Cholesterol side-chain cleavage enzyme deficiency caused by a novel homozygous variant in P450 sidechain cleavage enzyme gene (CYP11A1) in a 46,XX Korean girl

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother.Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS)

Background and Objectives@#Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. @*Methods@#and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. @*Conclusions@#Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

A Recognition Survey by Psychiatry Residents Regarding the Quality of Psychotherapy Training and Psychotherapy Competencies in Korea / 신경정신의학

Objectives@#This study surveyed the quality of psychotherapy training and psychotherapy competencies during residency in Korea. @*Methods@#A questionnaire developed by The Committee of Residency Training of the Korean Neuropsychiatric Association was completed by fourth-year residents of Korean psychiatry (n=120). The questionnaire examined their demographic characteristics, their experience of clinical psychotherapy training, their degree of satisfaction in the quality of psychotherapy training, and self-rated competence regarding the six types of psychotherapies, including supportive psychotherapy, cognitive behavioral therapy, interpersonal psychotherapy, psychoanalytic psychotherapy, group psychotherapy, and family psychotherapy. @*Results@#The degree of satisfaction of the residents with the psychotherapy training was diverse among the types of psychotherapy and contents of training. Across all types of psychotherapies, the satisfaction levels of the quantity and quality of supervision education were low, except for psychoanalytic psychotherapy. Overall, more than 70% of residents were not satisfied with the theoretical education, clinical practice, and supervision education in three types of psychotherapies, including interpersonal psychotherapy, group psychotherapy, and family psychotherapy. A positive correlation was found between the degree of satisfaction with the quality of training experience and self-rated competence of psychotherapy. Specifically, the self-rated competence of psychotherapy was more highly correlated with the experience of clinical cases and supervision than theoretical education @*Conclusion@#This study showed the quantitative and qualitative status of psychotherapy training in Korean psychiatry residency programs, and the satisfaction level of psychotherapy education was low except for psychoanalytic psychotherapy. There is a strong need for the improvement of psychotherapy training programs in Korea.

A Recognition Survey by Psychiatry Residents Regarding the Quality of Psychotherapy Training and Psychotherapy Competencies in Korea / 신경정신의학

Objectives@#This study surveyed the quality of psychotherapy training and psychotherapy competencies during residency in Korea. @*Methods@#A questionnaire developed by The Committee of Residency Training of the Korean Neuropsychiatric Association was completed by fourth-year residents of Korean psychiatry (n=120). The questionnaire examined their demographic characteristics, their experience of clinical psychotherapy training, their degree of satisfaction in the quality of psychotherapy training, and self-rated competence regarding the six types of psychotherapies, including supportive psychotherapy, cognitive behavioral therapy, interpersonal psychotherapy, psychoanalytic psychotherapy, group psychotherapy, and family psychotherapy. @*Results@#The degree of satisfaction of the residents with the psychotherapy training was diverse among the types of psychotherapy and contents of training. Across all types of psychotherapies, the satisfaction levels of the quantity and quality of supervision education were low, except for psychoanalytic psychotherapy. Overall, more than 70% of residents were not satisfied with the theoretical education, clinical practice, and supervision education in three types of psychotherapies, including interpersonal psychotherapy, group psychotherapy, and family psychotherapy. A positive correlation was found between the degree of satisfaction with the quality of training experience and self-rated competence of psychotherapy. Specifically, the self-rated competence of psychotherapy was more highly correlated with the experience of clinical cases and supervision than theoretical education @*Conclusion@#This study showed the quantitative and qualitative status of psychotherapy training in Korean psychiatry residency programs, and the satisfaction level of psychotherapy education was low except for psychoanalytic psychotherapy. There is a strong need for the improvement of psychotherapy training programs in Korea.

Impending Cardiac Tamponade and Hemorrhagic Pleural Effusion as Initial Presentations of Incomplete Kawasaki Disease: A Case Report

Kawasaki disease (KD) is an acute febrile illness that is characterized by systemic inflammation usually involving medium-sized arteries and multiple organs during the acute febrile phase, leading to associated clinical findings. The diagnosis is based on the principal clinical findings including fever, extremity changes, rash, conjunctivitis, oral changes, and cervical lymphadenopathy. However, KD diagnosis is sometimes overlooked or delayed because other systemic organ manifestations may predominate in acute phase of KD. As a cardiovascular manifestation, an acute pericarditis usually shows a small pericardial effusion, but large pericardial effusion showing clinical signs of cardiac tamponade is very rare. Here, we described a case of incomplete KD presenting with impending cardiac tamponade, and recurrent fever and pleural effusion.

Association between Colorectal Adenoma and Hand Grip Strength in the Elderly

BACKGROUND: Obesity is known as an important risk factor for colorectal adenoma. However, for the elderly with changes in body composition, reduced muscle, and increased fat, the body mass index (BMI), one of the most commonly used indicators of obesity, is limited in predicting a link to colorectal cancer. This study aimed to investigate the relationship between colorectal adenoma and grip strength that can predict muscle reduction in the elderly. METHODS: This study included 262 participants aged ≥65 years who underwent medical examination between June 2015 and August 2018. The control group comprised participants with normal findings or hyperplasia and other benign lesions, except adenoma on colonoscopy, whereas the adenoma group consisted of participants with more than one adenoma. Grip strength was alternately measured twice for each hand using a hydraulic dynamometer. RESULTS: The grip strength was statistically lower in the adenoma group than in the control group among women (P=0.042). For both sexes, grip strength was significantly lower in participants with ≥5 adenomas than in those with <5 adenomas (P=0.021, P=0.007). Similarly, men with large adenomas (≥7 mm) exhibited significantly lower grip strength than did those with small adenomas (<7 mm) (P=0.004). Even after correction for age, BMI, smoking status, alcohol consumption, exercise, insulin resistance, hypertension, and diabetes, the negative correlation between grip strength and number of adenomas among men and women remained (P=0.034, P=0.019). CONCLUSIONS: A significant relationship between hand grip strength and number of colorectal adenomas was noted.

Comparative analysis of case series for the prosthetic rehabilitation of edentulous patients using suction denture / 대한치과보철학회지

In patients with severely resorbed alveolar bone, it is difficult to gain retention in denture. Lack of retention makes denture unstable and lead to trouble in using denture. Suction denture seals the entire denture border with movable mucosa and this sealing mechanism forms negative pressure beneath the denture and produce higher retention and stability to denture. In this case, 4 edentulous patients visited for lack of retention with dentures. Considering their high expectation with retention, suction denture concept was used to fabricate retentive and stable denture. The purpose of this case report is to compare and analyze the considerations of suction denture restorations in edentulous patients.

Association between Educational Level of Parents and Adolescent Depression Feeling: Based on 14th Korean Youth Health Behavior Survey / 보건행정학회지

BACKGROUND@#This study aimed to demonstrate the association between the education level of parents and adolescent depression feeling.@*METHODS@#We used the chi-square test and the multiple logistic regression model to analyze the data of the “Korean Youth Health Behavior Survey in 2018” (n=43,220) conducted by the Korea Centers for Disease Control and Prevention.@*RESULTS@#As a result of the analysis, a group whose parents' education level is ‘above the university graduation (including the graduation of the college)’ had statistically significant experience of depression than a group whose parents' education level is ‘high school graduation.’@*CONCLUSION@#When preparing a policy on adolescent depression feeling, we need to consider the association between the education level of parents and adolescent depression feeling. Especially, a higher level of education of parents needs attention and management to foster positive mental health rather than excessive academic pressure, especially in the parent-child relationship of the same gender.

Long-term Treatment Outcome of Intravitreal Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy

PURPOSE: To evaluate long-term treatment outcomes of intravitreal aflibercept monotherapy for polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective review of medical records was performed with 46 patients who were diagnosed with PCV and treated with aflibercept monotherapy for 24 months. Best-corrected visual acuity (BCVA) values measured at diagnosis, 3 months, 12 months, and 24 months were compared. Baseline morphological factors associated with the 24 month BCVA were additionally investigated. RESULTS: The mean age of the patients was 65.8 ± 7.9 years. The patients were treated with a mean of 7.0 ± 2.3 aflibercept injections. The mean logarithm of the minimal angle of resolution (logMAR) BCVA at diagnosis, 3 months, 12 months, and 24 months was 0.56 ± 0.40, 0.36 ± 0.36, 0.45 ± 0.42, and 0.52 ± 0.47, respectively. When compared with baseline values, the BCVA was significantly improved at 3 months (p < 0.001) and 12 months (p = 0.022). However, the value at 24 months was not significantly different (p = 1.000). The BCVA was improved or maintained in 35 eyes (76.1%). Extrafoveal polypoidal lesions were associated with a better 24 month visual outcome than subfoveal/juxtafoveal lesions. CONCLUSIONS: Aflibercept monotherapy was found to be an effective method to maintain or improve long-term visual acuity in PCV patients. The location of polypoidal lesions was a predictive factor for long-term visual outcomes.

