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Purpose Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. Method Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants’ treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. Results In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. Conclusion ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. Trial registration: CRIS, KCT0006066. Registered 7 April 2021—Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071).

Purpose: To investigate the relationship between peripapillary vessel density (pVD) and visual field sensitivity (VFS) and between peripapillary retinal nerve fiber layer thickness (pRNFLT) and VFS, based on Garway-Heath sectorization in open-angle glaucoma patients. Methods: Sixty-six eyes of healthy subjects and 84 eyes of glaucoma subjects were included. All subjects underwent several eye examinations, including standard automated perimetry and optical coherence tomography angiography. Sectoral structure-function relationships based on the Garway-Heath sectorization were compared among normal subjects, the ‘mild glaucoma,’ and ‘moderate-to-severe glaucoma’ group. Multivariate analyses were performed for each sector to determine the factors related to VFS. The diagnostic abilities of vessel density parameters and RNFLT were evaluated by calculating the area under the receiver operating characteristic curves (AUROC). Results: The correlation between pVD-VFS and pRNFLT-VFS was statistically significant in the glaucoma group independent of the VFS sector. In the glaucoma group, VFS in the temportal sector was statistically related in a multivariate model to pVD, pRNFLT and age (R2 = 0.721; P = 0.007, < 0.001, .15, respectively). We found pRNFLT and age were significantly associated with VFS in glaucoma. The AUROC values of pVD in the inferotemporal sector of the total, mild, and moderate-to-severe glaucoma (0.843, 0.714, and 0.972, respectively) were comparable to pRNFLT in this sector (0.833, 0.718, 0.948, respectively). Conclusion: Since the relationship between pVD and VFS in the papillomacular area was significant, measuring pVD and RNFLT in the corresponding area will be valuable in expanding our pathophysiologic knowledge of the paracentral field defects in glaucoma.

Background Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. Methods A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. Results Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14–4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). Conclusion This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Background Although Thrombolysis in Cerebral Infarction (TICI) grade 2B or 3 is considered successful after endovascular thrombectomy (EVT) for acute ischemic stroke, TICI 2B was found to be associated with poorer outcomes than was 3. Furthermore, the newly proposed TICI 2C grade seems to be clinically equivalent to TICI 3 rather than to 2B. This network meta-analysis aimed to assess the differences in clinical outcomes between TICI grades and redefine successful reperfusion. Methods PubMed, Embase, and Cochrane Central Register were queried. A random-effect model with frequentist framework was applied to evaluate outcomes using odds ratios (ORs) and 95% confidence intervals (CIs). Using surface under the cumulative ranking curve (SUCRA), the hierarchy of TICI grades was indicated. Results Analysis of 12 studies, with 2084 patients, indicated that TICI 2C (OR, 2.28; 95% CI, 1.65–3.13) and 3 (OR, 2.40; 95% CI, 1.74–3.30) were significantly more associated with favorable 90-day clinical outcomes than were 2B; there was no significant difference between TICI 2C and 3 (OR, 1.05; 95% CI, 0.76–1.46). Based on the SUCRA, TICI 2C and 3 were considered as more effective reperfusion end points than was 2B (TICI 3, 80.8%; 2C, 69.2%; 2B, 0.0%) and showed significant association with lower rates of mortality and symptomatic intracranial hemorrhage. Conclusions Patients with TICI 2C grade would be distinguished from those with 2B, because 2C is clinically equivalent to 3 and has a better outcome than 2B. Therefore, achieving 2C or 3 is likely to be closer to the successful aim of endovascular thrombectomy in acute ischemic stroke than achieving 2B.

Compliance with a mandibular advancement device is important for the optimal treatment of obstructive sleep apnea. Recent advances in information and communication technology-based monitoring and intervention for chronic diseases have enabled continuous monitoring and personalized management. Self-evaluation and self-regulation through objective monitoring and feedback may improve compliance. The aim of this study was to evaluate the effects of information and communication technology-based remote monitoring and feedback services, using a smartphone application, on the objective compliance with a mandibular advancement device in patients with obstructive sleep apnea. Forty individuals who were diagnosed with obstructive sleep apnea by polysomnography were randomly assigned to groups A and B. During an initial 6-week evaluation period, the mandibular advancement device-wearing time was monitored with the smartphone application in group B, but not in group A. The two groups then switched the monitoring procedures during the second 6-week period (the smartphone application was then used by group B, but not by group A). If no input data were indicated on the cloud server of the smartphone application during the monitored period, push notifications were provided twice daily. Objective compliance, monitored by a micro-recorder within the mandibular advancement device, was noted and compared based on whether the monitoring service was provided. The number of mandibular advancement device-wearing days was significantly higher in the monitored period than in the unmonitored period. The mandibular advancement device-wearing time did not differ significantly between the two groups. In conclusion, information and communication technology-based remote monitoring and feedback services demonstrated a potential to increase the objective measures of compliance with mandibular advancement devices.

