes (PRKCB, BECN1, and CDKN2A) in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common of the neurodegenerative diseases. Recent diagnostic criteria have defined a preclinical disease phase during which neuropathological substrates are thought to be present in the brain. There is an urgent need to find measurable alterations in this phase as well as a good peripheral biomarker in the blood. We selected a cohort of 100 subjects (controls = 47; preclinical AD = 11; patients with AD = 42) and analyzed whole blood expression of 20 genes by quantitative polymerase chain reaction. The selected genes belonged to calcium signaling, senescence and autophagy, and mitochondria/oxidative stress pathways. Additionally, two genes associated with an increased risk of developing AD (clusterin (CLU) and bridging integrator 1 (BIN1)) were also analyzed. We detected significantly different gene expressions of BECN1 and PRKCB between the control and the AD groups and of CDKN2A between the control and the preclinical AD groups. Notably, these three genes are also considered tumor suppressor (CDKN2A and BECN1) or tumor promoter (PRKCB) genes. Gene-gene expression Pearson correlations were computed separately for controls and patients with AD. The significant correlations (p < 0.001) were represented in a network analysis with Cytoscape tool, which suggested an uncoupling of mitochondria-related genes in AD group. Whole blood is emerging as a valuable tissue in the study of the physiopathology of AD.

Sistemas personalizados de dosificación en atención primaria: un estudio multidisciplinar / Dose dispensing service in a prymary health care area: A multidisciplinary study

Introducción: los sistemas personalizados de dosificación (SPD) preparados en farmacias son una opción para mejorar la adherencia terapéutica. Objetivo: describir las características y grado de implantación de los SPD bajo la perspectiva de profesionales sanitarios de un centro de salud, farmacéuticos comunitarios y pacientes adscritos a ese centro. Método: estudio descriptivo transversal en la zona de influencia del centro de salud Daroca (Madrid). Participaron 64 profesionales del centro de salud, 37 farmacéuticos comunitarios y 29 usuarios de SPD. Se utilizaron cuestionarios para cada una de las categorías con preguntas sobre conocimientos y opiniones de los SPD, gestión, preparación y satisfacción con el servicio. Resultado: conocen los SPD el 61,4 % de los profesionales del centro de salud y el 94 % creen que son útiles. Trece farmacias ofrecen los SPD: el 55,6 % considera que hay que contactar con el médico, el 41,7 % pone precio al servicio y el 92,3 % lo hace manualmente. Cinco farmacias preparan SPD a 18 pacientes de la zona. Criterios de inclusión más utilizados: edad, polimedicación y sospecha de mal cumplimiento. Perfil de paciente usuario de SPD: mujer octogenaria con estudios primarios polimedicada que vive sola. El 66,7 % de los pacientes encuestados tomaba los medicamentos directamente de la caja y al 88,9 % de ellos les recomendó el SPD el farmacéutico. El cien por cien de los usuarios de SPD está muy satisfecho con el servicio. Conclusión: aunque todos los colectivos estudiados creen que los SPD son útiles para mejorar la adherencia, existe una baja implantación de los SPD en nuestra zona

Introduction: Dose Dispensing Service (SPD) prepared in pharmacies are an option to improve therapeutic adherence. Objective: to describe the characteristics and implantation of SPD from the perspective of professionals of a health center, community pharmacists and patients attached to that center. Methods: Descriptive cross-sectional study in the area of influence of Daroca health center (Madrid). 64 health center professionals, 37 community pharmacists and 29 SPD users participated. Questionnaires were used for each of the categories with questions about knowledge and opinions of SPDs, management, preparation and satisfaction with the service. Results: 61.4% of health center professionals know SPD and 94% believe they are useful. 13 pharmacies offer SPD: 55.6% consider that they should contact the doctor, 41.7% charge for the service and 92.3% do so manually. 5 pharmacies prepare SPD for 18 patients in our local zone. Most used inclusion criteria: age, polymedication and suspicion of poor compliance. Patient profile using SPD: octogenarian woman polymedicated with primary studies living alone. 66.7% of the patients took the medications directly from the box. Pharmacists recommended SPD to 88.9% of patients. 100% of SPD users are very satisfied with the service. Conclusion: Although all the groups studied believe that SPDs are useful for improving adherence, SPDs have a low implementation in our area

7 años de DarocaFarmacias: programa de coordinación entre el Centro de Salud Daroca y los Farmacéuticos Comunitarios de su Zona Básica de Salud / 7 years of DarocaFarmacias: coordination program between Daroca Primary Health Center and Community Pharmaceuticals in a Basic Health Area

OBJETIVO: Evaluar el funcionamiento y el grado de satisfacción de los profesionales implicados en un programa de colaboración entre el Centro de Salud Daroca y las Farmacias Comunitarias de su zona de influencia (DarocaFarmacias) en Madrid, España. MÉTODOS: Participan 36 oficinas de farmacia y 81 profesionales sanitarios del centro de salud Daroca en un área urbana con 53.600 pacientes. Existe un correo electrónico y un teléfono directo en el centro de salud para facilitar la comunicación con las farmacias. Se realizan conjuntamente trabajos de investigación, sesiones de formación y actividades de educación para la salud. Se preguntó sobre los diferentes aspectos del proyecto (comunicación, relación interprofesional, sesiones de formación y satisfacción) mediante una encuesta anónima a los integrantes de DarocaFarmacias. RESULTADOS: Contestaron 67 profesionales (32 farmacéuticos, 21 médicos y 13 enfermeros). El 95,5% cree que ha mejorado la relación entre profesionales y el 82% que ha favorecido la comunicación. Para el 43,7% de los farmacéuticos la mejor vía de comunicación es el teléfono (92% de llamadas resolutivas), para el 31,2% el correo electrónico y el 53,1% ha acudido alguna vez al centro para resolver el problema. Acude a las sesiones de formación el 82% y resultan muy útiles para el 92,5%. El 91% de los profesionales está bastante o muy satisfecho con DarocaFarmacias. CONCLUSIÓN: DarocaFarmacias es un ejemplo de colaboración entre centros de salud y oficinas de farmacia en aras de una mejor atención a los pacientes

OBJECTIVE: To assess the performance and degree of satisfaction of the healthcare professionals involved in a cooperation programme between Daroca Health Centre and Community Pharmaceuticals in a Basic Health Area (DarocaFarmacias) in Madrid, Spain. METHODS: Thirty-six community pharmacies and 81 health care professionals of the Daroca Health Centre took part in this study, affecting an urban area of 53600 patients. Communications between Health Centre and Community Pharmacies were done by email and direct phone. Researching, clinical sessions and educational activities were collaboratively carried out. Different aspects of the project were analysed, such as communication, interprofessional relationship, training sessions and global satisfaction. With this aim, a blinded survey was submitted to the DarocaFarmacias members. RESULTS: Sixty-seven health professionals took part (32 community pharmacists, 21 physicians and 12 nurses) in the study. Among them, 95.5% are of the opinion that professional relationship improved and 82% agreed for a better-quality communication between health professionals. Most of the community pharmacists (43.7%) considered telephone as the preferred channel of communication (92% problem solving), followed by e-mail (31.2%), although half of them (53.1%) visited the Health Centre to solve a relevant question. Eighty-two out of 100 attended to the clinical sessions and educational activities, being considered as beneficial by 92.5% of them. Over nine out of ten (91%) of the health professionals were quite or very satisfied with DarocaFarmacias project. CONCLUSION: DarocaFarmacias is a positive experience of collaboration between Health Centre and community pharmacies in pursuit of a better attendance of the patients

Manejo del duelo en familiares de pacientes oncopediátricos / Management of grief in family members of oncopediatric patients

Introducción: La recuperación del dolor de una familia por la muerte de un niño obedece a la forma en la que se cuida la etapa final de su vida, y es especialmente en esta etapa, donde Enfermería juega un papel fundamental en el apoyo a la familia que enfrenta la enfermedad crítica y la muerte de un hijo.Objetivos: Revisar la literatura científica existente sobre el manejo del duelo en familiares de pacientes oncopediátricos.Metodología: Revisión integradora exhaustiva en las bases de datos Pudmed, Scopus, Scielo y Cochrane. Fueron empleados los términos “oncology pediatric”, “family”, “grief” y “nursing”, unidos por el operador boleano “AND”.Resultados: Se han identificado las experiencias emocionales que siente la familia del paciente oncohematológico pediátrico y las habilidades en la práctica enfermera que protegen el cuidado emocional de la misma. Por su relevancia en este ámbito, cabe destacar la relación terapéutica entre la familia, el niño, y el equipo sanitario, y el poder de la habilidad comunicativa en la etapa final de la vida y la muerte.Conclusiones: El cuidado de la integridad emocional y del curso natural del duelo es vital dentro del plan de cuidados del niño y su familia. Subrayar la magnitud que tendría el entrenamiento de Enfermería en habilidades emocionales, comunicativas y psico-conductuales dentro de la atención integral del niño y su familia. (AU)

