BackgroundAlthough various physical risk factors for delirium have been identified, the effect of psychological aspects is currently unknown. This study aimed to examine psychological risk factors for postoperative delirium and to identify hidden subgroups of delirium in clinical and psychological feature space.MethodsAmong 200 patients with hip fracture, 78 elderly patients were prospectively evaluated for clinical and psychological assessments before surgery. As delirium was assessed from the next day to the 7th day after surgery, postoperative delirium was found in 40 patients, but not in 38 patients. Univariate and multivariate logistic regression analyses were used to explore risk factors for postoperative delirium. Phenotypic subgroups of delirium were assessed using Topological Data Analysis, in which the significant risk factors were used for evaluating filter and distance metrics.ResultsMini-Mental State Examination, neuroticism, conscientiousness, and regional anesthesia were identified as a predictive risk factor for postoperative delirium. The filter metric showed significant negative correlations with nutrition-related factors such as total protein and albumin. When filter metric and Euclidean distances were entered, delirious patients were bifurcated as a function of personality traits and anesthesia method in the patient-patient network.ConclusionsA personality trait of neuroticism and conscientiousness may predispose elderly patients to postoperative delirium and this influence may be amplified by regional anesthesia. This study verifies the contribution of psychological risk factors to delirium and provides new insight for complex etiologies of delirium by mapping various clinical variables in the topological space.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1079-z) contains supplementary material, which is available to authorized users.
Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD). We investigated resting-state functional connectivity (rs-FCN) of the left and right amygdala with various brain regions and functional lateralization in patients with SAD.Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala.Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044). The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS), and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037).Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function plays a central role in the pathophysiology of SAD.
The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF) regulates the progression of several types of cancer. However, although LIF overexpression during breast cancer progression was observed in our previous report, the molecular mechanisms responsible for this deregulation remain largely unknown. Here we show that LIF expression is epigenetically up-regulated via DNA demethylation and changes in histone methylation status within its promoter region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs within the promoter region are hypermethylated in normal breast epithelial cells, but extensively demethylated as breast cancer progresses. In agreement with the DNA methylation pattern, our chromatin immunoprecipitation showed that inactive epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation significantly decreased during the progression to breast cancer but an active histone mark was increased in an inverse manner. Also, the occupancy of the transcription factor Sp1, which has higher affinity for hypomethylated CpGs, increased. RNAimediated knockdown of LIF expression resulted in a significant reduction of cell growth and colony formation in breast cancer cells, suggesting the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer cells. Collectively, our data suggest that the epigenetic up-regulation of the LIF gene likely play an important role in the development of breast cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.