The impact on infant caregiver as a reservoir of pathogens has not been exploited with perspective to powdered infant formula (PIF). Here we reveal novel route of pathogen transfer through hand-spoon-PIF unexpectedly occurred by even typical practices of caregivers, handling of PIF and storage of feeding-spoon in PIF container. Hand-spoon-PIF contamination route was simulated to analyze the transfer and subsequent survival of pathogens. Major pathogens associated with infantile fatal diseases (Cronobacter sakazakii, Salmonella enterica, Staphylococcus aureus) were readily transmitted to PIF from skin (3−6 log CFU/hand) via spoons following long-term survival of transferred pathogens (3 weeks; use-by date of PIF) as the excessive level of infectious dose, highlighting direct onset of diseases. Low bacterial load on skin (ca. 1 log CFU/hand) could prevent cross-contamination of PIF, however, at least 72 h survival of transferred pathogen on spoons demonstrated the probability on re-contamination of PIF. To our knowledge, this is the first study to investigate the cross-contamination of utensils in contact with powdered-foods. Bacterial load on hands is the key determinant of pathogen transfer and the extent of risk are species-dependent. These evidential results redefine risk of caregivers’ practices and facilitate incorporation of cross-contamination into risk-assessment as underestimated route of infection.

Background Equol is a major isoflavone metabolite, and equol-producing bacteria have been isolated and characterized; however, fermentation has been performed with soybean-based products as substrates. Pueraria lobata has been reported as a plant with higher content of isoflavones. Results The genome of new equol-producing bacteria, Lactobacillus paracasei JS1, was analyzed. Also, the effect of P. lobata extract fermented with L. paracasei JS1 (FPE) on the skin and intestinal immune response was examined. With gene expression analysis, it was proven that seven skin-related proteins, hyaluronan synthase-1, -2, -3, collagen, elastin, epidermal growth factor, and epidermal growth factor receptor were differentially expressed upon FPE treatment. The messenger RNA expression increased with treatment with the FPE, and a skin moisturizing effect was confirmed by a hematoxylin-eosin staining experiment. In addition, such an experiment showed that proinflammatory cytokines, tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1β, -4, and -6, were reduced in large intestine when treated with FPE. Conclusion L. paracasei JS1 has the ability to produce equol having beneficial effects on the skin. Moreover, FPE also has an inhibitory effect on inflammation cytokines in the large intestine. Thus, the novel and edible equol-producing L. paracasei JS1 and FPE have thepotential to be developed as nutricosmetic resources. © 2019 Society of Chemical Industry.

The aim of this study was to investigate distinct neurometabolites in the right and left thalamus and insula of patients with complex regional pain syndrome (CRPS) compared with healthy controls using proton magnetic resonance spectroscopy. Levels of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), myo-inositol (ml), glutamine (Gln), glycerophosphocholine (GPC), glutathione (GSH), and alanine (Ala) relative to total creatine (tCr) levels, including creatine and phosphocreatine, were determined in the right and left thalamus and insula in 12 patients with CRPS compared with 11 healthy controls using magnetic resonance spectroscopy. Levels of NAAG/tCr and Ala/tCr were higher in patients with CRPS than in controls in the left thalamus. NAAG/tCr, ml/tCr, and Gln/tCr levels were higher but NAA/tCr levels were lower in the right insula of patients with CRPS compared with controls. There were negative correlations between GSH/tCr and pain score (McGill Pain Questionnaire) in the left thalamus. These findings are paramount to understand and determine all aspects of the complex pathophysiological mechanisms that underlie CRPS, including involvement of the central and parasympathetic nervous systems as well as oxidative stress and antioxidants. Thus, the distinct metabolites presented herein may be essential to understand a strong diagnostic and prognostic potential for CRPS and to develop effective medical treatments.

Studies report that autoimmune thyroid disease and elevated levels of thyroid autoantibodies are associated with fibromyalgia and widespread chronic pain. The aim of this meta-analysis was to investigate the relationship between fibromyalgia and thyroid autoimmunity. Clinical symptoms and depression associated with fibromyalgia were also investigated in relation to the presence of thyroid autoantibodies.A literature search was conducted on PubMed and Embase for studies published between January, 1980 and February, 2020 on thyroid autoimmunity in fibromyalgia patients. Two reviewers independently screened and assessed the quality of the articles. Meta-analysis was performed to analyse the difference in frequency of thyroid autoantibody positivity between fibromyalgia patients and healthy controls. Clinical symptoms and depression were also analysed according to the presence of thyroid autoantibodies.Data from 10 original studies were included in the systematic review, and 5 case-control studies that satisfied the selection criteria were subjected to meta-analysis. Thyroid autoantibody positivity was more common in fibromyalgia patients compared to healthy controls (thyroid peroxidase antibody: OR 3.41, 95% CI 1.97-5.90; thyroglobulin antibody: OR 2.23, 95% CI 1.23-4.01). The frequency of postmenopausal status was significantly higher in fibromyalgia patients with thyroid autoantibodies (OR 1.95, 95% CI 1.23-3.08). However, the severity of disease (pain and fatigue level, fibromyalgia impact questionnaire score, and disease duration) and prevalence of depression did not show a statistically significant difference according to thyroid autoantibody positivity.Thyroid autoimmunity should be considered in fibromyalgia patients. The percentage of women in menopause was higher in thyroid autoantibody positive fibromyalgia patients.

Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.

