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@#Objective: To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo. Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine (BrdU) assay kit. Western blot analysis was performed to determine the protein expressions of related factors. The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay. Chemical composition analysis was performed using high-performance liquid chromatography (HPLC). Results: Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway. It also induced metabolic changes, increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase. In an in vivo study, the extract-treated mice showed improved motor abilities, such as muscular endurance and grip strength. Additionally, HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength. Conclusions: Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles, suggesting its potential as an effective natural agent for improving muscular strength.
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With recent advances in adeno-associated virus (AAV)-based gene therapy, efficacy and toxicity screening have become essential for developing gene therapeutic drugs for retinal diseases. Retinal organoids from human pluripotent stem cells (hPSCs) offer a more accessible and reproducible human test platform for evaluating AAV-based gene therapy.In this study, hPSCs were differentiated into retinal organoids composed of various types of retinal cells. The transduction efficiencies of AAV2 and AAV8, which are widely used in clinical trials of inherited retinal diseases, were analyzed using retinal organoids. These results suggest that retinal organoids derived from hPSCs serve as suitable screening platforms owing to their diverse retinal cell types and similarity to the human retina. In summary, we propose an optimal stepwise protocol that includes the generation of retinal organoids and analysis of AAV transduction efficacy, providing a comprehensive approach for evaluating AAV-based gene therapy for retinal diseases.
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Background@#Sarcopenia is associated with postoperative complications; however, its impact on the quality of postoperative recovery, such as postoperative nausea and vomiting (PONV) and pain, remains unclear. We investigated the association of preoperative lumbar skeletal muscle mass index (LSMI) with PONV, postoperative pain, and complications. @*Methods@#Medical records of 756 patients who underwent pylorus-preserving pancreatoduodenectomy (PPPD) were retrospectively reviewed. The skeletal muscle areas were measured on abdominal computed tomography (CT) images. LSMI was calculated by dividing the skeletal muscle area by the square of the patient’s height. We analyzed the correlations between preoperative LSMI calibrated with confounding variables and PONV scores, PONV occurrence, pain scores, rescue analgesic administration, postoperative complications, and length of hospital stay. @*Results@#The median (1Q, 3Q) LSMI was 47.72 (40.74, 53.41) cm2/m2. The incidence rates of PONV according to time period were as follows: post-anesthesia care unit, 42/756 (5.6%); 0–6 h, 54/756 (7.1%); 6–24 h, 120/756 (15.9%); 24–48 h, 46/756 (6.1%); and overall, 234/756 (31.0%). The incidence of PONV was inversely correlated with LSMI 24–48 h post-surgery and overall. LSMI and PONV scores were negatively associated 6–24 h and 24–48 h post-surgery. There was no association between LSMI and postoperative pain scores, rescue analgesic administration, complications, or length of hospital stay. @*Conclusions@#Preoperative LSMI was associated with PONV in patients undergoing PPPD. Therefore, LSMI measured on preoperative abdominal CT can be a predictive indicator of PONV. Appropriate PONV prophylaxis is necessary in patients with low LSMI before PPPD.
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Background@#Implant-based immediate breast reconstruction surgery with nipple-sparing mastectomy has recently been favored by patients. However, in patients who do not wish to undergo balancing procedures, it is difficult to select the appropriate implant size, making it challenging to achieve a symmetrical breast shape. Therefore, this study investigated the differences in breast asymmetry and other complications in patients who underwent a two-stage procedure or direct-to-implant (DTI) breast reconstruction to determine whether the two-stage procedure can produce more favorable outcomes. @*Methods@#The participants of this study were patients who underwent immediate two-stage breast reconstruction or DTI breast reconstruction from May 2018 to April 2022, did not receive postoperative radiotherapy, and did not wish to undergo any balancing procedures. An acellular dermal matrix was used for breast reconstruction in all patients, and a single reconstructive surgeon performed all the operations. Statistical significance was set at P<0.05. @*Results@#No significant differences in complications were found between the patients who underwent DTI breast reconstruction and those who underwent two-stage breast reconstruction. In the two-stage breast reconstruction group, breast volume asymmetry was observed in 18.4% (seven patients), which was significantly lower than the percentage of 44.7% (17 patients) observed in the DTI group. @*Conclusions@#Breast asymmetry was observed in a significant proportion of the patients in both groups. However, because breast volume asymmetry was more common in the DTI group than in the two-stage breast reconstruction group, two-stage breast reconstruction may be a favorable method for patients who do not wish to undergo balancing procedures.
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Purpose@#Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. @*Materials and Methods@#We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. @*Results@#Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. @*Conclusion@#Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.
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The cellular homeostasis of proteins (proteostasis) and RNA metabolism (ribostasis) are essential for maintaining both the structure and function of the brain. However, aging, cellular stress conditions, and genetic contributions cause disturbances in proteostasis and ribostasis that lead to protein misfolding, insoluble aggregate deposition, and abnormal ribonucleoprotein granule dynamics. In addition to neurons being primarily postmitotic, nondividing cells, they are more susceptible to the persistent accumulation of abnormal aggregates. Indeed, defects associated with the failure to maintain proteostasis and ribostasis are common pathogenic components of age-related neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, the neuronal deposition of misfolded and aggregated proteins can cause both increased toxicity and impaired physiological function, which lead to neuronal dysfunction and cell death. There is recent evidence that irreversible liquid–liquid phase separation (LLPS) is responsible for the pathogenic aggregate formation of disease-related proteins, including tau, α-synuclein, and RNA-binding proteins, including transactive response DNA-binding protein 43, fused in sarcoma, and heterogeneous nuclear ribonucleoprotein A1. Investigations of LLPS and its control therefore suggest that chaperone/disaggregase, which reverse protein aggregation, are valuable therapeutic targets for effective treatments for neurological diseases. Here we review and discuss recent studies to highlight the importance of understanding the common cell death mechanisms of proteostasis and ribostasis in neurodegenerative diseases.
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Purpose@#To evaluate the extent to which myopia correction decreases distant exodeviation in patients with intermittent exotropia (IXT) and myopia. @*Methods@#The medical records of patients with IXT who underwent myopia correction without surgical intervention were retrospectively reviewed. No patient evidenced anisometropia or amblyopia; all exhibited distant angles of deviation greater than 10 prism diopters (PD). The refractive errors of the eye with greater myopia were analyzed. Patients who underwent at least 3 months of follow-up were included. We recorded age, sex, the angle of deviation, the stereoacuity, and suppression status. Patients who did and did not evidence improvement were analyzed at 9 months in terms of change in the distant angle of deviation. @*Results@#A total of 30 patients were analyzed. The average age was 8.27 ± 2.59 years. There were 18 (60%) males and 12 (40%) females. Twenty-four (80%) exhibited statistically significant decreases in the distant angle of deviation after wearing glasses for 3 months; the average value was 5.54 ± 3.59 PD (range 2-16 PD) (p 9 months (1.17 ± 3.63 PD) (p = 0.129). In patients evidencing no improvement at 3 months, we found no significant change in the distant angle of deviation at either 3 months (3.00 ± 4.56 PD) (p = 0.102) or 9 months (-3.66 ± 4.41 PD) (p = 0.132). @*Conclusions@#Eighty percent of IXT patients with myopia exhibited significant decreases in the distant angle of deviation after wearing glasses for 3 months, and this was well-maintained after 9 months.
