THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059.

Background and Objectives: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. Materials and Methods: Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. Results: Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11bhigh THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DRlow and CD206low), M1 (HLA-DRhigh and CD206low), and M2 (HLA-DRlow and CD206high), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. Conclusions: We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.

Prosthetic Materials Protrusion After Surgical Wall Reconstruction of Temporomandibular Joint Herniation.

ABSTRACT: Herniation of the temporomandibular joint (TMJ) into the external auditory canal (EAC) is rare. The TMJ and EAC are separated by the anterior bony wall of the EAC. Such a defect can be caused by trauma, infection, neoplasm, inflammation, and in rare cases, congenital bony defects. If asymptomatic or mildly symptomatic, supplemental treatment is primarily given, but if the symptoms are severe enough that the patient regularly feels discomfort, surgical procedure is considered. To our knowledge there are no reports about surgery-related complications and recurrence during the postoperative follow-up period for TMJ herniation in English literature. Here, the authors report the first case of implant protrusion after TMJ herniation surgery along with a literature review.

Perceptions of social dominance through facial emotion expressions in euthymic patients with bipolar I disorder.

The ability to accurately perceive dominance in the social hierarchy is important for successful social interactions. However, little is known about dominance perception of emotional stimuli in bipolar disorder. The aim of this study was to investigate the perception of social dominance in patients with bipolar I disorder in response to six facial emotional expressions. Participants included 35 euthymic patients and 45 healthy controls. Bipolar patients showed a lower perception of social dominance based on anger, disgust, fear, and neutral facial emotional expressions compared to healthy controls. A negative correlation was observed between motivation to pursue goals or residual manic symptoms and perceived dominance of negative facial emotions such as anger, disgust, and fear in bipolar patients. These results suggest that bipolar patients have an altered perception of social dominance that might result in poor interpersonal functioning. Training of appropriate dominance perception using various emotional stimuli may be helpful in improving social relationships for individuals with bipolar disorder.

The Significance of Rhinologic Evaluation and Pretreatment for Patients Undergoing Two-Jaw Surgery Through Nasotracheal Intubation.

The aim of this study is to determine whether rhinologic preoperative evaluation and pretreatments reduce intranasal trauma and decrease postoperative complications, such as nasal obstruction and epistaxis, in patients undergoing 2-jaw surgery with nasotracheal intubation. This study included 360 patients with malocclusion (Class III) who underwent 2-jaw surgery under general anesthesia via nasotracheal intubation in our hospital from January to December 2013 and categorized into 3 groups. Nasotracheal intubation was performed according to the nasal cavity the patient was able to breathe comfortably (Group I). The site of nasotracheal intubation was decided by 1 rhinologic specialist who evaluated preoperative dental computed tomography (Group II). The site of nasotracheal intubation was decided upon nasal endoscopic findings, dental computed tomography evaluation, and rhinologic pretreatment (Group III).Group II and Group III showed less damage to the nasal mucosa compared with the nasal status of Group I. Upon comparing Group II and Group III, Group III showed better overall status of the nasal mucosa compared with Group II. Visual analogue scale scores for nasal obstruction were pretty similar for all groups on the first postoperative day. In Group III, the nasal mucosa, however, was improved to that of preoperative status on the third postoperative day.In conclusion, it may be useful to pre-evaluate the mucosal and anatomical status of the nasal cavity to select patients requiring rhinologic pretreatment and decide the site for nasotracheal intubation to minimize complications arising from nasotracheal intubation.

Manic patients exhibit more utilitarian moral judgments in comparison with euthymic bipolar and healthy persons.

Both emotional and cognitive processes are involved in moral judgments. Ventromedial prefrontal lesions are related to impaired prosocial emotions and emotional dysregulation, and patients with these lesions exhibit increased utilitarian judgments of emotionally salient personal moral dilemmas. Bipolar patients experiencing manic episode also have impaired emotional regulation and behavioral control. We investigated the characteristics of moral judgment in manic and euthymic patients with bipolar disorder using the 50 hypothetical moral dilemma task (17 non-moral, 20 personal, and 13 impersonal). Our study included 27 manic bipolar patients, 26 euthymic bipolar patients, and 42 healthy controls. Subjects were instructed to determine whether or not each dilemma was morally acceptable, and their reaction times were recorded. Manic patients showed significantly greater utilitarian judgment than euthymic patients and normal controls for personal moral dilemmas. However, there were no significant between-group differences for the non-moral and impersonal moral dilemmas. Our results suggest that increased utilitarian judgments of personal moral dilemmas may be a state-related finding observed only in manic patients. This difference in moral judgment assessments may reflect the decision-making characteristics and underlying neurobiological mechanisms of bipolar disorder, especially during the manic state.

Pattern of pharmacotherapy by episode types for patients with bipolar disorders and its concordance with treatment guidelines.

This study aimed to investigate the overall prescription pattern for patients with bipolar disorders in Korea and its relevance to the practice guidelines. Prescription records from all patients with bipolar I and II disorders who have been admitted or who started the outpatient treatment during the year of 2009 in 10 academic setting hospitals were reviewed. A total of 1447 patients with bipolar I and II disorders were included in this study. Longitudinal prescription patterns of inpatients and outpatients were analyzed by episode types and compared with the clinical practice guideline algorithms. In all phases, polypharmacy was chosen as an initial treatment strategy (>80%). The combination of mood stabilizer and atypical antipsychotics was the most favored. Antipsychotics were prescribed in more than 80% of subjects across all phases. The rate of antidepressant use ranged from 15% to 40%, and it was more frequently used in acute treatment and bipolar II subjects. The concordance rate of prescriptions for manic inpatients to the guidelines was higher and relatively more consistent (43.8%-48.7%) compared with that for depressive inpatients (18.6%-46.9%). Polypharmacy was the most common reason for nonconcordance. In Korean psychiatric academic setting, polypharmacy and atypical antipsychotics were prominently favored in the treatment of bipolar disorder, even with the lack of evidence of its superiority. More evidence is needed to establish suitable treatment strategies. In particular, the treatment strategy for acute bipolar depression awaits more consensuses.

Autobiographical memory and its association with neuropsychological function in bipolar disorder.

OBJECTIVE: The aim of this study was to investigate the overgeneralization of autobiographical memory (AM) in bipolar disorder (BD) and assess its association with multiple cognitive domains. METHOD: Twenty-eight clinically stable bipolar I patients and an equal number of age- and gender-matched healthy controls (HC) were included. All participants were examined using the autobiographical memory test (AMT) and the neuropsychological battery including the general intelligence, attention, verbal memory, verbal fluency, visual memory, and executive functions domain. Demographic, clinical, and test variables were compared between BD and HC groups. Correlation analyses of AMT scores with cognitive functions were performed within each group, controlling for demographic and clinical variables. RESULTS: Total and negative scores of AMT were significantly lower in BD patients compared to HC individuals. AMT scores were significantly correlated with WAIS similarities, WCST perseverative errors, and WCST categories completed in BD, whereas AMT scores were correlated with verbal memory and verbal fluency in HC. CONCLUSION: Our findings suggest that overgeneral AM is a characteristic of BD and is related to executive function. Future studies should investigate the benefit of additional treatment focusing on overgeneral AM in BD.

Assessment of implicit self-esteem in bipolar manic and euthymic patients using the implicit association test.