Purpose To quantitatively evaluate the effects of 0.05% cyclosporine A (CsA) on lipid layer thickness (LLT) and meibomian glands after cataract surgery using the LipiView® ocular surface interferometer. Methods This study was a prospective randomized double-masked clinical trial conducted by Pusan National University Yangsan Hospital between April 04, 2019, and November 31, 2019. Sixty-two participants were recruited, and 12 of them were not enrolled because they had undergone previous treatments for ocular surface diseases. The participants were adult patients with cataract, exhibiting normal lid position; they did not present any other ocular disease and did not meet the exclusion criteria of the clinical trial. Fifty subjects were enrolled in the study. The randomized subjects received treatment with 0.05% CsA (group A) or 0.5% carboxymethyl cellulose (CMC) (group B) over the 3 months following the cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits. Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), and Schirmer’s I test were performed by the same surgeon, and LLT and meiboscore were determined using the LipiView® interferometer. Results Fifty subjects subjects enrolled consisted of men (50%) and women (50%), with a mean (SD) age of 65.94 (10.35) years. Four subjects in group A and five in group B were excluded from the analysis as they were lost to follow-up within 1 month after cataract surgery. Thus, the study comprised 41 eyes of 41 subjects; 21 subjects were treated with CsA and 20 subjects with CMC. Comparing the clinical measurements between groups A and B taken at the last visit, while controlling the effects of the preoperative values, TBUT and LLT showed significant differences (p = 0.035 and p = 0.047, respectively, by ANCOVA). The TBUT between the subjects using CsA and those using CMC after cataract surgery showed a significant difference during follow up (p = 0.003 by repeated measures ANOVA). In the multivariate analysis, preoperative LLT and the use of CsA were found to be independent parameters for postoperative LLT (R2 = 0.303; p = 0.008 and p = 0.045, respectively), whereas the follow-up duration exhibited a positive correlation with the difference between the preoperative and postoperative values of LLT in the group treated with CsA (R2 = 0.738 and p < 0.001). Conclusion Treatment with 0.05% CsA following cataract surgery is effective in improving TBUT and LLT in comparison with 0.5% CMC. A higher preoperative value of LLT and the postoperative use of CsA could be significant determinants of a higher postoperative LLT value. Trial registration ISRCTN registry with ISRCTN 10173448.

Objective: Children with cerebral palsy (CP) have an impaired cardiac autonomic function. Attenuated heart rate recovery (HRR), which is a valuable prognostic parameter for autonomic nervous system...

Purpose The purpose of this study was to identify the influence of self-care on burnout experienced by primary family caregivers of persons with dementia. Methods The subjects of the study were 156 primary family caregivers of persons with dementia at home in Korea. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficient, and hierarchical multiple regression using IBM SPSS Statistics ver. 24.0 for Windows. Results The mean scores for self-care and burnout were 42.35 and 61.60, respectively. Self-care, subjective health status, living with a person with dementia, and behavioral and psychological symptoms of dementia were significant factors affecting burnout in family caregivers. Self-care was identified as the strongest factor affecting burnout, explaining 13.9% of burnout with controlling factors in caregivers and care receivers. Conclusion To prevent burnout in primary family caregivers of persons with dementia, self-care of family caregivers should be emphasized. In nursing education, family caregivers should be recognized and approached as nursing clients who are responsible for taking care of their health. In nursing practice and research, digital self-care or self-care improvement intervention programs should be designed to help family caregivers, and further studies on self-care centered on health of family caregivers should be conducted.

Background One of the challenges neurosurgeons are facing in the global public health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic is to balance COVID-19 screening with timely surgery. We described a clinical pathway for patients who needed emergency brain surgery and determined whether differences in the surgery preparation process caused by COVID-19 screening affected clinical outcomes. Methods During the COVID-19 period, patients in need of emergency brain surgery in our institution were managed using a novel standardized pathway designed for COVID-19 screening. We conducted a retrospective review of patients who were hospitalized through the emergency room and underwent emergency brain surgery. A total of 32 patients who underwent emergency brain surgery from February 1 to June 30, 2020 were included in the COVID-19 group, and 65 patients who underwent surgery from February 1 to June 30, 2019 were included in the pre-COVID-19 group. The baseline characteristics, disease severity indicators, time intervals of emergency processes, and clinical outcomes of the two groups were compared. Subgroup analysis was performed between the immediate surgery group and the semi-elective surgery group during the COVID-19 period. Results There were no significant differences in baseline characteristics and severity indicators between the pre-COVID-19 group and COVID-19 group. The time interval to skin incision was significantly increased in the COVID-19 group (P = 0.027). However, there were no significant differences in the clinical outcomes between the two groups. In subgroup comparison, the time interval to skin incision was shorter in the immediate surgery group during the COVID-19 period compared with the pre-COVID-19 group (P = 0.040). The screening process did not significantly increase the time interval to classification and admission for immediate surgery. The time interval to surgery initiation was longer in the COVID-19 period due to the increased time interval in the semi-elective surgery group (P < 0.001). Conclusion We proposed a clinical pathway for the preoperative screening of COVID-19 in patients requiring emergency brain surgery. No significant differences were observed in the clinical outcomes before and after the COVID-19 pandemic. The protocol we described showed acceptable results during this pandemic., Graphical Abstract