Introduction: Recovery from the pain of a family due to the death of a child is due to the way in which the final stage of life is cared for, and it is especially at this stage where Nursing plays a fundamental role in supporting the family facing critical illness and the death of a child.Objectives: To review the existing scientific literature on the management of grief in relatives of oncopediatric patients.Methodology: Comprehensive integrative review in the Pudmed, Scopus, Scielo and Cochrane databases. The terms «pediatric oncology», «family», «mourning» and «nursing» were used, joined by the Boolean operator «Y».Results: The emotional experiences felt by the family of the pediatric oncohematological patient and the skills in nursing practice that protect the emotional care of the same have been identified. Due to its relevance in this area, it is worth highlighting the therapeutic relationship between the family, the child, and the healthcare team, and the power of communication skills in the final stage of life and death.Conclusions: Caring for the emotional integrity and the natural course of grief is vital in the care plan for the child and his family. Emphasize the magnitude that should be the nursing training in emotional, communication and psycho-behavioral skills for the comprehensive care of the child and his family. (AU)

La apolipoproteína A-II altera la composición apolipoproteica de HDL y su capacidad para activar la lipoproteína lipasa / Apolipoprotein A-II affects HDL apolipoprotein composition and HDL-mediated lipoprotein lipase activation

Introducción La apolipoproteína (apo) A-II es la segunda proteína cuantitativamente más importante de las HDL; sin embargo su función es poco conocida. Los estudios realizados en humanos y ratones modificados genéticamente han demostrado un efecto de la apoA-II sobre el metabolismo de los triglicéridos. El objetivo principal de este estudio es analizar la relación entre la apoA-II y la composición apolipoproteica de las HDL así como la capacidad de estas lipoproteínas de modular la actividad de la enzima lipoproteína lipasa (LPL) y, por tanto, la concentración de triglicéridos. Métodos Se recogieron muestras de sangre en 32 voluntarios sanos tras 11h de ayuno. Se recogieron los datos antropométricos y se determinaron los parámetros lipídicos y apolipoproteicos. Las HDL aisladas por ultracentrifugación fueron incubadas con una emulsión radioactiva de triglicéridos y LPL bovina. En 14 de los voluntarios, se obtuvo una muestra adicional de sangre, 3h después de un desayuno. Resultados La concentración de apoA-II correlacionó de forma positiva con la concentración de triglicéridos (R=0,55, p<0,05) y de forma inversa con el cociente apoC-II+apoE/apoC-III en HDL (R=−0,43, p<0,05). La apoA-II también correlacionó inversamente con la capacidad de las HDL de modular la actividad LPL (R=−0,35, p<0,05). Por ultimo, la concentración de apoA-II correlacionó positivamente con los triglicéridos postprandiales (R=0,58, p<0,05).Conclusión Estos resultados sugieren que la apoA-II en HDL tiene un papel importante en la regulación del metabolismo de los triglicéridos y sugieren que, en parte, ello es debido a la alteración en la capacidad de las HDL de modular la actividad LPL (AU)

Introduction Apolipoprotein (apo)A-II is the second most abundant HDL protein but its function remains largely unknown. Studies in humans and genetically-modified mice have demonstrated a role for apoA-II in triglyceride metabolism. The main objective of this study was to evaluate the relationship between apoA-II and HDL apolipoprotein composition, as well as HDL-mediated lipoprotein lipase (LPL) coactivation and plasma triglyceride concentration.Methods Eleven-hour fasting blood samples were taken from 32 healthy volunteers. Anthropometric data and lipid and apolipoprotein parameters were analyzed. HDL isolated by ultracentrifugation was incubated in the presence of a triolein-based emulsion and bovine LPL. In 14 of these volunteers, an additional blood sample was taken 3h after breakfast.Results ApoA-II concentration was directly correlated with plasma triglycerides (R=0.55, p<0.05) and inversely correlated with the HDL-apoC-II+apoE/apoC-III ratio (R=−0.43, p<0.05). ApoA-II was also inversely correlated with HDL-mediated LPL coactivation (R=−0.35, p<0.05). ApoA-II concentration was directly correlated with plasma triglycerides 3h after the fat-loading test (R= 0.58, p<0.05).Conclusion These results show that HDL-apoA-II levels play a crucial role in triglyceride catabolism and suggest that, at least in part, this is due to modulation of LPL activity (AU)