Detecting Alu Element Insertion Variant in RP1 Gene Using Whole Genome Sequencing in Patients with Retinitis Pigmentosa.

Background/Objectives:Alu element insertion in the exon 4 of the RP1 gene was newly identified through whole genome sequencing (WGS). This was not detected in previous next-generation sequencing (NGS) analysis. We report three cases of Korean retinitis pigmentosa (RP) patients with compound heterozygous variants including Alu element insertion in the RP1 gene, indicating that Alu element insertion could be a cause of RP; Methods: Among patients diagnosed with RP having variants in the RP1 gene in the Asan Medical Center, WGS was additionally performed for genetically unsolved cases in previous NGS analysis to detect any presence of Alu element insertion. For cases detected to have Alu element insertion in the exon 4 of the RP1 gene, genetic and clinical characteristics were analyzed; Results: Among 16 patients with RP, 3 patients were detected to have Alu element insertion in the RP1 gene. Alu element insertion in the RP1 gene was also detected using WGS. It was revealed to be a pathogenic variant. Therefore, RP1 gene mutation was the confirmed genetic cause of RP for these three cases and genetic counseling was enabled for them; Conclusions: Alu element insertion in the RP1 gene could be a genetic cause of autosomal recessive RP patients with compound heterozygous variants. Through WGS, the identification of this pathogenic variant was possible. Confirmation is needed to check the presence of Alu element insertion in patients with compound heterozygous variants in the RP1 gene.

Efficacy and safety of Sipjeondaebo-tang for cancer-related fatigue: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 52% of patients with cancer experience cancer-related fatigue (CRF), which negatively impacts both prognosis and quality of life (QoL). CRF is characterized by exhaustion, which is linked to cancer or treatment. Sipjeondaebo-tang (SDT) is an herbal medicine that is effective in alleviating fatigue and potentially easing CRF; however, there is currently insufficient clinical or scientific evidence to support the efficacy of SDT in managing CRF. AIM OF THE STUDY: We assessed the efficacy and safety of SDT for CRF by performing a systematic literature review and meta-analysis. MATERIALS AND METHODS: We collected randomized controlled trials (RCTs) on CRF by searching nine databases, including EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials, on November 30, 2023. Based on the predefined inclusion and exclusion criteria, two reviewers independently screened and selected the literature, followed by data extraction. We assessed the quality of the selected studies using version 2 of the Cochrane Collaboration Risk of Bias tool. Review Manager software was used for the data synthesis. A meta-analysis was conducted when two or more studies shared comparable interventions and outcome measures. For all other cases, a qualitative analysis was performed. The certainty of evidence for each result was assessed employing the Grading of Recommendations, Assessment, Development, and Evaluation method. RESULTS: This study contained eleven studies with a total of 754 participants. SDT significantly reduced CRF and improved QoL compared with the control group, both when used as an adjuvant therapy and as a monotherapy. Specifically, low-certainty evidence suggested that SDT, when used as an adjunctive therapy, could effectively reduce CRF, as indicated by a reduction in lack of strength (standardized mean difference = -1.28, 95% confidence interval (CI): -1.78 to -0.78, P < 0.00001). Additionally, moderate-certainty evidence indicated that SDT as an adjunctive therapy could improve QoL, as measured by Karnofsky Performance Status (mean difference = 4.67, 95% CI: 2.19 to 7.14, P = 0.0002). No serious adverse events occurred with SDT, whether it was used as an adjuvant therapy or as a monotherapy. CONCLUSIONS: This systematic review elucidated the safety and efficacy of SDT in managing CRF. Nevertheless, the low quality of the included studies highlights the need for carefully planned large-scale RCTs.

Endocrine Complications in Hepatic Glycogen Storage Diseases: A Long-term Perspective.

OBJECTIVE: Patients with hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs. METHODS: This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (one patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed. RESULTS: The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5 ± 1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR = 36.1; P-value < 0.001). Among 33 patients who reached final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0 ± 1.3 at the L-spine. CONCLUSIONS: This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Prospective proof-of-concept observational RESEarch about traditional herbal preparation Treatment for Chronic Obstructive Pulmonary Disease (RESET-COPD-1).