Background Attention problems and decreased quality of life are frequently accompanied in Cerebral Palsy (CP), which can negatively affect rehabilitation of physical disability. However, the majority of affected children remain untreated in the aspects of attention or psychosocial factors. Equine-Assisted Activities and Therapies (EAAT) use horse as a therapeutic modality including grooming as well as mounted riding activities in which patients exercise and experience mounted stimulation. It is known to help improve attention in children with ADHD, so that it can be an exercise therapy that is expected to improvement of attention as well as rehabilitating effects in CP patients. EAA may be a promising strategy to address the unmet need for CP patients. This study aims to investigate the efficacy of EAA for children with CP, those with both CP and ADHD and confirm the comorbidity between CP and ADHD. Methods Forty-six children with cerebral palsy participated in this study. For the exercise group, they participated in a 40-min session twice a week for a 16-week period, while the control group engaged in daily life without any special treatments. Each children individually were assessed on attention and psychological wellbeing at baseline and post-treatment. Comorbidity were identified based on the Diagnostic and Statistical Manual of Mental Disorder 5th edition (DSM-5) and confirmed by Korean Kiddie-Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL). Results Perseveration rated using the Conner’s Performance Test (CPT) showed a significant decrease only in the exercise group (p . However, no significant improvement in children’s quality of life was observed after EAA program compared with control group. Among the total participants, fifteen children (31.91%) were diagnosed with ADHD. When conducting an additional analysis with the subsample of CP patients diagnosed with ADHD, the d’, commission error and perseveration showed a significant decrease only in the exercise group. Children with CP and ADHD reported an improvement in quality of life both in exercise and control group, but only in the exercise group social functioning exhibited a significant difference. Conclusion The positive effects of the EAA on attention and quality of life were confirmed. Children with CP in the exercise group were more capable to sustain their attention longer. Those with CP and ADHD showed an increase in attention and perceived to have better social skills after receiving 16 weeks of EAA compared to those in the control group. Considering high comorbidity of CP and ADHD, it seems that the EAA program could be the better alternative treatment for CP with attentional problem. The results of this study will contribute to growing evidence for the efficacy of EAA in children especially with CP and ADHD. Trial registration This trial was registered on ClinicalTrials.gov (NCT03870893). Registered 26 July 2017.

Tethered cord syndrome (TCS) is characterized by progressive spinal cord degeneration secondary to congenital spinal dysraphism. The associated accompanying physical inactivity and musculoskeletal deformities have raised interest in the growth profile of adult TCS patients. However, few previous studies have investigated the growth profile of adult TCS patients. We retrospectively reviewed the demographic data and medical records of 20-year-old Korean conscription examinees who were registered between April 2004 and September 2019. In total, 151 examinees with a diagnosis of TCS were enrolled. The height, weight, and body mass index (BMI) of 300 randomly selected examinees were compared to the TCS group. Obesity was defined by the World Health Organization and Asian-Pacific criteria for BMI and compared between the groups. Growth profile differences according to tethering location and musculoskeletal deformities were analyzed in both groups. The mean height, weight, and BMI values of the TCS group were lower than those of the control group. The TCS group had a lower proportion of obese and overweight individuals, and a higher proportion of underweight individuals, according to both BMI criteria. The tethering level was not associated with the degree of obesity in the tethered group. The mean height, weight, and BMI were lower in the tethered group regardless of the existence of musculoskeletal deformity. Enrollees with a history of TCS were smaller than controls of the same age. Monitoring of health behaviors, including nutrition, diet, and exercise, is warranted for TCS patients.

Objective To determine whether modified constraint-induced movement therapy (mCIMT) with continuous restraint is feasible and effective in improving the use of the paretic arm in the real world among infants and toddlers with unilateral cerebral palsy (CP). Design Single-blind randomized controlled trial. Setting Tertiary hospital. Participants Children aged 7 to 36 months with unilateral CP (N = 24; 16 boys, 8 girls). Intervention The experimental group received 2-hour clinic-based mCIMT sessions (5 days per week for 3 weeks), and a continuous restraint was applied. Main Outcome Measures Standardized assessments were conducted. Peabody Developmental Motor Scales-2 (PDMS-2), Gross Motor Function Measure-66, Pediatric Motor Activity Log (PMAL), and Pediatric Evaluation of Disability Inventory were measured pre- and postintervention. Children who agreed to participate in the accelerometer study additionally wore accelerometers on both their wrists for 3 days before and after the intervention. Results The mCIMT group exhibited greater improvement in PMAL-how often (p = 0.048; ηp2 = 0.173), PMAL-how well (p = 0.008; ηp2 = 0.289), and PDMS-2 visual motor integration (p = 0.014; ηp2 = 0.256) posttreatment than the control group. The percentage of time in moderate-to-vigorous physical activity (z = –2.24; p = 0.03) and vector magnitude average counts (z = –2.52; p = 0.01) significantly increased in children in who wore accelerometers (N = 8) after the 3-week mCIMT protocol. Conclusion mCIMT with continuous restraint applied to infants and toddlers with unilateral CP appeared to have a positive effect on paretic hand use in the real world. Clinical Trial Registration Number NCT03418519

Actin-interacting protein 1 (AIP1), also known as WD repeat-containing protein 1 (WDR1), is ubiquitous in eukaryotic organisms, and it plays critical roles in the dynamic reorganization of the actin cytoskeleton. However, the biological function and mechanism of AIP1 in mammalian oocyte maturation is still largely unclear. In this study, we demonstrated that AIP1 boosts ADF/Cofilin activity in mouse oocytes. AIP1 is primarily distributed around the spindle region during oocyte maturation, and its depletion impairs meiotic spindle migration and asymmetric division. The knockdown of AIP1 resulted in the gathering of a large number of actin-positive patches around the spindle region. This effect was reduced by human AIP1 (hAIP1) or Cofilin (S3A) expression. AIP1 knockdown also reduced the phosphorylation of Cofilin near the spindle, indicating that AIP1 interacts with ADF/Cofilin-decorated actin filaments and enhances filament disassembly. Moreover, the deletion of AIP1 disrupts Cofilin localization in metaphase I (MI) and induces cytokinesis defects in metaphase II (MII). Taken together, our results provide evidence that AIP1 promotes actin dynamics and cytokinesis via Cofilin in the gametes of female mice.

Recurrence of chronic subdural hematoma (CSDH) frequently occurs after surgical evacuation. However, the value of follow-up postoperative imaging and measuring volumetric factors to predict recurrence are still controversial. Herein, we aimed to assess the optimal timing for follow-up referential imaging and the critical depressed brain volume for CSDH recurrence. A total of 291 patients with CSDH who underwent burr hole craniotomy between January 2012 and December 2018 were consecutively enrolled in this study. Patients’ medical records and radiologic data were evaluated to predict the recurrence and analyzed using receiver operating characteristics (ROC) and binary logistic regression. Of the 291 patients, 29 (10.0%) showed recurrence after surgical evacuation. Based on ROC analysis, comparisons of depressed brain volume pre-operation, 24 h post-operation, and 7 days post-operation showed that the depressed brain volume at 7 days after surgery featured the largest area under the curve (AUC: 0.768, 95% CI, 0.709–0.811). The cut-off value of the depressed brain volume on postoperative day 7 was 51.6 cm3; this value predicted the recurrence of CSDH with a sensitivity and specificity of 79.3% and 67.9%, respectively. In the multivariate analysis, the depressed brain volume (>50 cm3) at 7 days was the sole significant risk factor related to the recurrence of CSDH in this series (OR: 6.765, 95% CI, 2.551–17.942, p 50 cm3 visualized on CT scans at postoperative 7 day is the critical volume affecting recurrence of CSDHs. This result could be helpful carrying in patients with CSDH to determine the proper postoperative treatment strategy.

Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM). A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10–14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24–28 weeks. Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p

BACKGROUND Thalassemia is highly prevalent in Southeast Asia but is rare in Korea; however, Southeast Asian immigrant population is recently rising in Korea. We investigated the prevalence of thalassemia in Korea in the context of increasing immigration. METHODS This prospective, observational, multicenter study was conducted between September 2015 and August 2017. A total of 669 subjects

Aim: To design and manufacture a patient-specific assistive device optimized for patient function after estimating the disability status of a patient with brain injury through 3D printing technique Materials and methods: The left hand of a man with right-side hemiparesis was scanned with a three-dimensional scanner, and the left-hand image was flipped over to the right side to design the orthosis. To change devices easily, a connector was designed to connect the devices and was easily detachable with the orthosis by using the magnetics. To enable the writing, a round-shaped ring was attached to the orthosis to fix a pen. The Jebsen-Taylor Hand Function Test (JHFT) and Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) were evaluated one month after the application. Results: The JHFT score improved after application 3D printed devices. In most QUEST items, 3D printed devices showed better results than ready-made assistive devices. The typing speed became faster in 3D printed devices than in ready-made assistive devices. The patient was satisfied with the orthosis in writing a pen, eating food and typing keyboard because of its fitness to his hand and easy-to-use. Conclusion: We designed and manufactured a patient-specific assistive device optimized for patient function after estimating the disability status of a patient with brain injury through 3D printing techniques. We hope to provide low-cost, customized devices to disabled patients through 3D printing techniques. Implications for Rehabilitation We designed and manufactured a patient-specific assistive device optimized for patient function through 3D printing technique. We hope to provide low-cost, customized devices to disabled patients through 3D printing techniques.

This trial aimed to determine the effect of a standardized Cynanchum wilfordii Radix extract (CWE) on the lipid profiles of individuals with elevated total cholesterol (T-Chol) using a double-blind randomized placebo-controlled design. Ninety-six Korean individuals with elevated T-Chol level (200-240 mg/dL) were recruited and randomly allocated to groups that received VasH300 (300 mg CWE/day, n = 32), VasH600 (600 mg CWE/day, n = 32), or a placebo (n = 32) groups. Primary outcomes included T-Chol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, and safety (adverse events, biochemical parameters, and hematological parameters). Data were compared using a one-way analysis of variance followed by Duncan's post-hoc tests (among groups) and paired t tests (within groups). Values for T-Chol and LDL-cholesterol were significantly reduced in the VasH300 and groups (VasH300: 4.0 and 6.4%, respectively; VasH600; 3.8 and 5.8% respectively; both p < .05) compared with the placebo group and were not dose-dependent. VasH300 significantly improved the lipid profiles of individuals with elevated T-Chol without any serious side effects. Daily supplementation with VasH might be an alternative strategy with which to modify cholesterol-related parameters, especially in individuals with elevated T-Chol levels.

Background The relationship between physical and psychopathological features in complex regional pain syndrome (CRPS) has been a subject of constant interest, but no data are available in adolescents. Therefore, we aimed to identify the factors associated with psychopathology in adolescents with CRPS ahead of military service. Methods We retrospectively reviewed all conscription examinees who had completed a Military Personality Inventory (MPI) during a period between February 2013 and December 2016. A total of 63 persons with a history of CRPS (19-years of age for all) were enrolled. Basic demographic and pain-related data were analyzed to examine their association with MPI results. The mean FGR score as well as the 8 subdomain scores were compared between those with pain duration at n = 30) versus ≥15 months (n = 33). Binary MPI results (normal-abnormal) were also compared between the two groups. Results In multivariate analysis, abnormal MPI was associated with pain duration, with an odds ratio (OR) at 1.05 for every 1-month increase (95% confidence interval (CI) 1.02–1.08; P = 0.002). Subjects with pain duration at ≥15 months have lower faking good response score (P P Conclusions Pain duration is associated with psychopathology in adolescents with CRPS. Psychopathologic features increased as the disease duration increased. A comprehensive understanding of time-dependent psychopathological factors could support the planning of multimodal approaches for managing adolescent CRPS.

Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that functions in cooperation with various cofactors to regulate gene expression. In the immune system, YY1 enhances cytokine production and T helper (Th) 2 effector cell differentiation, resulting in the activation of inflammation. However, no studies have reported the role of YY1 in Th17 cell regulation, which is implicated in rheumatoid arthritis (RA). We investigated the expression of YY1 in Th17 cells in vitro and revealed increased levels of YY1 mRNA and protein. To elucidate the function of YY1 pathogenesis in RA, we used a collagen-induced arthritis (CIA) mouse model with YY1 deficiency. Deficiency of YY1 reduced the severity of arthritis and joint destruction. Moreover, Th17 cells were dramatically reduced in YY1-deficient mice. The cytokine interleukin (IL)-17 was decreased in YY1-deficient CD4+ T cells ex vivo and in vivo. Interestingly, the level of signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor-α, IL-17, IL-6, and IL-1β were markedly decreased in YY1-deficient mice with CIA. The cytokine-inducing function of YY1 was more specific to IL-17 than to interferon-γ. YY1 plays a role in Th17 cell differentiation and RA pathogenesis. Our findings suggest that future RA therapies should target the regulatory mechanism involved in Th17 cell differentiation, in which YY1 may cooperate with the STAT3 signaling pathway.

Pharmacotherapy among children with attention-deficit/hyperactivity disorder (ADHD) is effective, but many patients suffer from secondary psychiatric problems even after improvement of ADHD core symptoms. Hippotherapy have been used as adjunct treatment options for physical and psychosocial rehabilitation as well as to ameliorate core symptoms. The aim of this study was to investigate the effects of Hippotherapy versus pharmacotherapy for children with ADHD.Thirty-four participants with ADHD were randomly assigned at a 1:1 ratio to either 24 sessions of a twice-weekly hippotherapy or pharmacotherapy. To assess therapeutic effects, the ADHD Rating Scale (ARS) was used pretreatment and posttreatment as the primary outcome measure. Secondary outcomes included the Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), Pediatric Quality of Life Inventory (PedsQL) child and parent report version, Developmental Coordination Disorder Questionnaire (DCDQ), Clinical Global Impressions-Severity (CGI-S), and quantitative electroencephalography.Both groups showed marked improvements in ADHD symptoms, CGI-S. No significant differences between groups were detected regarding treatment outcome except thought problem subscales of CBCL. Twelve weeks of hippotherapy improved attention, impulsivity/hyperactivity, and quality of life.This trial is promising, but further studies are required to evaluate the long-term clinical effectiveness of hippotherapy. The study is registered with ClinicalTrials.gov, number NCT 02482649.

Context: Cynanchum wilfordii (Maximowicz) Hemsley (Apocynaceae), Arctium lappa L. var. rubescens Frivald (Asteraceae) and Dioscorea opposite Thunb (Dioscoreaceae) root extracts have been widely used as an alternative for intervening obesity. Objectives: The synergistic effect of three-herb mixture of C. wilfordii, A. lappa and D. opposita was determined on aortic and liver inflammatory responses. Materials and methods: CWE, ALE and DOE were prepared from the root of C. wilfordii, A. lappa and D. opposite by 70% ethanol extraction, respectively. CADE was prepared using a powder mixture of 2 CWE:1 ALE:1 DOE. C57BL/6 mice were fed an atherogenic diet combined with 10% fructose (ATHFR) in the presence of 200 mg/kg/day CWE, ALE, DOE or CADE for 8 weeks (each group, n = 6). Biochemical profiles, protein expression of vascular cell adhesion molecule-1 (VCAM-1) on the aorta and liver were determined. Results: CADE could significantly suppress the protein expression of VCAM-1 in both the aorta and liver (80% reduction) compared to ATHFR-fed mice. Impairment of liver function was significantly ameliorated by CADE supplement, as determined by GOT (60% reduction) and GPT (51% reduction) levels. Conclusions: CADE should be considered when developing medications to suppress the vascular and liver inflammatory responses for individuals who are either non-responsive or resistant to lipid-lowering drugs.

