Left-Sided Poland’s Syndrome without Limb Anomalies

“Poland’s syndrome” is a rare congenital disease whereby defects can accompany the chest, nipple, chest wall, and extremities on one side of the body. We diagnosed a 19-year-old male patient who presented to another hospital for a routine physical exam before enlisting in the military and was suspected of having a left brachial plexus injury. His chief complaint was the flatness of the left anterior chest wall without any significant functional inconvenience. Aplasia of the pectoralis minor and costosternal portion of the pectoralis major was observed through physical examination and computed tomography (CT). The patient was diagnosed with left-sided Poland’s syndrome without any limb abnormalities. Poland Syndrome should be highly considered in patients presenting with bilateral chest wall imbalance in the absence of with a recent traumatic history.

Persistent Symptoms After Acute COVID-19 Infection in Omicron Era

Background@#We aim to compare the clinical characteristics and subjectively reported symptoms of the acute coronavirus disease (COVID) phase and those of the post-acute COVID phase to examine varying factors that affect the number of persistent symptoms and their categories. @*Methods@#We categorized 1,122 patients who visited the post coronavirus disease 2019 (COVID-19) clinic into two groups: “acute group” ( 4 weeks following diagnosis of COVID-19). We statistically compared clinical characteristics between the two groups and determined which factors are associated with the number of persistent symptoms and their categories. @*Results@#The persistent symptoms of post COVID-19 conditions were classified into three categories as follows: Category A (the prevalence of symptoms is higher in the acute-visit group than in the post-acute-visit group), Category B (the prevalence of symptoms is not different between the two groups) and Category C (the prevalence of symptoms is higher in the post-acute-visit group than in the acute-visit group). Category A mainly included respiratory symptoms. Category B had generalized weakness, weight loss, cardiologic symptoms, hypogeusia, hyposmia, anxiety, and various gastrointestinal symptoms. Category C included fatigue, decreased attention, depression, blurred vision, hair loss, and sexual dysfunction.Anxiety, depression, fatigue and age were also associated with the number of symptoms and their categories, and anxiety is the most correlated factor (P < 0.001) among them. @*Conclusion@#The persistent symptoms of post COVID-19 condition involve multi-organ and continue for four weeks or greater. Therefore, long-term observation and multidisciplinary interventions are essential for patients with post COVID-19 conditions.

Cognitive and Emotional Empathy in Young Adolescents: an fMRI Study

Objectives@#We investigated the differences in cognitive and emotional empathic ability between adolescents and adults, and the differences of the brain activation during cognitive and emotional empathy tasks. @*Methods@#Adolescents (aged 13–15 years, n=14) and adults (aged 19–29 years, n=17) completed a range of empathic ability questionnaires and were scanned functional magnetic resonance imaging (fMRI) during both cognitive and emotional empathy task. Differences in empathic ability and brain activation between the groups were analyzed. @*Results@#Both cognitive and emotional empathic ability were significantly lower in the adolescent compared to the adult group. Comparing the adolescent to the adult group showed that brain activation was significantly greater in the right transverse temporal gyrus (BA 41), right insula (BA 13), right superior parietal lobule (BA 7), right precentral gyrus (BA 4), and right thalamus whilst performing emotional empathy tasks. No brain regions showed significantly greater activation in the adolescent compared to the adult group while performing cognitive empathy task. In the adolescent group, scores of the Fantasy Subscale in the Interpersonal Reactivity Index, which reflects cognitive empathic ability, negatively correlated with activity of right superior parietal lobule during emotional empathic situations (r=-0.739, p=0.006). @*Conclusion@#These results strongly suggest that adolescents possess lower cognitive and emotional empathic abilities than adults do and require compensatory hyperactivation of the brain regions associated with emotional empathy or embodiment in emotional empathic situation. Compensatory hyperactivation in the emotional empathy-related brain areas among adolescents are likely associated with their lower cognitive empathic ability.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L).We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

Brain Activation Related to Perspective-Taking in Adolescents: Differences from Adults

