Excellent diagnostic characteristics for ultrafast gene profiling of DEFA1-IL1B-LTF in detection of prosthetic joint infections

The timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making. Intraoperatively, delivery of the result within an hour is required. Alpha-defensin lateral immunoassay of joint fluid (JF) is precise for the intraoperative exclusion of PJI; however, for patients with a limited amount of JF and/or in cases where the JF is bloody, this test is unhelpful. Important information is hidden in periprosthetic tissues that may much better reflect the current status of implant pathology. We therefore investigated the utility of the gene expression patterns of 12 candidate genes (TLR1, -2, -4, -6, and 10, DEFA1, LTF, IL1B, BPI, CRP, IFNG, and DEFB4A) previously associated with infection for detection of PJI in periprosthetic tissues of patients with total joint arthroplasty (TJA) (n = 76) reoperated for PJI (n = 38) or aseptic failure (n = 38), using the ultrafast quantitative reverse transcription-PCR (RT-PCR) Xxpress system (BJS Biotechnologies Ltd.). Advanced data-mining algorithms were applied for data analysis. For PJI, we detected elevated mRNA expression levels of DEFA1 (P < 0.0001), IL1B (P < 0.0001), LTF (P < 0.0001), TLR1 (P = 0.02), and BPI (P = 0.01) in comparison to those in tissues from aseptic cases. A feature selection algorithm revealed that the DEFA1-IL1B-LTF pattern was the most appropriate for detection/exclusion of PJI, achieving 94.5% sensitivity and 95.7% specificity, with likelihood ratios (LRs) for positive and negative results of 16.3 and 0.06, respectively. Taken together, the results show that DEFA1-IL1B-LTF gene expression detection by use of ultrafast qRT-PCR linked to an electronic calculator allows detection of patients with a high probability of PJI within 45 min after sampling. Further testing on a larger cohort of patients is needed.Web of Science5592697268

Health related quality of life outcomes in HIV-Infected patients starting different combination regimens in a randomised multinational trial: the INITIO-QoL Substudy

The health-related quality of life (HRQoL) outcomes in HIV-infected, treatment-naive patients starting different HAART regimens in a 3-year, randomized, multinational trial were compared. HRQoL was measured in a subgroup of patients enrolled in the INITIO study (153/911), using a modified version of the MOS-HIV questionnaire. The regimens compared in the INITIO trial were composed by two NRTIs (didanosine + stavudine) plus either an NNRTI (efavirenz) or a PI (nelfinavir), or both (efavirenz + nelfinavir). Primary HRQoL outcomes were Physical and Mental Health Summary scores (PHS and MHS, respectively). During follow-up, an increase of PHS score was observed in all treatment arms. The MHS score remained substantially unchanged with the four-drug combination and showed with both NNRTI- and PI-based three-drug regimens a marked trend toward improvement, which became statistically significant when a multiple imputation method was used to adjust for missing data. Overall, starting all the combination regimens compared in the INITIO study was associated with a maintained or slightly improved HRQOL status, consistently with the positive immunological and virological changes observed in the main study. The observed differences in the MHS indicate a possible HRQoL benefit associated to the use of three-drug, two-class regimens and no additional benefit for the use of four-drug, three-class regimens, confirming that three-drug, two-class regimens that include two NRTIs plus either an NNRTI or a PI should be preferred as initial treatment of HIV infection

The Non-Canonical Wnt/PKC Pathway Regulates Mitochondrial Dynamics through Degradation of the Arm-Like Domain-Containing Protein Alex3

The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation

A factor analytic study of the Italian National Institute of Health Quality of Life – Core Evaluation Form (ISSQoL-CEF)

Objectives: The Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF) is a specific questionnaire measuring health-related quality of life for human immunodeficiency virus-infected people in the era of highly active antiretroviral therapy. The main goal of this study was to examine the construct validity of this questionnaire by confirmation of its hypothesized dimensional structure. Methods: Baseline quality of life data from four clinical studies were collected and a confirmatory factor analysis of the ISSQoL-CEF items was carried out. Both first-order and secondorder factor models were tested: Model 1 with nine correlated first-order factors; Model 2 with three correlated second-order factors (Physical, Mental, and Social Health); Model 3 with two correlated second-order factors (Physical and Mental/Social Health); Model 4 with only one second-order factor (General Health). Results: A total of 261 patients were surveyed. Model 1 had a good fit to the data. Model 2 had an acceptable fit to the data and it was the best of all hierarchical models. However, Model 2 fitted the data worse than Model 1. Conclusions: The findings of in this study, consistent with the results of previous study, pointed out the construct validity of the ISSQoL-CEF. © 2010 Lauriola et al, publisher and licensee Dove Medical Press Ltd

Análisis de diversidad genética en poblaciones de Bauhinia forficata subsp. pruinosa (Pezuña de vaca, o buey, Pata de vaca) mediante el uso de marcadores moleculares

