Auditory verbal hallucinations and childhood trauma subtypes across the psychosis continuum: a cluster analysis.

Introduction: A strong link between voice-hearing experience and childhood trauma has been established. The aim of this study was to identify whether there were unique clusters of childhood trauma subtypes in a sample across the clinical spectrum of auditory verbal hallucinations (AVH) and to examine clinical and phenomenological features across these clusters.Methods: Combining two independent international datasets (the Netherlands and Australia), childhood trauma subtypes were examined using hierarchical cluster analysis. Clinical and phenomenological characteristics were compared across emerging clusters using MANOVA and chi-squared analyses.Results: The total sample (n = 413) included 166 clinical individuals with a psychotic disorder and AVH, 122 non-clinical individuals with AVH and 125 non-clinical individuals without AVH. Three clusters emerged: (1) low trauma (n = 299); (2) emotion-focused trauma (n = 71); (3) multi-trauma (n = 43). The three clusters differed significantly on their AVH ratings of amount of negative content, with trend-level effects for loudness, degree of negative content and degree of experienced distress. Furthermore, perceptions of voices being malevolent, benevolent and resistance towards voices differed significantly.Conclusion: The data revealed different types of childhood trauma had different relationships between clinical and phenomenological features of voice-hearing experiences. Thus, implicating different mechanistic pathways and a need for tailored treatment approaches.

Elucidating temporal trends in trace element exposure of green turtles (Chelonia mydas) using the toxicokinetic differences of blood and scute samples.

Blood is considered a suitable biomonitoring matrix for evaluating relatively recent exposure to environmental contaminants since abrupt changes in exposure regimes are rapidly reflected in blood. On the other hand, keratinized tissues, such as turtle scutes, are known to integrate trace element exposure over relatively long time periods. This study aimed to test the use of the differences in blood and scute to inform on the historical trace element exposure of green turtles. We propose a blood-scute kinetic model to predict how an increase in exposure would affect the concentrations in these two matrices over time. We then tested the relationship between blood and scute concentrations for 19 trace elements in two green turtle populations presumed to experience relatively constant exposure conditions. Significant log-log and linear correlations were observed between blood and scute concentrations for Co, As, Mo, Sb, and Cd. We then analysed blood-scute ratios in turtles from two coastal sites with known elevated exposure to various trace elements from previous studies. Deviations from the steady-state were clearly evident in these coastal turtles (for Co and Cd) and were consistent with the model prediction of changes in exposure. These field data provide evidence that blood-scute ratios can provide a valuable tool for examining the historical trace element exposure of turtles. We further present a method by which the general model may be refined and validated, by using data from individual turtles that had been recaptured across multiple years. Although the timeframe and number of recaptured samples available for this study were limited, the temporal changes in blood-scute ratios in these animals were generally consistent with those suggested by the model. Thus, the ratio between paired blood and scute trace element concentrations could be used to establish a temporal exposure index in turtles.

Application of the group contribution volume translated Peng-Robinson equation of state to new commercial refrigerant mixtures.

This work evaluates the performance of the group contribution volume translated Peng-Robinson model when predicting the vapor-liquid equilibrium and single phase densities of 28 commercial refrigerant mixtures with low global warming potential and zero ozone depletion potential. Cubic equations of state, and particularly the Peng-Robinson equation of state, are widely used in the refrigeration industry due to their easy applicability for new substances, and their low computational time, although generally lower prediction accuracies must be expected compared to multiparameter equations of state. The group contribution volume translated Peng-Robinson equation of state combines the Peng-Robinson equation of state with a new attraction term, improved mixing rules using a group contribution approach, and volume translation. The results are compared with the estimates obtained using the non translated Peng-Robinson equation of state, and a multiparameter equation of state.

Phylogenetic Variation of Chelonid Alphaherpesvirus 5 (ChHV5) in Populations of Green Turtles Chelonia mydas along the Queensland Coast, Australia.

