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Asthma is a heterogeneous disease that can be broadly classified into type 2, which is primarily steroid-sensitive and eosinophilic, and non-type 2, which is primarily steroid-resistant and neutrophilic. While the mechanisms leading to the development of molecular-targeted therapies for type 2 asthma are being elucidated, much remains to be learned about non-type 2 asthma. To investigate the role of oxidative stress in refractory allergic airway inflammation, we compared asthma models generated by immunizing wild-type and nuclear factor erythroid-2-related factor 2 (Nrf2)-deficient mice with the house dust mite antigen. Both asthma models had similar levels of airway inflammation and hyperresponsiveness, but the Nrf2-deficient mice had increased oxidative stress and exacerbated neutrophilic airway inflammation compared with the wild-type mice. Type 2 cytokines and the expression of GATA3, a transcription factor that is important for Th2 cell differentiation, had decreased in Nrf2-deficient mice compared with the wild-type mice, whereas helper T (Th) 17 cytokines and the expression of RORγt, which is important for Th17 cell differentiation, had increased. Furthermore, the neutrophilic airway inflammation caused by Nrf2 deficiency was ameliorated by interleukin (IL)-17 neutralization. We have concluded that the disruption of the Nrf2-mediated antioxidant defense system contributed to the induction of Th17 differentiation and exacerbated allergic neutrophilic airway inflammation.
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Yellow nail syndrome (YNS) can induce bilateral exudative pleural effusion; however, to the best of our knowledge, no standard treatment for YNS has been established. The present study describes a patient with YNS for whom the pleural effusion was controlled by prednisolone. A 73-year-old man was referred to the University of Tsukuba Hospital (Ibaraki, Japan) complaining of shortness of breath, which was diagnosed as being due to bilateral pleural effusion. Based on the presence of yellowing and growth retardation of the toenails, lymphedema, bilateral exudative pleural fluid of unknown etiology, and lymphatic congestion on lymphoscintigraphy, the patient was diagnosed with YNS. The pleural fluid was predominantly lymphocytic and responded to systemic steroid administration [prednisolone 30 mg/day (0.5 mg/kg) for 2 weeks, with subsequent weekly tapering]. The general condition of the patient and their dyspnea also improved with treatment. These findings indicated that systemic steroid administration should be considered as one of the treatment options for patients with YNS who are reluctant to undergo chest drainage or pleurodesis due to the potential for a decrease in their ability to perform daily activities and respiratory function.
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Antiasmáticos , Anticorpos Monoclonais Humanizados , Asma , Eosinófilos , Fenótipo , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Asma/sangue , Eosinófilos/imunologia , Antiasmáticos/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Eosinofilia/tratamento farmacológico , Eosinofilia/sangue , Adulto , Contagem de Leucócitos , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Recent advances in fatty acid analysis have highlighted the links between lipid disruption and disease development. Lipid abnormalities are well-established risk factors for many of the most common chronic illnesses, and their involvement in asthma is also becoming clear. Here, we review research demonstrating the role of abnormal lipid metabolism in asthma, with a focus on saturated fatty acids and sphingolipids. High levels of palmitic acid, the most abundant saturated fatty acid in the human body, have been found in the airways of asthmatic patients with obesity, and were shown to worsen eosinophilic airway inflammation in asthma model mice on a high-fat diet. Aside from being a building block of longer-chain fatty acids, palmitic acid is also the starting point for de novo synthesis of ceramides, a class of sphingolipids. We outline the three main pathways for the synthesis of ceramides, which have been linked to the severity of asthma and act as precursors for the dynamic lipid mediator sphingosine 1-phosphate (S1P). S1P signaling is involved in allergen-induced eosinophilic inflammation, airway hyperresponsiveness, and immune-cell trafficking. A recent study of mice with mutations for the elongation of very long-chain fatty acid family member 6 (Elovl6), an enzyme that elongates fatty acid chains, has highlighted the potential role of palmitic acid composition, and thus lipid balance, in the pathophysiology of allergic airway inflammation. Elovl6 may be a potential therapeutic target in severe asthma.
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Asma , Ceramidas , Elongases de Ácidos Graxos , Ácidos Graxos , Metabolismo dos Lipídeos , Ácido Palmítico , Esfingolipídeos , Asma/metabolismo , Asma/etiologia , Humanos , Animais , Esfingolipídeos/metabolismo , Ceramidas/metabolismo , Camundongos , Ácidos Graxos/metabolismo , Ácido Palmítico/metabolismo , Elongases de Ácidos Graxos/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Acetiltransferases/metabolismo , Modelos Animais de Doenças , Obesidade/metabolismo , Transdução de Sinais , Dieta Hiperlipídica/efeitos adversosRESUMO
BACKGROUND: Junctional epidermolysis bullosa is a rare skin and mucosal disorder characterized by blister formation in response to minor trauma and extracutaneous manifestations. There have been no reports of cardiac surgery and prognostication in patients with epidermolysis bullosa due to skin and mucosal fragility. CASE PRESENTATION: A 55-year-old man presented with congenital junctional epidermolysis bullosa, hypertension, and vasospastic angina. He complained of dyspnea on exertion, and transthoracic echocardiography revealed severe aortic valve regurgitation, moderate aortic valve stenosis (tricuspid valve), and severe mitral valve regurgitation. Considering that the skin condition in the right chest wall was relatively healthy, the right thoracotomy approach was preferred and totally endoscopic concomitant mitral valve repair and aortic valve replacement were performed using a sutureless bioprosthetic valve (Perceval™ (Corcym, Group, Milan, Italy)). Polyurethane and silicon dressing foams were used to protect the skin at the site of contact with the bag valve mask, arterial pressure catheter, intravenous catheter, and the tracheal intubation tube. Vertical mattress sutures were used for the skin sutures. The postoperative course was uneventful, and the patient was discharged nine days after the operation. There was no indication for reoperation until three years follow-up period. CONCLUSIONS: The totally endoscopic concomitant aortic and mitral valve surgery using Perceval™ prosthesis can be performed safely in patients with junctional epidermolysis bullosa by adequate protection of the skin and mucosa.
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Procedimentos Cirúrgicos Cardíacos , Epidermólise Bolhosa Juncional , Insuficiência da Valva Mitral , Masculino , Humanos , Pessoa de Meia-Idade , Epidermólise Bolhosa Juncional/complicações , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Vesícula , Valva Aórtica/cirurgiaRESUMO
Objectives: This study aimed to determine the relationship between covering the intercostal artery branching of the Adamkiewicz artery (ICA-AKA) and spinal cord ischemia (SCI) during thoracic endovascular aortic repair (TEVAR). Methods: Patients who underwent TEVAR from 2008 to 2022 were enrolled. Stent grafts covered the ICA-AKA in 108 patients (covered AKA group) and stent grafts didn't cover the ICA-AKA in 114 patients (uncovered AKA group). The characteristics of 58 patients from each group were matched based on propensity scores. Results: No significant differences in SCI rates were detected between the covered AKA (10%; 11/108) and uncovered AKA (3.5%; 4/114) groups (P = .061). Shaggy aorta (odds ratio [OR], 5.16; 95% confidence interval [CI], 1.74-15.3, P = .003), iliac artery access (OR, 6.81; 95% CI, 2.22-20.9, P = .001), and procedural time (OR, 1.01; 95% CI, 1.00-1.02, P = .003) were risk factors for SCI in the entire cohort. Although covering the ICA-AKA (OR, 2.60; 95% CI, 0.86-7.88, P = .058) was not a significant risk factor, shaggy aorta (OR, 8.15; 95% CI, 2.07-32.1, P = .003), iliac artery access (OR, 9.09; 95% CI, 2.22-37.2, P = .002), and procedural time (OR, 1.01; 95% CI, 1.01-1.02, P = .008) were risk factors for SCI in the covered AKA group. No significant risk factors were detected in the uncovered AKA group. Conclusions: Covering the ICA-AKA was not an independent risk for SCI in TEVAR. However, covering the ICA-AKA was indirectly associated with the risk of SCI in patients with shaggy aorta, iliac access, and procedural time.
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BACKGROUND: A short yet reliable cognitive measure is needed that separates treatment and placebo for treatment trials for Alzheimer's disease. Hence, we aimed to shorten the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) and test its use as an efficacy measure. METHODS: Secondary data analysis of participant-level data from five pivotal clinical trials of donepezil compared with placebo for Alzheimer's disease (N = 2,198). Across all five trials, cognition was appraised using the original 11-item ADAS-Cog. Statistical analysis consisted of sample characterization, item response theory (IRT) to identify an ADAS-Cog short version, and mixed models for repeated-measures analysis to examine the effect sizes of ADAS-Cog change on the original and short versions in the placebo versus donepezil groups. RESULTS: Based on IRT, a short ADAS-Cog was developed with seven items and two response options. The original and short ADAS-Cog correlated at baseline and at weeks 12 and 24 at 0.7. Effect sizes based on mixed modeling showed that the short and original ADAS-Cog separated placebo and donepezil comparably (ADAS-Cog original ES = 0.33, 95% CI = 0.29, 0.40, ADAS-Cog short ES = 0.25, 95% CI =0.23, 0.34). CONCLUSIONS: IRT identified a short ADAS-cog version that separated donepezil and placebo, suggesting its clinical potential for assessment and treatment monitoring.
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Doença de Alzheimer , Transtornos Cognitivos , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Donepezila/uso terapêutico , CogniçãoRESUMO
Subthreshold depression impairs young people's quality of life and places them at greater risk of developing major depression. Cognitive behavioral therapy (CBT) is an evidence-based approach for addressing such depressive states. This study identified subtypes of university students with subthreshold depression and revealed discrete profiles of five CBT skills: self-monitoring, cognitive restructuring, behavioral activation, assertive communication, and problem solving. Using data from the Healthy Campus Trial (registration number: UMINCTR-000031307), a hierarchical clustering analysis categorized 1,080 students into three clusters: Reflective Low-skilled, Non-reflective High-skilled, and Non-reflective Low-skilled students. Non-reflective Low-skilled students were significantly more depressed than other students (p < .001). The severity of depression seemed to be related to the combination of self-monitoring skills and other CBT skills. Considering the high prevalence of poor self-monitoring skills in persons with autism, the most severe depression was observed in the significant association between Non-reflective Low-skilled students and autistic traits (p = .008). These findings suggest that subthreshold depression can be categorized into three subtypes based on CBT skill profiles. The assessment of autistic traits is also suggested when we provide CBT interventions for Non-reflective Low-skilled students.
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Depressão , Qualidade de Vida , Humanos , Adolescente , Depressão/terapia , Universidades , Estudantes/psicologia , CogniçãoAssuntos
Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagemRESUMO
A 17-year-old male complained of exertional dyspnea and was referred to our hospital after he was diagnosed with a right coronary artery fistula into the left ventricle. Surgical repair was considered to improve the symptoms. We identified the distal end of the right coronary artery entering the left ventricle under cardiopulmonary bypass with cardiac arrest. The fistula was transected at the distal end of the right coronary artery and closed at both ends without incision of the left ventricle. Coronary angiography revealed the patency of the right coronary artery and the peripheral branches four months after surgery. The coronary computed tomography four years and four months after operation showed no pseudoaneurysm formation, no thrombosis, and subsequent regression of the dilated right coronary artery. Learning objective: The coronary artery fistula is a rare congenital anomaly, and the treatment strategies of the coronary fistula are controversial. We performed ligation of the coronary fistula under cardiac arrest on cardiopulmonary bypass without incision of the left ventricle. This strategy may contribute to the accurate identification and ligation of the fistula without pseudoaneurysm formation.
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A 69-year-old male was referred to our hospital due to extensive thoracic aortic aneurysm with right aortic arch and isolated left subclavian artery. We chose staged hybrid repair to avoid the risk of spinal cord injury and bilateral recurrent nerve paralysis. First, ascending aorta replacement with elephant trunk and reconstruction of the cervical branches were underwent. Second, we performed the thoracic endovascular aortic repair for aortic arch and descending aortic aneurysm. The postoperative course was satisfactory and, computed tomography (CT) showed successful aortic repair without any type of endoleak. He was discharged on the ninth day after the second operation. To our knowledge, this is the first report of surgical repair for an aortic aneurysm with right aortic arch and isolated subclavian artery.
