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The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.
We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.
We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.
Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.
Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis show variable otorhinolaryngological involvement. Up to 14 per cent of granulomatosis with polyangiitis patients have subglottis involvement; little is known about the laryngeal involvement in eosinophilic granulomatosis with polyangiitis.
A literature review was conducted, together with a prospective cross-sectional analysis of 43 eosinophilic granulomatosis with polyangiitis patients. All patients underwent fibre-optic laryngoscopy with narrow-band imaging, and completed health-related questionnaires.
The literature review showed only two cases of laryngeal involvement in eosinophilic granulomatosis with polyangiitis; in our cohort, no cases of subglottis stenosis were found, but local signs of laryngeal inflammation were present in 72 per cent of cases. Of the patients, 16.2 per cent had a pathological Reflux Finding Score (of 7 or higher).
Laryngeal inflammation in eosinophilic granulomatosis with polyangiitis is frequent. It is possibly due more to local factors than to eosinophilic granulomatosis with polyangiitis itself. However, ENT evaluation is needed to rule out possible subglottis inflammation. These findings are in line with current literature and worthy of confirmation in larger cohorts.
Since baseline executive dysfunction predicts worsening Instrumental Activities of Daily Living (i-ADL) over time and progression to Alzheimer's Disease (AD), we aimed to analyze the role of neuropsychological variables to outline which factors can contribute to functional impairment. Specific attention to executive functions (EFs) has been given.
A total of 144 subjects complaining of different cognitive deficits – ranging from “MCI likely due to AD” to “mild AD patients” – underwent an overall neuropsychological assessment. The Behavioral Assessment of the Dysexecutive Syndrome was used to analyze EFs. We conducted multiple linear regression analyses to study whether the level of independent living skills – assessed with the Lawton-scale – could be associated with cognitive and behavioral measurements.
We found a significant association between i-ADL and specific EFs measured by Rule Shift Cards (p = 0.04) and Modified Six Elements (p = 0.02). Moreover, considering i-ADL scores, we observed an involvement of mood changes and a reduced awareness of deficits in terms of Hamilton Depression Rating Scale (p = 0.02) and Awareness of Deficit Questionnaire – Dementia scale (p < 0.0001), respectively.
Our results suggest the importance of considering the association between a reduction in i-ADL and executive dysfunction in patients who have AD etiopathology, for which the ability to inhibit a response, self-monitoring, set-shifting and mood deflection play a key role. Besides, no straightforward associations between i-ADL scores and global cognition, memory, language comprehension, attention, and perspective taking abilities were found.
This work presents the results of physiological studies developed to understand modifications linked to the reduction of seed dormancy provoked by domestication processes. The experiments performed compared wild and domesticated Cucurbita subspecies and their hybrids developed by reciprocal crossings. Seeds of two accessions of the wild subspecies presented dormancy, but it was largely reduced in seeds from the domesticated genotype, and partially reverted in hybrids, especially in those obtained when the domesticated genotype was used as the mother plant. In addition, naked embryos of all subspecies did not display dormancy when incubation was performed at 28°C, but embryo germination was progressively reduced only in the wild genotype under decreasing incubation temperatures (22 and 16°C). In the embryos, abscisic acid (ABA) concentrations were similar in both domesticated and wild subspecies, whereas in the seed coat, it was threefold higher in the wild subspecies. The naked embryos from the wild subspecies were far more responsive to ABA than those from the domesticated subspecies. These results indicate that dormancy in the wild subspecies is imposed by the seed coat tissues and that this effect is mediated by their high ABA content and the sensitivity of the embryos to ABA. These physiological aspects were apparently removed by domestication along with the temperature-dependent response for germination.
Since bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania.
To estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder.
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes.
Five RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD= −0.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found.
Our finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation.
“Reversible molecular interactions are at the heart of the dance of life.” Lubert Stryer
Biochemical systems, their communication pathways, and the related transformations that take place are based on molecular interactions, so we may safely say that these regulate life at a molecular level. For basic science studies or for therapeutic purposes, we can perturb these systems with chemical manipulations. Because of the accumulated knowledge in the fields of organic chemistry and molecular recognition, our investigative instruments have become increasingly powerful. During the last fifty years, there has been a continuous evolution in chemical approaches to interact with biological systems, and fragment-based drug discovery can be considered one of the products of this evolution . In short, fragment-based ligand discovery (FBLD) may be described as the search for a ligand for a macromolecule, which may constitute a lead for a medicinal chemistry program, through the use of very small molecules. This approach, as we will see, may provide a number of advantages over the classical approaches together with the logical consequence that the observed affinities for a good lead compound will fall in the micromolar-millimolar range rather than in the nanomolar range, necessitating that chemists and biologists leave behind the high-affinity paradigm.
This chapter discusses in detail the historical background, key concepts, and basis for the FBLD approach. An illustration of the technology involved will follow, together with a selection of practical and successful applications.
Nine european national metrology institutes (NMIs) are collaborating in a new project funded by the european metrology research programme (EMRP) to establish traceable dynamic measurement of the mechanical quantities force, pressure, and torque. The aim of this joint research project (JRP) is to develop appropriate calibration methods, mathematical models, and uncertainty evaluation. The duration of the project is 3 years for a global amount of €3.6 million. It began in September 2011.
A reliable evaluation of crop nutritional status is crucial for supporting fertilization aiming at maximizing qualitative and quantitative aspects of production and reducing the environmental impact of cropping systems. Most of the available simulation models evaluate crop nutritional status according to the nitrogen (N) dilution law, which derives critical N concentration as a function of above-ground biomass. An alternative approach, developed during a project carried out with students of the Cropping Systems Masters course at the University of Milan, was tested and compared with existing models (N dilution law and approaches implemented in EPIC and DAISY models). The new model (MAZINGA) reproduces the effect of leaf self-shading in lowering plant N concentration (PNC) through an inverse of the fraction of radiation intercepted by the canopy. The models were tested using data collected in four rice (Oryza sativa L.) experiments carried out in Northern Italy under potential and N-limited conditions. MAZINGA was the most accurate in identifying the critical N concentration, and therefore in discriminating PNC of plants growing under N-limited and non-limited conditions, respectively. In addition, the present work proved the effectiveness of crop models when used as tools for supporting education.
Objectives: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.
Methods: A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.
Results: Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered €2,116 as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (€68) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to €5,300.
Conclusions: Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.
Aims – To obtain a new, well-balanced mental health funding system, through the creation of i) a list of psychiatric interventions provided by Italian Community-based Psychiatric Services (CPS), and associated costs; ii) a new prospective funding system for patients with a high use of resources, based on packages of care. Methods – Five Italian Community-based Psychiatric Services collected data from 1250 patients during October 2002. Socio-demographical and clinical characteristics and GAF scores were collected at baseline. All psychiatric contacts during the following six months were registered and categorised into 24 service contact types. Using elasticity equation and contact characteristics, we estimate the costs of care. Cluster analysis techniques identified packages of care. Logistic regression defined predictive variables of high use patients. Multinomial Logistic Model assigned each patient to a package of care. Results – The sample's socio-demographic characteristics are similar, but variations exist between the different CPS. Patients were then divided into two groups, and the group with the highest use of resources was divided into three smaller groups, based on number and type of services provided. Conclusions – Our findings show how is possible to develop a cost predictive model to assign patients with a high use of resources to a group that can provide the right level of care. For these patients it might be possible to apply a prospective per-capita funding system based on packages of care.
In this work TF values for 90Sr and 137Cs were measured for reference plants grown in lysimeters containing soils representative of large agricultural areas in Brazil: Ferralsol, Nitisol and Acrisol. These results were discussed in the light of pedological analyses and results from the follow sequential chemical extraction protocol: 1) slightly acidic phase containing readily bioavailable elements;
2) easily reducible phase containing elements bound to Mn oxides; 3) oxidizable phase containing elements bound to labile organic matter; 4) alkaline phase containing mainly elements bound to Fe compounds; 5) resistant phase not potentially available to crops. These results showed that the main soil factors influencing the 137Cs transfer to these soils were: exchangeable K, organic matter and iron oxides content. These results showed that 90Sr plant uptake was influenced by exchangeable Ca. All these finds are in accord with previous studies and seems confirm the vulnerability of Ferralsol and Acrisol to 137Cs contamination
We report the results of a study carried out in 2002 on the main limnological characteristics and on the ostracod communities of 16 wetlands of the Parco Oglio Sud (Northern Italy). Physical and hydrochemical variables were measured and ostracod samples were collected in different seasons (April, June, August, and October). Most of the considered sites were characterised by high concentrations of nitrogenous compounds due to washing out from cultivated areas, intermittent river flooding and internal recycling. Observed differences in macrophyte communities were consistent with trophic status of waters, with pleustonic forms dominating most degraded areas. Both morphology of valves (by scanning electron microscopy) and anatomy of soft parts were analysed for ostracod species identification. Nineteen ostracod species in five families were found. Two species, Candona weltneri and Pseudocandona compressa, are new records for Italy. Cypria ophthalmica was collected from all sampling sites; other relatively common species were Cypridopsis vidua, Cyclocypris ovum, and Candona weltneri. No clear seasonality was observed in community structure; highest species diversity occurred in June in most of the studied wetlands. The maximum number of species per site was seven, and a maximum of six species was found in a single sample. Ostracod occurrence in relation to environmental factors was examined using Canonical correspondence analysis (CCA). Total alkalinity and pH were the most important variables structuring the species assemblages. The ostracod fauna found in this area was compared to the known distribution of recent non-marine ostracods in Italy, and the validity of published checklists is discussed.
A survey of parasites was conducted on 258 Symphodus ocellatus (Teleostei: Labridae) collected in Corsica National Park (west Mediterranean). In addition, the total length, sex and social status were recorded for each individual fish. Three species of trematodes were found in the digestive tract. One of the parasites, Genitocotyle mediterranea, was only present, with one exception, in males of large size, and principally in the individuals that had the highest status and that were involved in nest construction. Two hypotheses are suggested to explain this particular distribution of a parasite: the immunocompetence handicap and the changing trophic behaviour as the fish grows.
The anatomy of Xanthomaculna convolute shows adaptation to a vagrant life form and to the moisture conditions of its habitat. The differential swelling of the irregularly thickened upper cortex and the medulla, in addition to the rigid medullary structure, due to the deposition of calcium oxalate, allow orderly hygroscopic thalline movements. The architecture of the medulla appears to be closely related to masonry-like arches where the material is only stressed by compression and the stresses are distributed at the hinges. The possible role of crystalline medullary deposition as a radiation reflector is also suggested.
A new system of integral equations for the exterior 2D time harmonic
scattering problem is investigated. This system was first proposed by B. Després in . Two new derivations of this system are given:
one from elementary manipulations
of classical equations, the other based on a minimization of a quadratic
functional. Numerical issues are addressed to investigate the potential
of the method.
The aim of this work was to study the structure of the parasite communities of Digeneans of 2 families of Teleost fishes
(Sparidae and Labridae) of the Mediterranean sea. We tried to quantify the importance of both the microhabitat
requirements of the parasite species and the effect of host biological factors on the parasite communities. We applied, for
the first time in parasite community studies, the Canonical Correspondence Analysis (CCA) to analyse (i) the spatial
distribution of parasite species within the digestive tract of the hosts; (ii) the host's biological factors (such as diet, host
length, gregariousness and abundance) that may influence this spatial distribution of parasite species. Our results showed
that potential microhabitats were vacant in the 2 host families studied revealing a lack of niche saturation because either
there was little inter- and/or intraspecific competition or there were enough available space and resources within the host.
Our results also indicated that the position of the parasite in the digestive tract is much more important than host biological
factors for the structure of parasite community. Finally, we highlight the potential use of the CCA method for controlling
for phylogenetic constraints in multi-species analyses.
At the end of the third section of the preceding chapter, we pointed out how the major schools of psychology – psychoanalysis, behaviorism, and cognitivism – presented some of the characteristics of teleonomic projects, meaning the repetition of constant factors and regularities. Furthermore, we showed how these psychological schools do not fully satisfy the teleonomic requirements, in that they tend not to express in their paradigms the possibility for autonomous morphogenesis, which is to say, the capacity for the self-generation of negentropic psychic states.
To the contrary, these schools emphasize homeostatic and mechanistic aspects of the psyche. For this very reason, such theories, at least as they present themselves to date, do not seem to be fully suited to satisfy the fundamental function of psychic processes as proposed and highlighted in the introductory sections of this volume. Once again, such a function consists in the regular replication of specific psychic states and, at the same time, in an ordered and self-determined evolution of the complexity of information contained in these same psychic processes, or connected to them. Fulfilling such tasks, psychological teleonomy becomes, as we have seen, the bridge between biological and cultural processes.
The theories presented in the last sections of the first chapter share instead a number of aspects that tend to better satisfy the teleonomic requirements concerning the increase of complexity.