Inflammasome is a cytosolic multiprotein complex to activate caspase-1 leading to the subsequent processing of inactive pro-interleukin-1-beta (Pro-IL-1beta) into its active interleukin-1 beta (IL-1beta) in response to pathogen- or danger-associated molecular pattern. In recent years, a huge progress has been made to identify inflammasome component as a molecular platform to recruit and activate caspase-1. Nucleotide-binding oligomerization domain-like receptor (NLR) family proteins such as NLRP1, NLRP3 or interleukin-1beta-converting enzyme (ICE)-protease activating factor (IPAF) have been first characterized to form inflammasome complex to induce caspase-1 activation. More recently, non-NLR type, pyrin-domain (PYD)-containing proteins such as pyrin or absent in melanoma2 (AIM2) were also proposed to form caspase-1-activating inflammasome machinery with apoptosis-associated speck-like protein containing a CARD (ASC), an essential adaptor molecule. Inflammasome pathways were shown to be crucial for protecting host organisms against diverse pathogen infections, but accumulating evidences also suggest that excessive activation of inflammasome/caspase-1 might be related to the pathogenesis of inflammation-related diseases. Indeed, mutations in NLRP3 or pyrin are closely associated with autoinflammatory diseases such as familial Mediterranean fever (FMF) syndrome or Muckle-Wells syndrome (MWS), indicating that the regulation of caspase-1 activity by inflammasome is a central process in these hereditary inflammatory disorders. Here, recent advances on the molecular mechanism of caspase-1 activation by PYD-containing inflammasomes are summarized and discussed.
Cryopyrin-Associated Periodic Syndromes ; Cytoskeletal Proteins ; Cytosol ; Familial Mediterranean Fever ; Humans ; Immunity, Innate ; Inflammasomes ; Interleukin-1beta ; Proteins

Purpose: This study was done to identify the mediating effect of compassion competence on the relationship between communication competence and caring behavior in clinical nurses. Methods: A structured self-report questionnaire was used to measure caring behavior, communication competence, and compassion competence. During September 2019, data were collected from 170 nurses working at general hospitals. Data were analyzed using hierarchical multiple linear regression with SPSS for Windows version 23.0 and Hayes's SPSS process macro (version 3.5). Results: Communication skills (β=.52) and compassion ability (β=.77) were identified as important predictors of nurses’ caring behavior. These variables explained approximately 54% of the variance in nurses’ caring behavior. Compassion competence also had a total mediating effect on the relationship between communication competence and caring behavior. Conclusion In order to enhance the caring behavior of clinical nurses, enhancing compassion competence by strengthening communication development should be considered as a strategy.

OBJECTIVE: We examined whether childhood exposure to psychological trauma is associated with greater suicidality and whether specific psychiatric disorders modulate this association in a representative sample of Korean adults. METHODS: The Korean version of the Composite International Diagnostic Interview 2.1 was administered to 6,027 subjects aged 18-74 years. Subjects who experienced a traumatic event before the age of 18 years, the childhood-trauma-exposure group, were compared with controls without childhood trauma exposure. RESULTS: Childhood exposure to psychological trauma was associated with lifetime suicidal ideation (OR=3.19, 95% CI=2.42-4.20), suicide plans (OR=4.15, 95% CI=2.68-6.43), and suicide attempts (OR=4.52, 95% CI=2.97-6.88). These associations weakened after further adjustment for any psychiatric disorders, but they were not eliminated. The risk of suicide attempts related to childhood trauma increased with the presence of a concurrent alcohol use, depressive, or eating disorder. CONCLUSION: In terms of clinical implications, patients with these disorders who have a history of childhood trauma should be carefully assessed for their suicide risk and aggressively treated for psychiatric disorders.
Adult ; Feeding and Eating Disorders ; Humans ; Suicidal Ideation ; Suicide*

