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Many patients discontinue antidepressant therapy long before the six-month minimum duration recommended for the treatment of major depression and many other diagnoses.
To estimate the duration of antidepressant treatment and to analyse the following factors in relation to treatment adherence: age, sex, polypharmacy and type of drug.
Retrospective cohort followed up for five years (2003–2007) based on prescription database. Selection criteria: Users who had received at least one antidepressant prescription in 2003 and who had not received antidepressants during the previous 12 months.
Age, sex, drug, polypharmacy, period of treatment, packs dispensed. Adequate adherence was defined as dispensation of medication during at least 80% of the treatment period, and compliance was defined as good when, in addition, the treatment lasted more than four months.
Of the 7525 patients selected, 56% abandoned medication during the first four months. Men were more likely to give up medication before time than women. Good compliance was recorded in 22% of patients and was twice as frequent in patients with high levels of polypharmacy than in those with low levels (31% vs. 15.3%). Patients receiving maprotiline, venlafaxine, mirtazapine, citalopram, clomipramine and fluoxetine presented the highest percentages of good compliance.
Only one out of five patients complied with treatment for over four months. Treatment periods were shorter in men. In chronic processes, patients receiving polypharmacy presented the best compliance.
Contemporary cognitive models emphasize the importance of certain dysfunctional beliefs in the development and maintenance of Obsessive-Compulsive Disorder (OCD): overimportance of thoughts, need to control thoughts, perfectionism, intolerance of uncertainty, inflated responsibility, and overestimation of threat. Although a recent twin study suggests that these dysfunctional beliefs are significantly heritable, there have been no previous attempts to analyze candidate genes associated with them.
Our study aimed to investigate the possible association between OC-related dysfunctional beliefs and variants of two functional polymorphisms of the COMT (Val158Met) and BDNF (Val66Met) genes in 141 OCD patients.
The non-synonymous mutation Val158Met (rs4680) in the COMT gene and the Val66Met functional variant (rs6265) in the BDNF gene were genotyped with the KASPar assay system. The validated Spanish short version of the Obsessive Beliefs Questionnaire, (OBQ-44), was used to assess dysfunctional beliefs. Multivariate analysis of covariance (MANCOVA) and a post hoc one-way analysis of covariance (ANCOVA) were perfomed.
Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype when examining the two genes in isolation, but we detected a significant COMT x BDNF interaction effect on responsibility and overestimation of threat scores. These cognitive distortions were significantly higher among OCD subjects with the BDNF Met-present genotype who were also carriers of the COMT Val/Met and Met/Met genotypes.
Our data suggest that an interaction between dopaminergic and neurotrophic functional gene variants influences some of the dysfunctional belief domains hypothesized to contribute to the etiology of OCD.
Research integrating neuroimaging and molecular genetics has yielded important insights into how variability in brain chemistry predicts brain function and structure, behaviour and risk for psychopathology. Disrupted neurotransmission of glutamate within corticalstriatal-thalamocortical circuitry has been hypothesized to play a role in the pathogenesis of Obsessive-Compulsive Disorder (OCD). Candidate gene studies have identified associations between variants in glutamate system genes and OCD, particularly for SLC1A1, although these results remain controversial after GWAS and meta-analytical approaches.
To examine the effects of multiple polymorphisms of the glutamatergic pathway on frontostriatal connectivity, measured by resting state functional magnetic resonance imaging (fMRI), in OCD.
Individual multilocus genetic profile scores (MGPS) reflecting the additive effects of multiple alleles of the glutamatergic pathway, analysed by the Affymetrix GeneticChip® SNP array, were compiled for 134 OCD patients and 63 healthy controls. Association between these genetic scores and brain functional connectivity patterns between the dorsal and ventral striatal regions and limbic cortical areas including the orbitofrontal cortex and surrounding areas, such as the anterior prefrontal and perigenual anterior cingulate cortex, were investigated.
In the entire group, glutamatergic MGPS were significantly associated with connectivity patterns involving the ventral striatum and orbitofrontal cortex. Distinct relationships between MGPS and functional connectivity between the ventral striatum, amygdala, ventromedial frontal cortex and insula between OCD and healthy subjects emerged.
Glutamatergic genetic risk variants are related to normal frontostriatal connectivity; a fact that might explain the role of glutamatergic pathway disruptions in the susceptibility to develop OCD.
Recent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).
One hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.
Among 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P = 0.046).
Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.