Sea turtle fibropapillomatosis (FP) is a disease marked by the proliferation of benign but debilitating cutaneous and occasional visceral tumors, likely to be caused by chelonid alphaherpesvirus 5 (ChHV5). This study presents a phylogeny of ChHV5 strains found on the east coast of Queensland, Australia, and a validation for previously unused primers. Two different primer sets (gB-1534 and gB-813) were designed to target a region including part of the UL27 glycoprotein B (gB) gene and part of UL28 of ChHV5. Sequences obtained from FP tumors found on juvenile green turtles Chelonia mydas (<65 cm curved carapace length) had substantial homology with published ChHV5 sequences, while a skin biopsy from a turtle without FP failed to react in the PCRs used in this study. The resulting sequences were used to generate a neighbor-joining tree from which three clusters of ChHV5 from Australian waters were identified: north Australian, north Queensland, and Queensland clusters. The clusters reflect the collection sites on the east coast of Queensland with a definitive north-south trend. Received October 22, 2016; accepted May 7, 2017.

Trace element reference intervals in the blood of healthy green sea turtles to evaluate exposure of coastal populations.

Exposure to essential and non-essential elements may be elevated for green sea turtles (Chelonia mydas) that forage close to shore. Biomonitoring of trace elements in turtle blood can identify temporal trends over repeated sampling events, but any interpretation of potential health risks due to an elevated exposure first requires a comparison against a baseline. This study aims to use clinical reference interval (RI) methods to produce exposure baseline limits for essential and non-essential elements (Na, Mg, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, Ba, and Pb) using blood from healthy subadult turtles foraging in a remote and offshore part of the Great Barrier Reef. Subsequent blood biomonitoring of three additional coastal populations, which forage in areas dominated by agricultural, urban and military activities, showed clear habitat-specific differences in blood metal profiles relative to the those observed in the offshore population. Coastal turtles were most often found to have elevated concentrations of Co, Mo, Mn, Mg, Na, As, Sb, and Pb relative to the corresponding RIs. In particular, blood from turtles from the agricultural site had Co concentrations ranging from 160 to 840 µg/L (4-25 times above RI), which are within the order expected to elicit acute effects in many vertebrates. Additional clinical blood biochemistry and haematology results indicate signs of a systemic disease and the prevalence of an active inflammatory response in a high proportion (44%) of turtles from the agricultural site. Elevated Co, Sb, and Mn in the blood of these turtles significantly correlated with elevated markers of acute inflammation (total white cell counts) and liver dysfunction (alkaline phosphatase and total bilirubin). The results of this study support the notion that elevated trace element exposures may be adversely affecting the health of nearshore green sea turtles.

Multi-centre Raman spectral mapping of oesophageal cancer tissues: a study to assess system transferability.

The potential for Raman spectroscopy to provide early and improved diagnosis on a wide range of tissue and biopsy samples in situ is well documented. The standard histopathology diagnostic methods of reviewing H&E and/or immunohistochemical (IHC) stained tissue sections provides valuable clinical information, but requires both logistics (review, analysis and interpretation by an expert) and costly processing and reagents. Vibrational spectroscopy offers a complimentary diagnostic tool providing specific and multiplexed information relating to molecular structure and composition, but is not yet used to a significant extent in a clinical setting. One of the challenges for clinical implementation is that each Raman spectrometer system will have different characteristics and therefore spectra are not readily compatible between systems. This is essential for clinical implementation where classification models are used to compare measured biochemical or tissue spectra against a library training dataset. In this study, we demonstrate the development and validation of a classification model to discriminate between adenocarcinoma (AC) and non-cancerous intraepithelial metaplasia (IM) oesophageal tissue samples, measured on three different Raman instruments across three different locations. Spectra were corrected using system transfer spectral correction algorithms including wavenumber shift (offset) correction, instrument response correction and baseline removal. The results from this study indicate that the combined correction methods do minimize the instrument and sample quality variations within and between the instrument sites. However, more tissue samples of varying pathology states and greater tissue area coverage (per sample) are needed to properly assess the ability of Raman spectroscopy and system transferability algorithms over multiple instrument sites.

Analysis of horse movements and events during the 2007 outbreak of equine influenza in New South Wales, Australia.

