Neural correlates of emotion processing comparing antidepressants and exogenous oxytocin in postpartum depressed women: An exploratory study

Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women’s neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample

The Impact of Gain- and Loss-Framed Messages on Young Adults' Sexual Decision Making: An Experimental Study

Messages that frame a target behavior in terms of its benefits (gain frame) or costs (loss frame) have been widely and successfully used for health promotion and risk reduction. However, the impact of framed messages on decisions to have sex and sexual risk, as well as moderators of these effects, has remained largely unexplored. We used a computerized laboratory task to test the effects of framed messages about condom use on young adults' sexual decision making. Participants (N = 127) listened to both gain- and loss-framed messages and rated their intentions to have sex with partners who posed a high and low risk for sexually transmitted infections (STIs). The effects of message frame, partner risk, participant gender, ability to adopt the messages, and message presentation order on intentions to have sex were examined. Intentions to have sex with high-risk partners significantly decreased after the loss-framed message, but not after the gain-framed message, and intentions to have sex increased for participants who received the gain-framed message first. Yet, participants found it easier to adopt the gain-framed message. Results suggest that loss-framed messages may be particularly effective in reducing intentions to have sex with partners who might pose a higher risk for STIs, and that message presentation order may alter the relative effectiveness of gain- and loss-framed messages on sexual decision making. Future studies should examine the precise conditions under which gain- and loss-framed messages can promote healthy sexual behaviors and reduce sexual risk behaviors

Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and post-menopausal women. We used baseline data from 898 peri- and post-menopausal women recruited from multiple communities, ages 42–62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and post-menopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and post-menopausal women

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance