Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non-melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women.
Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes.
In a previous clinical controlled trial (Lopes et al., 2014), narrative therapy (NT) showed promising results in ameliorating depressive symptoms with comparable outcomes to cognitive-behavioral therapy (CBT) when patients completed treatment. This paper aims to assess depressive symptoms and interpersonal problems in this clinical sample at follow-up.
To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility.
Sixteen triterpenoids (1-16), previously isolated from the aerial parts of the African medicinal plant Momordica balsamina or obtained by derivatization, were evaluated for their activity against liver stages of Plasmodium berghei, measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luccon. Toxicity of compounds (1-16) was assessed on the same cell line through the fluorescence measurement of cell confluency. The highest activity was displayed by a derivative bearing two acetyl residues, karavoate B (7), which led to a dose-dependent decrease in the P. berghei infection rate, exhibiting a very significant activity at the lowest concentration employed (1 ?M) and no toxicity towards the Huh-7 cells. It is noteworthy that, in previous studies, this compound was found to be a strong inhibitor of blood-stages of Plasmodium falciparum, thus displaying a dual-stage antimalarial activity.
The use of mosses as biomonitors operates as an indicator of their concentration in the environment, becoming a methodology which provides a significant interpretation in terms of environmental quality. The different types of pollution are variables that can not be measured directly in the environment - latent variables. Therefore, we propose the use of factor analysis to estimate these variables in order to use them for spatial modelling. On the contrary, the main aim of the commonly used principal components analysis method is to explain the variability of observed variables and it does not permit to explicitly identify the different types of environmental contamination. We propose to model the concentration of each heavy metal as a linear combination of its main sources of pollution, similar to the case of multiple regression where these latent variables are identified as covariates, though these not being observed. Moreover, through the use of geostatistical methodologies, we suggest to obtain maps of predicted values for the different sources of pollution. With this, we summarize the information acquired from the concentration measurements of the various heavy metals, and make possible to easily determine the locations that suffer from a particular source of pollution.
Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study.
This study intends to provide new insights into the incidence and care of mucositis by the epidemiological characterization of patients with hematological malignancy treated at our institution. It also aims to understand the effectiveness of several treatments used.
Abstract Objective: Ambivalence can be understood as a cyclical movement between an emerging narrative novelty-an Innovative Moment (IM)-and a return to a problematically dominant self-narrative. The return implies that the IM, with its potential for change is devalued right after its emergence. Our goal is to test the hypothesis that the probability of the client expressing such form of ambivalence decreases across treatment in good-outcome cases but not in poor-outcome cases.
Abstract Literature regarding the effects of sildenafil citrate on sperm function remains controversial. In the present study, we specifically wanted to determine if mitochondrial dysfunction, namely membrane potential, reactive oxygen species production, and changes in energy content, are involved in in vitro sildenafil-induced alterations of human sperm function. Sperm samples of healthy men were incubated in the presence of 0.03, 0.3, and 3??M sildenafil citrate in a phosphate buffered saline (PBS)-based medium for 2, 3, 12, and 24 hours. Sperm motility and viability were evaluated and mitochondrial function, i.e., mitochondrial membrane potential and mitochondrial superoxide production were assessed using flow-cytometry. Additionally, adenosine triphosphate (ATP) levels were determined by high performance liquid chromatography (HPLC) analysis. Results show a decrease in sperm motility correlated with the level of mitochondria-generated superoxide, without a visible effect on mitochondrial membrane potential or viability upon exposure to sildenafil. The effect on both motility and superoxide production was higher for the intermediate concentration of sildenafil (0.3?µM) indicating that the in vitro effects of sildenafil on human sperm do not vary linearly with drug concentration. Adenosine triphosphate levels also decreased following sildenafil exposure, but this decrease was only detected after a decrease in motility was already evident. These results suggest that along with the level of ATP and mitochondrial function other factors are involved in the early sildenafil-mediated decline in sperm motility. However, the further decrease in ATP levels and increase in mitochondria-generated reactive oxygen species after 24 hours of exposure might further contribute towards declining sperm motility.
