Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field

Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders.

Functional aspects of distal oesophageal spasm: the role of onset velocity and contraction amplitude on bolus transit

Distal oesophageal spasm is a rare and under-investigated motility abnormality. Recent studies indicate effective bolus transit in varying percentages of distal oesophageal spasm patients.

Monitoring Butterfly Abundance: Beyond Pollard Walks

Most butterfly monitoring protocols rely on counts along transects (Pollard walks) to generate species abundance indices and track population trends. It is still too often ignored that a population count results from two processes: the biological process (true abundance) and the statistical process (our ability to properly quantify abundance). Because individual detectability tends to vary in space (e.g., among sites) and time (e.g., among years), it remains unclear whether index counts truly reflect population sizes and trends. This study compares capture-mark-recapture (absolute abundance) and count-index (relative abundance) monitoring methods in three species (Maculinea nausithous and Iolana iolas: Lycaenidae; Minois dryas: Satyridae) in contrasted habitat types. We demonstrate that intraspecific variability in individual detectability under standard monitoring conditions is probably the rule rather than the exception, which questions the reliability of count-based indices to estimate and compare specific population abundance. Our results suggest that the accuracy of count-based methods depends heavily on the ecology and behavior of the target species, as well as on the type of habitat in which surveys take place. Monitoring programs designed to assess the abundance and trends in butterfly populations should incorporate a measure of detectability. We discuss the relative advantages and inconveniences of current monitoring methods and analytical approaches with respect to the characteristics of the species under scrutiny and resources availability.

Identifying mechanisms of treatment effects and recovery in rehabilitation of schizophrenia: longitudinal analytic methods

The longitudinal dimension of schizophrenia and related severe mental illness is a key component of theoretical models of recovery. However, empirical longitudinal investigations have been underrepresented in the psychopathology of schizophrenia. Similarly, traditional approaches to longitudinal analysis of psychopathological data have had serious limitations. The utilization of modern longitudinal methods is necessary to capture the complexity of biopsychosocial models of treatment and recovery in schizophrenia. The present paper summarizes empirical data from traditional longitudinal research investigating recovery in symptoms, neurocognition, and social functioning. Studies conducted under treatment as usual conditions are compared to psychosocial intervention studies and potential treatment mechanisms of psychosocial interventions are discussed. Investigations of rehabilitation for schizophrenia using the longitudinal analytic strategies of growth curve and time series analysis are demonstrated. The respective advantages and disadvantages of these modern methods are highlighted. Their potential use for future research of treatment effects and recovery in schizophrenia is also discussed.

Cupiennin 1a, an antimicrobial peptide from the venom of the neotropical wandering spider Cupiennius salei, also inhibits the formation of nitric oxide by neuronal nitric oxide synthase

Cupiennin 1a (GFGALFKFLAKKVAKTVAKQAAKQGAKYVVNKQME-NH2) is a potent venom component of the spider Cupiennius salei. Cupiennin 1a shows multifaceted activity. In addition to known antimicrobial and cytolytic properties, cupiennin 1a inhibits the formation of nitric oxide by neuronal nitric oxide synthase at an IC50 concentration of 1.3 +/- 0.3 microM. This is the first report of neuronal nitric oxide synthase inhibition by a component of a spider venom. The mechanism by which cupiennin 1a inhibits neuronal nitric oxide synthase involves complexation with the regulatory protein calcium calmodulin. This is demonstrated by chemical shift changes that occur in the heteronuclear single quantum coherence spectrum of 15N-labelled calcium calmodulin upon addition of cupiennin 1a. The NMR data indicate strong binding within a complex of 1 : 1 stoichiometry.

Prediction of spatial orientation and morphology of calcaneonavicular coalitions

BACKGROUND: Calcaneonavicular coalitions (CNC) have been reported to be associated with anatomical aberrations of either the calcaneus and/or navicular bones. These morphological abnormalities may complicate accurate surgical resection. Three-dimensional analysis of spatial orientation and morphological characteristics may help in preoperative planning of resection. MATERIALS AND METHODS: Sixteen feet with a diagnosis of CNC were evaluated by means of 3-D CT modeling. Three angles were defined that were expressed in relation to one reproducible landmark (lateral border of the calcaneus): the dorsoplantar inclination, anteroposterior inclination, and socket angle. The depth and width of the coalitions were measured and calculated to obtain the estimated contact surface. Three-dimensional reconstructions of the calcanei served to evaluate the presence, distortion or absence of the anterior calcaneal facet and presence of a navicular beak. The interrater correlations were assessed in order to obtain values for the accuracy of the measurement methods. Sixteen normal feet were used as controls for comparison of the socket angle; anatomy of the anterior calcaneal facet and navicular beak as well. RESULTS: The dorsoplantar inclination angle averaged 50 degrees (+/-17), the anteroposterior inclination angle 64 degrees (+/-15), and the pathologic socket angle 98 degrees (+/-11). The average contact area was 156 mm(2). Ninety-four percent of all patients in the CNC group revealed a plantar navicular beak. In 50% of those patients the anterior calcaneal facet was replaced by the navicular portion and in 44% the facet was totally missing. In contrast, the socket angle in the control group averaged 77 degrees (+/-18), which was found to be statistically different than the CNC group (p = 0.0004). Only 25% of the patients in the control group had a plantar navicular beak. High, statistically significant interrater correlations were found for all measured angles. CONCLUSION: Computer-aided CT analysis and reconstructions help to determine the spatial orientations of CNC in space and provide useful information in order to anticipate morphological abnormalities of the calcaneus and navicular.