OBJECTIVES: The purpose of this study was to investigate the differences between adolescents and adults, in the perspective-taking ability, as well as the brain activation patterns during the perspective-taking situation.METHODS: We recruited healthy adolescents aged 13 years to 15 years (n = 20) and adults aged 19 years to 29 years (n = 20). All the subjects were scanned while performing the perspective-taking task, in which an emotional situation was presented in the form of statements comprising first person, as well as third person perspectives. Differences in brain activation between groups were assessed by contrasting neural activity during the tasks.RESULTS: In the between-group analysis, while performing the third-person perspective-taking task, the adolescent group showed greater neural activities in the middle frontal gyrus and precentral gyrus as compared to the adult group. Positive correlation was observed between the activity in the frontal areas (Brodmann area 6/9) and the score of scales related to perspective-taking and social cognition in the adolescent group.CONCLUSIONS: This study suggests that several frontal brain areas of adolescents needs to be overactivated in order to compensate for low perspective-taking ability when they ought to take another person's point of view.

A De Novo RAPGEF2 Variant Identified in a Sporadic Amyotrophic Lateral Sclerosis Patient Impairs Microtubule Stability and Axonal Mitochondria Distribution

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is frequently linked to microtubule abnormalities and mitochondrial trafficking defects. Whole exome sequencing (WES) of patient-parent trios has proven to be an efficient strategy for identifying rare de novo genetic variants responsible for sporadic ALS (sALS). Using a trio-WES approach, we identified a de novo RAPGEF2 variant (c.4069G>A, p.E1357K) in a patient with early-onset sALS. To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila. Patient fibroblasts display reduced microtubule stability and defective microtubule network morphology. The intracellular distribution, ultrastructure, and function of mitochondria are also impaired in patient cells. Overexpression of the RAPGEF2 mutant in Drosophila motor neurons reduces the stability of axonal microtubules and disrupts the distribution of mitochondria to distal axons and neuromuscular junction (NMJ) synapses. We also show that the recruitment of the pro-apoptotic protein BCL2-associated X (BAX) to mitochondria is significantly increased in patient fibroblasts compared with control cells. Finally, increasing microtubule stability through pharmacological inhibition of histone deacetylase 6 (HDAC6) rescues defects in the intracellular distribution of mitochondria and BAX. Overall, our data suggest that the RAPGEF2 variant identified in this study can drive ALS-related pathogenic effects through microtubule dysregulation.

Autism and Beauty: Neural Correlates of Aesthetic Experiences in Autism Spectrum Disorder

OBJECTIVES: The purpose of this study was to investigate whether the neural activity of autism spectrum disorder (ASD) patients is different from that of normal individuals when performing aesthetic judgments. METHODS: We recruited typical ASD patients without savant skills (ASD group, n=17) and healthy controls (HC group, n=19) for an functional magnetic resonance imaging study. All subjects were scanned while performing aesthetic judgment tasks on two kinds of artwork (magnificent landscape images and fractal images). Differences in brain activation between the two groups were assessed by contrasting neural activity during the tasks. RESULTS: The aesthetic judgment score for all images was significantly lower in the ASD group than in the HC group. During the aesthetic judgment tasks, the ASD group showed less activation than the HC group in the anterior region of the superior frontal gyrus, and more activation in the temporoparietal area and insula, regardless of the type of images being judged. In addition, during the aesthetic judgment task for the fractal images, the ASD group exhibited greater neural activity in the amygdala and the posterior region of the middle/inferior temporal gyrus (Brodmann area 37) than the HC group. CONCLUSION: The results of this study suggest that the brain activation patterns associated with aesthetic experiences in ASD patients may differ from those of normal individuals.

Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.

