Effectiveness and safety of pamidronate treatment in nonambulatory children with low bone mineral density.

PURPOSE: Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. METHODS: We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. RESULTS: The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. CONCLUSION: Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

A potential role of protein extractions from Metagonimus yokogawai in amelionating inflammation in patients with ankylosing spondylitis.

Helminth infections and their components has been recognized to have a positive impact on the immune system. This study aimed to investigate the potential of Metagonimus yokogawai-derived proteins (MYp) to provide protection against ankylosing spondylitis (AS) through modulation of immune responses. The cytotoxicity of MYp at various doses was first assessed using MTS and flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from AS patients, and the production of inflammatory cytokines was analyzed through flow cytometry. In the experiments with SKG mice, MYp or vehicle was administered and inflammation was evaluated through immunohistochemistry and enzyme-linked immunosorbent assay. The results showed that MYp did not decrease cell viability of PBMCs even after 48 h. Additionally, the frequencies of IFN-γ and IL-17A producing cells were significantly reduced after MYp treatment in the PBMC cultures. Furthermore, MYp treatment significantly suppressed arthritis and enthesitis in the SKG mouse model. The results suggest the first evidence that MYp can effectively alleviate clinical symptoms and restore cytokine balance in patients with AS.

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.

Stand age-driven tree size variation and stand type regulate aboveground biomass in alpine-subalpine forests, South Korea.

Alpine and subalpine forests in mountains worldwide are ecologically significant because of their unique biodiversity and increased vulnerability to climate change. This study was conducted to explore the possibilities and ways to preserve the ecological diversity of alpine-subalpine forests and their function as important carbon sinks. In this study, data from 664 plots (400 m2) were collected in the alpine-subalpine zones above 1000 m elevation in South Korea, we divided 664 plots into four stand types: conifer, conifer-dominant mixed, broadleaved-dominant mixed, and broadleaved stands. Abiotic drivers and forest successional stage-related factor including topographic, climatic drivers and stand age class were used. Biotic drivers including taxonomic, phylogenetic, functional, stand structural diversity, and community-weighted mean of functional traits were used to find independent variables controlling aboveground biomass (AGB) for each stand type. We employed multi-model averaging approach as well as piecewise structural equation modeling (pSEM) for the identification of the most influential variables affecting AGB in each stand type of alpine-subalpine forests and to quantify their interrelationships and strengths. The main results showed that tree size variation (i.e., DBH STD) induced by stand age had direct effects on AGB, with varying degrees of significance (ß) ranging from 0.146 to 0.241 across all stand types in alpine-subalpine forests. Following these results, as forest succession progresses, tree species adapted to the specific environmental conditions, such as topography and climate, become dominant by creating their own niche, which increases AGB in each stand type. Additionally, climatic and topographic conditions played an important role in controlling biotic drivers depending on the stand type. In this study, we suggest that AGB should be managed and conserved depending on forest stand types according to forest succession. Furthermore, increasing size variation among tree individuals through proper forest treatments is important for increasing AGB in alpine-subalpine forests.

Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis.

BACKGROUND: This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA. METHODS: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging. RESULTS: In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group. CONCLUSION: Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.

Effects of Early Wake-Up Time on Obesity in Adolescents.

Background: Although numerous studies have reported that obesity in adolescents is related to shorter sleep duration, few studies have reported the effect of sleep timing, particularly early wake-up time, on obesity. Objectives: To investigate the association between wake-up time and adolescent obesity. Methods: Using the Korean National Health and Nutrition Examination Survey VII data, 1301 middle school and high school students were selected and grouped according to BMI. Sleep timing and lifestyle factors were evaluated using self-reported questionnaires. Results: The mean bedtime and wake-up time were 00:09 am and 07:06 am, respectively. Despite similar bedtimes, the group with overweight/obesity woke up earlier than the group with underweight/normal weight. The BMI z-score and the overweight/obesity relative risk decreased as the wake-up time was delayed, even after adjustment for covariates. Participants who woke up before 06:50 am had a 1.82-fold higher risk of having overweight/obesity than those who woke up after 07:30 am. Participants who woke up late tended to sleep longer than those who woke up early. Conclusions: Waking up early is significantly associated with an increased BMI z-score in adolescents and may be a risk factor for overweight/obesity.

Bone Age Estimation and Prediction of Final Adult Height Using Deep Learning.

PURPOSE: The appropriate evaluation of height and accurate estimation of bone age are crucial for proper assessment of the growth status of a child. We developed a bone age estimation program using a deep learning algorithm and established a model to predict the final adult height of Korean children. MATERIALS AND METHODS: A total of 1678 radiographs from 866 children, for which the interpretation results were consistent between two pediatric endocrinologists, were used to train and validate the deep learning model. The bone age estimation algorithm was based on the convolutional neural network of the deep learning system. The test set simulation was performed by a deep learning program and two raters using 150 radiographs and final height data for 100 adults. RESULTS: There was a statistically significant correlation between bone age interpreted by the artificial intelligence (AI) program and the reference bone age in the test set simulation (r=0.99, p<0.001). In the test set simulation, the AI program showed a mean absolute error (MAE) of 0.59 years and a root mean squared error (RMSE) of 0.55 years, compared with reference bone age, and showed similar accuracy to that of an experienced pediatric endocrinologist (rater 1). Prediction of final adult height by the AI program showed an MAE of 4.62 cm, compared with the actual final adult height. CONCLUSION: We developed a bone age estimation program based on a deep learning algorithm. The AI-derived program demonstrated high accuracy in estimating bone age and predicting the final adult height of Korean children and adolescents.

Effect of catch-up sleep on obesity in Korean adolescents: a nationwide cross-sectional study.

Background: Adolescents have weekday/weekend sleep discrepancies and may compensate for weekday sleep debt through sleep extension on weekends. Objective: We investigated the effects of total sleep duration on weekdays/weekends on obesity and determined if weekend catch-up sleep has an ameliorating effect on obesity in Korean adolescents. Methods: Using data from the KNHANES VII, 1,306 middle and high school students were assessed for total sleep duration on weekdays, weekends, and the entire week, as well as weekend sleep extension. Participants were classified into four groups according to weekend sleep extension. Results: Total sleep duration and weekend sleep duration were negatively associated with body mass index z-score. Increased weekend sleep duration and sleep extension on weekends decreased the relative risk of overweight/obesity with each 30 min increment, reducing the risk by a factor of 0.39 and 0.93, respectively. The risk of overweight/obesity in adolescents who slept less than 6 h on weekdays increased by a factor of 1.93 when they slept for less than 3 h on weekends. Conclusion: Weekend catch-up sleep had a negative dose-dependent association with obesity in Korean adolescents. Sleeping longer on weekends may be associated with a decreased risk of obesity, even if the adolescent obtains less sleep during weekdays. However, further prospective studies are needed to establish the causality between extended weekend sleep and obesity.

CCIDB: a manually curated cell-cell interaction database with cell context information.

Cell-cell interaction (CCI) is a crucial event in the development and function of multicellular organisms. The development of CCI databases is beneficial for researchers who want to analyze single-cell sequencing data or study CCI through molecular experiments. CCIs are known to act differently according to cellular and biological contexts such as cell types, gene mutations or disease status; however, previous CCI databases do not completely provide this contextual information pertaining to CCIs. We constructed a cell-cell interaction database (CCIDB) containing the biological and clinical contexts involved in each interaction. To build a database of cellular and tissue contexts, we collected 38 types of context features, which were categorized into seven categories, including 'interaction', 'cell type', 'cofactor', 'effector', 'phenotype', 'pathology' and 'reference'. CCIs were manually retrieved from 272 studies published recently (less than 6 years ago). In the current version of CCIDB, 520 CCIs and their 38 context features have been manually collected and curated by biodata engineers. We suggest that CCIDB is a manually curated CCI resource that is highly useful, especially for analyzing context-dependent alterations in CCIs. Database URL https://ccidb.sysmed.kr/.

Effects of light-emitting diode therapy on hand stiffness and pain in non-steroidal anti-inflammatory drug-refractory patients with tenosynovitis.

Objective: The objective of this study was to evaluate the safety and efficacy of light-emitting diode therapy (LEDT) in the management of pain and stiffness in patients with refractory hand tenosynovitis to non-steroidal anti-inflammatory drugs. Methods: A total of 12 patients were enrolled in the study and received LEDT twice a week for four weeks. Sociodemographic, clinical, and laboratory data were collected, and the visual analog scale (VAS) pain and stiffness scores of each hand were assessed every two weeks. The thickness of the flexor tendon in the patients' hand was evaluated using ultrasonography. To investigate the molecular effects of LEDT, we measured the expression levels of type III collagen in tendon cells, with and without LEDT treatment. Results: After undergoing LEDT, participants showed clinically significant improvements in VAS pain scores at weeks 2, 4, and 8 compared to their baseline, and in VAS stiffness scores at weeks 4 and 8. According to the ultrasonography results, there was a decreasing tendency in tendon thickness for each finger in week 8 compared to the baseline, but the difference was not statistically significant. No adverse events were reported. Additionally, our results indicated a significant increase in type III collagen levels in the LEDT group compared to the control group (1.48±0.18 vs. 0.99±0.02, p=0.031), indicating a potential molecular mechanism for the observed clinical improvements. Conclusion: LEDT may provide a viable alternative to pharmacological treatments in the future, due to its simple and easy method of administration.