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Aneurisma da Aorta Torácica , Aneurisma Aórtico , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Humanos , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma Aórtico/cirurgia , Resultado do Tratamento , Stents , Procedimentos Endovasculares/métodosRESUMO
BACKGROUND: Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear. OBJECTIVES: This study sought to evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma. METHODS: Expressions of ELOVL6 and other isoforms were examined in the airways of patients who are severely asthmatic and in mouse models of asthma. Wild-type and ELOVL6-deficient (Elovl6-/-) mice were analyzed for ovalbumin-induced, and also for house dust mite-induced, allergic airway inflammation by cell biological and biochemical approaches. RESULTS: ELOVL6 expression was downregulated in the bronchial epithelium of patients who are severely asthmatic compared with controls. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides, and sphingosine-1-phosphate were higher in the lungs of ovalbumin-immunized Elovl6-/- mice compared with those of wild-type mice, while the aggravated airway inflammation was ameliorated by treatment with fumonisin B1 or DL-threo-dihydrosphingosine, inhibitors of ceramide synthase and sphingosine kinase, respectively. CONCLUSIONS: This study illustrates a crucial role for ELOVL6 in controlling allergic airway inflammation via regulation of fatty acid composition and ceramide-sphingosine-1-phosphate biosynthesis and indicates that ELOVL6 may be a novel therapeutic target for asthma.
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Asma , Ceramidas , Animais , Camundongos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Ovalbumina/efeitos adversosRESUMO
BACKGROUND: Internet-cognitive behavioural therapy (iCBT) for depression can include multiple components. This study explored depressive symptom improvement prognostic factors (PFs) and effect modifiers (EMs) for five common iCBT components including behavioural activation, cognitive restructuring, problem solving, self-monitoring, and assertion training. METHODS: We used data from a factorial trial of iCBT for subthreshold depression among Japanese university students (N = 1093). The primary outcome was the change in PHQ-9 scores at 8 weeks from baseline. Interactions between each component and various baseline characteristics were estimated using a mixed-effects model for repeated measures. We calculated multiplicity-adjusted p-values at 5 % false discovery rate using the Benjamini-Hochberg procedure. RESULTS: After multiplicity adjustment, the baseline PHQ-9 total score emerged as a PF and exercise habits as an EM for self-monitoring (adjusted p-values <0.05). The higher the PHQ-9 total score at baseline (range: 5-14), the greater the decrease after 8 weeks. For each 5-point increase at baseline, the change from baseline to 8 weeks was bigger by 2.8 points. The more frequent the exercise habits (range: 0-2 points), the less effective the self-monitoring component. The difference in PHQ-9 change scores between presence or absence of self-monitoring was smaller by 0.94 points when the participant exercised one level more frequently. Additionally, the study suggested seven out of 36 PFs and 14 out of 160 EMs examined were candidates for future research. LIMITATIONS: Generalizability is limited to university students with subthreshold depression. CONCLUSIONS: These results provide some helpful information for the future development of individualized iCBT algorithms for depression.
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Terapia Cognitivo-Comportamental , Depressão , Humanos , Depressão/terapia , Universidades , Prognóstico , Terapia Cognitivo-Comportamental/métodos , Internet , Estudantes , Resultado do TratamentoRESUMO
There is insufficient research on the usefulness of psychological interventions, such as psychological first aid (PFA), during outbreaks. We searched for and critically appraised systematic reviews that examined the effectiveness of PFA during infectious disease outbreaks, such as the novel coronavirus disease (COVID-19). Systematic reviews that examined the efficacy of PFA in the severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus, Ebola virus disease, and COVID-19 outbreaks were searched through PubMed on February 19, 2021. The three included systematic reviews were critically appraised and assessed using AMSTAR-2. One review's overall confidence in its findings was evaluated as "high," which suggested that PFA training had a favorable effect on healthcare personnel. Furthermore, the review also demonstrated that PFA was commonly used during outbreaks and could be delivered through multiple methods, such as a phone or video call. Although it was anticipated that PFA would improve subjective well-being, reports showed no evidence of reduced depression or insomnia. Future studies should examine additional numbers of PFA recipients and conduct quasi-experimental studies to better understand the effectiveness of PFA. Evidence on its effectiveness in infectious disease outbreaks is still lacking, along with research and evaluation methods. Quasi-experimental studies, such as comparisons with other psychological interventions, are required to better understand the effectiveness of PFA.