OBJECTIVE: To analyse horse event and horse movement registration data collected between September 2007 and December 2008 during the outbreak of equine influenza in New South Wales, Australia. RESULTS: A total of 9356 events were registered, involving 504,382 horses and 242,952 riders. Registered horse movements totalled 224,084, involving 349,327 horses (excluding mobs) travelling 34.4 million km with an average of 154 km per journey. The number of recorded events and movements were low while movement controls were most stringent, then increased from December 2007 as restrictions were eased, to peak in April 2008 with up to 290 events and 15,730 movements weekly, after which registrations declined as the disease was eradicated. The main types of events registered were pony clubs (38%), race meetings and trials (17%), competition (13%), and clinics and lessons (11%). CONCLUSIONS: Registration of horse events and movements allowed movement controls to be progressively eased while retaining the ability to trace the movements of large numbers of horses if needed. The number of recorded events, movements and distances travelled confirms the highly mobile nature of the recreational horse industries, helps to explain the rapid and widespread dispersal of the disease before movement restrictions were imposed, and also demonstrates the value of those restrictions as a control measure. The data provide a quantitative snap-shot of horse events and movements, albeit distorted by the prevailing movement restrictions as well as by limitations in the data recording that should be addressed when developing traceability systems for horses in future.

Primary peritoneal mesothelioma: case series and literature review.

Primary peritoneal mesothelioma is a rare and aggressive tumour. We present six consecutive cases treated by our institution in the last three years. All were between 56-65 years old and only one gave a history of direct contact with asbestos. Four of the patients showed a thrombocytosis on presentation but other blood tests and evaluation of ascitic fluid were normal. In all cases, the diagnosis was made through investigation of mixed abdominal symptoms with CT scanning and laparoscopic biopsy. Despite the use of modern chemotherapy, response to treatment was unpredictable, with survival from ten weeks to three years.

Homeopathy--quackery or a key to the future of medicine?

This is an edited transcript of a debate held at the University of Connecticut Health Center, Farmington, Connecticut, USA on 25 October 2007. Homeopathy is a widely used but controversial form of complementary and alternative medicine. Six distinguished international speakers, including advocates and skeptics concerning homeopathy, debated the plausibility, theoretical principles, clinical and basic research evidence, ethical and other issues surrounding homeopathy.

Transcriptional landscape of the human and fly genomes: nonlinear and multifunctional modular model of transcriptomes.

Regions of the genome not coding for proteins or not involved in cis-acting regulatory activities are frequently viewed as lacking in functional value. However, a number of recent large-scale studies have revealed significant regulated transcription of unannotated portions of a variety of plant and animal genomes, allowing a new appreciation of the widespread transcription of large portions of the genome. High-resolution mapping of the sites of transcription of the human and fly genomes has provided an alternative picture of the extent and organization of transcription and has offered insights for biological functions of some of the newly identified unannotated transcripts. Considerable portions of the unannotated transcription observed are developmental or cell-type-specific parts of protein-coding transcripts, often serving as novel, alternative 5' transcriptional start sites. These distal 5' portions are often situated at significant distances from the annotated gene and alternatively join with or ignore portions of other intervening genes to comprise novel unannotated protein-coding transcripts. These data support an interlaced model of the genome in which many regions serve multifunctional purposes and are highly modular in their utilization. This model illustrates the underappreciated organizational complexity of the genome and one of the functional roles of transcription from unannotated portions of the genome.

Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo.

