EEG-based automatic classification of 'awake' versus 'anesthetized' state in general anesthesia using Granger Causality

Background

General anesthesia is a reversible state of unconsciousness and depression of reflexes to afferent stimuli induced by administration of a “cocktail” of chemical agents. The multi-component nature of general anesthesia complicates the identification of the precise mechanisms by which anesthetics disrupt consciousness. Devices that monitor the depth of anesthesia are an important aide for the anesthetist. This paper investigates the use of effective connectivity measures from human electrical brain activity as a means of discriminating between ‘awake’ and ‘anesthetized’ state during induction and recovery of consciousness under general anesthesia.

Methodology/Principal Findings

Granger Causality (GC), a linear measure of effective connectivity, is utilized in automated classification of ‘awake’ versus ‘anesthetized’ state using Linear Discriminant Analysis and Support Vector Machines (with linear and non-linear kernel). Based on our investigations, the most characteristic change of GC observed between the two states is the sharp increase of GC from frontal to posterior regions when the subject was anesthetized, and reversal at recovery of consciousness. Features derived from the GC estimates resulted in classification of ‘awake’ and ‘anesthetized’ states in 21 patients with maximum average accuracies of 0.98 and 0.95, during loss and recovery of consciousness respectively. The differences in linear and non-linear classification are not statistically significant, implying that GC features are linearly separable, eliminating the need for a complex and computationally expensive non-linear classifier. In addition, the observed GC patterns are particularly interesting in terms of a physiological interpretation of the disruption of consciousness by anesthetics. Bidirectional interaction or strong unidirectional interaction in the presence of a common input as captured by GC are most likely related to mechanisms of information flow in cortical circuits.

Conclusions/Significance

GC-based features could be utilized effectively in a device for monitoring depth of anesthesia during surgery.     

ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach

Recently, we identified a peptide (ERα17p, P(295)LMIKRSKKNSLALSLT(311)) that corresponds to the 295-311 sequence of the estrogen receptor α (ERα, hinge region) and which exerts a panel of pharmacological effects in breast cancer cells. Remarkably, these effects can result from the interaction of ERα17p with the plasma membrane. Herein, we show that ERα17p adopts a β-sheet secondary structure when in contact with anionic phospholipids and that it is engulfed within the lipid bilayer. While ERα17p increases the fluidity of membrane mimics, it weakly internalizes in living cells. In light of the above, one may evoke one important role of the 295-311 region of the ERα: the corresponding peptide could be secreted/delivered to the extracellular medium to interact with neighboring cells, both intracellularly and at the membrane level. Finally, the 295-311 region of ERα being in proximity to the cystein-447, the palmitoylation site of the ERα raises the question of its involvement in the interaction/stabilization of the protein with the membrane.     

Diversity of saproxylic basidiomycetes in Quercus ilex woodlands of central and insular Greece

The sclerophyllous forests of Quercus ilex (holm oak) possess a unique position in earth’s biosphere, existing only in countries of the Mediterranean basin. However, very little information exists about mushrooms associated with holm oak in east Mediterranean, including Greece, where Q. ilex appears mostly in relict forests and fragmented stands. A pertinent long-term investigation was undertaken in selected Q. ilex dominated habitats of Crete, Andros, Naxos and Ikaria islands (Aegean Archipelago) as well as in mountains of Attica. Specimens of xylotrophic basidiomycetes were collected and identified. As a result, 74 species were recorded; among them Hemimycena cephalotricha, Hyphoderma cremeoalbum, Hyphodontia radula, Irpex litschaueri, Mycena algeriensis, Phanerochaete martelliana, Phloeomana alba and Phlebia unica constitute new records for the Greek mycobiota, while 68 species are reported for the first time on Q. ilex in Greece. Moreover, the presence of Fomitiporia mediterranea on this host was evidenced through ITS sequencing, and comments are made about its relationship to F. punctata and F. pseudopunctata. The importance of findings is discussed in conjunction with their environmental value; five species could be assigned in the “Species of Special Interest” categories, and other five polypores are proposed as suitable indicators for Q. ilex habitat assessment and conservation.     

Adjusting Breast Cancer Patient Prognosis with Non-HER2-Gene Patterns on Chromosome 17

Background

HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients.

Methods

Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials.

Principal Findings

HER2-genes CN strongly correlated to each other (Spearman’s rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1–3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS).

Conclusions

TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis.     

Genetic analysis of G protein-coupled receptor expression in Escherichia coli: inhibitory role of DnaJ on the membrane integration of the human central cannabinoid receptor

The overexpression of G protein-coupled receptors (GPCRs) and of many other heterologous membrane proteins in simple microbial hosts, such as the bacterium Escherichia coli, often results in protein mistargeting, aggregation into inclusion bodies or cytoplasmic degradation. Furthermore, membrane protein production is very frequently accompanied by severe cell toxicity. In this work, we have employed a genetic strategy to isolate E. coli mutants that produce markedly increased amounts of the human central cannabinoid receptor (CB1), a pharmacologically significant GPCR that expresses very poorly in wild-type E. coli. By utilizing a CB1 fusion with the green fluorescent protein (GFP) and fluorescence-activated cell sorting (FACS), we screened an E. coli transposon library and identified an insertion in dnaJ that resulted in a large increase in CB1-GFP fluorescence and a dramatic enhancement in bacterial production of membrane-integrated CB1. Furthermore, the dnaJ::Tn5 inactivation suppressed the severe cytotoxicity associated with CB1 production. This revealed an unexpected inhibitory role of the chaperone/ co-chaperone DnaJ in the protein folding or membrane insertion of bacterially produced CB1. Our strategy can be easily adapted to identify expression bottlenecks for different GPCRs or any other integral membrane protein, provide useful and unanticipated mechanistic insights, and assist in the construction of genetically engineered E. coli strains for efficient heterologous membrane protein production.     

Diversity, ecological structure, and conservation of the landbird community of Dadia reserve, Greece

Birds are integral to many environmental monitoring schemes. However, there has been little research on the ecological basis of utilizing bird species as indicators of their respective communities and habitats. We used point counts to survey 72 landbird species, 16 of conservation concern, in the Dadia Nature Reserve, Greece, in order to understand the ecology of bird diversity patterns, analyse community composition, identify species characteristic of major vegetation types, and improve long-term management and monitoring protocols. We sampled 36 sites representing 21 vegetation types. Highly heterogeneous sites were the most species rich and rural mosaics (small fields and pastures of low intensity land use, separated by thick hedgerows and tree lines) were twice as rich as intensified crop monocultures. Using multivariate analysis, we found that vegetation cover and height affected the composition of the avifauna. Twenty-one predefined vegetation categories clustered into eight distinct bird habitat types: field crops, rural mosaics, mosaic sites, poplar trees, broadleaved woods, pinewoods, shrubs, and heaths. Ten bird species were highly characteristic of the main bird habitat types in the study area. Our results emphasize the importance of conserving rural mosaics, hedgerows, and openings within forests for landbird conservation in the Mediterranean countryside. We also provide evidence in support of maintaining horizontal heterogeneity at a local scale. Finally, we suggest that monitoring populations of certain indicator bird species can be a cost-effective and efficient way to monitor the state and habitat quality of the entire landbird community, thereby integrating the knowledge of community structure into conservation decision-making.     

The effect of denture quality attributes on satisfaction and eating difficulties

Objectives: The development of a measure, with complimentary normative and perceived needs, for the investigation of functional impairment of individual patients and the investigation of the physical causative bases of impairment. Subjects: A consecutive sample of 119 complete denture (CD) wearers attending a Greek department of prosthetic dentistry took part in the study. All subjects presented with some complaint(s) of their dentures. Method: Functional assessment of dentures (FAD) criteria and structured questionnaires were used covering denture satisfaction (DS) and food difficulties with CDs. The questions used a five‐point Likert scale. Results: The results showed that there were statistically significant associations between satisfaction from dentures and eating specified foods. Statistically significant associations were also found between denture qualities and movement of upper dentures and difficulty eating specified foods, but not with an open question on the difficulty of eating unspecified foods. Conclusions: This study successfully validated a suitable model for the combined evaluation of denture quality with clear diagnostic criteria and closed questions on DS and perceived difficulties when eating specified foods. This could predict the need for treatment, monitor the impact of care and provide a feasible measure to meet the need of everyday clinical situations.