Cut-Off Values for Visceral Fat Area Identifying Korean Adults at Risk for Metabolic Syndrome / 가정의학회지

BACKGROUND: Cut-off values for visceral fat area (VFA) measured by computed tomography (CT) for identifying individuals at risk of metabolic syndrome (MetS) have not been clearly established in Korean adults, particularly for large populations. We aimed to identify optimal VFA and waist circumference (WC) cut-off values and compare the ability of VFA and WC to predict the presence of ≥2 metabolic risk factors. METHODS: We included 36,783 subjects aged 19–79 years undergoing abdominal fat CT during regular health checkups between January 2007 and February 2015 in Seoul. The risk factors for MetS except WC were based on the International Diabetes Federation criteria. Receiver operating characteristic curve analyses were used to determine the appropriate VFA and WC cut-off values for MetS. RESULTS: VFA was a more significant predictor of metabolic risk factors than WC and body mass index (BMI). The optimal cut-off values for VFA and WC were 134.6 cm2 and 88 cm for men and 91.1 cm2 and 81 cm for women, respectively. We estimated age-specific cut-off values for VFA, WC, and BMI. VFA cut-off values increased with age, particularly among women. CONCLUSION: This large population study proposed the cut-off values for VFA and WC for identifying subjects at risk of MetS among Korean adults. For more accurate diagnosis, different age-specific cut-off values for VFA and WC may be considered.

A Case of Refractory SAPHO Syndrome Treated with Etanercept

SAPHO syndrome, which has different skin changes and osteoarticular inflammation, is an acronym that stands for synovitis, acne, pustulosis, hyperostosis, and osteitis. Treatment of SAPHO syndrome includes non-steroidal anti-inflammatory drugs (NSAIDs), anti-rheumatic drugs, such as colchicines, corticosteroids and bisphosphonates, and disease-modifying agents. However, the treatment of SAPHO syndrome is controversial because it is a new clinical entity with unclear etiopathogenesis and inadequate clinical studies. We report a case with refractory SAPHO syndrome, which was successfully treated with a tumor necrosis factor (TNF)-alpha blocker.

Hyperprolactinemia-Associated Breast Uptake of Radioiodine Following 131I Postablation Scan in Differentiated Thyroid Cancer

Scanning with whole-body 131I scintigraphy after surgery has been a valuable diagnostic modality in the surveillance of patients with differentiated thyroid cancer. Radioiodine uptake is rarely observed in non-lactating breast tissue, which mimics thyroid cancer metastasis. We now report a case of a 45-year-old female thyroid cancer patient who underwent radioiodine therapy, and in whom breast uptake of radioiodine was observed on a post-therapy whole body scan. Her serum prolactin level was elevated to 328 ng/mL at the time of the radioiodine uptake, and the hyperprolactinemia was induced by her antipsychotic medications. Six months after she discontinued that medication, her serum prolactin level was normalized to 12.6 ng/mL and breast uptake of iodine was no longer present in a follow-up whole body scan.