OBJECTIVE: To assess the efficacy of individualized classical homeopathy in the treatment of fibromyalgia. METHODS: This study was a double-blind, randomized, parallel-group, placebo-controlled trial of homeopathy. Community-recruited persons (N = 62) with physician-confirmed fibromyalgia (mean age 49 yr, s.d. 10 yr, 94% women) were treated in a homeopathic private practice setting. Participants were randomized to receive oral daily liquid LM (1/50,000) potencies with an individually chosen homeopathic remedy or an indistinguishable placebo. Homeopathic visits involved joint interviews and concurrence on remedy selection by two experienced homeopaths, at baseline, 2 months and 4 months (prior to a subsequent optional crossover phase of the study which is reported elsewhere). Tender point count and tender point pain on examination by a medical assessor uninvolved in providing care, self-rating scales on fibromyalgia-related quality of life, pain, mood and global health at baseline and 3 months, were the primary clinical outcome measures for this report. RESULTS: Fifty-three people completed the treatment protocol. Participants on active treatment showed significantly greater improvements in tender point count and tender point pain, quality of life, global health and a trend toward less depression compared with those on placebo. CONCLUSIONS: This study replicates and extends a previous 1-month placebo-controlled crossover study in fibromyalgia that pre-screened for only one homeopathic remedy. Using a broad selection of remedies and the flexible LM dose (1/50,000 dilution factor) series, the present study demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia.

Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency.

The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-aminopyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of farnesyl-protein transferase.

A series of amino acid-based linkers was used to investigate the effects of various substituents upon the potency, pharmacokinetic properties, and conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a result of the studies described herein, highly potent FTIs with improved pharmacokinetic profiles have been identified.

EEG beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical intolerance.

Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report concomitant intolerance for low levels of environmental chemicals (CI). Previous investigators have hypothesized that the chronic pain and chemical intolerance reflect sensitization of different central nervous system limbic and/or mesolimbic reward pathways. We evaluated electroencephalographic (EEG) beta activity and blood glucose responses of FM patients with and without CI and normals during three repeated sucrose ingestion sessions and during a final, water-only session (testing for conditioning). The FM with CI exhibited oscillation (reversal in direction of change from session to session) at rest and then sensitization (progressive amplification) of EEG beta 1 over time across the 3 sucrose sessions versus controls. FM with CI showed sensitization of blood glucose over the 3 sucrose sessions, which, like the EEG findings, reverted toward baseline in the final water-only session. The data suggest that the subset of FM patients with CI have increased susceptibility to oscillation and physiological sensitization without conditioning, perhaps contributing to fluctuations in their chronic course.

Down-modulation of the costimulatory molecule, CD28, is a conserved activity of multiple SIV Nefs and is dependent on histidine 196 of Nef.

In this study Nef proteins derived from simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) were compared to assess their abilities to down-modulate the cell surface levels of the T-cell costimulatory molecule CD28. We demonstrate that in addition to Nef derived from the prototypic SIVmac239, Nef proteins encoded by the pathogenic SIVsmmPBj molecular clone and the SIVsmmB670 isolate also down-modulate cell surface CD28. In contrast, Nef proteins derived from HIV failed to down-modulate CD28. We have also identified H196 as a critical residue which influences the capacity of SIVmac Nef to down-modulate CD28. Nef derived from SIVmacJ5 failed to down-modulate cell surface CD28, whereas a Q196H substitution mutant of SIVmacJ5 Nef was able to down-modulate cell surface CD28. Conversely, substitution of H196 to Q196 in SIVmac239 Nef resulted in a mutant that had minimal effect on cell surface CD28 expression, despite retaining the capacity to down-modulate cell surface CD3epsilon. H196 lies immediately adjacent to a documented di-leucine endocytic motif and mutation of this motif also abrogated the ability of SIVmac239 Nef to down-modulate CD28. These findings demonstrate that down-modulation of the costimulatory molecule, CD28, and clonotypic TCR/CD3 complex are conserved attributes of SIV Nef.

Sensitization studies in chemically intolerant individuals: implications for individual difference research.