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Purpose@#To compare the long-term clinical outcomes of patients with refractive accommodative esotropia (RAET) and infantile esotropia (IET). @*Methods@#The medical records of patients with RAET and IET who were followed-up for more than 36 months were retrospectively analyzed. The RAET patients were prescribed spectacles to correct cycloplegic refraction and those with IET underwent bilateral, medial rectus recession. Visual acuity, refraction, the angle of esodeviation at far and near distances, and near-stereopsis were measured at each visit. The IET patients were divided into two groups by the time of surgery (before and after 24 months of age). Patients in both groups who underwent reoperations after diagnosis of partially accommodative esotropia (PAET) and recurrent IET during follow-up were analyzed. @*Results@#Sixty-nine patients (40 with RAET and 29 with IET) were included. The follow-up period was 69.48 ± 28.41 months. At the final visit, the angles of esodeviation were 2.82 ± 5.46 prism diopters (PD) in the RAET group and 9.28 ± 8.37 PD in the IET group (p < 0.01). In IET patients who underwent surgery before and after 24 months of age, the angles of esodeviation were 4.62 ± 5.25 and 13.06 ± 8.63 PD and the median near-stereopsis values 60 and 140 arcsec at the final visit (p < 0.01, 0.03). Seven patients (17.5%) in the RAET group, and 2 (15.4%) and 10 (62.5%) IET patients who underwent surgery before and after 24 months of age, required reoperations (p < 0.01). @*Conclusions@#RAET and IET patients who underwent surgery before 24 months of age exhibited better alignment and stereopsis at the final visit than those who underwent later surgery and the reoperation rate was lower.
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of upper motor neurons in the brainstem and spinal cord and lower motor neurons. ALS was first described by Jean-Martin Charcot in 1874 based on clinical features and postmortem examinations. In 1990, the first diagnostic criteria for ALS were developed based on clinical features. Subsequently, three additional diagnostic criteria were published. In this article, we introduce the clinical features, diagnostic criteria, and diseases that need to be differentiated in ALS.
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Purpose@#Awareness of environmental control is considered a major influence on the performance of asthma self-management behaviors that are involved in maintaining effective control of asthma. The aim of this study was to investigate whether immersive virtual reality (VR) education is effective in environmental control education for asthmatic children. @*Methods@#Thirty asthmatic children aged 9 to 13 years with aeroallergen sensitization were enrolled. Environmental control education for asthmatic subjects were performed using either immersive VR (VR group) or conventional leaflets provided by asthma specialists (control group). Five questionnaires, such as awareness of environmental control, memory, assessment of intent to act, satisfaction test, and asthma control test (ACT) questionnaires were used for estimating the effects of education. @*Results@#Awareness of environmental control, memory, and intent to act scores were significantly increased after education in both groups and the scores were maintained high until 4 weeks after education. In both group, ACT scores were maintained high scores before and 4 weeks after education. Satisfaction scores were very high in the VR group. @*Conclusion@#The increased scores in awareness of environmental control and intent to act indicate that the environmental control education using VR is worthy of attention as an effective educational tool for asthma management. Application of further developed techniques, including active environmental intervention by participants in VR, could be applied to effective asthma management.
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Objective@#Dysphagia is a common symptom of stroke and affects 23–50% of such patients. In addition, bulbar involvement, which causes dysphagia, is the primary initial symptom in approximately 25–30% of amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to compare patterns of swallowing difficulties in stroke and ALS patients. @*Methods@#We retrospectively recruited 84 ALS patients with dysphagia and 294 stroke patients with dysphagia between January 2017 and December 2019. Swallowing processes were reviewed by videofluoroscopic swallowing studies (VFSSs). The presence of oral residues and oral transit times (OTTs) were measured in the oral phase, and the presence of penetration and aspiration and residues in valleculae or pyriform sinuses were evaluated. Statistical analysis was performed using SPSS 25.0 and comparisons using the Chi-square test. @*Results@#ALS patients more frequently had delayed OTTs and oral residues than stroke patients, and stroke patients more frequently experienced aspiration and had delayed thin liquid pharyngeal transit times (PTTs). However, no significant intergroup difference was observed for the presence of penetration, residues in valleculae or pyriform sinuses, or thick liquid PTTs. @*Conclusion@#The study shows that ALS patients exhibit slower food processing in the oral cavity and more significant bulbar muscle weakness than stroke patients. On the other hand, stroke patients had greater thin liquid aspiration rates than ALS patients. These findings should be considered when choosing treatments for ALS and stroke.