Gait analysis in normal and spinal contused mice using the TreadScan system

Advances in spinal cord injury (SCI) research are dependent on quality animal models, which in turn rely on sensitive outcome measures able to detect functional differences in animals following injury. To date, most measurements of dysfunction following SCI rely either on the subjective rating of observers or the slow throughput of manual gait assessment. The present study compares the gait of normal and contusion-injured mice using the TreadScan system. TreadScan utilizes a transparent treadmill belt and a high-speed camera to capture the footprints of animals and automatically analyze gait characteristics. Adult female C57Bl/6 mice were introduced to the treadmill prior to receiving either a standardized mild, moderate, or sham contusion spinal cord injury. TreadScan gait analyses were performed weekly for 10 weeks and compared with scores on the Basso Mouse Scale (BMS). Results indicate that this software successfully differentiates sham animals from injured animals on a number of gait characteristics, including hindlimb swing time, stride length, toe spread, and track width. Differences were found between mild and moderate contusion injuries, indicating a high degree of sensitivity within the system. Rear track width, a measure of the animal's hindlimb base of support, correlated strongly both with spared white matter percentage and with terminal BMS. TreadScan allows for an objective and rapid behavioral assessment of locomotor function following mild-moderate contusive SCI, where the majority of mice still exhibit hindlimb weight support and plantar paw placement during stepping.

Continental-scale temperature variability during the past two millennia

Past global climate changes had strong regional expression. To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia. The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century. At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them. There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century. The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions. Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years.

Gender-specific modulation of immune system complement gene expression in marine medaka Oryzias melastigma following dietary exposure of BDE-47

BDE-47 is one of the most widely found congeners of PBDEs in marine environments. The potential immunomodulatory effects of BDE-47 on fish complement system were studied using the marine medaka Oryzias melastigma as a model fish. Three-month-old O. melastigma were subjected to short-term (5 days) and long-term (21 days) exposure to two concentrations of BDE-47 (low dose at 290 +/- 172 ng/day; high dose at 580 +/- 344 ng/day) via dietary uptake of BDE-47 encapsulated in Artemia nauplii. Body burdens of BDE-47 and other metabolic products were analyzed in the exposed and control fish. Only a small amount of debrominated product, BDE-28, was detected, while other metabolic products were all under detection limit. Transcriptional expression of six major complement system genes involved in complement activation: C1r/s (classical pathway), MBL-2 (lectin pathway), CFP (alternative pathway), F2 (coagulation pathway), C3 (the central component of complement system), and C9 (cell lysis) were quantified in the liver of marine medaka. Endogenous expression of all six complement system genes was found to be higher in males than in females (p < 0.05). Upon dietary exposure of marine medaka to BDE-47, expression of all six complement genes were downregulated in males at day 5 (or longer), whereas in females, MBl-2, CFP, and F2 mRNAs expression were upregulated, but C3 and C9 remained stable with exposure time and dose. A significant negative relationship was found between BDE-47 body burden and mRNA expression of C1r/s, CFP, and C3 in male fish (r = -0.8576 to -0.9447). The above findings on changes in complement gene expression patterns indicate the complement system may be compromised in male O. melastigma upon dietary exposure to BDE-47. Distinct gender difference in expression of six major complement system genes was evident in marine medaka under resting condition and dietary BDE-47 challenge. The immunomodulatory effects of BDE-47 on transcriptional expression of these complement components in marine medaka were likely induced by the parent compound instead of biotransformed products. Our results clearly demonstrate that future direction for fish immunotoxicology and risk assessment of immunosuppressive chemicals must include parallel evaluation for both genders.

Patient-reported outcomes in meta-analyses - part 2: methods for improving interpretability for decision-makers

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complimented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95%CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27%relative reduction in the mean depression score).