Chemical intolerance (CI) is an individual difference trait in which persons report feeling ill in multiple physiological systems from low levels of a wide range of chemically unrelated environmental substances. This paper discusses the neural sensitization model for progressive host amplification of polysymptomatic responses elicited by chemical exposures following an initiating event. The sensitization model accommodates hypotheses for initiating and eliciting CI in human populations that involve both environmental chemicals and physical or psychological stressors. Recent studies in this laboratory have demonstrated sensitization in individuals with CI over repeated sessions for dependent variables such as electroencephalographic (EEG) activity and diastolic blood pressure. Psychological distress variables alone do not explain these findings. Individuals with CI and/or vulnerability to sensitization share specific characteristics, for example, female gender, certain genetic background (offspring of alcohol-preferring parents), and personal preference for high sugar/ carbohydrate intake. Overall, the data suggest that the 15-30% of the general population who report heightened CI are highly sensitizable. Sensitizability may serve an adaptive, sentinel function in threatening environments with poor signal-to-noise ratios. However, as sensitization gradually shifts operating set points of physiological systems out of the normal range in response to allostatic load, this process may contribute to the development of chronic, polysymptomatic health conditions such as multiple chemical sensitivity and/or fibromyalgia. Individual response specificity and stereotypy rather than toxicant properties may determine which types of central, autonomic, and/or peripheral nervous system dysfunctions manifest at subclinical and clinical levels.

Plausibility of homeopathy and conventional chemical therapy: the systemic memory resonance hypothesis.

The controversy surrounding clinical observations and double-blind studies on homeopathic treatments is lessened when modern dynamical systems analysis is applied to high-dilution therapies. The logic of recurrent feedback loops, which applies to all dynamical network systems, inexorably leads to the systemic memory hypothesis - that complex patterns of emergent information and energy are stored to various degrees in physical, chemical, and biological systems. The addition of resonance, a dynamic pattern recognition process, explains many classic observations using high-dilution therapies. The systemic memory resonance hypothesis potentially provides a plausible biophysical mechanism for explaining not only how high-dilution therapies contribute to healing, but by extension, how information and energy in low-dilution and chemical therapies contribute to healing as well.

The T-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus Nef interacts and mediates down-modulation.

We have recently demonstrated that simian immunodeficiency virus (SIV) Nef binds to the zeta chain of the T-cell receptor (TCR), leading to its down-modulation from T-cell surfaces (I. Bell, C. Ashman, J. Maughan, E. Hooker, F. Cook, and T. A. Reinhart, J. Gen. Virol. 79:2717-2727, 1998). Using a panel of human as well as rhesus macaque TCR zeta cytoplasmic domain mutants, we have identified in this report two linear peptides in the cytoplasmic domain of TCR zeta which independently interact with SIV Nef. Each SIV Nef interaction domain was sufficient in the absence of the other for interaction with SIV Nef in a yeast two-hybrid assay. In parallel, we demonstrated that Nef down-modulation of CD8-TCR zeta fusion proteins containing full-length or truncated portions of the TCR zeta cytoplasmic domain occurs in transiently transfected 293T cells. Furthermore, using proteins expressed in Escherichia coli, a glutathione S-transferase-Nef fusion protein coprecipitated histidine-tagged portions of the TCR zeta cytoplasmic domain which contained SNID-1 or SNID-2. The peptides targeted by SIV Nef, YNELNL and YSEIGMKGERRR, are portions of the first and second of three immunoreceptor tyrosine-based activation motifs which are important in signal transduction, thymocyte development, and TCR biogenesis. These results demonstrate that SIV Nef binds to two distinct domains on TCR zeta in the absence of other T-cell-specific factors, and that interaction with either domain is sufficient to cause down-modulation of TCR zeta.

Electroencephalographic registration of low concentrations of isoamyl acetate.

Previous research has demonstrated electroencephalogram (EEG) changes in response to low-odor concentrations, resulting in near-chance detection. Such findings have been taken as evidence for olfaction without awareness. We replicated and extended previous work by examining EEG responses to water-water control, 0.0001, 0. 001, 0.01, and 1 ppm isoamyl acetate (IAA) in water paired with water only. Detection was above chance (>50%) for.001 and above, and alpha decreased only to those concentrations, suggesting that EEG changes corresponded to IAA awareness. However, when correct trial EEGs were compared to incorrect trial EEGs during.001 ppm, right posterior/central alpha decreased during incorrect trials and alpha decreased more globally (including frontal sites) during correct trials. These data may not reflect awareness or unawareness per se. Instead, results are discussed regarding activation of perceptual systems in the posterior region during incorrect trials and the activation of frontal action systems during a subset of correct trials.