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Background: Perioperative management of body fluid levels after cardiovascular surgery with cardiopulmonary bypass is essential. Fluid management using tolvaptan with conventional diuretics is effective in maintaining urine output without worsening renal function. This study aimed to improve the in-out balance in the early perioperative phase using low-dose tolvaptan (3.75 mg/day). MethodsâandâResults: This prospective, single-center, randomized, open-label study included 199 patients who underwent cardiovascular surgery with cardiopulmonary bypass in Kobe City Medical Center General Hospital between September 2018 and December 2020. Treatment with tolvaptan and loop diuretics (tolvaptan group; 99 patients) was compared with treatment with loop diuretics alone (control group; 100 patients) to evaluate achievement of preoperative body weight as the primary outcome. Secondary outcomes were urine volume, the incidence of worsening renal function (WRF), and postoperative paroxysmal atrial fibrillation (POAF). There was no significant difference between groups in the return to preoperative body weight on postoperative Day 6. The tolvaptan group had significantly increased urine volume (2,530 vs. 2,150 mL/day) and decreased total furosemide dose (24 vs. 32 mg) compared with the control group. No significant differences were observed in the development of WRF and POAF between the 2 groups. Conclusions: Although low-dose tolvaptan administration did not shorten the time to achieving preoperative body weight, it did significantly increase urine volume without WRF and POAF.
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Rupture of intercostal artery aneurysms has been reported in patients with neurofibromatosis type 1. Many reports have demonstrated the efficacy of endovascular interventions. Herein, we present a case of successful treatment with thoracic endovascular aortic repair for traction-induced avulsion injury of the previously embolized intercostal artery. We further report the potential postoperative risk of rapid aneurysmal enlargement, possibly owing to changes in the thoracic arterial regional network. Even after successful treatment, vascular surgeons should pay attention to other aneurysmal events in the acute phase and avulsion injuries in the chronic phase. Close follow-up is essential.
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BACKGROUND: Patient characteristics may predict the progression of Alzheimer's disease (AD) and may moderate the effects of donepezil. OBJECTIVE: To build a personalized prediction model for patients with AD and to estimate patient-specific treatment effects of donepezil, using individual patient characteristics. METHODS: We systematically searched for all double-masked randomized controlled trials comparing oral donepezil and pill placebo in the treatment of AD and requested individual participant data through its developer, Eisai. The primary outcome was cognitive function at 24 weeks, measured with the Alzheimer's Disease Assessment Scale-cognitive component (ADAS-cog). We built a Bayesian meta-analytical prediction model for patients receiving placebo and we performed an individual patient data meta-analysis to estimate patient-level treatment effects. RESULTS: Eight studies with 3,156 participants were included. The Bayesian prediction model suggested that more severe cognitive and global function at baseline and younger age were associated with worse cognitive function at 24 weeks. The individual participant data meta-analysis showed that, on average, donepezil was superior to placebo in cognitive function (ADAS-cog scores, -3.2; 95% Credible Interval (CrI) -4.2 to -2.1). In addition, our results suggested that antipsychotic drug use at baseline might be associated with a lower effect of donepezil in ADAS-cog (2.0; 95% CrI, -0.02 to 4.3). CONCLUSION: Although our results suggested that donepezil is somewhat efficacious for cognitive function for most patients with AD, use of antipsychotic drugs may be associated with lower efficacy of the drug. Future research with larger sample sizes, more patient covariates, and longer treatment duration is needed.
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Doença de Alzheimer , Antipsicóticos , Humanos , Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/uso terapêutico , Teorema de Bayes , Inibidores da Colinesterase/uso terapêutico , Donepezila/uso terapêutico , Indanos/uso terapêutico , Piperidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The Japanese Big Five Scale Short Form (JBFS-SF), a 29-item self-report scale, has recently been used to measure the Big Five personality traits. However, the scale lacks psychometric validation. This study examined the validity and reliability of the JBFS-SF with data collected from 1,626 Japanese university students participating in a randomized controlled clinical trial. Structural validity was tested with exploratory and confirmatory factor analysis and measurement invariance tests were conducted across sex. Internal consistency was evaluated with McDonald's omega. Additionally, construct validity was estimated across factors using the PHQ-9, GAD-7, AQ-J-10, and SSQ. EFA results showed that the JBFS-SF can be classified according to the expected five-factor structure, while three items had small loadings. Therefore, we dropped these three items and tested the reliability and validity of the 26-item version. CFA results found that a 26-item JBFS-FS has adequate structural validity (GFI = 0.907, AGFI = 0.886, CFI = 0.907, and RMSEA = 0.057). The omega of each factor was 0.74-0.85. Each JBFS-SF factor was specifically correlated with the PHQ-9, GAD-7, and SSQ. This research has shown that the JBFS-SF can be a clinically useful measure for assessing personality characteristics.