Anti-neuronal anti-bodies in patients with early psychosis.

It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues.

Precuneus functioning differentiates first-episode psychosis patients during the fantasy movie Alice in Wonderland.

BACKGROUND: While group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP). METHOD: We recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the 'sense of reality' in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns. RESULTS: Most (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10-8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients. CONCLUSIONS: These findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.

Cortical salience network activation precedes the development of delusion severity.

BACKGROUND: Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown. METHOD: To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale. RESULTS: Both tasks activated the CSN in comparison with rest. Activation of CSN ('illness evaluation v. control task' contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation. CONCLUSIONS: Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.

Effect of photocatalytic and hydrophobic coatings on brewery surface microorganisms.

The aim of this study was to determine whether process hygiene in the beverage industry could be improved by applying new coating techniques to process surfaces. Photocatalytic titanium dioxide (TiO(2)) and hydrophobic coatings applied to stainless steel with or without added antimicrobial compounds were studied in laboratory attachment tests and in a 15-month process study. No clear reductions in numbers of attached microbes were obtained with photocatalytic coatings, except for coatings to which silver had been added. These TiO(2)+Ag coatings reduced microbial coverage in laboratory studies and in some process samples. Hydrophobic coatings reduced the area coverage of microorganisms in 4-h laboratory studies but did not affect colony counts in laboratory or process studies. The surfaces had changed from hydrophobic into hydrophilic during the process study. The coatings did not mechanically fully withstand process conditions; part of the hydrophobic coatings had peeled off, most of the precipitated Ag had dissolved, and some of the TiO(2) coatings were damaged. In conclusion, functional coatings have potential for reducing microbial loads on beverage industry surfaces, but these coatings need further development.

Bone attachment to glass-fibre-reinforced composite implant with porous surface.

A method has recently been developed for producing fibre-reinforced composites (FRC) with porous surfaces, intended for use as load-bearing orthopaedic implants. This study focuses on evaluation of the bone-bonding behaviour of FRC implants. Three types of cylindrical implants, i.e. FRC implants with a porous surface, solid polymethyl methacrylate (PMMA) implants and titanium (Ti) implants, were inserted in a transverse direction into the intercondular trabeculous bone area of distal femurs and proximal tibias of New Zealand White rabbits. Animals were sacrificed at 3, 6 and 12 weeks post operation, and push-out tests (n=5-6 per implant type per time point) were then carried out. At 12 weeks the shear force at the porous FRC-bone interface was significantly higher (283.3+/-55.3N) than the shear force at interfaces of solid PMMA/bone (14.4+/-11.0 N; p<0.001) and Ti/bone (130.6+/-22.2N; p=0.001). Histological observation revealed new bone growth into the porous surface structure of FRC implants. Solid PMMA and Ti implants were encapsulated mostly with fibrous connective tissue. Finite element analysis (FEA) revealed that porous FRC implants had mechanical properties which could be tailored to smooth the shear stress distribution at the bone-implant interface and reduce the stress-shielding effect.

Development of a multi-component fiber-reinforced composite implant for load-sharing conditions.

Fiber-reinforced composites (FRC) have the potential for use as load-bearing orthopaedic implants if the high strength and elastic modulus of FRC implant can be matched with local requirements. This study tested the in vivo performance of novel FRC implants made of unidirectional glass fibers (E-glass fibers in Bis-GMA and TEGDMA polymeric matrix). The implant surface was covered with bioactive glass granules. Control implants were made of surface-roughened titanium. Stress-shielding effects of the implants were predicted by finite element modelling (FEM). Surgical stabilization of bone metastasis in the subtrochanteric region of the femur was simulated in 12 rabbits. An oblong subtrochanteric defect of a standardized size (reducing the torsional strength of the bones approximately by 66%) was created and an intramedullary implant made of titanium or the FRC composite was inserted. The contralateral femur served as the intact control. At 12 weeks of healing, the femurs were harvested and analyzed by radiography, torsional testing, micro-CT imaging and hard tissue histology. The functional recovery was unremarkable in both groups, although the final analysis revealed two healed undisplaced peri-implant fractures in the group of FRC implants. FEM studies demonstrated differences in stress-shielding effects of the titanium and FRC implants, but the expected biological consequences did not become evident during the follow-up time of the animal study. Biomechanical testing of the retrieved femurs showed no significant differences between the groups. The torsional strength of the fixed bones had returned the level of contralateral intact femurs. Both implants showed ongrowth of intramedullary new bone. No adverse tissue reactions were observed. Based on these favorable results, a large-scale EU-project (NewBone, www.hb.se/ih/polymer/newbone) has been launched for development of orthopaedic FRC implants.

Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure.

BACKGROUND: The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2-60 months) after cessation of exposure by following up lung function and bronchial inflammation. METHODS: Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 mug a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects. RESULTS: Nonspecific bronchial hyperreactivity diminished significantly (P = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased (P = 0.012) and that of macrophages increased (P = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up. CONCLUSION: Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.

Are FPCIs a source of increased risk for children? Results of a multicenter, experimental study comparing children's behaviour with FPCIs and toys.

INTRODUCTION: Food Products Containing Inedibles (FPCIs) are believed to represent a source of higher choking risk in children. The aim of this study was to set up a controlled study, conducted on children aged 3-6 in a laboratory setting, in order to understand their behavior when interacting with FPCIs (with reference to mouthing activities, double nature recognition, and toy assembling ability). METHOD: The experimental phase was divided into two sessions: a FPCI session and a Toy session, to which 247 children were randomly assigned. During these sessions children were observed in order to catch their mouthing activity according to the two types of objects available to them (FPCIs and Toys). RESULTS: This study shows that: (a) children's behavior with respect to toys contained in FPCIs and toys presented alone is not significantly different; (b) children's ability to distinguish between the edible and non-edible part of the FPCI was very high; and (c) mouthing episodes of the inedible parts were negligible and comparable between FPCIs and toys presented alone. This strongly suggests that, with respect to choking risk, FPCIs are not per se distinguishable from toys containing small parts. IMPACT ON INDUSTRY: Restrictions on the sale of FPCIs with small toys exist in the U.S. market. In Europe, FPCIs are allowed to be on sale, under the condition that, in case, they will follow the general regulatory requirements of small toys packaged and sold alone. In this case, they must provide age warnings and labels. Our findings do not justify the different attention that toys in FPCIs are at times afforded by regulators when compared to "stand alone" toys.

Effect of temporin A modifications on its cytotoxicity and antimicrobial activity.

Temporin A (TA), a short alpha-helical antimicrobial peptide isolated from the skin of the frog Rana temporaria, is effective against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium strains. TA interacts directly with the cell membrane of the microorganism and it has been reported to be non-toxic to erythrocytes at concentrations that are antimicrobial. Less is known about the effects on the viability and growth of nucleated eukaryotic cells. In this study we have tested antibacterial and growth-inhibitory properties of TA, its dimeric analogue (TAd), and all-L (TAL L512) and all-D (TAD L512) enantiomeric derivatives of modified TA towards S. aureus and cultured human keratinocytes, respectively. All molecules were antibacterial at concentrations from 1.5 microM to 10 microM. In keratinocyte cultures, TAD L512, as well as TAd, showed cytotoxicity. The original TA and TAL L512 did not affect the viability of the cells at their bacteriolytic concentrations. The growth of keratinocytes in low- and high-calcium media was only slightly inhibited by temporins at concentrations which were antibacterial to S. aureus. This suggests that original TA and its modification, TAL L512, are promising molecules against multiresistant bacterial infections.

Layer Buildup on Two-Layered Porous Substrate by Dip-Coating: Modeling and Effect of Additives on Growth Rate.

A model was developed to describe layer buildup on a two-layered substrate during dip-coating. In this model, the growth rate can be used to estimate the permeability of the cast layer. Layers of submicron alumina were dip-coated onto the asymmetric porous substrate to evaluate the model. The layer buildup and properties were studied with different slip additives. Slips were deflocculated with nitric acid or sodium poly(methacrylic acid) (Na-PMAA) to achieve electrostatic or electrosteric stabilization. Properties of the slips with electrostatic stabilization were varied with poly(vinyl alcohol) (PVA) concentration. Properties of the slips with electrosteric stabilization were varied with Na-PMAA concentration. PVA addition decreased the growth rate of the layer by reducing capillary pressure and increasing the viscosity of the filtrate. Electrostatic stabilization of the slip with PVA addition also led to almost complete deflocculation and a rather high density of layers. Na-PMAA addition led to fast growth of the layer. Na-PMAA addition increased the capillary pressure and had a minor effect on the viscosity of the liquid phase. Na-PMAA addition led to an incomplete dispersion of particles and therefore a high porosity of layers. Permeability values of coated layers obtained from the model were compared with permeability values predicted by the Kozeny-Carman equation. In the case of complete deflocculation of the slip, the permeability values estimated with the model correlated reasonably well with the predicted values. Incomplete deflocculation led to higher permeability values than predicted by the Kozeny-Carman equation. Copyright 2000 Academic Press.