Abstract Objectives: We understand ambivalence as a cyclical movement between two opposing parts of the self. The emergence of a novel part produces an innovative moment, challenging the current maladaptive self-narrative. However, the novel part is subsequently attenuated by a return to the maladaptive self-narrative. This study focused on the analysis of the therapeutic collaboration in episodes in which a relatively poor-outcome client in narrative therapy expressed ambivalence. Method: For our analysis we used the Therapeutic Collaboration Coding System, developed to assess whether and how the therapeutic dyad is working within the therapeutic zone of proximal development (TZPD). Results: Results showed that when the therapist challenged the client after the emergence of ambivalence, the client tended to invalidate (reject or ignore) the therapists intervention. Conclusions: This suggests that in such ambivalence episodes the therapist did not match the clients developmental level, and by working outside the TZPD unintentionally contributed to the maintaining the clients ambivalence.
Abstract The Assimilation of Problematic Experiences Scale (APES) and the Innovative Moments Coding System were applied to transcripts of a successful case of linguistic therapy of evaluation independently by different research groups. Assimilation theory and research suggest that higher APES scores reflect therapeutic gains, with a level of approximately 4.0 separating good from poor outcome cases. The innovative moments (IMs) model suggests that IMs classified as reconceptualization and performing change occur mainly in good outcome cases, whereas action, reflection and protest occur in both good and poor outcome cases. Passages coded as reconceptualization and performing change were rare in this case, but 100% of them were rated at or above APES 4. By contrast, 63% passages coded as action, reflection or protest were rated below APES 4 (Chi-square = 28.62, p < .001). Implications for research are discussed.
To evaluate the reproducibility of estimation of cerebral blood flow (CBF), bolus arrival time (BAT), and arterial blood volume (aBV) from arterial spin labeling (ASL) data acquired at multiple postlabeling delays (PLDs).
Abstract Several studies have proposed that self-narrative transformation occurs through the elaboration of "Innovative Moments" (IMs), which are alternative experiences to the problematic self-narrative. This study aimed to analyze the emergence of IMs among 6 complicated grief women undergoing grief therapy according to the meaning reconstruction approach and to examine associations of IMs to the severity of grief symptomatology, assessed by the "Inventory of Complicated Grief." Eighty-three sessions were analyzed using the "Innovative Moments Coding System" (IMCS). A generalized linear model analysis (GLM) showed a significant association between the emergence of IMs and the interaction between time and symptomatic improvement, indicating a higher rate of IM production over time in cases with better clinical outcomes. These results reinforce IMs relevance in studying narrative change among cases with distinct clinical progressions.
Having identified a novel human DNA topoisomerase II? (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors.
