Multivariate patterns of gray matter volume in thalamic nuclei are associated with positive schizotypy in healthy individuals.

BACKGROUND: Previous models suggest biological and behavioral continua among healthy individuals (HC), at-risk condition, and full-blown schizophrenia (SCZ). Part of these continua may be captured by schizotypy, which shares subclinical traits and biological phenotypes with SCZ, including thalamic structural abnormalities. In this regard, previous findings have suggested that multivariate volumetric patterns of individual thalamic nuclei discriminate HC from SCZ. These results were obtained using machine learning, which allows case-control classification at the single-subject level. However, machine learning accuracy is usually unsatisfactory possibly due to phenotype heterogeneity. Indeed, a source of misclassification may be related to thalamic structural characteristics of those HC with high schizotypy, which may resemble structural abnormalities of SCZ. We hypothesized that thalamic structural heterogeneity is related to schizotypy, such that high schizotypal burden would implicate misclassification of those HC whose thalamic patterns resemble SCZ abnormalities. METHODS: Following a previous report, we used Random Forests to predict diagnosis in a case-control sample (SCZ = 131, HC = 255) based on thalamic nuclei gray matter volumes estimates. Then, we investigated whether the likelihood to be classified as SCZ (π-SCZ) was associated with schizotypy in 174 HC, evaluated with the Schizotypal Personality Questionnaire. RESULTS: Prediction accuracy was 72.5%. Misclassified HC had higher positive schizotypy scores, which were correlated with π-SCZ. Results were specific to thalamic rather than whole-brain structural features. CONCLUSIONS: These findings strengthen the relevance of thalamic structural abnormalities to SCZ and suggest that multivariate thalamic patterns are correlates of the continuum between schizotypy in HC and the full-blown disease.

Effects of topical polydeoxyribonucleotide on radiation-induced oral mucositis.

INTRODUCTION: Oral mucositis, the most common adverse effect of radiotherapy (RT) and/or chemotherapy is observed in almost 97% of patients with head and neck cancer. Although several agents like corticosteroids, lidocaine and vitamins are available for its prevention or management, results are often disappointing. Here we report on the effects of a topically applied, highly purified natural deoxyribonucleic acid from sturgeon gonads on three cases of moderate to severe oral mucositis in patients with head and neck cancer. CASE DESCRIPTION: Three patients who had undergone RT and/or chemotherapy received an oral spray containing sodium salt-based natural deoxyribonucleic acid (PDRN) for Grade 3 oral mucositis. Treatment continued for one month after the end of RT. No patient reported any allergic reactions. RT and chemotherapy were not interrupted and opioid therapy was not given to any patient. Pain was relieved about 2-3 days after starting treatment and oral mucositis was reduced to G2 within one week. CONCLUSIONS: Outcomes in all 3 cases showed topical use of the sodium salt-based PDRN derived from sturgeon gonads was acceptable and safe when used topically for therapeutic and regenerative purposes.Present results are encouraging and suggest a more in-depth study is warranted on its use in a larger patient cohort with RT-induced oral mucositis.

The complex relationship between self-reported 'personal recovery' and clinical recovery in schizophrenia.

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view. By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles.

Grey matter volume patterns in thalamic nuclei are associated with familial risk for schizophrenia.

Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder. We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients. Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder.

Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

OBJECTIVE: Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. METHODS: Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. RESULTS: Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. CONCLUSIONS: These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

Association of familial risk for schizophrenia with thalamic and medial prefrontal functional connectivity during attentional control.

Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder.

BDNF rs6265 methylation and genotype interact on risk for schizophrenia.

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.

[Validation of Body Image Relationship Scale for women with breast cancer]. / Validação do Body Image Relationship Scale para mulheres com câncer de mama.

PURPOSE: To validate the instrument Body Image Relationship Scale (BIRS) for Brazilian women with breast cancer. METHODS: The instrument was administered by trained interviewers to 139 women who used the Brazilian Unified Health System (SUS). All of them had been submitted to cancer treatments between 2006 and 2010. The instrument was validated considering internal consistency and reliability. In order to compare the techniques, the same factorial analysis as used in the original paper was carried out. RESULTS: The Spearman-Brown correlation value was 0.8, indicating high internal reliability. The Cronbach's alpha found was 0.9, indicating a high level of internal consistency. Factorial analysis showed that four items had low factorial load and no discriminatory power, and another five items were relocated to other factors. When the instrument was applied, it showed variability to that of the original instrument. CONCLUSION: The Brazilian version of the Body Image Relationship Scale (BIRS), named Escala de Relacionamento e Imagem Corporal (ERIC), showed evidence of adequate reliability and internal consistency, making this instrument suitable to be recommended for application to Brazilian women with breast cancer, despite some limitations.

Validação do Body Image Relationship Scale para mulheres com câncer de mama / Validation of Body Image Relationship Scale for women with breast cancer

ResumoOBJETIVOValidar o instrumento Body Image Relationship Scale (BIRS) em mulheres brasileiras acometidas pelo câncer de mamaMÉTODOSO instrumento foi aplicado por entrevistadoras treinadas em 139 usuárias do Sistema Único de Saúde que foram submetidas aos tratamentos do câncer entre 2006 e 2010. O instrumento foi aferido considerando-se a consistência interna e a confiabilidade. Para efeito de comparação as técnicas de análise fatorial utilizadas no artigo original foram aplicadasRESULTADOSO valor de correlação Spearman-Brown foi 0,8, o que indica alto nível de confiabilidade, e o alfa de Cronbach encontrado foi 0,9, indicando alto nível de consistência interna. A análise fatorial mostrou que quatro questões não tinham poder discriminatório e carga fatorial baixa e outras cinco foram realocadas em outros domínios. Dessa forma, foi aplicada e mostrou variabilidade semelhante ao instrumento originalCONCLUSÃOA versão brasileira do BIRS, renomeada como Escala de Relacionamento e Imagem Corporal (ERIC), apresentou evidências de adequada confiabilidade e consistência interna, o que torna esse instrumento recomendável para aplicação em mulheres brasileiras com câncer de mama, apesar de alguns poucos limites.

AbstractPURPOSETo validate the instrument Body Image Relationship Scale (BIRS) for Brazilian women with breast cancerMETHODSThe instrument was administered by trained interviewers to 139 women who used the Brazilian Unified Health System (SUS). All of them had been submitted to cancer treatments between 2006 and 2010. The instrument was validated considering internal consistency and reliability. In order to compare the techniques, the same factorial analysis as used in the original paper was carried outRESULTSThe Spearman-Brown correlation value was 0.8, indicating high internal reliability. The Cronbach's alpha found was 0.9, indicating a high level of internal consistency. Factorial analysis showed that four items had low factorial load and no discriminatory power, and another five items were relocated to other factors. When the instrument was applied, it showed variability to that of the original instrumentCONCLUSIONThe Brazilian version of the Body Image Relationship Scale (BIRS), namedEscala de Relacionamento e Imagem Corporal (ERIC), showed evidence of adequate reliability and internal consistency, making this instrument suitable to be recommended for application to Brazilian women with breast cancer, despite some limitations.

Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control.

Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load.

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.

"Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine.

RATIONALE: Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. OBJECTIVE: We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). METHODS: Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. RESULTS: On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. CONCLUSIONS: These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Association of GSK-3ß genetic variation with GSK-3ß expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia.

OBJECTIVE Glycogen synthase kinase 3ß (GSK-3ß) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3ß gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3ß functional variation with 1) GSK-3ß mRNA expression from postmortem prefrontal cortex, 2) GSK-3ß and ß-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3ß (rs12630592) was associated with reduced GSK-3ß mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3ß protein expression and kinase activity, as well as with downstream effects on ß-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3ß variation is implicated in multiple phenotypes relevant to schizophrenia.

[Reproductive and sexual history of women treated of breast cancer]. / História reprodutiva e sexual de mulheres tratadas de câncer de mama.

PURPOSE: To understand the reproductive and sexual life of women treated for breast cancer. METHODS: A total of 139 women with a diagnosis made at least 6 months ago were interviewed after being randomly selected in a rehabilitation service. The interviews were carried out between 2006 and 2010. The inclusion criteria were: to have used a rehabilitation service between 2006 and 2010, to be a Unified Health System user, to have been a patient at a regional hospital and to be resident in the area of DRS XIII-Ribeirão Preto, state of São Paulo. The interviewees were visited at home where a face to face questionnaire regarding sociodemographic features and questions about the disease and reproductive and sexual life was administered. For the last one, the Female Sexual Function Index instrument was used. Data were analyzed statistically by the χ² test, Fisher exact test, Student's t test, multivariate analysis by logistic regression, factorial analysis and the Cronbach's alpha. RESULTS: Most patients had between 2 to 3 children and 80% used some contraceptive. About half of them had had sexual intercourse in the last month, 45.3% had interrupted sexual intercourse during treatment and 25.9% did not. There were reports of decreasing sexual activity, although half of the interviewees had re-started sexual life during the first six months after treatment. About half presented sexual dissatisfaction. An active sexual life is associated with being younger than 40 years of age and to have a partner. No association was found between active sexual life and diagnosis and types of treatment. CONCLUSION: Sexual activity of women treated for breast cancer is not associated with the treatments, but with age and with the opportunity of having sex.

História reprodutiva e sexual de mulheres tratadas de câncer de mama / Reproductive and sexual history of women treated of breast cancer

OBJETIVO: Compreender a vida sexual e reprodutiva de mulheres tratadas de câncer de mama. MÉTODOS: Foram entrevistadas 139 mulheres com diagnóstico há pelo menos seis meses, selecionadas aleatoriamente em um serviço de reabilitação. As entrevistas foram feitas entre 2006 e 2010. Todas eram usuárias do SUS, pacientes de um hospital regional e moradoras da região DRS XIII-Ribeirão Preto, Estado de São Paulo. As entrevistadas foram visitadas em seu domicílio onde foi aplicado um questionário face a face que abordava questões relativas às características sociodemográficas, da doença e da vida reprodutiva e sexual, para esta última aplicou-se o instrumento Índice de Função Sexual Feminina (IFSF). A análise estatística incluiu o teste do χ², o teste exato de Fisher e o teste t de Student, análise multivariada por regressão logística e análise fatorial e alfa de Cronbach. RESULTADOS: A maioria teve entre 2 e 3 filhos e 80% utilizaram algum método anticoncepcional. Cerca de metade das mulheres tiveram relação sexual no último mês, 45,3% interromperam as relações sexuais durante o tratamento e 25,9% não interromperam. Houve relato de diminuição da frequência sexual, embora metade das entrevistadas tenha retomado a vida sexual nos primeiros seis meses após o tratamento. Pouco mais de metade apresentou insatisfação sexual. Encontrou-se vida sexual ativa associada à idade menor que 40 anos e a ter parceiro. Não foi encontrada associação entre vida sexual ativa e ao diagnóstico e tipos de tratamento. CONCLUSÃO: A atividade sexual de mulheres tratadas para câncer de mama não está associada aos tratamentos, mas à idade e à oportunidade de ter sexo.

PURPOSE: To understand the reproductive and sexual life of women treated for breast cancer. METHODS: A total of 139 women with a diagnosis made at least 6 months ago were interviewed after being randomly selected in a rehabilitation service. The interviews were carried out between 2006 and 2010. The inclusion criteria were: to have used a rehabilitation service between 2006 and 2010, to be a Unified Health System user, to have been a patient at a regional hospital and to be resident in the area of DRS XIII-Ribeirão Preto, state of São Paulo. The interviewees were visited at home where a face to face questionnaire regarding sociodemographic features and questions about the disease and reproductive and sexual life was administered. For the last one, the Female Sexual Function Index instrument was used. Data were analyzed statistically by the χ² test, Fisher exact test, Student's t test, multivariate analysis by logistic regression, factorial analysis and the Cronbach's alpha. RESULTS: Most patients had between 2 to 3 children and 80% used some contraceptive. About half of them had had sexual intercourse in the last month, 45.3% had interrupted sexual intercourse during treatment and 25.9% did not. There were reports of decreasing sexual activity, although half of the interviewees had re-started sexual life during the first six months after treatment. About half presented sexual dissatisfaction. An active sexual life is associated with being younger than 40 years of age and to have a partner. No association was found between active sexual life and diagnosis and types of treatment. CONCLUSION: Sexual activity of women treated for breast cancer is not associated with the treatments, but with age and with the opportunity of having sex.

DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver.

BACKGROUND: An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery. We decided to test this finding in a randomized, double-blind trial. METHODS: Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were randomly assigned to have the surgical incision dressed with Aquacel Ag Hydrofiber dressing or a common dressing. To blind the patient and the nursing and medical staff to the nature of the dressing used, scrub nurses covered Aquacel Ag Hydrofiber with a common wound dressing in the experimental arm, whereas a double common dressing was applied to patients of control group. The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery. RESULTS: A total of 112 patients (58 in the experimental arm and 54 in the control group) qualified for primary end-point analysis. The characteristics of the patient population and their surgical procedures were similar. The overall rate of surgical-site infection was lower in the experimental group (11.1% center 1, 17.5% center 2; overall 15.5%) than in controls (14.3% center 1, 24.2% center 2, overall 20.4%), but the observed difference was not statistically significant (P = 0.451), even with respect to surgical-site infection grade 1 (superficial) versus grades 2 and 3, or grade 1 and 2 versus grade 3. CONCLUSIONS: This randomized trial did not confirm a statistically significant superiority of Aquacel Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00981110.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

OBJECTIVE: Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. METHODS: Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. RESULTS: Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. INTERPRETATION: The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease.