Objectives: . FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. Methods: . A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results: . In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient’s CI outcomes showed significant improvement over 1-year post-CI. Conclusion . A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Background and Objectives: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. Methods: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. Results: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. Conclusions Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.

BACKGROUND: Modified Phemister operation has been widely used for the treatment of acute acromioclavicular (AC) joint dislocation. Additionally, the use of suture anchor for coracoclavicular (CC) fixation has been reported to provide CC stability. This study was conducted to evaluate the clinical and radiological results of a modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation. METHODS: Seventy-four patients underwent the modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation and were followed-up for an average of 12.3 months. The visual analogue scale (VAS), range of motion, Constant score, and Korean shoulder scoring system (KSS) were used for clinical assessment. Acromioclavicular interval (ACI), coracoclavicular distance (CCD), and acromioclavicular distance (ACD) were obtained to evaluate the radiological assessments. RESULTS: At the last follow-up, the mean VAS Score was 1.7 points, the mean joint range of the forward flexion was 164.6°, external rotation at the side was 61.2°, and internal rotation to the posterior was a level of T12. The mean Constant score and the mean KSS was 82.7 points and 84.2 points, respectively. At the mean ACI, CCD, and ACD, significant differences were found preoperatively and at the last follow-up. When the ACI, CCD, and ACD were compared with the contralateral unaffected shoulder at the last follow-up, the affected shoulders had significantly higher values. CONCLUSIONS: The modified Phemister operation with CC ligament augmentation using suture anchor is clinically and radiologically effective at acute AC joint dislocation.
Acromioclavicular Joint ; Dislocations ; Follow-Up Studies ; Humans ; Joints ; Ligaments ; Range of Motion, Articular ; Shoulder ; Suture Anchors ; Sutures

BACKGROUND: Modified Phemister operation has been widely used for the treatment of acute acromioclavicular (AC) joint dislocation. Additionally, the use of suture anchor for coracoclavicular (CC) fixation has been reported to provide CC stability. This study was conducted to evaluate the clinical and radiological results of a modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation. METHODS: Seventy-four patients underwent the modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation and were followed-up for an average of 12.3 months. The visual analogue scale (VAS), range of motion, Constant score, and Korean shoulder scoring system (KSS) were used for clinical assessment. Acromioclavicular interval (ACI), coracoclavicular distance (CCD), and acromioclavicular distance (ACD) were obtained to evaluate the radiological assessments. RESULTS: At the last follow-up, the mean VAS Score was 1.7 points, the mean joint range of the forward flexion was 164.6°, external rotation at the side was 61.2°, and internal rotation to the posterior was a level of T12. The mean Constant score and the mean KSS was 82.7 points and 84.2 points, respectively. At the mean ACI, CCD, and ACD, significant differences were found preoperatively and at the last follow-up. When the ACI, CCD, and ACD were compared with the contralateral unaffected shoulder at the last follow-up, the affected shoulders had significantly higher values. CONCLUSIONS The modified Phemister operation with CC ligament augmentation using suture anchor is clinically and radiologically effective at acute AC joint dislocation.

BACKGROUND: The currently available reverse shoulder arthroplasty (RSA) designs can be classified into medial glenoid/medial humerus (MGMH), lateral glenoid/medial humerus (LGMH), and medial glenoid/lateral humerus (MGLH) prosthesis designs. The purpose of this study was to radiologically analyze the effect of different RSA designs on humeral position following RSA. METHODS: A total of 50 patients who underwent primary RSA were retrospectively analyzed. Among 50 patients, 33 patients (group A: MGMH) underwent RSA with Aequalis system (Wright, Inc, Bloomington, MN, USA), 6 (group B: LGMH) with Aequalis system using bony increased offset, and 11 (group C: MGLH) with Aequalis Ascend Flex system. The acromiohumeral distance, acromioepiphyseal distance (AED), lateral humeral offset (LHO), LHO from the center of rotation (LHO(COR)), and deltoid length were radiologically measured to quantify the distalization and lateralization of the humerus. RESULTS: The increment in postoperative AED was 19.92 ± 3.93 mm in group A, 24.52 ± 5.25 mm in group B, and 25.97 ± 5.29 mm in group C, respectively (p=0.001). The increment in postoperative LHO was 0.13 ± 6.30 mm, 8.00 ± 12.14 mm, and 7.42 ± 6.88 mm, respectively (p=0.005). The increment in postoperative LHOCOR was 20.76 ± 6.06 mm, 22.04 ± 5.15 mm, and 28.11 ± 4.14 mm, respectively (p=0.002). CONCLUSIONS: The radiologic analysis of the effect of different RSA designs on humeral position following RSA showed significant differences in the increment in postoperative AED, LHO, and LHO(COR) between the 3 groups. Therefore, MGLH design seems to be more effective for humeral distalization and lateralization compared to original Grammont design.
Arthroplasty ; Humans ; Humerus ; Prosthesis Design ; Retrospective Studies ; Shoulder

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.
Amygdala ; Autism Spectrum Disorder* ; Autistic Disorder* ; Beauty* ; Brain ; Fractals ; Humans ; Judgment ; Magnetic Resonance Imaging ; Prefrontal Cortex ; Temporal Lobe

BACKGROUND/AIMS: Although bisacodyl is a widely administered laxative, its underlying mechanism of action remains generally unknown. This study focuses on investigating the effects of bisacodyl on the human colon muscle contraction, and elucidating its mechanism of action. METHODS: Sigmoid colon muscle strips (20 longitudinal and 18 circular muscles) were obtained from 20 subjects who underwent colectomy for colon cancer. Isometric force measurements were calculated in response to electrical field stimulation (EFS, 0.3 milliseconds in trains of 10 Hz for 20 seconds, 150 V). Peak and nadir (tone) during and after EFS, were measured in a controlled state, and after sequential addition of bisacodyl (1 μM), atropine (1 μM), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM), and tetrodotoxin (TTX, 1 μM) to the organ bath. RESULTS: Transient phasic contractions were observed during EFS, and after cessation of EFS. In the longitudinal muscles, nadir during EFS, and tone after EFS, significantly increased after addition of bisacodyl, and persisted after sequential addition of atropine, L-NNA, MRS2500, and TTX, indicating a direct action of bisacodyl on the smooth muscle. In the second experiment, pretreatment of TTX abolished EFS-induced phasic contractions. Although no phasic contraction was produced after perfusion of bisacodyl, tone was increased, thereby supporting evidence of a direct mechanism of action of bisacodyl on the colon smooth muscle. CONCLUSIONS: Bisacodyl increases the tone of longitudinal muscle in the human sigmoid colon through a direct action on the smooth muscle. Further study is warranted to investigate the neural mechanism of action of bisacodyl.
Atropine ; Baths ; Bisacodyl ; Colectomy ; Colon ; Colon, Sigmoid ; Colonic Neoplasms ; Humans ; In Vitro Techniques ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Perfusion ; Physiology ; Tetrodotoxin

Genus Artemisia occurs as a hardy plant and has a wide range of culinary and medicinal features. In this study, we aimed to describe the melanin inhibitory activity of one Artemisia species, i.e., Artemisia capillaris Thunb. Ethanol extracts of fermented Artemisia capillaris (Art.EtOH.FT) and non-fermented Artemisia capillaris (Art.EtOH.CT) were tested for their ability to inhibit tyrosinase activity and melanin pigmentation. Both extracts showed dose-dependent inhibition against α-melanocyte stimulating hormone-stimulated melanin formation and tyrosinase activity, without cytotoxicity. At 100 µg/mL, both extracts showed greater inhibition than kojic acid, the positive control. Protein expressions of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) at the transcriptional level were determined by using real-time and semi-quantitative polymerase chain reaction. To complete the mechanistic study, presences of upstream elements of MITF, the phosphorylated-extracellular signal-regulated kinase (p-ERK), and phosphorylated-mitogen-activated protein kinase kinase (p-MEK) were confirmed by using western blot analysis. Expressions of p-TYR, p-TRP-1 and p-TRP-2, downstream factors for p-ERK and p-MITF, were translationally inhibited by both extracts. Art.EtOH.FT induced more potent effects than Art.EtOH.CT, especially signal transduction effects. In summary, Artemisia capillaris extracts appear to act as potent hypopigmentation agents.
Artemisia ; Blotting, Western ; Ethanol ; Hypopigmentation ; Melanins ; Melanoma ; Microphthalmia-Associated Transcription Factor ; Monophenol Monooxygenase ; Phosphotransferases ; Pigmentation ; Plants ; Polymerase Chain Reaction ; Protein Kinases ; Signal Transduction