This study compared two methods of detecting ruptures in therapy sessions, a procedure based on a self-report measure, the Working Alliance Inventory (WAI), and an observational Rupture Resolution Rating System (3RS). We anticipated that the 3RS would detect more ruptures than the WAI. We examined the longitudinal data of 38 patient-therapist dyads in a cognitive-behavioral therapy condition. The sample included cases that did not complete treatment (dropped cases) as well as good-outcome and poor-outcome cases. At the end of each session, patients completed the WAI self-report questionnaire. Six judges were trained to observe and detect the occurrence of ruptures, and then rated 201 videotaped sessions. Longitudinal statistical models were applied to the data retrieved from the WAI questionnaires completed by patients. We found discrepancies in the ability of the two methods to detect rupture events with the observational 3RS detecting more ruptures than the WAI. Thus, the use of observational systems for the detection of alliance ruptures is crucial for effectively assessing the quality of the therapeutic alliance over the course of treatment. Furthermore, observational systems proven to detect ruptures can be used to improve clinical practice and training of new clinicians. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Pulsed arterial spin labeling (PASL) techniques potentially allow the absolute, noninvasive quantification of brain perfusion using MRI. This can be achieved by fitting a kinetic model to the data acquired at a number of sampling times. However, the intrinsically low signal-to-noise ratio of PASL measurements usually requires substantial signal averaging, which may result in undesirably long scanning times. A judicious choice of the sampling points is, therefore, crucial in order to minimize scanning time, while optimizing estimation accuracy. On the other hand, a priori information regarding the model parameters may improve estimation performance. Here, we propose a Bayesian framework to determine an optimal sampling strategy and estimation method for the measurement of brain perfusion and arterial transit time (ATT). A Bayesian Fisher information criterion is used to determine the optimal sampling points and a MAP criterion is employed for the estimation of the model parameters, both taking into account the uncertainty in the model parameters as well as the amount of noise in the data. By Monte Carlo simulations, we show that using optimal compared to uniform sampling strategies, as well as the Bayesian estimator relative to a standard least squares approach, improves the accuracy of perfusion and ATT measurements. Moreover, we also demonstrate the applicability of the proposed approach to real data, with the advantage of reduced intersubject variability relative to conventional sampling and estimation approaches.
The new clinically available arterial spin labeling (ASL) perfusion imaging sequences present some advantages relatively to the commonly used blood oxygen level-dependent (BOLD) method for functional brain studies using magnetic resonance imaging (MRI). In particular, regional cerebral blood flow (CBF) changes are thought to be more directly related with neuronal activation. In this study, we aimed to investigate the accuracy of the functional localization of the hand motor area obtained by simultaneous CBF and BOLD contrasts provided by ASL functional MRI (fMRI) and compare it with a standard BOLD fMRI protocol. For this purpose, we measured the distance between the center of gravity of the activation clusters obtained with each contrast (CBF, BOLD(ASL), and Standard BOLD) and 11 positions defined on a well-established anatomical landmark of the hand motor area (the omega in the axial plane of the precentral gyrus). We found that CBF measurements were significantly closer to the anatomical landmark than the ones obtained using either simultaneous BOLD(ASL) or standard BOLD contrasts. Moreover, we also observed reduced intersubject variability of the functional localization, as well as percent signal change, for CBF relative to both BOLD contrast measurements. In conclusion, our results add further evidence in support to the notion that CBF provides a more accurate localization of motor activation than BOLD contrast, indicating that ASL may be an appropriate technique for clinical fMRI studies.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Garlic has a wide range of actions, including antibacterial, antiviral, antifungal, antiprotozoal and anthelmintic actions. This antiparasitic activity has been attributed to allicin, which is the main constituent of garlic. The present study aimed to investigate the in vitro activity of allicin on the tegument of adult Schistosoma mansoni worms using scanning electron microscopy.
Innovative moments (IMs) are exceptions to a clients problematic self-narrative in the therapeutic dialogue. The innovative moments coding system is a tool which tracks five different types of IMs-action, reflection, protest, reconceptualization and performing change. An in-depth qualitative analysis of six therapeutic cases of emotion-focused therapy (EFT) investigated the role of two of the most common IMs-reflection and protest-in both good and poor outcome cases. Through this analysis two subtypes (I and II) of reflection and protest IMs were identified, revealing different evolution patterns. Subtype II of both reflection and protest IMs is significantly higher in the good outcome group, while subtype I of both IMs types does not present statistically significant differences between groups. The evolution from subtype I to subtype II across the therapeutic process seems to reflect a relevant developmental progression in the change process.