OBJECTIVE: Although self-esteem is thought to be an important psychological factor in bipolar disorder, little is known about implicit and explicit self-esteem in manic patients. In this study, we investigated differences in implicit and explicit self-esteem among bipolar manic patients, bipolar euthymic patients, and healthy controls using the Implicit Association Test (IAT). METHODS: Participants included 19 manic patients, 27 euthymic patients, and 27 healthy controls. Participants completed a self-esteem scale to evaluate explicit self-esteem and performed the self-esteem IAT to evaluate implicit self-esteem. RESULTS: There were no differences among groups in explicit self-esteem. However, there were significant differences among groups in implicit self-esteem. Manic patients had higher IAT scores than euthymic patients and a trend toward higher IAT scores than healthy controls. CONCLUSIONS: Our findings suggest that, on the latent level, a manic state is not simply the opposite of a depressed state. Furthermore, there may be a discontinuity of implicit self-esteem between manic and euthymic states. These unexpected results may be due to characteristics of the study participants or the methods used to assess implicit self-esteem. Nevertheless, they provide greater insights on the psychological status of manic patients.

Antipsychotic polypharmacy and high-dose prescription in schizophrenia: a 5-year comparison.

OBJECTIVE: The co-prescription of multiple antipsychotic drugs continues to increase despite a lack of evidence supporting this practice. The purpose of this study was to quantify and describe recent trends of antipsychotic polypharmacy in Korean schizophrenic inpatients by comparing prescribed medications between the years of 2005 and 2010. METHODS: We reviewed comprehensive medication profiles of schizophrenic patients discharged from a university psychiatric hospital in 2005 (n=194) or 2010 (n=201). Antipsychotic polypharmacy was defined as the concurrent receipt of two or more chemically distinct antipsychotics for at least 14 days. High antipsychotic dose was defined as a prescribed daily dose to defined daily dose ratio of greater than 1.5. RESULTS: Antipsychotic polypharmacy increased between 2005 (37.1%) and 2010 (48.3%, p=0.025). The most frequently used drug within combinations of antipsychotics was haloperidol in 2005 (51.4%) and quetiapine in 2010 (48.5%). Overall, no changes were observed between 2005 and 2010 in the rate of prescribing high-dose antipsychotics. High-dose antipsychotic monotherapy decreased across years (from 30.4 to 18.4%), but high-dose antipsychotic polypharmacy increased (from 34.0 to 45.3%). Regression analysis revealed that antipsychotic polypharmacy was strongly associated with high doses of prescribed antipsychotics (odds ratio=18.60, p<0.001). CONCLUSIONS: The practice of prescribing multiple antipsychotics to patients with schizophrenia is increasing, and high-dose antipsychotic drugs are more likely to be prescribed in combination than in isolation. The reasons for this pattern of prescription and its impact warrants further study.

Differential patterns of neuropsychological performance in the euthymic and depressive phases of bipolar disorders.

AIMS: Patients with bipolar disorders (BD) show a broad range of neurocognitive impairments. We compared the patterns of neuropsychological performance in depressed and euthymic patients with BD, and explored the state-dependent cognitive markers of bipolar depression. METHODS: The study participants included 32 BD patients (15 depressed and 17 euthymic) and 42 healthy controls. All of the subjects completed tests that assessed attention, psychomotor speed, verbal and visual memory, and executive functions. Between-group neuropsychological performance differences were examined. Multidimensional scaling (MDS) was used to compare the patterns of cognitive variables in euthymic and depressed BD patients. RESULTS: Compared to the euthymic BD patients and healthy controls, the depressed BD patients performed lower in verbal memory and executive functions. No significant differences were found between the three groups in attention, psychomotor speed, and visual memory. The depressed BD patients showed a lower level of association between psychomotor speed and the time to initial concept formation than the healthy controls and euthymic BD patients. In contrast, the correlation between word association and verbal memory was stronger in the depressed group than either the control or euthymic groups. CONCLUSION: The depressed BD patients showed greater impairments in verbal memory and executive functions than the euthymic BD patients. In addition, our study identified a differential pattern of correlations between the cognitive domains of euthymic and depressed BD patients, which suggests the potential role of verbal memory and executive functions as cognitive markers of BD.

Temporomandibular joint herniation into the external auditory canal presenting as clicking tinnitus: A case report.

BACKGROUND: Herniation of the temporomandibular joint (TMJ) into the external auditory canal (EAC) due to a bony defect in the EAC is rare. Such bony defects can be secondary to inflammation, neoplasm, trauma. In rare instances, TMJ herniation can occur when the Huschke foramen is constantly exposed. TMJ herniation can induce clicking tinnitus, otalgia, conductive hearing loss, and otorrhea, but can also present with no symptoms. This study reports a case of TMJ herniation. CLINICAL PRESENTATION: A male patient presented with clicking tinnitus that had developed 3 years ago. Dome-shaped soft tissue was found on the anterior EAC wall, which protruded and depressed with mouth movement. The patient underwent surgical reconstruction of the bony defect with titanium mesh, and the symptoms resolved after surgery. CONCLUSION: This case highlights the importance of surgical reconstruction of a bony defect in the EAC using appropriate materials.

A Case of Unilateral Simultaneous Preauricular Sinus and Postauricular Sinus in an Adult.

Preauricular sinuses are relatively common congenital anomalies of the soft tissues of the ear. By strict definition, when they connect 2 separate spaces, they are referred to as a preauricular fistula. This clinical entity was first described by Heusinger in 1864. Most preauricular sinuses have a small opening located anterior to the root of the helix. In rare cases, they are found posterior to the tragus, near the crus of the helix, and the ear lobule. The latter is the variant type preauricular sinus, also referred to as the "postauricular sinus," as the sinus tract opens posterior to the auricle. Recurrent infections or persistent discharge may require surgical excision which is ideally performed at a time when there is no inflammation. There are a variety of techniques for excision. Regardless of the surgical approach taken, it is of critical importance to remove the subcutaneous sac completely. We present a very rare case involving the co-occurrence of a preauricular sinus and postauricular sinus in a 33-year-old woman. We report this case with a review of the literature.

Apolipoprotein E gene polymorphism, alcohol use, and their interactions in combat-related posttraumatic stress disorder.

BACKGROUND: The symptomatology of posttraumatic stress disorder (PTSD) is related not only to the intensity of the causative trauma, but also to alcohol use and genetic factors. Among the many candidate genes, the apolipoprotein E gene (APOE) is thought to be associated with stress reactivity. METHODS: Korean veterans of the Vietnam War with (n = 128) or without (n = 128) PTSD participated in this study. The Clinician-Administered PTSD Scale and Combat Exposure Scale were administered, and the severity of alcohol use was assessed among these veterans. The APOE polymorphism and clinical variables of the subjects were compared, and associations between PTSD and potential explanatory variables were tested using logistic regression analysis. RESULTS: Higher frequencies of APOE ε2 alleles and a greater number of individuals with the ε2 allele were found in the PTSD group. Among patients with PTSD, ε2-allele noncarriers consumed alcohol in greater amounts and more frequently than did ε2-allele carriers. Regression analysis revealed a significant interactional effect between harmful drinking and the absence of the ε2 allele associated with PTSD risk. CONCLUSIONS: These results suggest that the APOE ε2 allele operates as a susceptibility gene for combat-related PTSD, with the relationship between alcohol use and PTSD differing according to the ε2-allele status. Future studies should determine the role of the APOE in adaptation to extreme stress, the development of PTSD, and comorbid alcohol-related disorders.

Reevaluation of patients with bipolar disorder on manic episode: improving the diagnosing of mixed episode.

Mixed manic/depressive episodes in patients with bipolar disorder are underdiagnosed because of restrictive diagnostic criteria. Using the broader definition of a mixed episode represented by the Cincinnati criteria, we reevaluated the medical records of patients with bipolar disorder hospitalized for a manic episode. We also examined the predictive power of previously unrecognized depressive symptoms. Of 520 inpatients with mania, we retrospectively diagnosed 59 (11.3%) as having a probable mixed episode. Compared with the patients with pure mania, the patients with mixed episodes were more likely to have a family history of psychiatric illness, comorbid personality disorder, and a history of suicide attempts. Binary logistic regression revealed that loss of interest, loss of energy, feelings of worthlessness, and feelings of helplessness had good positive predictive value (>0.7) for mixed episodes. Accurate diagnosis of mixed episodes may require a broadening of diagnostic criteria and emphasis on symptoms such as loss of interest, loss of energy, and feelings of worthlessness and helplessness.