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Purpose@#To evaluate the effect of classroom illuminance on the development and progression of myopia in elementary school children. @*Methods@#The daylight factor, a ratio of inside and outside illuminance, was obtained in 50 elementary schools. The firstgrade students in the school with the lowest daylight (LD) factor (LD school, 145 subjects; 0.51%) and with the highest daylight (HD) factor (HD school, 147 subjects; 13.35%) were selected. A survey was conducted to evaluate parental myopia, the amount of near-work and outdoor activities. The refractive error and axial length (AL) were measured at initial and after 6 months. The spherical equivalent, AL, and the survey results were compared between the two schools. The mean AL of the emmetropic children was obtained, and all subjects were divided into two groups, more and less than mean AL. Changes in refractive errors and AL were also compared according to AL. @*Results@#The amount of change in spherical equivalent and AL after 6 months were not different between the two schools. Initial prevalence of myopia was high in the HD school. However, it became similar between the two schools after 6 months. The mean AL of 155 emmetropic children was 22.7 ± 0.63 mm. In the 185 children with AL ≥22.7 mm, there was no difference in the AL change between the two schools. However, the change in AL in 107 children with AL <22.7 mm was significantly larger in the LD school (0.19 mm) than that in the HD school (0.15 mm, p = 0.049). Parental myopia, near-work and outdoor activities were not different between the two schools. @*Conclusions@#High classroom illuminance during the day reduced axial elongation in eyes of children with a shorter AL. Increase in classroom light level by permitting more sunlight can be a protective measure against the development of myopia.
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Human endogenous retroviruses (HERVs) are originated from ancient exogenous retroviruses, which infected human germ line cells millions of years ago. HERVs have generally lost their replication and retrotransposition abilities, but adopted physiological roles in human biology. Though mostly inactive, HERVs can be reactivated by internal and external factors such as inflammations and environmental conditions. Their aberrant expression can participate in various human malignancies with complex etiology. This review describes the features and functions of HERVs in urological subjects, such as urological cancers and human reproduction. It provides the current knowledge of the HERVs and useful insights helping practice in urology clinics.
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Molar incisor malformation (MIM) has been introduced as a new type of dental anomaly. Currently, the morphological and histological characteristics of MIM are known; however, its etiology has not been clearly identified. To date, the long-term prognosis of first permanent molars (FPM) affected by MIM has rarely been reported, and few treatment guidelines have been established. The purpose of this case report was to present guidelines for the extraction of FPM affected by MIM, depending on the presence of the third molar. In patients with a third molar, spontaneous mesial shift of the posterior molars might be induced by extracting the FPM at an appropriate time, that is, when the second permanent molar is at an early furcation stage of the tooth. However, it is recommended that FPM be preserved for as long as possible if a third molar does not exist. When an FPM needs to be extracted, it is suggested to consider space maintenance.
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Background@#In recent years, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has emerged as an important concern. At our institution, patients who received breast reconstruction using Allergan implants were informed individually about BIA-ALCL. The present study analyzed correlations between patients’ level of satisfaction with their breast shape and whether they chose to undergo reoperation (implant removal or replacement). @*Methods@#Breast reconstruction with Allergan implants was performed between December 2014 and April 2018. In total, 107 patients were interviewed, excluding those who had died, were unreachable, or had already undergone reoperation. The mean follow-up period was 53 months (range, 26–73 months). @*Results@#After the interviews, 68 patients postponed reoperation, 29 had their implant replaced, and 10 had their implant removed. Nearly one-fifth (18.9%) of patients who were satisfied with their breast shape (13 out of 69) underwent reoperation due to anxiety over ALCL. Meanwhile, 68.4% of patients who were not satisfied due to capsular contracture or scar contracture (26 out of 38) underwent reoperation. Sixteen of the 30 patients who received postoperative radiotherapy (53.3%) chose to undergo reoperation. @*Conclusions@#Satisfaction with the cosmetic outcomes of implant placement played a meaningful role in patients’ decisions to undergo reoperation. This tendency may be linked to postoperative radiotherapy, which is a major contributor to complications such as contracture. Nonetheless, a substantial proportion of patients who were satisfied with the outcomes chose to undergo reoperation due to concerns regarding ALCL.
