The geometrical nature of optical resonances : from a sphere to fused dimer nanoparticles

We study the electromagnetic response of smooth gold nanoparticles with shapes varying from a single sphere to two ellipsoids joined smoothly at their vertices. We show that the plasmonic resonance visible in the extinction and absorption cross sections shifts to longer wavelengths and eventually disappears as the mid-plane waist of the composite particle becomes narrower. This process corresponds to an increase of the numbers of internal and scattering modes that are mainly confined to the surface and coupled to the incident field. These modes strongly affect the near field, and therefore are of great importance in surface spectroscopy, but are almost undetectable in the far field

Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

BACKGROUND: Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer's Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer's and Parkinson's disease (PD). RESULTS: Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r(2) ≥ 0.39, p ≤ 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) ≥ 0.4, p ≤ 0.03) with phosphorylated-tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups. CONCLUSIONS: Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD

Progress in Alzheimer&apos;s disease research in the last year

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with a prevalence of 5 % after 65 years of age, increasing to about 30 % in people aged 85 years or older. It is characterized by progressive cognitive impairment, including impaired judgment, decision-making and orientation, and in some cases accompanied by psycho behavioral disturbances or language impairment. Herein, we summarize and discuss the main articles describing novel findings in AD published over the last year, including clinical, therapeutic, and research issues. \ua9 2013 Springer-Verlag Berlin Heidelberg

Quality of life, depression and fatigue in mildly disabled patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study.

BACKGROUND: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. OBJECTIVE: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. METHODS: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing-remitting MS treated with subcutaneous interferon beta-1a. RESULTS: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points. CONCLUSION: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found

"Somos los descamisados": a representação do peronismo nascente na mídia impressa porteña (1945-1946)

O presente trabalho tem como objetivo compreender as diferentes formas de representação da classe trabalhadora argentina, politizada através do nascente movimento peronista, pelo principal jornal de grande circulação da capital nesse período, o jornal La Nación. Leva-se em conta que, por buscar a representação de um processo histórico e não a concretude do mesmo, o trabalho está na intersecção entre a história política argentina e a história da mídia, compreendendo que – de acordo com Capelato (1988) – a mídia, ao representar uma realidade, também atua para conformá-la. A hipótese inicial levantada é a de que o jornal La Nación tem uma visão racista e preconceituosa dos trabalhadores peronistas, entendendo que a relação entre eles e o então coronel Juan Domingo Perón era uma relação verticalizada de obediência e devoção. A conotação racista se dá pela clivagem, na representação, entre trabalhadores imigrantes supostamente democráticos e trabalhadores de ascendência indígena migrando das províncias do norte da Argentina, propensos, de acordo com o jornal, a barbárie, tese essa utilizada posteriormente pela historiografia conservadora. O recorte temporal se dá entre outubro de 1945 e fevereiro de 1946, tendo como marco inicial as manifestações multitudinárias que libertaram Perón da prisão e como marco final sua eleição como presidente da Argentina.El presente trabajo tiene por objetivo comprender las múltiples maneras de representar la clase trabajadora de la Argentina en el proceso de toma de conciencia fruto del naciente movimiento peronista, por medio del principal medio de comunicación impresa del período en la capital, el diario La Nación. Teniendo en cuenta que, por buscar la representación de un proceso histórico y no la concretud del mismo, el trabajo está en la intersección de la historia política argentina y la historia de los medios. También teniendo en cuenta que - según Capelato (1988) - los medios, al representar una realidad, también actúan para conformarla. La hipótesis inicial planteada es la de que el diario La Nación tiene una visión racista y prejuiciosa de los trabajadores peronistas, comprendiendo que la relación entre ellos y el entonces coronel Juan Domingo Perón era una relación verticalizada de obediencia y de devoción. La connotación racista se explica por el clivaje, en la representación, entre trabajadores con un supuesto perfil democrático, provenientes de las olas inmigratorias y trabajadores de ascendencia indígena provenientes de las provincias del norte de la Argentina y propensos, según el diario, a la barbarie, tesis que fue utilizada a posteriori por la historiografía conservadora. El recorte temporal se da en el período entre octubre de 1945 y febrero de 1946, teniendo como marco inicial las multitudinarias manifestaciones que liberaron de la cárcel a Perón y como marco final su elección como presidente de la Argentina

Role of oxidative damage in alzheimer’s disease and neurodegeneration: From pathogenic mechanisms to biomarker discovery

Alzheimer’s disease (AD) is a neurodegenerative disorder accounting for over 50% of all dementia patients and representing a leading cause of death worldwide for the global ageing population. The lack of effective treatments for overt AD urges the discovery of biomarkers for early diagnosis, i.e., in subjects with mild cognitive impairment (MCI) or prodromal AD. The brain is exposed to oxidative stress as levels of reactive oxygen species (ROS) are increased, whereas cellular antioxidant defenses are decreased. Increased ROS levels can damage cellular structures or molecules, leading to protein, lipid, DNA, or RNA oxidation. Oxidative damage is involved in the molecular mechanisms which link the accumulation of amyloid-β and neurofibrillary tangles, containing hyperphosphorylated tau, to microglia response. In this scenario, microglia are thought to play a crucial role not only in the early events of AD pathogenesis but also in the progression of the disease. This review will focus on oxidative damage products as possible peripheral biomarkers in AD and in the preclinical phases of the disease. Particular attention will be paid to biological fluids such as blood, CSF, urine, and saliva, and potential future use of molecules contained in such body fluids for early differential diagnosis and monitoring the disease course. We will also review the role of oxidative damage and microglia in the pathogenesis of AD and, more broadly, in neurodegeneration

Effects of immunomodulatory treatment with subcutaneous interferon beta-1a oncognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score <or=4.0) were assigned IFNbeta therapy at the physician's discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNbeta-1a (44 mcg: n = 236; 22 mcg: n = 223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480-0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNbeta-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNbeta-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P = 0.03), although a trend was also seen at the baseline (P = 0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNbeta-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26-0.99) compared with the lower dose of IFNbeta-1a. These findings suggest that sc IFNbeta-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNbeta-1a treatment