Bauhinia. forficata Link. subsp. pruinosa (Vogel) Fortunato & Wunderlin, crece naturalmente desde Paraguay, Sur de Brasil hasta Argentina, y tiene antecedente de uso ornamental y terapéutico (diurético, antidiarreico, hipoglucemiante). Este proyecto tiene como objetivo la caracterización de poblaciones de bauhinia forficata subsp pruinosa utilizando marcadores moleculares. Existen SSRs diseñados en taxones afines: Cercis canadensis L. y C. chinensis, de los que hay antecedentes de transferibilidad entre especies. Por ello se evaluó su transferencia en las poblaciones de Bauhinia. Estos resultados asociados a los que se obtengan de las evaluaciones químicas permitirán conocer su relación con los biotipos que se identifiquen.  Para esto, se extrajo ADN mediante el método de Dellaporta (1983) de 10 individuos del Jardín botánico Arturo E. Ragonese, se cuantificó y se realizó PCR de los SSRs seleccionados. El producto se sembró, junto con un marcador de peso molecular, en geles desnaturalizantes de poliacrilamida en cubas de secuenciación teñidos con nitrato de plata y revelados con hidróxido de sodio. Hasta el momento, se evaluaron 15 SSRs (6 provinieron de C. chinensis   y 9 de C. canandensis). De estos 15 SSRs, 11 mostraron productos de amplificación. De ellos 9 fueron polimórficos indicando diferencias interpoblacionales, que podrían indicar variabilidad química y por lo tanto resta correlacionar la actividad biológica de los distintos biotipos. Además, algunos SSRs mostraron más de un locus, información que respalda lo señalado por Poggio et al. que en la subfamilia Cercidoideae, Bauhinia (2n=28) se generó por hibridación y poliploídia a partir del ancestro Cercis (2n= 14). Además, se realizó el muestreo de 20 puntos de colecta distribuidas en las provincias de Misiones, Córdoba y Buenos Aires de por lo menos tres individuos por punto. Estos individuos serán evaluados mediante técnicas de SSR para determinar mediante distintos parámetros la variabilidad intra e interpoblacional

Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease

We have recently reported that a polymorphism in the cell division cycle (CDC2) gene, designated Ex6 + 7I/D, is associated with Alzheimer's disease (AD). The CDC2 gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, CDC2 is a promising candidate susceptibility gene for AD. We investigated the possible effects of the CDC2 polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. CDC2 genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and beta-amyloid (1-42) in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The CDC2 Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F-2,F- 626 = 7.0, p = 0.001) and the homozygous CDC2Ex6 +7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13-2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD. Copyright (C) 2005 S. Karger AG, Basel

Sexual and individual foraging segregation in Gentoo penguins Pygoscelis papua from the Southern Ocean during an abnormal winter

Knowledge about sexual segregation and gender-specific, or indeed individual specialization, in marine organisms has improved considerably in the past decade. In this context, we tested the “Intersexual Competition Hypothesis” for penguins by investigating the feeding ecology of Gentoo penguins during their austral winter non-breeding season. We considered this during unusual environmental conditions (i.e. the year 2009 had observations of high sea surface and air temperatures) in comparison with the long term average at Bird Island, South Georgia. Through conventional (i.e. stomach contents) and stable isotopic values from red blood cells, plasma and feathers of both male and female Gentoo penguins, we showed that there were significant differences between sexes, with males feeding mainly on fish (54% by mass) followed by crustaceans (38%) whereas females fed mainly on crustaceans (89% by mass) followed by fish (4%). Themisto gaudichaudii was the most important crustacean prey for males (64% by mass; 82% by number; 53% by frequency of occurrence) and females (63% by mass; 77% by number; 89% by frequency of occurrence), contrasting with all previous studies that found Antarctic krill Euphausia superba were generally the main prey. Stable isotopic data showed that, in terms of habitat use (based on δ 13C), there were significant differences in short-term carbon signatures between males and females (based on plasma and red blood cells), suggesting that both sexes explored different habitats, with females exploring more offshore pelagic waters and males feeding more in coastal benthic waters. Based on δ 15N, males fed on significantly higher trophic level than females (based on plasma and red blood cells), in agreement with our diet results., Thus, Gentoo penguins behave in a similar manner to other non-breeding penguins species (e.g. king, macaroni and rockhopper penguins), albeit at a smaller spatial scale (as they do not disperse as these other penguins do), in that they have a wider habitat and trophic niche during the Antarctic Winter (in comparison to Summer). We also detected individual specialization in feeding/trophic levels for each gender, with certain males feeding mainly on fish and certain females mainly on crustaceans, which may be driven the prevailing environmental conditions that lead individuals to search for alternative prey, and cause sexual diet segregation. Our results provide further information to help improve understanding about sexual segregation and individual specialization of marine organisms, while contributing valuable information on the winter diet for Antarctic monitoring programs and for modelling Antarctic marine food webs

Prospects for K+→π+ννˉK^+ \to \pi^+ \nu \bar{ \nu } at CERN in NA62

The NA62 experiment will begin taking data in 2015. Its primary purpose is a 10% measurement of the branching ratio of the ultrarare kaon decay $K^+ \to \pi^+ \nu \bar{ \nu }$, using the decay in flight of kaons in an unseparated beam with momentum 75 GeV/c.The detector and analysis technique are described here.Comment: 8 pages for proceedings of 50 Years of CP

Accuracy of dementia diagnosis—a direct comparison between radiologists and a computerized method

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimer's disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimer's disease and controls into their respective groups. Radiologists correctly classified 65–95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimer's disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimer's disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimer's disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice