Patients’ Preference and Experiences of Forced Medication and Seclusion

This study examined patients’ preferences for coercive methods and the extent to which patients’ choices were determined by previous experience, demographic, clinical and intervention-setting variables. Before discharge from closed psychiatric units, 161 adult patients completed a questionnaire. The association between patients’ preferences and the underlying variables was analyzed using logistic regression. We found that patients’ preferences were mainly defined by earlier experiences: patients without coercive experiences or who had had experienced seclusion and forced medication, favoured forced medication. Those who had been secluded preferred seclusion in future emergencies, but only if they approved its duration. This suggests that seclusion, if it does not last too long, does not have to be abandoned from psychiatric practices. In an emergency, however, most patients prefer to be medicated. Our findings show that patients’ preferences cannot guide the establishment of international uniform methods for managing violent behaviour. Therefore patients’ individual choices should be considered

Neuroprotective effects of consuming bovine colostrum after focal brain ischemia/reperfusion injury in rat model

To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1β, IL-6, and TNF-α levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model

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

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

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

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

Evidence for positive selection in the gene fruitless in Anastrepha fruit flies

<p>Abstract</p> <p>Background</p> <p>Many genes involved in the sex determining cascade have indicated signals of positive selection and rapid evolution across different species. Even though <it>fruitless </it>is an important gene involved mostly in several aspects of male courtship behavior, the few studies so far have explained its high rates of evolution by relaxed selective constraints. This would indicate that a large portion of this gene has evolved neutrally, contrary to what has been observed for other genes in the sex cascade.</p> <p>Results</p> <p>Here we test whether the <it>fruitless </it>gene has evolved neutrally or under positive selection in species of <it>Anastrepha </it>(Tephritidae: Diptera) using two different approaches, a long-term evolutionary analysis and a populational genetic data analysis. The first analysis was performed by using sequences of three species of <it>Anastrepha </it>and sequences from several species of <it>Drosophila </it>using the ratio of nonsynonymous to synonymous rates of evolution in PAML, which revealed that the <it>fru </it>region here studied has evolved by positive selection. Using Bayes Empirical Bayes we estimated that 16 sites located in the connecting region of the <it>fruitless </it>gene were evolving under positive selection. We also investigated for signs of this positive selection using populational data from 50 specimens from three species of <it>Anastrepha </it>from different localities in Brazil. The use of standard tests of selection and a new test that compares patterns of differential survival between synonymous and nonsynonymous in evolutionary time also provide evidence of positive selection across species and of a selective sweep for one of the species investigated.</p> <p>Conclusions</p> <p>Our data indicate that the high diversification of <it>fru </it>connecting region in <it>Anastrepha </it>flies is due at least in part to positive selection, not merely as a consequence of relaxed selective constraint. These conclusions are based not only on the comparison of distantly related taxa that show long-term divergence time, but also on recently diverged lineages and suggest that episodes of adaptive evolution in <it>fru </it>may be related to sexual selection and/or conflict related to its involvement in male courtship behavior.</p

Younger age as a prognostic indicator in breast cancer: A cohort study

<p>Abstract</p> <p>Background</p> <p>The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort.</p> <p>Methods</p> <p>Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade.</p> <p>Results</p> <p>The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher <it>HER2 </it>over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and <it>HER2 </it>(p = 0.002) status and treatment received were independent predictors of OS</p> <p>Conclusion</p> <p>Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population.</p