Background: Despite advances in medical science, chronic obstructive pulmonary disease (COPD) continues to impact patients' lives significantly, due to symptom management limitations. Cheongsangboha-tang (CSBHT; Qing Shang Bu Xia Tang) and Hyunggaeyeongyo-tang (HGYGT; Jing Jie Lian Qiao Tang) have been used to treat respiratory diseases, including COPD. However, clinical data supporting their efficacy are lacking. We prospectively observed the response of patients with COPD to CSBHT and HGYGT as adjunctive therapies and assessed the feasibility of future research. Methods: Patients with COPD who were prescribed adjunctive HGYGT or CSBHT according to the COPD clinical practice protocol of Kyung Hee University Korean Medicine Hospital were recruited. Participants visited the hospital every month, for 6 months, to receive herbal preparations according to a Korean Medicine doctor's diagnosis and prescription and outcome evaluations. The primary outcome was the 6-min walking test (6-MWT). Secondary outcomes included the pulmonary function test (PFT), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and modified Medical Research Council (mMRC) score. Syndrome differentiation, adverse events, and patient adherence were recorded. Results: Thirty-seven patients were initially enrolled and followed up for a mean period of 154.1 days. CSBHT was prescribed to 36 patients, while one patient received either CSBHT or HGYGT, or both, throughout the entire period. During the herbal preparation treatment period, no statistically significant changes were observed in the 6-MWT. The CAT score (mean ± standard deviation) changed from 17.0 ± 5.0 to 12.5 ± 3.6, and the visual analogue scale score for dyspnea changed from 47.5 ± 18.9 to 28.4 ± 18.6 (both statistically significant from visit 5). The coronavirus disease 2019 pandemic precluded the PFT. SGRQ and mMRC scores did not change significantly. During the study period, seven patients dropped out, two experienced mild dyspepsia, and one experienced mild headache. No serious adverse effects were observed. Conclusion: We illustrated the therapeutic potential of CSBHT and provided preliminary clinical data on its efficacy and safety in patients with COPD. Our study highlights the need to derive optimal herbal formulations, which should be administered for an appropriate duration, based on the therapeutic goals for the treatment of COPD.

Exploring novel MYH7 gene variants using in silico analyses in Korean patients with cardiomyopathy.

BACKGROUND: Pathogenic variants of MYH7, which encodes the beta-myosin heavy chain protein, are major causes of dilated and hypertrophic cardiomyopathy. METHODS: In this study, we used whole-genome sequencing data to identify MYH7 variants in 397 patients with various cardiomyopathy subtypes who were participating in the National Project of Bio Big Data pilot study in Korea. We also performed in silico analyses to predict the pathogenicity of the novel variants, comparing them to known pathogenic missense variants. RESULTS: We identified 27 MYH7 variants in 41 unrelated patients with cardiomyopathy, consisting of 20 previously known pathogenic/likely pathogenic variants, 2 variants of uncertain significance, and 5 novel variants. Notably, the pathogenic variants predominantly clustered within the myosin motor domain of MYH7. We confirmed that the novel identified variants could be pathogenic, as indicated by high prediction scores in the in silico analyses, including SIFT, Mutation Assessor, PROVEAN, PolyPhen-2, CADD, REVEL, MetaLR, MetaRNN, and MetaSVM. Furthermore, we assessed their damaging effects on protein dynamics and stability using DynaMut2 and Missense3D tools. CONCLUSIONS: Overall, our study identified the distribution of MYH7 variants among patients with cardiomyopathy in Korea, offering new insights for improved diagnosis by enriching the data on the pathogenicity of novel variants using in silico tools and evaluating the function and structural stability of the MYH7 protein.

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

Cross-cultural validation of the genetic counseling outcome scale in Korea.

The Genetic Counseling Outcome Scale (GCOS-24) was developed to measure patient-reported outcomes to evaluate the effectiveness of genetic counseling and testing services. In the current study, the Korean version of GCOS (K-GCOS) was developed to reflect the sociocultural characteristics of Korea, and its clinical applicability was assessed. Overall, 231 Koreans, including patients with genetic diseases and their family members, participated and completed the K-GCOS, Hospital Anxiety and Depression Scale (HADS), Multidimensional Health Locus of Control (MHLC) scale, and Satisfaction with Life Scale (SWLS). Validity was examined by assessing the correlations between K-GCOS scores and other relevant scale scores. Reliability was confirmed using Cronbach's alpha and test-retest scores, measured over 2 weeks. We performed exploratory factor analysis of the five structures of GCOS-24. For K-GCOS, four-factor structures were identified: "cognitive-behavioral control," "uncertainty about control," "hope," and "emotional regulation." Four original GCOS-24 items were removed because of low factor loadings and small inter-item correlations. K-GCOS-20 scores were positively correlated with SWLS (r = 0.456) and MHLC-internal (r = 0.213) scores but negatively correlated with HADS (anxiety r = -0.428, depression r = -0.469) and MHLC-internal (r = -0.278) scores. These findings demonstrate that K-GCOS-20 is a reliable and valid tool for evaluating genetic counseling services in Korea.

Effects of Postprandial Factors and Second Meal Intake Time on Bioequivalence Investigation of Tadalafil-Loaded Orodispersible Films in Human Volunteers.

Tadalafil (TD) has poor water solubility but is well absorbed without affecting food intake when administered orally. Owing to patient adherence and therapeutic characteristics, a TD-loaded orodispersible film (TDF) is preferable. However, the mechanistic role of dietary status on the clinical pharmacokinetic analysis of TDF in human volunteers should be investigated because the gastrointestinal environment varies periodically according to meal intervals, although commercial 20 mg TD-loaded tablets (TD-TAB, Cialis® tablet) may be taken with or without food. TDF was prepared by dispersing TD in an aqueous solution and polyethylene glycol 400 to ensure good dispersibility of the TD particles. In the fasting state, each T/R of Cmax and AUC between TD-TAB and TDF showed bioequivalence with 0.936-1.105 and 1.012-1.153, respectively, and dissolution rates in 1000 mL water containing 0.5% SLS were equivalent. In contrast, TDF was not bioequivalent to TD-TAB under the fed conditions by the Cmax T/R of 0.610-0.798. The increased dissolution rate of TDF via the micronization of drug particles and the reduced viscosity of the second meal content did not significantly affect the bioequivalence. Interestingly, an increase in second meal intake time from 4 h to 6 h resulted in the bioequivalence by the Cmax T/R of 0.851-0.998 of TD-TAB and TDF. The predictive diffusion direction model for physical digestion of TD-TAB and TDF in the stomach after the first and second meal intake was successfully simulated using computational fluid dynamics modeling, accounting for the delayed drug diffusion of TDF caused by prolonged digestion of stomach contents under postprandial conditions.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Associations of Insulin Resistance and High-Sensitivity C-Reactive Protein with Metabolic Abnormalities in Korean Patients with Type 2 Diabetes Mellitus: A Preliminary Study.

We conducted this single-center, retrospective, cohort study to examine whether insulin resistance (IR) and high-sensitivity C-reactive protein (hsCRP) have a relationship with metabolic abnormalities in patients with type 2 diabetes mellitus (T2DM). In a total of 3758 patients (n = 3758) with T2DM, we analyzed medical records and thereby evaluated their baseline characteristics such as age, sex, duration of T2DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference, body mass index (BMI), visceral fat thickness (VFT), fasting plasma insulin levels, C-peptide levels, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-ß), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), albuminuria, intima-media thickness (IMT) and hsCRP. The patients were stratified according to the tertile of the K index of the insulin tolerance test (KITT) or hsCRP. Thus, they were divided into the lowest (≥2.37), middle (1.54-2.36) and highest tertile (0-1.53) of KITT and the lowest (0.00-0.49), middle (0.50-1.21) and highest tertile (≥1.22) of hsCRP. Moreover, associations of KITT and hsCRP with metabolic abnormalities, such as steatotic liver disease (SLD), metabolic syndrome (MetS), albuminuria, diabetic retinopathy and carotid atherosclerosis, were also analyzed. There was a significant positive correlation between the prevalence of SLD, MetS, albuminuria and diabetic retinopathy and KITT (p < 0.001). Moreover, there was a significant positive association between the prevalence of SLD, MetS and albuminuria and hsCRP (p < 0.001). In conclusion, our results indicate that clinicians should consider the relationships of IR and hsCRP with metabolic abnormalities in the management of patients with T2DM. However, further large-scale, prospective, multi-center studies are warranted to confirm our results.

Development and verification of the Korean version of the genetic counseling self-efficacy scale.

A self-reported Genetic Counseling Self-Efficacy Scale (GCSES) was developed in English to measure genetic counselors' self-efficacy, a factor known to affect their job performance. This study verified the reliability and validity of the GCSES for use in Korea. The scale was translated and back-translated into Korean for cultural fit verification. Expert analysis was performed to ensure content validity. For construct validity, a confirmatory factor analysis of the six-factor structures of the GCSES and an exploratory factor analysis (EFA) of the K-GCSES were conducted. To confirm the convergent validity and discriminant validity of the items, a multitrait/multi-item matrix analysis of the relationship between items and subscales was conducted. The reliability was evaluated by examining internal consistency and test-retest reliability. A total of 62 participants were recruited from certified genetic counselors associated with the Korean Society of Medical Genetics and Genomics and from four graduate schools offering genetic counseling programs. Confirmatory factor analysis showed an inadequate fit to the original GCSES structure. Through EFA, three-factor structures were identified: "counseling competence and psychosocial skills," "genetic testing," and "information gathering." Of the original 38 GCSES items, five were removed due to low factor loadings and small inter-item correlations. The item convergent validity and discriminant validity of the Korean version of the GCSES were established, and the correlation between the subfactors showed statistical significance (0.711-0.983). Cronbach's alpha was 0.985, and the intraclass correlation coefficient ranged from 0.882 to 0.897, securing reliability. The K-GCSES has a three-factor structure with acceptable reliability and sufficient validity. Differences in the factor structure between the K-GCSES and GCSES may be due to cultural factors. K-GCSES can be used as a tool to evaluate the competence of genetic counselors and genetic counseling students in Korea and to improve the quality of professionalism and education.

Effect of humidity on postmortem changes in rats.

IMPORTANCE: In veterinary forensic science, accurately determining the postmortem interval (PMI) is crucial for identifying the causes of animal deaths. Autolysis, a significant postmortem process, influences PMI estimation, but its relationship with humidity is not well understood. OBJECTIVE: This study aimed to improve the accuracy of PMI estimates in veterinary forensic cases by looking into how different humidity levels affect autolysis in different organs of rats. METHODS: The study involved 38 male rats, examining histopathological changes in their heart, liver, and pancreas. These organs were subjected to controlled humidity levels (20%, 55%, and 80%) at a constant 22°C. Tissue samples were collected at several intervals (0 h, 12 h, 24 h, 3 days, and 8 days) for comprehensive analysis. RESULTS: Distinct autolytic characteristics in animal organs emerged under varying humidity conditions. The low-humidity environment rapidly activated autolysis more than the high-humidity environment. In addition, it was found that lower humidity caused nuclear pyknosis, cytoplasmic disintegration, and myofiber interruption. The liver, in particular, showed portal triad aggregation and hepatocyte individuation. The pancreas experienced cell fragmentation and an enlarged intracellular space. High humidity also caused the loss of striations in cardiac tissues, and the liver showed vacuolation. Under these conditions, the pancreas changed eosinophilic secretory granules. CONCLUSIONS AND RELEVANCE: The study successfully established a clear connection between the autolytic process in PMIs and relative humidity. These findings are significant for developing a more accurate and predictable method for PMI estimation in the field of veterinary forensic science.

A Phase III Head-to-Head Study to Compare the Efficacy and Safety of Fexuprazan and Esomeprazole in Treating Patients with Erosive Esophagitis.

