Anticipatory and Consummatory Pleasure and Displeasure in Major Depressive Disorder: An Experience Sampling Study

Pleasure and displeasure can be parsed into anticipatory and consummatory phases. However, existing research on pleasure and displeasure in major depressive disorder (MDD), a disorder characterized by anhedonia, has largely focused on deficits in the consummatory phase and most studies have been laboratory-based. Using experience sampling, we compared anticipatory and consummatory pleasure and displeasure for activities in the daily lives of adults with MDD (n = 41) and in healthy controls (n = 39). Participants carried electronic devices for one week and were randomly prompted eight times a day to answer questions about activities that they most and least looked forward to. Compared to healthy controls, MDD participants reported lower anticipatory and consummatory pleasure and higher anticipatory and consummatory displeasure for daily activities. Additionally, participants’ experiences of anticipatory and consummatory pleasure in daily life were inversely related to trait levels of anticipatory and consummatory anhedonia, respectively. Participants, independent of MDD status, accurately predicted pleasure but overestimated displeasure. These results are the first to provide evidence that, across both anticipatory and consummatory phases, people with MDD experience blunted pleasure and elevated displeasure for daily activities. Our findings clarify disturbances in pleasure and displeasure that characterize MDD, which should inform MDD treatment

What Can Online Doctor Reviews Tell Us? A Deep Learning Assisted Study of Telehealth Service

The present study develops a novel deep learning method which assists text mining of online doctor reviews to extract underlying sentiment scores. Those scores can be used to estimate a healthcare service quality model to investigate how the online doctor reviews impact the online doctor consultation demand. Based on the data from the largest online health platforms in China, our model results show that the underlying sentiment scores have statistically significant impacts on the demand of online doctor consultation. Theoretically, the present study constructs an innovative deep learning algorithm with a better performance than four widely used text mining methods, which can be applied to text mining of many online forums or social media texts. Empirically, our model results show what factors impact the health service quality and online doctor consultation demand, and following those factors, healthcare professionals can improve their service

Predictive values of PD‑L1 expression for survival outcomes in patients with cervical cancer: a systematic review and meta-analysis

Objectives: Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem in several countries. Given that the prognosis of patients with recurrent or metastatic disease is poor, it is necessary to identify valuable predictive indicators to estimate survival outcomes in patients with cervical cancer.Material and methods: We searched electronic databases such as PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and investigated the relationship between Programmed death-ligand 1(PD-L1) expression and prognosis. Chi squared tests and I2 were utilized to assess study heterogeneity, and publication bias was estimated using Begg’s funnel plot and Egger linear regression test.Results: Thirteen eligible studies with 1422 patients were included. Generally, high PD-L1 expression was conclusively associated with poor overall survival (OS) (HR: 1.31; 95% CI 1.03–1.66, p = 0.025). However, PD-L1 expression demonstrated no association with progression-free survival (HR: 0.93; 0.73–1.19, p = 0.57). High PD-L1 expression with a sample size over 100 indicated a shorter OS (HR: 1.51; 95% CI 1.13–2.01). High expression of PD-L1 in Asians represented a lower OS (HR: 1.52; 1.14–2.03). Overexpression of PD-L1 in tumor cells (HR: 1.57; 1.29–2.10) and tumor-infiltrating immune cells (HR: 1.75; 1.02-2.99) predicted poor OS. High PD-L1 expression (HR: 4.04; 2.58–6.31) showed a lower effect on OS with a cut-off value of 5%.Conclusions: Our results indicate that high PD-L1 expression could be a valuable biomarker for predicting clinical outcomes in patients with cervical cancer

Leptin deficiency in CD8+ T cells ameliorates non-segmental vitiligo by reducing interferon-γ and Granzyme B

BackgroundVitiligo is an autoimmune skin disease mainly mediated by CD8+ T cells, which affects about 0.1%-2% population of the world. Leptin plays a critical role in regulating the activation of CD8+ T cells. However, the effect of Leptin on vitiligo remains unclear.ObjectivesTo explore the effect of leptin on CD8+ T cells and its influence on vitiligo.MethodsRNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on Leptin KO mice.Results557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that LEPR expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-γ subset of CD8+LEPR+ T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-γ was significantly increased after leptin stimulation in vitro (p = 0.0217). In mice, Leptin deficiency resulted in less severe hair depigmentation. Leptin deficiency also resulted in significantly lower expressed vitiligo-related genes, such as Cxcl9 (p = 0.0497), Gzmb (p < 0.001), Ifng (p = 0.0159), and Mx1 (p < 0.001) after modeling.ConclusionLeptin could promote the progression of vitiligo by enhancing the cytotoxic function of CD8+ T cells. Leptin may become a new target for vitiligo treatment