CCL20 inhibition for treating inflammation in ankylosing spondylitis.

OBJECTIVES: Th17 cells are known to play a significant role in AS. C-C motif chemokine ligand 20 (CCL20) binds to C-C chemokine receptor 6 (CCR6) on Th17 cells, promoting their migration to inflammation sites. The aim of this research is to examine the effectiveness of CCL20 inhibition in treating inflammation in AS. METHODS: Mononuclear cells from peripheral blood (PBMC) and SF (SFMC) were collected from healthy individuals and AS. Flow cytometry was used to analyse cells producing inflammatory cytokines. CCL20 levels were determined using ELISA. The impact of CCL20 on Th17 cell migration was verified using a Trans-well migration assay. The in vivo efficacy of CCL20 inhibition was evaluated using an SKG mouse model. RESULTS: The presence of Th17 cells and CCL20 expressing cells was higher in SFMCs from AS patients compared with their PBMCs. The CCL20 level in AS SF was significantly higher than in OA patients. The percentage of Th17 cells in PBMCs from AS patients increased when exposed to CCL20, whereas the percentage of Th17 cells in SFMCs from AS patients decreased when treated with CCL20 inhibitor. The migration of Th17 cells was found to be influenced by CCL20, and this effect was counteracted by the CCL20 inhibitor. In the SKG mouse model, the use of CCL20 inhibitor significantly reduced joint inflammation. CONCLUSION: This research validates the critical role of CCL20 in AS and suggests that targeting CCL20 inhibition could serve as a novel therapeutic approach for AS treatment.

Effects of Androgen Treatment on Growth in Patients with 5-α-Reductase Type 2 Deficiency.

BACKGROUND: Patients with 5-α-reductase type 2 deficiency (5αRD2) require androgen treatment for the growth of normal male external genitalia. Since limited research has been conducted on the effects of androgen treatment on height in individuals with 5αRD2, we investigated the effect of androgen treatment on bone age (BA) and the height status in children with 5αRD2. METHODS: Of the 19 participants who were followed up for an average of 10.6 years, 12 received androgen treatment. BA and height standard deviation scores (SDS) were compared between the treatment and non-treatment groups, as well as between the dihydrotestosterone (DHT) and testosterone enanthate (TE) treatment groups. RESULTS: Despite the above-average height of the 19 patients with 5αRD2, the height SDS relative to BA (htSDS-BA) was below average, particularly in the androgen treatment group. DHT treatment did not lead to an increase in BA or htSDS-BA, whereas TE treatment resulted in BA advancement and decreased htSDS-BA, especially in the prepubertal period. CONCLUSIONS: DHT treatment is more favorable for height than TE treatment in patients with 5αRD2, particularly during the prepubertal period. Therefore, age and the type of androgen used should be carefully considered to minimize the risk of height reduction in these patient groups.

Gerstmann Syndrome as a Disconnection Syndrome: A Single Case Diffusion Tensor Imaging Study.

Gerstmann syndrome (GS) is a rare syndrome that occurs when there is a lesion of the dominant inferior parietal lobule (IPL), causing agraphia, acalculia, finger agnosia, and right-left disorientation. A 49-year-old right-handed male was diagnosed as GS after left parieto-occipital lobe hemorrhage. The patient showed mild anomic aphasia with agraphia in the language test and the neuropsychological test revealed acalculia, impaired right-left discrimination, and finger agnosia. In diffusion tensor tractography, the tracts of left superior longitudinal fasciculus (SLF), middle longitudinal fasciculus, U-fibers and posterior corpus callosum (CC) were disrupted around the left IPL. In addition, fractional anisotropy (FA) values were markedly decreased in left SLF, and posterior CC when compared to twelve healthy control subjects. Our clinical and neuroimaging findings support that GS is a disconnection syndrome caused by lesion in the white matter pathway surrounding IPL. In future, more studies of the correlation between the white matter disconnection and the development of GS including high quality imaging technique are needed.

Neurocognitive and psychosocial profiles of children with Turner syndrome.

PURPOSE: Patients with Turner syndrome (TS) have distinct neurocognitive and psychosocial characteristics. However, few clinical studies have reported neuropsychological findings in Korean patients. This study investigated the neurocognitive and psychosocial profiles of Korean children with TS. METHODS: This retrospective cross-sectional study analyzed 20 pediatric patients (<18 years) with TS at the Department of Pediatric Endocrinology at Yonsei University Severance Children's Hospital in South Korea from January 2016 to March 2019. We selected 20 age- and sex-matched controls from among those who visited the endocrinology clinic and were confirmed to have no clinical abnormalities. All participants underwent several neuropsychological tests. RESULTS: In the Korean Wechsler Intelligence Scale for Children-IV test, the Full-Scale Intelligence Quotient of the TS group was within the normal range. The Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index scores were significantly lower in the TS group than in the control group. In contrast, the Verbal Comprehension Index did not differ significantly between the groups. The Comprehensive Attention Test results showed that the TS group displayed borderline visual selective attention. The social quotient score was significantly lower in the TS group than in the control group. CONCLUSION: Pediatric patients with TS in Korea displayed distinct neurocognitive and psychosocial characteristics. Patients in the TS group maintained their verbal function, but their attention, visuospatial function, and social competence were low. Our findings will contribute to the development of education programs for patients with TS to improve their neurocognitive and psychosocial functioning.

Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty.

PURPOSE: There are no definite guidelines on the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for treatment of central precocious puberty (CPP). We compared growth outcomes of GnRH agonist at different dosages in girls with idiopathic CPP to assess the optimal dosage. METHODS: This retrospective study included 86 girls with idiopathic CPP who had been treated with GnRH agonist for at least one year and had attained their final adult height. Leuprolide was given as fixed dosage (3.75 mg every 4 weeks in body weight >20 kg, n=72) or weight-based dosage (60-85 µg/kg every 4 weeks, n=14). We compared suppression of advanced puberty and treatment response between the 2 groups. RESULTS: Peak estradiol and luteinizing hormone and bone age (BA)/chronological age after injection of GnRH agonist were effectively suppressed in both groups. In both groups, the height standard deviation score (SDS) for BA increased after treatment. Final adult height (FAH) (fixed dosage group,160.8±4.1 cm and weight-based dosage group, 161.2±4.4 cm) was significantly higher than the initial predicted adult height (PAH) (155.5±3.3 and 156.1±3.6 cm, respectively) (both P<0.001) and similar to midparental height (159.8±3.3 and 160.6±3.7 cm, respectively). There were no differences in gain in height SDS for BA and gain in height (FAH-PAH at the start) between the 2 groups. CONCLUSION: There were no differences in treatment outcome between fixed dosage (3.75 mg/4 wk) and weight-based dosage (60-85 µg/kg/4wk) of GnRH agonist. Therefore, a fixed dosage of GnRH agonist can be used more conveniently for CPP treatment without growth oversuppression.

Analysis of Single-Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40-Positive and Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Positive Pathogenic Th17 Cells.

OBJECTIVE: To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells. METHODS: This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used. RESULTS: We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model. CONCLUSION: Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.

A Probabilistic-Geometric Approach for UAV Detection and Avoidance Systems.

This paper proposes a collision avoidance algorithm for the detection and avoidance capabilities of Unmanned Aerial Vehicles (UAVs). The proposed algorithm aims to ensure minimum separation between UAVs and geofencing with multiple no-fly zones, considering the sensor uncertainties. The main idea is to compute the collision probability and to initiate collision avoidance manoeuvres determined by the differential geometry concept. The proposed algorithm is validated by both theoretical and numerical analysis. The results indicate that the proposed algorithm ensures minimum separation, efficiency, and scalability compared with other benchmark algorithms.

Association of hypercalciuria with vitamin D supplementation in patients undergoing ketogenic dietary therapy.

Background: Ketogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications. Materials and methods: Overall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children's Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for > 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients. Result: In total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912-0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden's J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was > 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was > 49.5 IU/kg for hypercalciuria prevention. Conclusion: An inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is > 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.

Individual and Co-Expression Patterns of FAM83H and SCRIB at Diagnosis Are Associated with the Survival of Colorectal Carcinoma Patients.

Background: FAM83H is important in teeth development; however, an increasing number of reports have indicated a role for it in human cancers. FAM83H is involved in cancer progression in association with various oncogenic molecules, including SCRIB. In the analysis of the public database, there was a significant association between FAM83H and SCRIB in colorectal carcinomas. However, studies evaluating the association of FAM83H and SCRIB in colorectal carcinoma have been limited. Methods: The clinicopathological significance of the immunohistochemical expression of FAM83H and SCRIB was evaluated in 222 colorectal carcinomas. Results: The expressions of FAM83H and SCRIB were significantly associated in colorectal carcinoma tissue. In univariate analysis, the nuclear expressions of FAM83H and SCRIB and the cytoplasmic expression of SCRIB were significantly associated with shorter survival of colorectal carcinomas. The nuclear expressions of FAM83H and SCRIB and the cytoplasmic expression of SCRIB were independent indicators of shorter cancer-specific survival in multivariate analysis. A co-expression pattern of nuclear FAM83H and cytoplasmic SCRIB predicted shorter cancer-specific survival (p < 0.001) and relapse-free survival (p = 0.032) in multivariate analysis. Conclusions: This study suggests that FAM83H and SCRIB might be used as prognostic markers of colorectal carcinomas and as potential therapeutic targets for colorectal carcinomas.