Background: Fexuprazan (Fexuclue®; Daewoong Pharmaceutical Co., Ltd., Seoul, Korea) is a novel potassium-competitive acid blocker (P-CAB). This multi-center, randomized, double-blind, active-controlled, parallel-group, therapeutic confirmatory, phase III study was conducted to assess its efficacy and safety compared with esomeprazole (Nexium®; AstraZeneca, Gothenburg, Mölndal, Sweden) in Korean patients with erosive esophagitis (EE). Methods: This study evaluated patients diagnosed with EE at a total of 25 institutions in Korea between 13 December 2018 and 7 August 2019. After voluntarily submitting a written informed consent form, the patients were evaluated using a screening test and then randomized to either of the two treatment arms. The proportion of the patients who achieved the complete recovery of mucosal breaks at 4 and 8 weeks, the proportion of those who achieved the complete recovery of heartburn at 3 and 7 days and 8 weeks, and changes in the GERD-Health-Related Quality of Life Questionnaire (GERD-HRQL) scores at 4 and 8 weeks from baseline served as efficacy outcome measures. The incidence of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) and the serum gastrin levels served as safety outcome measures. Results: The study population comprised a total of 231 patients (n = 231) with EE, including 152 men (65.80%) and 79 women (34.20%); their mean age was 54.37 ± 12.66 years old. There were no significant differences in the efficacy and safety outcome measures between the two treatment arms (p > 0.05). Conclusions: It can be concluded that the efficacy and safety of Fexuclue® are not inferior to those of esomeprazole in Korean patients with EE.

Early gastric cancer of young patients treated by endoscopic submucosal dissection: focusing on the different characteristics and prognosis of elderly patients.

BACKGROUND: A small portion of patients are diagnosed with early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at a young age. However, their clinical outcomes are rarely known. AIM: We investigated to identify the feasibility and clinical outcomes of ESD for EGC focusing on young patients. METHODS: We analyzed the clinical characteristics and outscomes of patients who had undergone ESD for the treatment of EGC at < 50 years of age. We enrolled patients who had been diagnosed with EGC and had undergone ESD between 2006 and 2020. We divided them by age as follows: ≤ 50 and > 50 years into the young age (YA) and other age (OA) groups, respectively. RESULTS: Altogether, 1681 patients underwent ESD for EGC (YA group: 124 [7.4%], OA group: 1557 [92.6%]). The YA group had less severe atrophy and more undifferentiated (37.1% vs. 13.9%, P < 0.001) and diffuse type (25% vs. 7.7%, P < 0.001) histology. The curative resection rate was not significantly different between the groups. However, among 1075 patients who had achieved curative resection and had been followed-up for > 12 months, the YA group had a lower incidence of MGN (5.2% vs. 17.5%, P = 0.004) and MGC (2.6% vs. 10.9%, P = 0.019) than those exhibited by the OA group. The YA group was a significant negative predictor of MGN (odds ratio [OR]: 2.983, 95% confidence interval [CI] 1.060-8.393, P = 0.038), and marginally negative predictor in MGC (OR: 3.909, 95% CI: 0.939-16.281, P = 0.061). CONCLUSION: ESD is a favorable and effective therapeutic modality for EGC patients aged < 50 years, once curative resection is achieved.

Clinical and molecular characteristics of Korean patients with Kabuki syndrome.

INTRODUCTION: Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS. METHODS: This study included 28 Korean patients (14 boys and 14 girls) with KS through molecular genetic testing, including direct Sanger sequencing, whole-exome sequencing, or whole-genome sequencing. RESULTS: The median age at clinical diagnosis was 18.5 months (IQR 7-58 months), and the median follow-up duration was 80.5 months (IQR 48-112 months). Molecular genetic testing identified different pathogenic variants of the KMT2D (n = 23) and KDM6A (n = 3) genes, including 15 novel variants. Patients showed typical facial features (100%), such as long palpebral fissure and eversion of the lower eyelid; intellectual disability/developmental delay (96%); short stature (79%); and congenital cardiac anomalies (75%). Although 71% experienced failure to thrive in infancy, 54% of patients showed a tendency toward overweight/obesity in early childhood. Patients with KDM6A variants demonstrated severe genotype-phenotype correlation. CONCLUSION: This study enhances the understanding of the clinical and genetic characteristics of KS.