This study addresses aspects of the phylogenetic relationships of the commercial Tehuelche scallop, Aequipecten tehuelchus s.l. (Bivalvia: Pectinidae), from southern South America using molecular techniques. The Tehuelche scallop presents two different putative subspecies, A. t. tehuelchus and A. t. madrynensis, and a potentially related sympatric species, Flexopecten felipponei. The Tehuelche scallop is a very important component of ecosystems and is the target of artisanal fisheries in the northern Patagonian gulfs of Argentina. Despite its importance, the systematic relationships of these taxa have not been fully addressed. The main goal of this study is to place the Tehuelche scallop within a partial phylogenetic framework of the family Pectinidae. Scallops were sampled at 10 localities distributed along the south-western Atlantic Ocean. Phylogenetic reconstructions were carried out from two mitochondrial (12S rRNA and 16S rRNA) and two nuclear markers (28S rRNA and H3) using Bayesian, maximum likelihood and maximum parsimony analyses. Our phylogenetic analysis indicates that the two putative subspecies of the Tehuelche scallop together with F. felipponei form a monophyletic clade, without differentiating at the specific level. Observed differences would be the result of phenotypic plasticity, probably caused by environmental factors. However, further analysis using genes with faster evolution rate are needed to corroborate it. Our phylogenetic analysis resolved to Aequipecten as polyphyletic. The Tehuelche scallop has a basal position within the Argopecten group and we recommend that it should be transferred to this genus. The relationship between the hypotheses about the origin of the Tehuelche scallop implicit in the literature and our results are discussed.
The assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive–compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity.
Eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses.
In comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus.
This study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.
Wind power, as an alternative to fossil fuels, is increasingly common, and is expanding worldwide. Wind farms cause mortality of flying animals through collision with moving rotor blades, and from electrocution on associated power lines. Avian mortality rates have been estimated from birds collected under turbines over varying time intervals. However, without adequate and frequent monitoring, dead birds may be removed by scavengers and thus cause an underestimation of fatalities. In this paper, we tested experimentally for possible errors arising in avian mortality caused by the removal of carcasses by scavengers. At two different wind farms and associated power lines in southern Spain, we placed pigeon and quail carcasses to determine their disappearance rate. All dead pigeons were radio-tagged to estimate distances taken by scavengers. We found significant differences in carcass disappearance rates of pigeons and quails, and between wind farms and power lines but not between habitats. All quails and 45% of pigeon carcasses had disappeared by the third and fourteenth day, respectively. Less than half (40%) of the carcasses were found < 100 m from where they were deposited. While scavenging losses may vary according to the location of the wind farm or power line, here we propose a method to estimate correctly the number of fatalities at any wind farm and power line. Using this method, we can improve our understanding of the real impact of wind structures on adjacent bird communities, and adopt appropriate measures to ensure their conservation.
The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD.
A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed.
Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r – 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results.
OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.
The same executive dysfunctions and alterations in neuroimaging tests (both functional and structural) have been found in obsessive-compulsive patients and their first-degree relatives. These neurobiological findings are considered to be intermediate markers of the disease. The aim of our study was to assess verbal and non-verbal memory in unaffected first-degree relatives, in order to determine whether these neuropsychological functions constitute a new cognitive marker for obsessive-compulsive disorder (OCD).
Recall and use of organizational strategies in verbal and non-verbal memory tasks were measured in 25 obsessive-compulsive patients, 25 unaffected first-degree relatives and 25 healthy volunteers.
First-degree relatives and healthy volunteers did not show differences on most measures of verbal memory. However, during the recall and processing of non-verbal information, deficits were found in first-degree relatives and patients compared with healthy volunteers.
The presence of the same deficits in the execution of non-verbal memory tasks in OCD patients and unaffected first-degree relatives suggests the influence of certain genetic and/or familial factors on this cognitive function in OCD and supports the hypothesis that deficits in non-verbal memory tasks could be considered as cognitive markers of the disorder.
An ATP diphosphohydrolase (EC 188.8.131.52) activity was identified in a Leishmania (Viannia) braziliensis promastigotes preparation (Lb). Ultrastructural cytochemical microscopy showed this protein on the parasite surface and also stained a possible similar protein at the mitochondrial membrane. Isolation of an active ATP diphosphohydrolase isoform from Lb was obtained by cross-immunoreactivity with polyclonal anti-potato apyrase antibodies. These antibodies, immobilized on Protein A-Sepharose, immunoprecipitated a polypeptide of approximately 48 kDa and, in lower amount, a polypeptide of approximately 43 kDa, and depleted 83% ATPase and 87% of the ADPase activities from detergent-homogenized Lb. Potato apyrase was recognized in Western blots by IgG antibody from American cutaneous leishmaniasis (ACL) patients, suggesting that the parasite and vegetable proteins share antigenic conserved epitopes. Significant IgG seropositivity in serum samples diluted 1:50 from ACL patients (n=20) for Lb (65%) and potato apyrase (90%) was observed by ELISA technique. Significant IgG antibody reactivity was also observed against synthetic peptides belonging to a conserved domain from L. braziliensis NDPase (80% seropositivity) and its potato apyrase counterpart (50% seropositivity), in accordance with the existence of shared antigenic epitopes and demonstrating that in leishmaniasis infection the domain r82-103 from L. braziliensis NDPase is a target for the human immune response.