Innate immune cells sense and respond to the cytoplasmic infection of bacterial pathogens through NLRP3, NLRC4 or AIM2 inflammasome depending on the unique molecular pattern of invading pathogens. The infection of flagellin- or type III secretion system (T3SS)-containing Gram-negative bacteria such as Salmonella enterica serovar Typhimurium (S. typhimurium) or Pseudomonas aeruginosa (P. aeruginosa) triggers NLRC4-dependent caspase-1 activation leading to the secretion of proinflammatory cytokines such as interleukin-1-beta (IL-1beta) and IL-18. Previous studies have shown that apoptosis-associated speck-like protein containing a CARD (ASC) is also required for Salmonella-induced caspase-1 activation, but it is still unclear how ASC contributes to the activation of NLRC4 inflammasome in response to S. typhimurium infection. In this study, we demonstrate that S. typhimurium triggers the formation of ASC oligomer in a potassium depletion-independent manner as determined by in vitro crosslinking and in situ fluorescence imaging. Remarkably, inhibition of potassium efflux failed to block Salmonella-promoted caspase-1 activation and macrophage cell death. These results collectively suggest that ASC is substantially oligomerized to facilitate the activation of caspase-1 in response to S. typhimurium infection. Contrary to NLRP3 inflammasome, intracellular potassium depletion is not critical for NLRC4 inflammasome signaling by S. typhimurium.
Cell Death ; Cytokines ; Cytoplasm ; Gram-Negative Bacteria ; Interleukin-18 ; Macrophages ; Optical Imaging ; Potassium ; Pseudomonas aeruginosa ; Salmonella ; Salmonella enterica

OBJECTIVE: We examined a functional model of acquired capability for suicide, which was elaborated from the “Interpersonal-Psychological Theory of Suicide”. METHODS: A total of 6,027 Korean community subjects were recruited from The Korean Epidemiologic Catchment Area study conducted in 2011. The subjects were assessed systematically using the Korean version of the Composite International Diagnostic Interview version 2.1, the Korean version of the Barratt Impulsiveness Scale, and the Korean version of the Mood Disorder Questionnaire. We used structural equation modeling to identify potential factors contributing to a suicide attempt. RESULTS: Most aspects of the model were supported by the data and “the short-term enhancer for the acquired capability for suicide” had direct effects on suicide attempts. However, the suicidal planning effects of “the short-term enhancer for the acquired capability for suicide” were eliminated by the rule of parsimony. CONCLUSION: The main finding was that “the short-term enhancer for the acquired capability for suicide” is relevant to suicide attempts when it's direct, indirect, and reciprocal effects are tested within a more complete system of relationships than found in existing studies. The implications of these findings are discussed with regard to future conceptual work and empirical research.
Adult* ; Empirical Research ; Humans ; Mood Disorders ; Suicidal Ideation ; Suicide*

Coeruleo-vestibular pathway which connects locus coeruleus and vestibular nuclei is noradrenergic. This study was designed to elucidate the effects of phenylephrine on the spontaneous activity of acutely isolated medial vestibular nuclear neurons of rat by whole-cell patch-clamp technique. Sprague-Dawley rats, aged 14 to 16 days, were used. After enzymatic digestion, dissociated medial vestibular neurons were transferred to a recording chamber mounted on an inverted microscope, and spontaneous action potentials were recorded by standard patch-clamp techniques. In current-clamp mode, the frequency of spontaneous action potential of medial vestibular nuclear neurons was decreased by phenylephrine (n=15). Phenylephrine increased the amplitude of afterhyperpolarization without changes in the resting membrane potential and spike width. In voltage-clamp mode, the whole potassium currents of the medial vestibular nuclear neurons were increased by phenylephrine (n=12). These experimental results suggest that alpha-receptor mediates the inhibitory effects on the neuronal activity of the medial vestibular nuclear neuron.
Action Potentials ; Animals ; Digestion ; Locus Coeruleus ; Membrane Potentials ; Neurons* ; Patch-Clamp Techniques ; Phenylephrine* ; Potassium ; Rats* ; Rats, Sprague-Dawley ; Vestibular Nuclei

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.