Expression of CYP1A1, CYP1B1 and CYP3A, and polycyclic aromatic hydrocarbon-DNA adduct formation in bronchoalveolar macrophages of smokers and non-smokers.

Variability in the expression of enzymes metabolizing carcinogens derived from cigarette smoke may contribute to individual susceptibility to pulmonary carcinogenesis. This study was designed to determine the effects of smoking and 3 major cytochrome P450 (CYP) enzymes, i.e., CYP1A1, CYP1B1 and CYP3A, which metabolize polycyclic aromatic hydrocarbons (PAH) on PAH-DNA adduct formation in the bronchoalveolar macrophages (BAM) of 31 smokers and 16 non-smokers. CYP protein levels were determined by immunoblotting and PAH-DNA adduct levels by the nuclease P1 enhanced (32)P-postlabeling method. The expression of specific CYP forms was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) from 10 additional samples. CYP3A protein, CYP3A5 by RT-PCR, was detected in the majority of samples from smokers and non-smokers. The levels of CYP3A appeared to be lower in active smokers than in ex-smokers (p = 0.10) or never smokers (p = 0.02). CYP1A1 was not detectable by either immunoblotting or RT-PCR. The expression of CYP1B1 was low or undetectable in most samples. The PAH-DNA adduct levels were higher (mean 1.57/10(8) nucleotides) in samples from smokers compared with non-smokers (mean 0.42/10(8) nucleotides, p < 0.001) and the number of adducts correlated with the number of cigarettes smoked daily (regression analysis, p < 0. 001). Higher levels of adducts were detected in samples from smokers with a high level of CYP3A compared with those with a low level (regression analysis, p = 0.002). As CYP3A5 is abundant in both lung epithelial cells and BAM, its association with adduct formation suggests that this CYP form may be important in the activation of cigarette smoke procarcinogens.

Recollections of faces: remembering differences and knowing similarities.

Components of recollective experience were investigated in 4 experiments in which participants studied either similarities or differences among faces (relational vs. distinctive processing). Subsequently, when recognizing a face, participants indicated whether their decision was based on explicit recollection (remembering) or assessment of familiarity (knowing). Type of encoding interacted with judgments of recollective experience, so that the incidence of "remember" responses was higher following distinctive encoding than following relational encoding, whereas the opposite pattern of results was obtained for "know" responses. Furthermore, recognition of appearance-changed faces was based on feelings of familiarity, rather than on explicit recollection. The results support the dual-component notion of recognition but are inconsistent with the idea that dissociations between remembering and knowing merely reflect differences in conceptual and perceptual processing.

Interrupting intentions: Zeigarnik-like effects in prospective memory.

In two experiments, we examined the effects of task interruption on memory for intentions. Participants studied a series of anagrams, of which they solved one-half (Exp. 1) or two-thirds (Exp. 2), whereas the solution of the remaining items was interrupted by the experimenter. Furthermore, four anagrams (prospective cue items) differed from the remaining anagrams in that the third letter of each item was underlined. Participants were instructed to decide whether a subsequently presented (target) anagram contained the same or a different third letter as the underlined letter of the cue item. The results of both experiments showed Zeigarnik-like effects in prospective memory, so that cue items that were associated with interruption in the anagram task were better reminders than were items that were associated with completion. These findings suggest that interruption of an ongoing activity facilitates subsequent prospective memory performance, possibly by increasing the level of activation of the underlying intention representation that, in turn, increases the individual's sensitivity to identify the target event.

Adult age differences in source recall: a population-based study.

Age differences in source recall were investigated in a population-based sample of healthy adults aged 35 to 80 years (N = 1000). Participants, who were screened on a variety of demographic, psychological, and biological variables, studied facts about well-known and unknown persons that were presented in four different ways, depicting four different sources of item information. An age-related deterioration of both item and source recall was observed, with source recall being more impaired than item recall. Source error analyses revealed an increase of source amnesia in subjects aged 75-80 years. Individual differences in background variables, age, gender, and word comprehension were related to source recall of well-known items, whereas age and years of formal education were related to source recall of unknown items. Source amnesia was accentuated in the two oldest cohorts and related to word comprehension. The age-related tendency to forget the source even when the fact is retained is suggested to be a specific feature of cognitive aging.

Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.

In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.

Recognition failure of categorised words: further evidence of exceptions.

When subjects study a list of B items paired with A items and are tested for recognition of the B items alone, and then for recall of the B items given the A items as cues, B items that can be recalled frequently go unrecognised. The extent of this recognition failure is predictable from a function discovered by Tulving and Wiseman (1975), which relates the probability of recognising the recallable items to the probability of recognising all items. Two kinds of exceptions to this function have been discovered: encoding exceptions and retrieval exceptions. Very few observations of retrieval exceptions exist. Four experiments described in this article provide further evidence that such exceptions occur when the B items are categorised and the A items are the names of the categories. According to a contextual account of the function and exceptions to it, these retrieval exceptions occur because the information provided by the A-item cues can be largely retrieved from the B items in the recognition test; hence, as cues, the A items do not provide much different contextual information to that provided by the B items. By this account, the function is an empirical law; exceptions fall outside the range of this law and define its boundary conditions.

Effectiveness of self-generated cues in early Alzheimer's disease.

The ability to utilize cognitive support in the form of self-generated cues in mild Alzheimer's disease (AD), and the factors promoting efficient cue utilization in this group of patients, were examined in two experiments on memory for words. Results from both experiments showed that normal old adults as well as AD patients performed better with self-generated cues than with experimenter-provided cues, although the latter type of cues resulted in gains relative to free recall. The findings indicate no qualitative differences in patterns of performance between the normal old and the AD patients. For both groups of subjects, cue effectiveness was optimized when (a) there was self-generation activity at encoding, and (b) encoding and retrieval conditions were compatible.

Asbestos bodies in bronchoalveolar lavage fluid in relation to occupational history.

Concentrations of asbestos bodies (AB) were assessed by optical microscopy of 10 ml iron-stained samples and compared with the exposure history acquired by personal interview for 156 patients. Concentrations equalling or exceeding 1 AB/ml were found in 85% of patients who had been heavily exposed to asbestos and only 7% of those who were unlikely to have been exposed. Elevated AB concentrations were observed among primary asbestos, shipyard and construction workers. Smoking was not found to affect the AB concentrations. The use of Papanicolaou-stained cytological Millipore preparations during routine screening was a less sensitive method for the assessment of AB concentrations than that involving iron-stained preparations. The expression of AB concentration as AB/ml or AB/million cells were found to be equally useful indicators of exposure. The correlation between AB concentration and exposure history was greater than in earlier studies on workers exposed to chrysotile. Concentrations exceeding 1 AB/ml were indicative of a nontrivial exposure to asbestos. Despite the observed correlation between AB concentration and exposure history, the individual variability of AB counts, methodological differences and laboratory-bound reference values are important in the interpretation of AB concentrations in bronchoalveolar lavage (BAL) fluid at individual level.

Remembering to remember: adult age differences in prospective memory.

Age-related differences in prospective memory were examined in a laboratory-based task in which younger and older adults performed different actions whenever a semantically defined target word occurred in the context of a free-association task. Requirements for self-initiated retrieval operations were manipulated by presenting target words that were typical or atypical instances (e.g., milk vs ink) of a given semantic category (liquid). The results showed that age differences in prospective memory were accentuated when atypical items were used as targets, but reduced when highly typical targets were presented. Furthermore, age differences were not limited to remembering when to perform action, but young subjects also showed better performance in remembering what was to be done. These findings indicate that the magnitude of age difference in prospective memory interacts with task complexity, and support the view that prospective memory failures are accentuated in tasks with high resource demands on self-initiated retrieval operations.

Components of recollective experience in cued recall.

Components of recollective experience were examined in relation to cue effectiveness by presenting subjects with their own or someone else's associations as retrieval cues. When recalling an item, subjects indicated whether they consciously recollected its prior occurrence ("remembering") or recalled it on some other basis, in the absence of conscious recollection ("knowing"). The results showed that cue compatibility (self-generated vs. someone else's cues) and retention interval (immediate vs. delayed test) selectively impaired retention accompanied by recollective experience, as measured by remember responses, but had reduced effects in the absence of recollective experience, as measured by know responses. The results are discussed in terms of variables dissociating judgments of recollective experience.