Radical prostatectomy is at high risk for intraoperative and postoperative bleeding due to surgical trauma, release of urokinase and tissue type plasminogen activator. We conducted this prospective, observational multi-centre study to assess the degree of systemic fibrinolysis or hypercoagulation in the perioperative period. We studied serial changes in standard laboratory values and in thrombelastographic (TEG®; Haemoscope Corporation, Skokie, IL, USA) parameters including lysis at 30 and 60 min (LY-30, LY-60), alpha-angle (α) and maximum amplitude.
In all, 49 patients undergoing radical retropubic prostatectomy in five Italian University Hospitals were included. Blood samples were taken before surgery (T1), at the removal of the prostate (T2), 4 h after surgery (T3) and then 1 day after surgery (T4). Native blood samples were analysed using a thrombelastograph Haemoscope 5000 (Haemoscope Corporation).
We did not see any relevant activation of fibrinolysis during any stage. Intraoperatively, we showed even more activated blood coagulation with consumption of fibrinogen and a reduced TEG® percentage clot lysis. Only at the first postoperative sample point we saw a trend towards a more fibrinolytic state indicated by increasing partial thromboplastin time, LY-30 and LY-60 values, and a peak of the fibrin degradation product D-dimers. This is consistent with a normal reaction to the hypercoagulable state before and is unlikely to be due to an intraoperative tissue type plasminogen activator release. We found no evidence of an uncontrolled activation of fibrinolysis on the day after surgery. On the contrary, α-values which indicate the rate of clot formation and which increase during hypercoagulation showed the tendency to rise slightly compared with the preoperative value.
Neither standard coagulation parameters nor TEG® values showed any significant activation of fibrinolysis or of hypercoagulation in the preoperative period. Nevertheless, hypercoagulation seems to have a substantial clinical impact as it has been shown that cardiovascular complications and pulmonary embolism were the most common causes of death after retropubic prostatectomy.
This paper reports the development of an experiment (TEPEE/GReAT) to test the Equivalence Principle (EP) at a level of accuracy equal to 5 × 10-15, by means of a differential accelerometer free falling in a cryogenic vacuum capsule released from a stratospheric balloon. Such an accuracy requires resolving a very small signal out of the instrument's intrinsic noise and the noise associated with the instrument's motion. Imperfections in the construction of the detector introduce gravity gradient noise that it is possible to separate from the violation signal spinning the detector around an horizontal axis in order to have the EP violation signal and the gravity gradients one modulated at two different frequencies. Experimental results on prototype instruments showing high sensitivity and common mode rejection factor are shown.
The ESA BepiColombo mission, scheduled for launch in 2013 with a two–satellite configuration, will represent an important step in the exploration of the Solar System and will contribute to fundamental physics. Among the main scientific objectives of this mission are the Radio Science Experiments: gravimetry and rotation of Mercury and tests of Einstein's theory of general relativity, to be achieved by the MPO (Mercury Planetary Orbiter) satellite. The ISA (Italian Spring Accelerometer) instrument will give a fundamental contribution to these experiments by providing a continuous measurement of the non–gravitational accelerations acting on the MPO. After a description of the mission, the rôle of the ISA accelerometer will be discussed, together with the current activity for its development.
From the beginning of 2002, Troyes prefecture has initiated a study about the management of a nuclear crisis caused by an accident at the Nogent-sur-Seine nuclear power plant. Several working groups were created, notably the `Decontamination of soil and food chain' group.
The first results of this group, which involves the District Agricultural and Forestry Department, the Farming Chamber, the Institute for Radiological Protection and Nuclear Safety and the Veterinary Division are presented here.
The scenario that had been developed for the accident considers the release of 3 radionuclides (131I, 134Cs and 137Cs) in the environment. The scale of the crisis didn't require the evacuation and the sheltering of the population during the emergency phase.
The consequences on the local agricultural products (cereal, sugar beet, vine, milk, cow meat ...) have been assessed up to 50 km and different strategies of agricultural countermeasures have been studied regarding to the local constraints (soil types, surfaces and quantities concerned) and to the consequences of their implementation (waste types and quantities, costs). Then, decision-making diagrams summed up the technical results and allowed to deepen the global thought.
