Delusional parasitosis is characterized by the unshakeable belief of being infested with tiny (microscopic) insects. Patients spend much time trying to get rid of the bugs and suffer from these symptoms. Patients prefer to go to dermatologists because they have a strong conviction over the presence of a somatic disease and do not accept any psychiatric advice for their complaints. 'Folie a deux' or shared psychotic disorder (SPD) is a relatively rare syndrome, which has long attracted clinical attention. Delusional parasitosis is associated in 5-15% of SPD and can run within a family. We experienced delusional parasitosis as 'Folie a Deux' between a mother and her son and successfully treated them through early psychiatric intervention. We believe that attention should be drawn to DP with SPD.
Adult ; Delusions/*diagnosis/*psychology ; Ectoparasitic Infestations/psychology ; Female ; Human ; Male ; Middle Aged ; Paranoid Disorders/diagnosis/psychology ; Shared Paranoid Disorder/*diagnosis/*psychology ; Social Isolation

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.
Diabetes Mellitus, Type 2 ; Fatty Liver ; Glucagon-Like Peptide 1 ; Glucose ; Homeostasis ; Incretins ; Insulin Resistance ; Lipogenesis ; Liver Diseases ; Receptors, Glucagon

Various types of stress affect mental health in the form of mood disorders, anxiety disorders, and suicidal ideation. Recently, the increasing suicide rate in the working-age population has become a major mental health concern in Korea. Thus, we investigated what kind of stress influence depression, anxiety, and suicidal ideation in Korean employees. The study participants were 189,965 employees who attended health screenings and responded to the Center for Epidemiologic Study-Depression Scale, the Beck Anxiety Inventory, and a questionnaire on the major causes of stress and suicidal ideation. We investigated the major causes of stress by gender and age categories and used binary logistic regression to determine the impact of the causes of stress on depression, anxiety and suicidal ideation. Of several stress causes, work-related stress was the most prevalent, regardless of age category and gender, followed by interpersonal relationships. However, interpersonal relationships and financial problems were the predominant causes of stress related to depression or suicidal ideation. This research suggests that despite the fact that work is the most common cause of stress for Korean employees, stress related to life problems other than work has a greater influence on the mental health of Korean employees.
Anxiety Disorders ; Anxiety* ; Depression* ; Korea ; Logistic Models ; Mass Screening ; Mental Health ; Mood Disorders ; Suicidal Ideation* ; Suicide

Purpose: Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies. Materials and Methods: We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results: Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I2=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I2=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies. Conclusion This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.
Activating Transcription Factor 6 ; alpha-2-HS-Glycoprotein* ; AMP-Activated Protein Kinases* ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Line ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress* ; Fatty Liver ; Glucagon-Like Peptide 1 ; Glycoproteins ; Hep G2 Cells ; Humans ; Insulin Resistance ; Palmitic Acid ; Phosphotransferases ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Small Interfering ; Selenoprotein P ; Transfection ; Tunicamycin ; Biomarkers ; Glucagon-Like Peptide-1 Receptor

PURPOSE: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-gamma, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-gamma agonist. METHODS: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, PPAR-alpha and PPAR-gamma from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. RESULTS: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPARalpha and PPAR-gamma increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-alpha, and TGF-beta mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-beta expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. CONCLUSION: PPAR-alpha and PPAR-gamma expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.
Adipokines ; Adiponectin ; Animals ; Bronchoalveolar Lavage ; Cell Count ; Cytokines ; Inflammation ; Leptin ; Lung ; Macrophages ; Mice ; Mice, Obese ; Neutrophils ; Obesity ; Ovalbumin ; Ovum ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; PPAR alpha ; Real-Time Polymerase Chain Reaction ; Receptors, Leptin ; RNA, Messenger ; Thiazolidinediones ; Transforming Growth Factor beta ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A

BACKGROUND: Tumor necrosis factor (TNF)-alpha and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated. METHODS: The key factors and mechanism of action of TNF-alpha and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2alpha) by Western blot and an immunofluorescence assay in 24-hour TNF-alpha-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation. RESULTS: Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-alpha-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-alpha and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2alpha, a component of the unfolded protein response signaling pathway, was observed in TNF-alpha or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-alpha-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2alpha. CONCLUSION: These data indicated that AICAR-induced AMPK activation attenuates TNF-alpha-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2alpha activity is a novel mechanism of the anti-lipolytic effect of AICAR.
2-Aminopurine ; Adipocytes* ; AMP-Activated Protein Kinases* ; Blotting, Western ; Endoplasmic Reticulum ; Fluorescent Antibody Technique ; Lipolysis* ; Necrosis* ; Phosphorylation ; Phosphotransferases ; Prokaryotic Initiation Factor-2 ; Protein Kinases ; Tumor Necrosis Factor-alpha ; Unfolded Protein Response

BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus
Animals ; Apoptosis ; Blood Glucose ; Caspase 3 ; Chemokine CCL2 ; Cytokines ; Diabetes Mellitus ; Endoplasmic Reticulum Stress* ; Endoplasmic Reticulum* ; Glucose Transport Proteins, Facilitative ; Humans ; Inflammation* ; Insulin ; Insulin Resistance ; Insulin-Secreting Cells ; Insulinoma ; Interleukin-6 ; Islets of Langerhans ; Mice ; Necrosis ; Obesity ; Peptide Initiation Factors ; Peroxisomes ; Repression, Psychology ; Transcription Factors

BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB). METHODS: We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels. RESULTS: Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends. CONCLUSION: Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.
Adenosine Triphosphate ; Animals ; Apoptosis ; GTP Phosphohydrolases ; Insulin ; Insulin-Secreting Cells ; Insulinoma ; Membrane Potential, Mitochondrial ; Metabolism ; Mice ; Mitochondria ; Mitochondrial Dynamics ; Oxidative Phosphorylation ; Oxygen Consumption ; Phosphotransferases ; Repression, Psychology ; RNA, Small Interfering ; Sphingolipids ; Sphingosine

Background: Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA). Methods: HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting. Results: Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation. Conclusion These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.