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Severe temporal hollowing deformities can occur in patients who undergo craniectomy after intracranial hemorrhage. Reconstruction surgery for cosmetic purposes using silicone implants in patients with temporal hollowing deformities after craniectomy is advantageous because the procedure is simple and rapid, with a short recovery time, resulting in lower overall treatment costs. Of paramount importance, this option yields highly satisfactory results for patients. The authors present three cases of simple and fast surgery using silicone implants where highly satisfactory outcomes were obtained.
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Purpose@#Inferior oblique overaction with a dissociated vertical deviation occurs secondary to infantile exotropia or esotropia. In terms of correction, asymmetric bilateral inferior oblique transposition has been the treatment of choice, but the surgical amount depended largely on the surgeon’s experience. We report successful bilateral inferior oblique transposition using our own standard methods. @*Methods@#We performed a retrospective medical chart review of patients with bilateral inferior oblique overaction and dissociated vertical deviation who underwent bilateral inferior oblique transposition at the Korea University Medical Center from January 2013 to December 2020. We performed either symmetric or asymmetric transposition; the reattachment sites of the bilateral inferior obliques were determined according to preoperative differences of the inter-eye deviations of dissociated vertical deviation. When the differences were < 5 prism diopters, correction was considered successful. To avoid the development of anti- elevation syndrome, the inferior oblique muscles were re-attached near the equator. @*Results@#Twenty-three patients were analyzed, all of whom underwent bilateral inferior oblique transposition; 12 required additional horizontal muscle surgery. The deviation difference (both eyes) and inferior oblique overaction grade were significantly lower postoperatively. We did not encounter any case of anti-elevation syndrome. @*Conclusions@#The surgical extent of asymmetric bilateral inferior oblique transposition should reflect the difference in dissociated vertical deviation the two eyes.
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Purpose@#We analyzed the effects of low-dose atropine on myopic progression in elementary schoolchildren aged 6-11 years. @*Methods@#Medical records were retrospectively reviewed before and after 6 months of low-dose atropine eyedrops. Myopia was defined as a spherical equivalent < -1 diopter. Low-dose atropine eyedrops (atropine sulfate 0.125% [w/v]) and artificial tear eyedrops (sodium hyaluronate 0.1% [w/v]) immediately afterwards were applied to both eyes daily, and all children regularly visited us for measurement of refractive power, axial length, pupil diameter, and near-point accommodation. symptoms (headache, light sensitivity, near-work disturbance, allergic reaction, dry eye, and poor night vision) were recorded. @*Results@#A total of 116 patients were included. Atropine was prescribed for 65 patients, the remaining 51 patients constituted the control group. In the atropine group, the mean age was 10.2 ± 1.8 years and 23 patients (35.4%) were male. At the initial visit, the mean refractive power was -4.7 ± 2.1 diopters (D) (-1.0 to -10.5) and the mean axial length was 24.95 ± 1.02 mm (22.58-27.99). At the 6-month follow-up, the change of refractive power was -0.9 ± 1.1 D (-0.75 to -4.75) and the change of axial length was 0.47 ± 0.39 mm (0.01-1.6). However, 6 months after application of low-dose atropine eyedrops, the change of refractive power was -0.1 ± 0.2 D (0 to -0.25) and the change of mean axial length was 0.15 ± 0.23 mm (0-1.05). The mean pupil diameter was 6.7 ± 0.6 mm (5.3-9.3) and the near accommodation point was 6.1 ± 2.0 cm (3.1-11.0). Two patients (3.1%) complained of near-work disturbance but none stopped taking the eyedrops. @*Conclusions@#Significant decreases in the changes of refractive power and axial length were evident in myopic elementary schoolchildren after low-dose atropine therapy. Low-dose atropine attenuates myopic progression without severe complications.
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Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.
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Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.