An epidemiological model was developed for rabies, linking the risk of disease in a secondary species (cats) to the temporal dynamics of disease in a wildlife reservoir (raccoons). Data were obtained from cats, raccoons, and skunks tested for rabies in the northeastern United States during 1992–2000. An epizootic algorithm defined a time-series of successive intervals of epizootic and inter-epizootic raccoon rabies. The odds of diagnosing a rabid cat during the first epizootic of raccoon rabies was 12 times greater than for the period prior to epizootic emergence. After the first raccoon epizootic, the risk for cat rabies remained elevated at levels six- to seven-fold above baseline. Increased monthly counts of rabid raccoons and skunks and decreasing human population density increased the probability of cat rabies in most models. Forecasting of the public health and veterinary burden of rabies and assessing the economics of control programmes, requires linking outcomes to dynamic, but predictable, changes in the temporal evolution of rabies epizootics.
Genetic variation was investigated in five subtidal locations from the north of San Matías Gulf (42°23′S) to the north of San Jorge Gulf (45°02′S). Fifteen loci were studied by means of vertical starch gel electrophoresis; ten loci were polymorphic. The percentages of polymorphic loci (P0·99 and P0·95 criteria) varied between 40% and 53·33% and between 33·33% and 46·67%, respectively. Expected mean heterozygosity per locus (He) ranged from 0·128 (Bajo Oliveira-El Sótano) to 0·160 (Puerto Madryn); this range is similar to those observed for other scallop species. All the loci were in Hardy–Weinberg equilibrium. The estimated genetic distances among populations were significantly lower than those reported for comparisons between populations of different pectinid species, suggesting that the five populations studied belong to the same species (Aequipecten tehuelchus). The absence of exclusive fixed alleles also supported that assumption. The results obtained suggest: (i) assignment of species or subspecies status to some morphological variants of the shells, like the ‘madrynensis’ form is not supported; (ii) the commercially exploited Tehuelche scallop from San Matías and San José Gulfs should be managed as distinct stocks.
An ATP diphosphohydrolase was identified in the plasma membranes isolated from promastigote forms of Leishmania amazonensis. Both ATP and ADP were hydrolysed at similar rates by the enzyme. Other nucleotides such as UTP, GTP and CTP were also degraded, revealing a broad substrate specificity. Adding ATP and ADP simultaneously, the amount of hydrolysis achieved was compatible with the presence of a single enzyme. ATPase activity was not affected by addition of vanadate, ouabain, thapsigargin, dicyclohexylcarbodiimide, oligomycin and bafilomycin A, thus excluding involvement of P-, F- and V-type ATPases. The effects of pH in the range 6·5–8·5 were examined using ATP or p-NPP as substrate. At pH 7·4, the phosphatase activity decreased, and did not show a significant contribution to ATP hydrolysis. In addition, the enzyme was not inhibited by levamisole and ammonium molybdate, excluding alkaline phosphatase and nucleotidase activities, respectively. Sodium azide (5–10 mM) caused inhibition of the ATP and ADP hydrolysis in a dose-dependent manner. Calcium was the best activating metal ion for both ATPase and ADPase activities. Ultrastructural cytochemical microscopy showed ATP diphosphohydrolase on the surface and flagellar pocket of the parasite. We have proposed that L. amazonensis ATP diphosphohydrolase may participate in the salvage pathway of nucleosides.
Time- and space-integrated emission spectra measurements have been performed in plasma produced by 308 nm wavelength XeCl laser radiation (IL = (4–10)·1012 W/cm2, τ = 10 ns) and by 248 nm wavelength KrF laser pulse train radiation (IL = 5·1015 W/cm2, τ = 7 ps, 16 pulses in train) on CF2 plane target. Theoretical modelling of Lyman series and He-like ion resonance series of fluorine and its fit of experimental data show considerable differences in the absorption of laser radiation in the two plasmas.
Compact solar flares are triggered by sudden energy release in magnetically confined plasma. This class of flares is well suited to be studied with numerical hydrodynamic models. In particular, one can compare the evolution of observed and synthetic X-ray spectra, computed under various assumptions for the mechanism of impulsive energy deposition, to constrain theoretical models and their parameter space. We discuss recent results on solar flares along this line, non thermal to models of energy depositions by relativistic electron beams. We shall also discuss possible applications of X-ray spectral synthesis to stellar flares.
The results obtained from this study of kaolinite dehydroxylation explain why different investigators have ascribed both first-order kinetics and a diffusion mechanism to this reaction. The fact that activation energies reported by these workers agree well, in spite of the different kinetics assumed when performing the calculations, is also explained. From a comparison of the results obtained by isothermal and non-isothermal methods it is concluded that, for reacted fractions, α, <0·6, kaolinite dehydroxylation is controlled by a diffusion process. A reaction mechanism explaining this behaviour is proposed.
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