Inherited CARD9 Deficiency Due to a Founder Effect in East Asia.

Autosomal recessive CARD9 deficiency can underly deep and superficial fungal diseases. We identified two Japanese patients, suffering from superficial and invasive Candida albicans diseases, carrying biallelic variants of CARD9. Both patients, in addition to another Japanese and two Korean patients who were previously reported, carried the c.820dup CARD9 variant, either in the homozygous (two patients) or heterozygous (three patients) state. The other CARD9 alleles were c.104G > A, c.1534C > T and c.1558del. The c.820dup CARD9 variant has thus been reported, in the homozygous or heterozygous state, in patients originating from China, Japan, or South Korea. The Japanese, Korean, and Chinese patients share a 10 Kb haplotype encompassing the c.820dup CARD9 variant. This variant thus originates from a common ancestor, estimated to have lived less than 4,000 years ago. While phaeohyphomycosis caused by Phialophora spp. was common in the Chinese patients, none of the five patients in our study displayed Phialophora spp.-induced disease. This difference between Chinese and our patients probably results from environmental factors. (161/250).

Survey of patient satisfaction with genetic counseling services in Korea.

Since the 1990s, genetic clinics have been established in South Korea, enabling the provision of clinical genetics services. However, genetic counseling services are not widely used in the medical system. In contrast, recently, the demand for genetic counseling has increased due to the rapid development of genomic medicine. Therefore, it is important for medical geneticists and genetic counselors to collaboratively provide genetic counseling services. This study aimed to evaluate the perception and satisfaction of patients with rare genetic diseases and their families regarding genetic counseling services provided by a genetics team at the medical genetics center of a tertiary general hospital for rare genetic diseases. From April to November 2021, a survey was conducted with 203 individuals, including 111 and 92 individuals in the patient and family groups, respectively. Overall, 164 individuals (80.8%) responded that they were aware of genetic counseling services, and 135 individuals (66.5%) responded that they were aware of the role of genetic counselors. Patients and their families wanted to receive information about the following from genetic counseling: clinical manifestation and prognosis of the diagnosed disease (78.8%), treatment and management of the disease (60.6%), risk of recurrence within the family (55.7%), treatment options and alternatives for family and prenatal testing, and various support services. The score of satisfaction with genetic counseling services provided by the genetics team was 8.19 ± 1.68 out of 10. Patients with rare genetic diseases and their families were satisfied with genetic counseling services regarding their diseases, test results, and treatment options. Moreover, the patients could receive psychosocial support and referrals to other medical service providers and support services. As a genetic team approach, collaboration between medical geneticists and certified genetic counselors would be useful in providing information and in diagnosing, treating, and managing patients.

A Systematic Review of the Effects of Interactive Telerehabilitation with Remote Monitoring and Guidance on Balance and Gait Performance in Older Adults and Individuals with Neurological Conditions.

Recognizing the growing interests and benefits of technology-assisted interactive telerehabilitation in various populations, the aim of this review is to systematically review the effects of interactive telerehabilitation with remote monitoring and guidance for improving balance and gait performance in older adults and individuals with neurological conditions. The study protocol for this systematic review was registered with the international prospective register of systematic reviews (PROSPERO) with the unique identifier CRD42024509646. Studies written in English published from January 2014 to February 2024 in Web of Science, Pubmed, Scopus, and Google Scholar were examined. Of the 247 identified, 17 were selected after initial and eligibility screening, and their methodological quality was assessed with the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. All 17 studies demonstrated balance and gait performance improvement in older adults and in individuals with stroke, Parkinson's disease, and multiple sclerosis following 4 or more weeks of interactive telerehabilitation via virtual reality, smartphone or tablet apps, or videoconferencing. The findings of this systematic review can inform the future design and implementation of interactive telerehabilitation technology and improve balance and gait training exercise regimens for older adults and individuals with neurological conditions.

A 10-year follow-up of high-dose ambroxol treatment combined with enzyme replacement therapy for neuropathic Gaucher disease.

High-dose ambroxol therapy combined with ERT in patients with neuropathic Gaucher disease.