Prodromes and coping types in bipolar patients with nonpsychotic or psychotic mania.

BACKGROUND: Bipolar disorder is a recurrent and cyclical illness frequently accompanied by psychotic symptoms. Detecting prodromes and enhancing coping skills for prodromal symptoms in bipolar patients are very important for relapse prevention. Psychotic features in bipolar patients are related to poor prognosis. We aimed to investigate the differences in prodromal symptoms and coping styles in psychotic and nonpsychotic bipolar patients. METHODS: Eighty-three euthymic bipolar patients with or without a history of manic psychosis were interviewed about their demographic, diagnostic, and clinical information and completed a 40-item checklist for prodromal symptoms. After the interview, they completed the Coping Inventory for Prodromes of Mania. RESULTS: The differences between the psychotic patients and the nonpsychotic patients were found in the prodromal durations, and a few prodromal symptoms such as afraid of going crazy (P = .03), energetic-very active (P = .01), and hearing hallucination (P = .02). The psychotic patients showed a higher score of denial or blame than the nonpsychotic ones (1.92 ± 0.73 in nonpsychosis, 2.32 ± 0.84 in psychosis; P = .03). Logistic regression revealed that the duration of prodromes (P = .02) and hearing hallucination (P = .01) were related to the presence of psychotic features. CONCLUSION: Psychotic patients had a tendency to use denial or blame coping strategy and to experience attenuated psychotic symptoms a little more during the prodromal period. Timely psychosocial approaches for detecting signs and enhancing coping strategies would improve the outcomes.

Assessment of risk factors related to suicide attempts in patients with bipolar disorder.

We compared the characteristics of patients with bipolar disorder with and without a history of suicide attempts to identify the risk factors of suicide in this disorder. Among 212 patients with bipolar disorder, 44 (21.2%) patients had histories of suicide attempts. Suicide attempters were younger and more likely to be diagnosed with bipolar II. The variables that differentiated those who did from those who did not attempt suicide included age at first contact, lifetime history of antidepressant use, major depressive episode, mixed episode, auditory hallucinations, rapid cycling, the number of previous mood episodes, age of first depressive episode, and age of first psychotic symptoms. Strong predictors of suicide attempts were younger age at onset, lifetime history of auditory hallucinations, and history of antidepressant use. Antecedent depressive episodes and psychotic symptoms predicted the first suicide attempt in patients with bipolar disorder. This study could help clinicians to understand the major risk factors of suicidal behavior in bipolar disorder.

Emotional priming with facial exposures in euthymic patients with bipolar disorder.

People with bipolar disorder have abnormal emotional processing. We investigated the automatic and controlled emotional processing via a priming paradigm with subliminal and supraliminal facial exposure. We compared 20 euthymic bipolar patients and 20 healthy subjects on their performance in subliminal and supraliminal tasks. Priming tasks consisted of three different primes according to facial emotions (happy, sad, and neutral) followed by a neutral face as a target stimulus. The prime stimuli were presented subliminally (17 msec) or supraliminally (1000 msec). In subliminal tasks, both patients and controls judged the neutral target face as significantly more unpleasant (negative judgment shift) when presented with negative emotion primes compared with positive primes. In supraliminal tasks, bipolar subjects showed significant negative judgment shift, whereas healthy subjects did not. There was a significant group × emotion interaction for the judgment rate in supraliminal tasks. Our finding of persistent affective priming even at conscious awareness may suggest that bipolar patients have impaired cognitive control on emotional processing rather than automatically spreading activation of emotion.

Altered behavioral and electrophysiological responses to social fairness in manic and euthymic patients with bipolar disorder.

BACKGROUND: Individuals with bipolar disorder show mood instability, including heightened anger and impulsivity. The Ultimatum Game (UG) is a tool used to evaluate emotional and social decision-making strategies. We investigated behavioral and electrophysiological responses to subjectively fair or unfair offers in the UG in patients with bipolar I disorder. METHODS: Twenty-four manic patients, 20 euthymic patients, and 30 healthy controls participated in this study. We analyzed their behaviors and collected electroencephalography data with which to analyze feedback-related negativity (FRN) as they played in the UG as responders. RESULTS: Manic patients exhibited significantly higher rejection rates for unfair offers than euthymic patients and healthy controls. Healthy individuals exhibited a greater (i.e., more negative) FRN amplitude in response to unfair offers than to fair offers, whereas euthymic patients exhibited a greater FRN amplitude in response to fair offers compared with unfair offers. Manic patients exhibited no difference in FRN amplitudes between fair and unfair offers. CONCLUSIONS: The current data suggest that different behavioral responses and FRN amplitude patterns can be associated with characteristic manifestations of mood instability in manic bipolar patients. In addition, electrophysiological alterations in response to unfair offers may be a trait abnormality independent of mood state.

Audiologic outcomes and complications of active middle ear implantation in older adults.

BACKGROUND: A few studies have reported the use of middle ear implants (MEIs) in older adults. OBJECTIVES: To evaluate the audiologic outcomes and postoperative complications of MEIs in older adults. METHODS: This retrospective study reviewed audiologic data and medical records from a single referral centre. We identified 34 patients aged ≥65 years who underwent middle ear implantation using the Vibrant SoundbridgeTM device. Preoperative audiometric testing and postoperative aided audiometric testing were performed to evaluate the functional hearing gain at 1 year postoperatively. Patients were divided into 2 groups depending on whether they underwent explantation because of poor hearing benefit. RESULTS: Follow-up duration ranged from <1 to 5.3 years. The functional gain with MEIs significantly improved relative to the preoperative air conduction thresholds at 0.5, 1, 2, and 4 kHz. Eight patients underwent explantation and 7 lost their external audio processor devices. Those who removed their implants because of the poor hearing (group 1) showed significantly worse hearing thresholds at 1 kHz and speech discrimination scores than the others (group 2). CONCLUSIONS AND SIGNIFICANCE: MEIs for auditory rehabilitation can provide improved speech recognition and significant functional gains in older adults. Patients must be given appropriate preoperative explanations regarding the expected outcomes.

Proxy and patients ratings on quality of life in patients with schizophrenia and bipolar disorder in Korea.

PURPOSE: This study aimed to assess the agreement between patient and proxy ratings of Quality of life (QoL) in patients with psychotic mental illnesses. METHODS: The abbreviated version of the WHO quality of life scale (WHOQOL-BREF) and 36-item short-form health survey (SF-36) were administered to patient-family proxy pairs of 81 schizophrenia patients with mild symptoms and 50 euthymic bipolar disorder patients. Paired t-tests and the intraclass correlation coefficient (ICC) were used to evaluate the level of agreement between patient and proxy ratings of QoL. RESULTS: At the group level, small standardized differences (0.0-0.3 for schizophrenia, 0.0-0.5 for bipolar disorder) between patient and proxy mean scores were found for most domains in both QoL measures. At the individual level, moderate to good agreement (ICC) was found (schizophrenia: ICC 0.4-0.7 on WHOQOL-BREF; 0.4-0.7 on SF-36; bipolar disorder: ICC 0.4-0.7 on WHOQOL-BREF; 0.6-0.7 on SF-36). The reported agreement was higher than that reported for similar measures in the psychiatric population. These results may be due to the fact that our subjects had mild clinical symptoms and frequent family interaction. CONCLUSION: These findings suggest that family proxy rating of patients' QoL can be used as a reasonable estimate of the patients' QoL for stable schizophrenia and bipolar patients in Korea.