In vivo and in vitro antiviral effects of berberine on influenza virus / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the potential effects of berberine on influenza virus infection both in vitro and in vivo.</p><p><b>METHODS</b>In vitro anti-influenza virus assays were performed by cytopathogenic effect and neuraminidase assays in Madin Darby canine kidney cells. In vivo anti-influenza virus assays were performed on the viral pneumonia model of mice. The numbers of mice that died within day 2 to day 14 postinfection were recorded to calculate the mortality. On days 2, 4, and 6, the viral titers in the lungs were determined by hemagglutination assay; hematoxylin/eosin staining was used to assess the pathogenic changes of lung tissues; the concentrations of tumor necrosis factor-alpha (TNF-α) and monocyte specific chemoattractant molecule (MCP-1) were measured by radio immunoassay or enzyme-linked immunosorbent assay; the concentrations of nitric oxide (NO) and inducible nitric oxide synthetase (iNOS) were detected by colorimetric method; reverse transcription polymerase chain reaction was used to detect the mRNA level of TNF-α and MCP-1.</p><p><b>RESULTS</b>Berberine showed inhibitory effects on cytopathogenic effects and neuraminidase activity of virus, with the therapeutic index 9.69. In vivo, berberine decreased mice mortality from 90% to 55%, reduced virus titers in the lungs on day 2 postinfection (P<0.05). The lung histology scores were 1.50 ± 0.67, 4.50 ± 1.00, and 5.50 ± 1.00 in the berberine group on days 2, 4, and 6, respectively, which were significantly reduced compared to 2.17 ± 0.22, 6.83 ± 0.44, and 8.50 ± 0.33 in the infected group (P<0.05). The productions of NO and iNOS were repressed by berberine compared with those in the infected group (P<0.01). The transcription and expression of TNF-α were inhibited by berberine on day 4 (P<0.01) and day 6 (P<0.05), and those of MCP-1 were inhibited on day 6 (P<0.01) compared with the infected group.</p><p><b>CONCLUSIONS</b>Berberine exhibited antiviral effects on the influenza virus both in vitro and in vivo. The possible therapeutic mechanism of berberine on influenza-induced viral pneumonia might be inhibiting the virus infection, as well as improving the pathogenic changes by repressing inflammatory substances release.</p>

Rifampin-induced Pseudomembranous Colitis with Rectosigmoid Sparing

Pseudomembranous colitis (PMC) is known to be associated with antibiotic treatment, but is not commonly related to antitubercular (anti-TB) agent, rifampin. PMC is frequently localized to rectum and sigmoid colon, which can be diagnosed with sigmoidoscopy. We report a case of rifampin-induced PMC with rectosigmoid sparing in a pulmonary tuberculosis patient. An 81-year-old man using anti-TB agents was admitted with a 30-day history of severe diarrhea and general weakness. On colonoscopy, nonspecific findings such as mucosal edema and erosion were found in sigmoid colon, whereas multiple yellowish plaques were confined to cecal mucosa only. Biopsy specimen of the cecum was compatible with PMC. Metronidazole was started orally, and the anti-TB medications excluding rifampin were readministerred. His symptoms remarkably improved within a few days without recurrence. Awareness of rectosigmoid sparing PMC in patients who develop diarrhea during anti-TB treatment should encourage early total colonoscopy.

PPARgamma Agonist and Angiotensin II Receptor Antagonist Ameliorate Renal Tubulointerstitial Fibrosis

The peroxisome proliferator activated receptor (PPAR)gamma agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARgamma agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-beta1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-beta/Smad2 in the treated groups, PAI-1 and TGF-beta are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARgamma agonist might be used in the treatment of renal fibrotic disease.

Prognostic Significance of Thymosin- 4 in Gastric Adenocarcinoma Patients

Background : Thymosin- 4 is an actin-sequestering protein that regulates actin polymerization. It is known to be associated with cell migration, angiogenesis and wound healing, as well as with tumor metastasis. Methods : We immunohistochemically evaluated the thymosin- 4 expression in gastric adenocarcinoma specimens, the relationship between this protein and the pathologic features and other tumor-related proteins, and its influence on the patient outcome. Results : We demonstrated that 40 specimens (26.3%) of 152 gastric adenocarcinomas showed positivity for thymosin- 4. The thymosin- 4 expression was statistically associated with advanced tumor stage (p=0.010), the nodal stage (p=0.029), the TNM stage (p=0.008), and the presence of lymphovascular invasion (p=0.009). The thymosin- 4 protein expression was closely related to the positivity for VEGF (p=0.000), c-Myc (p=0.007), and cyclin D1 (p=0.005), but it was not associated with the E-cadherin (p=0.861) or -catenin (p=0.640) expressions. The median survival and disease relapse time of patients showing thymosin-4 immunoreactivity were statistically shorter than those of patients without expression. Multivariate analysis showed that the tumor stage (p=0.003), nodal stage (p=0.005), thymosin- 4 expression (p=0.019) and Lauren's classification (p=0.037) were statistically important prognostic factors for gastric adenocarcinomas. Conclusions : The thymosin- 4 expression might be associated with disease progression of gastric adenocarcinomas and it should be regarded as an important prognostic factor for estimating patient survival.