DNA methylation/hydroxymethylation in melanoma

Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma. Moreover, 5-Aza-2′-deoxycytidine, an epigenetic modifier causing DNA demethylation, and ten-eleven translocation family dioxygenase (TET), which catalyzes the generation of 5-hmC, demonstrate therapeutic potential in melanoma treatment. In this review, we will summarize the latest progress in research on DNA methylation/hydroxymethylation in melanoma, and we will discuss and provide insight for epigenetic biomarkers and therapies for melanoma. Particularly, we will discuss the role of DNA hydroxymethylation in melanoma infiltrating immune cells, which may also serve as a potential target for melanoma treatment

Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus epidermidis </it>(SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation in <it>Staphylococcus aureus</it>. The deletion of <it>saeR </it>in <it>S. epidermidis </it>results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in <it>S. epidermidis </it>remains unclear.</p> <p>Results</p> <p>The <it>saeRS </it>genes of SE1457 were deleted by homologous recombination. The <it>saeRS </it>deletion mutant, SE1457<it>ΔsaeRS</it>, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457<it>saec</it>. Compared to SE1457 and SE1457<it>saec</it>, SE1457<it>ΔsaeRS </it>showed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457<it>ΔsaeRS </it>also released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as <it>atlE </it>and <it>aae</it>, was increased in SE1457<it>ΔsaeRS</it>. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457<it>ΔsaeRS</it>, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by <it>icaA</it>) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion of <it>saeRS.</it></p> <p>Conclusions</p> <p>Deletion of <it>saeRS </it>in <it>S. epidermidis </it>resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457<it>ΔsaeRS </it>was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.</p

The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation

The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases

Autophagy is a complicated cellular mechanism that maintains cellular and tissue homeostasis and integrity via degradation of senescent, defective subcellular organelles, infectious agents, and misfolded proteins. Accumulating evidence has shown that autophagy is involved in numerous immune processes, such as removal of intracellular bacteria, cytokine production, autoantigen presentation, and survival of lymphocytes, indicating an apparent and important role in innate and adaptive immune responses. Indeed, in genome-wide association studies, autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis of several autoimmune and inflammatory disorders, such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition, conditional knockdown of autophagy-related genes in mice displayed therapeutic effects on several autoimmune disease models by reducing levels of inflammatory cytokines and autoreactive immune cells. However, the inhibition of autophagy accelerates the progress of some inflammatory and autoimmune diseases via promotion of inflammatory cytokine production. Therefore, this review will summarize the current knowledge of autophagy in immune regulation and discuss the therapeutic and pathogenic role of autophagy in autoimmune diseases to broaden our understanding of the etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated therapies

Anticipatory and consummatory pleasure and displeasure in major depressive disorder: An experience sampling study

Pleasure and displeasure can be parsed into anticipatory and consummatory phases. However, research on pleasure and displeasure in major depressive disorder (MDD), a disorder characterized by anhedonia, has largely focused on deficits in the consummatory phase. Moreover, most studies in this area have been laboratory-based, raising the question of how component processes of pleasure and displeasure are experienced in the daily lives of depressed individuals. Using experience sampling, we compared anticipatory and consummatory pleasure and displeasure for daily activities reported by adults with MDD (n=41) and healthy controls (n=39). Participants carried electronic devices for one week and were randomly prompted eight times a day to answer questions about activities to which they most and least looked forward. Compared to healthy controls, MDD participants reported blunted levels of both anticipatory and consummatory pleasure and elevated levels of both anticipatory and consummatory displeasure for daily activities. Independent of MDD status, participants accurately predicted pleasure but overestimated displeasure. These results are the first to provide evidence that, across both anticipatory and consummatory phases, individuals with MDD experience blunted pleasure and elevated displeasure for daily activities. Our findings clarify the disturbances in pleasure and displeasure that characterize MDD and may inform treatment for this debilitating disorder