The aim of this study was to advance understanding of how clients construct their own process of change in effective therapy sessions. Toward this end, the authors applied a narrative methodological tool for the study of the change process in emotion-focused therapy (EFT), replicating a previous study done with narrative therapy (NT). The Innovative Moments Coding System (IMCS) was applied to three good-outcome and three poor-outcome cases in EFT for depression to track the innovative moments (IMs), or exceptions to the problematic self-narrative, in the therapeutic conversation. IMCS allows tracking of five types of IMs events: action, reflection, protest, reconceptualization, and performing change. The analysis revealed significant differences between the good-outcome and poor-outcome groups regarding reconceptualization and performing change IMs, replicating the findings from a previous study. Reconceptualization and performing change IMs seem to be vital in the change process.
Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.
There have been few attempts to estimate progression of kidney disease in people with diabetes in a single large population with predictive modelling. The aim of this study was to investigate the rate of progression of chronic kidney disease in people with diabetes according to their estimated glomerular filtration rate (eGFR) and presence of albuminuria.
A prospective study to assess fungaemia was conducted for 12 months at a Portuguese University Hospital. A total of 35 Candida albicans isolates obtained from 12 patients with fungaemia were compared by a multiplex PCR system using four microsatellite loci. Blood isolates were evaluated against concomitant isolates from urine, lower respiratory secretions and central venous catheters, as well as with successive isolates recovered from recurrent episodes of fungaemia. The data analyzed included the department of admission, underlying diseases and antifungal therapy. The susceptibility phenotypes of all isolates to amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin were determined according to the CLSI M27-A3 protocol. We observed a high degree of similarity between successive blood isolates and between blood and concomitant isolates from other sites of the same patient. This is suggestive of the recurrence of fungaemia and was due to the same strain, possibly as a result of the failure of antifungal therapy. The genetic similarity observed between some strains isolated from different patients suggested the likelihood that they were hospital acquired. Distinct patients were infected by the same strain at different time periods, and an increase in antifungal resistance was observed over time for some of these strains. Hospital-acquired exogenous nosocomial infections can be associated with higher risks of antifungal resistance and need to be closely monitored. Particular attention should also be given to endogenous non-blood Candida isolates which can be critical in high risk patients, as they often can become invasive in immunodeficient individuals.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winners curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 x 10(-5)) and between SND1 and strict autism (rs1881084, P=7.76 x 10(-5)) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1.
Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs.
Autism is a common, severe and highly heritable neurodevelopmental disorder. The International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen for linkage in affected sib-pair families identified a chromosome 7q susceptibility locus (AUTS1), that has subsequently shown evidence of increased sharing in several independent multiplex samples and in two meta-analyses. Taking into account the location of the MET gene under this linkage peak, and the fact that it has recently been reported to be associated with autism, the gene was further analyzed as a promising autism candidate. The gene encodes a transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor (HGF/SF). MET is best known as an oncogene, but its signalling also participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum (all of which have been observed earlier as being disregulated in individuals with autism). Here we present a family-based association analysis covering the entire MET locus. Significant results were obtained in both single locus and haplotype approaches with a single nucleotide polymorphism in intron 1 (rs38845, P<0.004) and with one intronic haplotype (AAGTG, P<0.009) in 325 multiplex IMGSAC families and 10 IMGSAC trios. Although these results failed to replicate in an independent sample of 82 Italian trios, the association itself was confirmed by a case-control analysis performed using the Italian cohort (P<0.02). The previously reported positive association of rs1858830 failed to replicate in this study. Overall, our findings provide further evidence that MET may play a role in autism susceptibility.
SHANK3 is located on chromosome 22q13.3 and encodes a scaffold protein that is found in excitatory synapses opposite the pre-synaptic active zone. SHANK3 is a binding partner of neuroligins, some of whose genes contain mutations in a small subset of individuals with autism. In individuals with autism spectrum disorders (ASDs), several studies have found SHANK3 to be disrupted by deletions ranging from hundreds of kilobases to megabases, suggesting that 1% of individuals with ASDs may have these chromosomal aberrations. To further analyse the involvement of SHANK3 in ASD, we screened the International Molecular Genetic Study of Autism Consortium (IMGSAC) multiplex family sample, 330 families, for SNP association and copy number variants (CNVs) in SHANK3. A collection of 76 IMGSAC Italian probands from singleton families was also examined by multiplex ligation-dependent probe amplification for CNVs. No CNVs or SNP associations were found within the sample set, although sequencing of the gene was not performed. Our data suggest that SHANK3 deletions may be limited to lower functioning individuals with autism.
