EEG microstate duration and syntax in acute, medication-naive, first-episode schizophrenia: a multi-center study

In young, first-episode, productive, medication-naive patients with schizophrenia, EEG microstates (building blocks of mentation) tend to be shortened. Koenig et al. [Koenig, T., Lehmann, D., Merlo, M., Kochi, K., Hell, D., Koukkou, M., 1999. A deviant EEG brain microstate in acute, neuroleptic-naïve schizophrenics at rest. European Archives of Psychiatry and Clinical Neuroscience 249, 205–211] suggested that shortening concerned specific microstate classes. Sequence rules (microstate concatenations, syntax) conceivably might also be affected. In 27 patients of the above type and 27 controls, from three centers, multichannel resting EEG was analyzed into microstates using k-means clustering of momentary potential topographies into four microstate classes (A–D). In patients, microstates were shortened in classes B and D (from 80 to 70 ms and from 94 to 82 ms, respectively), occurred more frequently in classes A and C, and covered more time in A and less in B. Topography differed only in class B where LORETA tomography predominantly showed stronger left and anterior activity in patients. Microstate concatenation (syntax) generally were disturbed in patients; specifically, the class sequence A→C→D→A predominated in controls, but was reversed in patients (A→D→C→A). In schizophrenia, information processing in certain classes of mental operations might deviate because of precocious termination. The intermittent occurrence might account for Bleuler's “double bookkeeping.” The disturbed microstate syntax opens a novel physiological comparison of mental operations between patients and controls.

Virtual implant planning in the edentulous maxilla: criteria for decision making of prosthesis design

OBJECTIVES To evaluate prosthetic parameters in the edentulous anterior maxilla for decision making between fixed and removable implant prosthesis using virtual planning software. MATERIAL AND METHODS CT- or DVT-scans of 43 patients (mean age 62 ± 8 years) with an edentulous maxilla were analyzed with the NobelGuide software. Implants (≥3.5 mm diameter, ≥10 mm length) were virtually placed in the optimal three-dimensional prosthetic position of all maxillary front teeth. Anatomical and prosthetic landmarks, including the cervical crown point (C-Point), the acrylic flange border (F-Point), and the implant-platform buccal-end (I-Point) were defined in each middle section to determine four measuring parameters: (1) acrylic flange height (FLHeight), (2) mucosal coverage (MucCov), (3) crown-Implant distance (CID) and (4) buccal prosthesis profile (ProsthProfile). Based on these parameters, all patients were assigned to one of three classes: (A) MucCov ≤ 0 mm and ProsthProfile≥45(0) allowing for fixed prosthesis, (B) MucCov = 0-5 mm and/or ProsthProfile = 30(0) -45(0) probably allowing for fixed prosthesis, and (C) MucCov ≥ 5 mm and/or ProsthProfile ≤ 30(0) where removable prosthesis is favorable. Statistical analyses included descriptive methods and non-parametric tests. RESULTS Mean values were for FLHeight 10.0 mm, MucCov 5.6 mm, CID 7.4 mm, and ProsthProfile 39.1(0) . Seventy percent of patients fulfilled class C criteria (removable), 21% class B (probably fixed), and 2% class A (fixed), while in 7% (three patients) bone volume was insufficient for implant planning. CONCLUSIONS The proposed classification and virtual planning procedure simplify the decision-making process regarding type of prosthesis and increase predictability of esthetic treatment outcomes. It was demonstrated that in the majority of cases, the space between the prosthetic crown and implant platform had to be filled with prosthetic materials.

Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland

Extensively drug-resistant (XDR) Klebsiella pneumoniae isolates usually carry a single carbapenemase (e.g. KPC, NDM, OXA-48-like). Here we describe an XDR K. pneumoniae of sequence type 101 that was detected in the screening rectal swab of a patient transferred from the intensive care unit of a hospital located in Belgrade (Serbia) to Bern University Hospital (Switzerland). The isolate was resistant to all antibiotics with the exception of colistin [minimum inhibitory concentration] (MIC≤0.125μg/mL), tigecycline (MIC=0.5μg/mL) and fosfomycin (MIC=2μg/mL). The isolate co-possessed class B (NDM-1) and class D (OXA-48) carbapenemases, class A extended-spectrum β-lactamase (CTX-M-15), class C cephalosporinase (CMY-16), ArmA 16S rRNA methyltransferase, substitutions in GyrA and ParC, loss of OmpK35 porin, as well as other genes conferring resistance to quinolones (qnrA), tetracyclines [tet(A)], sulfonamides (sul1, sul2), trimethoprim (dfrA12, dfrA14), rifampicin (arr-1), chloramphenicol (cmlA1, floR) and streptomycin (aadA1). The patient was placed under contact isolation precautions preventing the spread of this nearly untreatable pathogen.

EEG microstates during resting represent personality differences

We investigated the spontaneous brain electric activity of 13 skeptics and 16 believers in paranormal phenomena; they were university students assessed with a self-report scale about paranormal beliefs. 33-channel EEG recordings during no-task resting were processed as sequences of momentary potential distribution maps. Based on the maps at peak times of Global Field Power, the sequences were parsed into segments of quasi-stable potential distribution, the 'microstates'. The microstates were clustered into four classes of map topographies (A-D). Analysis of the microstate parameters time coverage, occurrence frequency and duration as well as the temporal sequence (syntax) of the microstate classes revealed significant differences: Believers had a higher coverage and occurrence of class B, tended to decreased coverage and occurrence of class C, and showed a predominant sequence of microstate concatenations from A to C to B to A that was reversed in skeptics (A to B to C to A). Microstates of different topographies, putative "atoms of thought", are hypothesized to represent different types of information processing.The study demonstrates that personality differences can be detected in resting EEG microstate parameters and microstate syntax. Microstate analysis yielded no conclusive evidence for the hypothesized relation between paranormal belief and schizophrenia.

Development of small molecular tools for the cellular study of adenosine receptors

The adenosine receptors are members of the G-protein coupled receptor (GPCR) family which represents the largest class of cell-surface proteins mediating cellular communication. As a result, GPCRs are formidable drug targets and it is estimated that approximately 30% of the marketed drugs act through members of this receptor class. There are four known subtypes of adenosine receptors: A1, A2A, A2B and A3. The adenosine A1 receptor, which is the subject of this presentation, mediates the physiological effects of adenosine in various tissues including the brain, heart, kidney and adipocytes. In the brain for instance, its role in epilepsy and ischemia has been the focus of many studies. Previous attempts to study the biosynthesis, trafficking and agonist-induced internalisation of the adenosine A1 receptor in neurons using fluorescent protein-receptor fusion constructs have been hampered by the sheer size of the fluorescent protein (GFP) that ultimately affected the function of the receptor. We have therefore initiated a research programme to develop small molecule fluorescent agonists that selectively activate the adenosine A1 receptor. Our probe design is based on the endogenous ligand adenosine and the known unselective adenosine receptor agonist NECA. We have synthesised a small library of non-fluorescent adenosine derivatives that have different cyclic and bicyclic moieties at the 6 position of the purine ring and have evaluated the pharmacology of these compounds using a yeast-based assay. This analysis revealed compounds with interesting behaviour, i.e. exhibiting subtype-selectivity and biased signalling, that can be potentially used as tool compounds in their own right for cellular studies of the adenosine A1 receptor. Furthermore, we have also linked fluorescent dyes to the purine ring and discovered fluorescent compounds that can activate the adenosine A1 receptor.

The functional significance of EEG microstates-Associations with modalities of thinking

The momentary, global functional state of the brain is reflected by its electric field configuration. Cluster analytical approaches consistently extracted four head-surface brain electric field configurations that optimally explain the variance of their changes across time in spontaneous EEG recordings. These four configurations are referred to as EEG microstate classes A, B, C, and D and have been associated with verbal/phonological, visual, attention reorientation, and subjective interoceptive-autonomic processing, respectively. The present study tested these associations via an intra-individual and inter-individual analysis approach. The intra-individual approach tested the effect of task-induced increased modality-specific processing on EEG microstate parameters. The inter-individual approach tested the effect of personal modality-specific parameters on EEG microstate parameters. We obtained multichannel EEG from 61 healthy, right-handed, male students during four eyes-closed conditions: object-visualization, spatial-visualization, verbalization (6 runs each), and resting (7 runs). After each run, we assessed participants' degrees of object-visual, spatial-visual, and verbal thinking using subjective reports. Before and after the recording, we assessed modality-specific cognitive abilities and styles using nine cognitive tests and two questionnaires. The EEG of all participants, conditions, and runs was clustered into four classes of EEG microstates (A, B, C, and D). RMANOVAs, ANOVAs and post-hoc paired t-tests compared microstate parameters between conditions. TANOVAs compared microstate class topographies between conditions. Differences were localized using eLORETA. Pearson correlations assessed interrelationships between personal modality-specific parameters and EEG microstate parameters during no-task resting. As hypothesized, verbal as opposed to visual conditions consistently affected the duration, occurrence, and coverage of microstate classes A and B. Contrary to associations suggested by previous reports, parameters were increased for class A during visualization, and class B during verbalization. In line with previous reports, microstate D parameters were increased during no-task resting compared to the three internal, goal-directed tasks. Topographic differences between conditions concerned particular sub-regions of components of the metabolic default mode network. Modality-specific personal parameters did not consistently correlate with microstate parameters except verbal cognitive style which correlated negatively with microstate class A duration and positively with class C occurrence. This is the first study that aimed to induce EEG microstate class parameter changes based on their hypothesized functional significance. Beyond, the associations of microstate classes A and B with visual and verbal processing, respectively and microstate class D with interoceptive-autonomic processing, our results suggest that a finely-tuned interplay between all four EEG microstate classes is necessary for the continuous formation of visual and verbal thoughts, as well as interoceptive-autonomic processing. Our results point to the possibility that the EEG microstate classes may represent the head-surface measured activity of intra-cortical sources primarily exhibiting inhibitory functions. However, additional studies are needed to verify and elaborate on this hypothesis.

Improving Surveying Accuracy and Efficiency in Connecticut: An Accuracy Assessment of GEOID03 and GEOID09

Comparing published NAVD 88 Helmert orthometric heights of First-Order bench marks against GPS-determined orthometric heights showed that GEOID03 and GEOID09 perform at their reported accuracy in Connecticut. GPS-determined orthometric heights were determined by subtracting geoid undulations from ellipsoid heights obtained from a network least-squares adjustment of GPS occupations in 2007 and 2008. A total of 73 markers were occupied in these stability classes: 25 class A, 11 class B, 12 class C, 2 class D bench marks, and 23 temporary marks with transferred elevations. Adjusted ellipsoid heights were compared against OPUS as a check. We found that: the GPS-determined orthometric heights of stability class A markers and the transfers are statistically lower than their published values but just barely; stability class B, C and D markers are also statistically lower in a manner consistent with subsidence or settling; GEOID09 does not exhibit a statistically significant residual trend across Connecticut; and GEOID09 out-performed GEOID03. A "correction surface" is not recommended in spite of the geoid models being statistically different than the NAVD 88 heights because the uncertainties involved dominate the discrepancies. Instead, it is recommended that the vertical control network be re-observed.

Examination of the quality of spinach leaves using hyperspectral imaging

The present research is focused on the application of hyperspectral images for the supervision of quality deterioration in ready to use leafy spinach during storage (Spinacia oleracea). Two sets of samples of packed leafy spinach were considered: (a) a first set of samples was stored at 20 °C (E-20) in order to accelerate the degradation process, and these samples were measured the day of reception in the laboratory and after 2 days of storage; (b) a second set of samples was kept at 10 °C (E-10), and the measurements were taken throughout storage, beginning the day of reception and repeating the acquisition of Images 3, 6 and 9 days later. Twenty leaves per test were analyzed. Hyperspectral images were acquired with a push-broom CCD camera equipped with a spectrograph VNIR (400–1000 nm). Calibration set of spectra was extracted from E-20 samples, containing three classes of degradation: class A (optimal quality), class B and class C (maximum deterioration). Reference average spectra were defined for each class. Three models, computed on the calibration set, with a decreasing degree of complexity were compared, according to their ability for segregating leaves at different quality stages (fresh, with incipient and non-visible symptoms of degradation, and degraded): spectral angle mapper distance (SAM), partial least squares discriminant analysis models (PLS-DA), and a non linear index (Leafy Vegetable Evolution, LEVE) combining five wavelengths were included among the previously selected by CovSel procedure. In sets E-10 and E-20, artificial images of the membership degree according to the distance of each pixel to the reference classes, were computed assigning each pixel to the closest reference class. The three methods were able to show the degradation of the leaves with storage time.

Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and cone function and retinal histopathology. Two classes of disease expression were found, and there was allele-specificity. Class A mutants lead to severely abnormal rod function across the retina early in life; topography of residual cone function parallels cone cell density. Class B mutants are compatible with normal rods in adult life in some retinal regions or throughout the retina, and there is a slow stereotypical disease sequence. Disease manifests as a loss of rod photoreceptor outer segments, not singly but in microscopic patches that coalesce into larger irregular areas of degeneration. Cone outer segment function remains normal until >75% of rod outer segments are lost. The topography of cone loss coincides with that of rod loss. Most class B mutants show an inferior-nasal to superior-temporal retinal gradient of disease vulnerability associated with visual cycle abnormalities. Class A mutant alleles behave as if cytotoxic; class B mutants can be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.

Transplantation of a 17-amino acid alpha-helical DNA-binding domain into an antibody molecule confers sequence-dependent DNA recognition.

Recombinant antibodies capable of sequence-specific interactions with nucleic acids represent a class of DNA- and RNA-binding proteins with potential for broad application in basic research and medicine. We describe the rational design of a DNA-binding antibody, Fab-Ebox, by replacing a variable segment of the immunoglobulin heavy chain with a 17-amino acid domain derived from TFEB, a class B basic helix-loop-helix protein. DNA-binding activity was studied by electrophoretic mobility-shift assays in which Fab-Ebox was shown to form a specific complex with DNA containing the TFEB recognition motif (CACGTG). Similarities were found in the abilities of TFEB and Fab-Ebox to discriminate between oligodeoxyribonucleotides containing altered recognition sequences. Comparable interference of binding by methylation of cytosine residues indicated that Fab-Ebox and TFEB both contact DNA through interactions along the major groove of double-stranded DNA. The results of this study indicate that DNA-binding antibodies of high specificity can be developed by using the modular nature of both immunoglobulins and transcription factors.

Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases

The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/ threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK There are now more than 50 proteins shown to be substrates for JNK These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.

Characterization of FITC-conjugated lectin binding to Candida albicans

Avidity of yeast and hyphal forms of Candida albicans for FITC-conjugated lectins was determined by flow cytometry and digital microscopy. Yeast phase cells bound Con A, a lectin with marked affinity for mannose, irrespective of growth phase, yet demonstrated little avidity for WGA and SBA. Yeast phase cell avidity for mannose-specific lectins was characterized through determination of FITC-conjugated Con A, LcH, PSA and GNA binding and subsequent calculation of Bmax, EC50 and Hn values. Such an approach, through comparison among FITC-conjugated lectins of differing specific activities, furnishes further insight into exposed outer cell wall mannose moieties. The rank order of lectin affinity as defined by EC50 values was GNA > Con A > LcH > PSA. Values for Hn suggest that lectins predominantly bind to a single receptor class, the relative abundance of which as defined by Bmax values was PSA > GNA > Con A > LcH. Hyphal surfaces in common with yeast phase cells demonstrated marked avidity for FITC-Con A, however, fluorescence of Candida morphological forms differed significantly, indicative of varying outer cell wall mannose exposure.

Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His7 and Ala8, can greatly improve resistance to this enzyme. Little research has assessed what effect Glu9-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu9 of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue (Lys9)GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys9)GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

Maltreatment, psychiatric symptoms and human immunodeficiency virus/sexual transmitted infection risk behavior among youth with alcohol and other drug use problems: A person-centered analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^

The effect of male -male competition and its underlying regulatory mechanisms on the electric signal of the gymnotiform fish Brachyhypopomus gauderio

Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.