Neural Correlates of Cognitive and Emotional Empathy in Patients with Autism Spectrum Disorder

OBJECTIVES: Individuals with autism spectrum disorder (ASD) are considered to have problems with empathy. It has recently been suggested that there are two systems for empathy; cognitive and emotional. We aimed to investigate the neural response to cognitive and emotional empathy and elucidate the neurobiological aspects of empathy in patients with ASD. METHODS: We recruited patients with ASD (N=17, ASD group) and healthy controls (HC) (N=22, HC group) for an functional magnetic resonance imaging study. All of the subjects were scanned while performing cognitive and emotional empathy tasks. The differences in brain activation between the groups were assessed by contrasting their neural activity during the tasks. RESULTS: During both tasks, the ASD group showed greater neural activities in the bilateral occipital area compared to the HC group. The ASD group showed more activation in the bilateral precunei only during the emotional empathy task. No brain regions were more activated in the HC group than in the ASD group during the cognitive empathy task. While performing the emotional empathy task, the HC group exhibited greater neural activities in the left middle frontal gyrus and right anterior cingulate gyrus than the ASD group. CONCLUSION: This study showed that the brain regions associated with cognitive and emotional empathy in ASD patients differed from those in healthy individuals. The results of this study suggest that individuals with ASD might have defects both in cognitive empathy and in emotional empathy.

What is Neuroaesthetics? : A New Paradigm in Psychiatry / 신경정신의학

Neuroaesthetics is an area of research on the essence of aesthetic experience according to the neurobiological perspective. The purpose of this article is to introduce both the important results from some studies based on neuroaesthetics and some neuroaesthetic reports in specific psychiatric disease. Aesthetic experience is thought to be a series of cognitive and affective processes for pursuing aesthetic judgment and aesthetic emotion. According to the present neuroaesthetic studies, the important domains are reward system, embodiment, aesthetic perspective in contrast with practical perspective, sublime, and so on. The neuroaesthetic approach to specific psychiatric disease is just beginning; however, case studies on the sudden appearance of artistic talents in neuropsychiatric patients have been frequently reported. We expect that neuroaesthetics is likely to continue to contribute new knowledge regarding the ultimate causes of various psychiatric diseases and the creativity of many psychiatric patients.

An fMRI Study Investigating Adolescent Brain Activation by Rewards and Feedback

OBJECTIVE: This study aimed to investigate the adolescent brain activation patterns in response to performance feedback (PF), social reward (SR) and monetary reward (MR) and their association with psychological factors. METHODS: Functional magnetic resonance imaging (fMRI) was performed while middle school boys (n=15) performed tests pertained to PF, SR and MR. The brain activation pattern in each condition was investigated, and the extent of brain activation in each of the three conditions was compared at once. RESULTS: The caudate and the dorsal prefrontal area were activated in all three conditions. Furthermore, the cuneus showed significantly greater activation in the PF condition than the SR or MR condition. And the self - related areas, such as the right precentral gyrus and paracenral lobule, were more activated in the SR condition than the PF or MR condition. The left middle frontal gyrus was more activated in the MR condition than the PF or SR condition. CONCLUSION: Not only various reward stimuli but also feedback stimulus might commonly activate dorsal prefrontal and subcortical area in adolescents. Moreover, several different brain activation patterns were also observed in each condition. The results of this study could be applied to planning of learning and teaching strategy for adolescents in various ways.

Targeted resequencing of candidate genes reveals novel variants associated with severe Behcet's uveitis

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent uveitis, oral and genital ulcers and skin lesions. To identify some pathogenic variants associated with severe Behcet's uveitis, we used targeted and massively parallel sequencing methods to explore the genetic diversity of target regions. A solution-based target enrichment kit was designed to capture whole-exonic regions of 132 candidate genes. Using a multiplexing strategy, 32 samples from patients with a severe type of Behcet's uveitis were sequenced with a Genome Analyzer IIx. We compared the frequency of each variant with that of 59 normal Korean controls, and selected five rare and eight common single-nucleotide variants as the candidates for a replication study. The selected variants were genotyped in 61 cases and 320 controls and, as a result, two rare and seven common variants showed significant associations with severe Behcet's uveitis (P<0.05). Some of these, including rs199955684 in KIR3DL3, rs1801133 in MTHFR, rs1051790 in MICA and rs1051456 in KIR2DL4, were predicted to be damaging by either the PolyPhen-2 or SIFT prediction program. Variants on FCGR3A (rs396991) and ICAM1 (rs5498) have been previously reported as susceptibility loci of this disease, and those on IFNAR1, MTFHR and MICA also replicated the previous reports at the gene level. The KIR3DL3 and KIR2DL4 genes are novel susceptibility genes that have not been reported in association with BD. In conclusion, this study showed that target enrichment and next-generation sequencing technologies can provide valuable information on the genetic predisposition for Behcet's uveitis.

Gene mapping study for constitutive skin color in an isolated Mongolian population

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD > or = 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

Characterization of the Rho GTPase-Activating Protein RhoGAP68F

Rho small GTPases control multiple aspects of neuronal morphogenesis by regulating the assembly and organization of the actin cytoskeleton. Although they are negatively regulated by GTPase activating proteins (GAPs), the roles of RhoGAPs in the nervous system have not been fully investigated. Here we describe a characterization of Drosophila RhoGAP68F that is mainly expressed in the embryonic central nervous system. RNA in situ hybridization analysis showed that expression of RhoGAP68F is highly restricted to the embryonic brain and ventral nerve cord. Database search revealed that RhoGAP68F contains an N-terminal Sec14 domain and a C-terminal RhoGAP domain. Rho-GTP pull-down assay demonstrated that the RhoGAP domain of RhoGAP68F inactivates RhoA but not Rac1 or Cdc42 in HEK293 cells. In addition, expression of RhoGAP68F in NIH3T3 cells suppressed LPA-induced stress fiber formation, which is mediated by RhoA. Finally, neuronal overexpression of RhoGAP68F causes synaptic overgrowth at the larval neuromuscular junction (NMJ). Taken together, these results suggest that RhoGAP68F may play a role in synaptic growth regulation by inactivating RhoA.

Development of ELISA-kit of Quantitative Analysis for Adiponectin and Their Correlation with Cardiovascular Risk Factors / 한국역학회지

PURPOSES: To develop a rapid, sensitive, qualitative ELISA-kit for serum adiponectin and examine correlation with adiponectin and cardiovascular risk factors. METHODS: On the base of monoclonal antibodies against adiponectin, apply indirect ELISA to study the performance parameter of the kit. The correlation was examined between adiponectin and cardiovascular risk factors including waist circumference, body mass index, triglyceride, and HDL cholesterol. RESULTS: The limited concentration of detection of the ELISA-kit was 1ug/ml. Linearity with R&D system and AdipoGen with this ELISA-kit was acceptable: the linear equation with R&D system was y=1.0116x + 0.4629 (R2=0.97) and linear equation with AdipoGen was y=0.9562x + 1.1961 (R2=0.93), respectively. The average recovery rate of the ELISA-kit ranged 92 to 104%. The correlation coefficient of waist circumference with adiponectin was -0.2276 (p<0.0001) among men and -0.2328 (p<0.0001) among women. CONCLUSION: This ELISA-kit was quick, sensitive, and stable and can be used to determine adiponectin in serum.

Tanshinone IIA inhibits osteoclast differentiation through down-regulation of c-Fos and NFATc1

Bone is a dynamic tissue that is regulated by the activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Excessive osteoclast formation causes diseases such as osteoporosis and rheumatoid arthritis. Natural substances may be useful as therapeutic drugs to prevent many diseases in humans because they avoid the many side effects of treatment with chemical compounds. Here we show that tanshinone IIA isolated from Salvia miltiorrhiza Bunge inhibits the receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation of osteoclast precursors. Tanshinone IIA suppressed the expression levels of c-Fos and NFATc1 induced by RANKL. However, retrovirus-mediated overexpression of c-Fos induced the expression of NFATc1 despite the presence of tanshinone IIA and reversed the inhibitory effect of tanshinone IIA on osteoclast differentiation. Also, the introduction of osteoclast precursors with the NFATc1 retrovirus led to osteoclast differentiation in the presence of tanshinone IIA. Our results suggest that tanshinone IIA may have a role as a therapeutic drug in the treatment of bone disease such as osteoporosis.