The objective was to analyze the risk factors associated with neonatal mortality in the city of Serra, ES. We studied non-concurrent cohort, using the technique of Linkage that relate the 32.275 live births with 273 neonatal deaths occurred in the period from 2001 to 2005, using data from SINASC and SIM. After adjustments in the logistic regression, factors associated with mortality were: uneducated mothers, maternal age <15 years and > 35 years old, born in a public hospital, no prenatal consultation, birth weight.
Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40?g/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40?g/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R(pred)(2) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40?g/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40?g/ml concentrations, respectively. For the same concentrations, the obtained R(pred)(2) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability.
FOXE1 is a transcription factor required for thyroid differentiation and function. FOXE1 locus polymorphisms (chromosome 9q22.33) were recently associated with increased sporadic thyroid cancer risk. In this study, we aimed to investigate the association of FOXE1 variants with nonmedullary thyroid cancer (NMTC), in both sporadic and familial (FNMTC) cases from the Portuguese population.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Acute cerebellitis is an inflammatory disorder usually involving both sides of the cerebellum and presenting with localized signs such as ataxia. Hemicerebellitis is extremely rare in children and may clinically and radiologically resemble a tumor. There are very few reports of hemicerebellitis needing decompressive surgery. We report a case of hemicerebellitis in a 15 year old child presenting with severe headache but no cerebellar symptoms whose brain CT revealed an ill-defined mass compressing the fourth ventricle (pseudotumoral). MRI of the posterior fossa revealed a swollen left cerebellar hemisphere, supra-tentorial hydrocephalus and tonsil herniation, without any cerebral or brain stem lesions. Due to worsening symptoms she required a decompressive craniectomy, and the biopsy revealed an inflammatory process, possibly viral. At follow-up she was asymptomatic and the MRI revealed only slight cerebellar atrophy. This case had an atypical clinical presentation and illustrates that though a self-limited evolution is expected, surgical intervention may be needed in acute cerebellitis.
According to the narrative approach, change in self-narratives is an important part of successful psychotherapy. In this view, several authors have highlighted the usefulness of narrating new experiences (like actions, thoughts, and stories) during therapy in contrast with maladaptive client self-narratives. These new experiences are termed here innovative moments (IMs), and different types can be specified: action, reflection, protest, reconceptualization, and performing change. With the aim of understanding which therapist skills are related to client IMs, we analyzed the association between exploration, insight, and action skills and IMs in two initial, two middle, and two final sessions of three good outcome (GO) and three poor outcome (PO) cases of emotion-focused therapy (EFT) for depression. IMs occurred more often in GO than PO cases. Furthermore, in GO more than PO cases, exploration and insight skills more often preceded action, reflection, and protest IMs in the initial and middle phases of EFT, but more often preceded reconceptualization and performing change IMs in the final phase. Action skills were more often associated with action, reflection, and protest IMs across all phases, especially in the final phase, of GO EFT.
Previous studies have used the Innovative Moments Coding System (IMCS) to describe the process of change in Narrative Therapy (NT) and in Emotion-Focused Therapy (EFT). This study aims to extend this research program to a sample of Client-Centered Therapy (CCT). The IMCS was applied to six cases of CCT for depression to track the Innovative Moments (IMs) which are exceptions to the problematic self-narrative in therapeutic conversation. Results suggest that IMCS can be applied to CCT, allowing the tracking of IMs emergence. The analysis based on a generalized linear model revealed that the overall amount of IMs is significantly associated with symptom improvement, which is congruent with former studies done with the IMCS.
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