Background Invasive aspergillosis (IA) is a rare condition that generally affects immunosuppressed patients. The mortality of IA is known to be >90% in liver transplantation (LT) recipients; the lung is the most commonly affected organ, followed by the brain. There have been reports in the literature of cerebral aspergillosis (CA) in LT recipients. In all previous reports, CA developed after LT. We present the first case (to the best of our knowledge) of preexisting CA diagnosed and successfully treated after LT. Case Report A 59-year-old male patient underwent emergency deceased-donor LT for alcoholic liver cirrhosis. Preoperative imaging showed multiple lesions in both cerebral hemispheres, indicative of brain abscess or metastases. Before definitive diagnosis of the brain lesion, the deceased-donor LT was performed. On postoperative day 15, the patient developed a fever of 38.0°C and drowsy mental status. Magnetic resonance imaging showed increased number and size of brain abscesses. Stereotactic brain abscess aspiration was performed, and pathologic findings revealed aspergillosis. Voriconazole was started immediately. The patient improved steadily and was discharged 1 month after initiation of voriconazole treatment. Conclusions This case is the first report of preexisting CA treated successfully after LT. Voriconazole is a potent therapeutic agent of CA. When LT is performed with an undiagnosed brain lesion, aggressive diagnostic measures are necessary postoperatively. If CA is diagnosed, successful treatment may be possible with voriconazole.

Variables derived from the cardiopulmonary exercise test (CPX) provide objective information regarding the exercise capacity of children with cerebral palsy (CP), which can be used as the basis for exercise recommendations. Performing maximal CPX might not be appropriate, safe, or practical for children with CP. In the present study, the safety and feasibility of symptom-limited CPX using the modified Naughton protocol, a submaximal protocol, were investigated in children with CP, Gross Motor Function Classification System (GMFCS) level I or II. The present study included 40 children aged 6 to 12 years with CP who underwent symptom-limited CPX. CPX was performed to measure cardiopulmonary fitness using a treadmill with a modified Naughton protocol. Motor capacity was assessed using the Gross Motor Function Measure (GMFM), Pediatric Balance Scale (PBS), Timed Up and Go (TUG) test, and 6-minute walk test. Thirty-seven children with CP successfully completed testing without any adverse events during or immediately after CPX (dropout rate 7.5%). The reason for test termination was dyspnea (51.4%) or leg fatigue (48.6%). Based on the respiratory exchange ratio (RER), 21 of 37 (56.8%) children chose premature termination. The relationship between the reason for test termination and RER was not statistically significant (Spearman rho = 0.082, P = .631). CPX exercise time was strongly correlated with GMFM (Spearman rho = 0.714) and moderate correlation with PBS (Spearman rho = 0.690) and TUG (Spearman rho = 0.537). Peak oxygen uptake during CPX showed a weak correlation with GMFM and a moderate correlation with PBS. This study revealed that symptom-limited CPX using the modified Naughton protocol was safe and feasible for children with CP and GMFCS level I or II.

Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjogren’s syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured. The activation of TFH cells was assessed using a specific marker of TFH cells. Ascl2 level was also measured in SS patients. Overexpression of Ascl2 increased the expression of C-X-C chemokine receptor type 5 (CXCR5) in both salivary and lacrimal glands (p

Background Ursodeoxycholic acid (UDCA) has been known that UDCA has prominent effects on liver, however, there is little known about its influence on autoimmune disease. Here, the benefit of UDCA on arthritis rheumatoid (RA) in vivo was tested. Methods RA mouse were induced using collagen II (CIA, collagen induced arthritis) where the disease severity or UDCA-related signaling pathway such as AMP-activated protein kinase (AMPK) or small heterodimer partner interacting leucine zipper protein (SMILE) was evaluated by westerblot and immunohistochemical staining. Gene expression was measured by realtime-polymerase chain reaction (PCR). Results The administration of UDCA effectively alleviated the arthritic score and incidence with decreased cartilage damage and lipid metabolic parameters. UDCA also suppressed the secretion of pro-inflammatory cytokines. It was confirmed that UDCA upregulated the expression of SMILE and transcriptional activity of PPARγ via controlling AMPK or p38 activity. Conclusions In the present study, the therapeutic effect of UDCA inducing SMILE through AMPK activation in rheumatoid arthritis mouse as well as other autoimmune disease was proposed.

The identity of the RNA binding proteins (RBPs) that govern cancer stem cell remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomics analysis of the MSI2 interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia and SYNCRIP was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell gene associated program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. We validated SYNCRIP as a novel RBP that controls the myeloid leukemia stem cell program and propose that targeting these functional complexes might provide a novel therapeutic strategy in leukemia.

hTERT contains a high density of minisatellites, of which rare alleles of hTERT-VNTR2-2A case-control study was performed using DNA from 818 cancer-free controls, 539 cases with gastric cancer, 275 cases with colon cancer and 274 cases with rectal cancer. To determine whether minisatellites affect gene expression, expression levels were examined using TERT-reporter vectors in cell lines. In addition, the length of the hTERT-VNTR2-2No statistically significant association between hTERT-VNTR2-2We suggest that minisatellites are associated with genomic instability in cancer and that the hTERT-VNTRs region may increase hTERT expression in gastrointestinal cancer cells.

Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products. Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed. To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients. In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.

Purpose The purpose of this study was to introduce a method of using three-dimensional (3D) curved-multiplanar reconstruction (MPR) images for sylvian dissection during microsurgical treatment of middle cerebral artery (MCA) aneurysms. Materials and methods Forty-nine patients who had undergone surgery for MCA aneurysms were enrolled. We obtained the 3D curved-MPR images along the sphenoid ridge using OsiriX MD™ imaging software, compared sylvian dissection time according to several 3D MPR image factors, and investigated the correlations between these images and intraoperative findings. Results Utilizing preoperative information of the sylvian fissure (SF) and peri-aneurysmal space on 3D curved-MPR images, we could predict the feasibility of sylvian dissection for a safe surgery. 3D curved-MPR images showed several features: first, perpendicular images to the sylvian surface in the same orientation as the surgeon's view; second, simultaneous visualization of the brain cortex, vessels, and cisternal space; and third, more accurate measurement of various parameters, such as depth of the MCA from the sylvian surface and the location and width of the SFs. Conclusion In addition to conventional image studies, 3D curved-MPR images seem to provide useful information for Sylvian dissection in the microsurgical treatment of MCA aneurysms.

Coxsackie virus and adenovirus receptor (CXADR) is a member of the immunoglobulin superfamily as well as a member of the junctional adhesion molecule family of adhesion receptor. In human pre-implantation embryos, CXADR was detected and co-localized with tight junction (TJ) proteins on the membrane of the trophectoderm. However, its physiological roles were not elucidated in terms of blastocyst formation. Here, we reported expression patterns and biological functions of CXADR in porcine pre-implantation embryos. The transcripts of CXADR were detected at all stages of pre-implantation. Particularly, its expression dramatically increased and preferentially localized at the edge of cell–cell contacts, rather than in the nucleus from the eight-cell stage onwards. CXADR expression was knocked down (KD) by microinjecting double-stranded RNA into one-cell parthenotes. The vast majority of CXADR KD embryos failed to develop to the blastocyst stage, and a few developed KD blastocysts did not expand fully. Analysis of adherens junction (AJ)- and TJ-associated genes/proteins using qRT-PCR, immunocytochemistry and assessment of TJ permeability using FITC-dextran uptake assay revealed that the developmental failure and relatively small cavities are attributed to the defects of TJ assembly. In summary, CXADR is necessary for the AJ and TJ assembly/biogenesis during pre-implantation development.

It is often difficult for standard blood banks in Korea to supply adequate amounts of blood for patients with rare phenotype. Moreover, the definition of a blood in need is ambiguous, and much remains to be learned. In this study, we determined the prevalence of various red blood cell (RBC) antigens from a donor viewpoint and estimated the demand for specific antigen-negative blood from a patient viewpoint. Our data will aid the establishment of a Rare Blood Program in Korea (KRBP). RBC genotyping of 419 blood donors was performed using a Lifecodes RBC/RBC-R typing kit (Immucor, Norcross, GA). A national recipient registry website has been established. Each hospital-based blood bank voluntarily enters data on antibodies detected and identified and the outcomes of specific antigen testing. We calculated the availabilities of specific antigen-negative blood components based on these registry data and predicted the prevalence of RBC antigens via RBC genotyping. The prevalences of various RBC antigens in the D-negative population were determined for the first time, and the Cartwright, Scianna, Dombrock, Colton, Landsteiner-Wiener, Cromer, and Knops blood group systems were identified. The availabilities of specific antigen-negative units differed when calculations were based on serotyping or genotyping, especially in the D-negative group. Data on the prevalences of various blood antigens are essential for estimating the availabilities of blood components that are appropriate for use by patients expressing relevant antibodies. Then, blood banks would be able to efficiently supply safe blood products.

Ethnopharmacological relevance Salvia miltiorrhiza is a traditional oriental medicine widely used for preventing and treating disorders of the liver, menstrual, and blood circulation systems. Osteoporosis, loss of bone with age and/or estrogen deficiency, is an important causal factor of fracture. S. miltiorrhiza extract has been used to alleviate dysmenorrhea and painful osteoarthritis. Aim of the study This study was performed to investigate the anti-osteoporosis activity of the Salvia miltiorrhiza ethanol extract (SME) in osteoporosis-prone conditions: ovariectomized (OVX) and naturally menopaused (NM) ICR mice. Materials and methods Anti-osteoporotic potentials of SME (50–200 mg/kg) were evaluated based on bone mineral density using microCT analysis, biochemical parameters, and changes in the gene expressions involved in bone resorption. Results SME ameliorated the loss of trabecular bone both in OVX and NM mice. SME was effective in correcting aberrant levels of RANKL, osteocalcin, and BALP, which are critically involved in bone resorption. In addition, SME suppressed the expression of TRAF6 and NFATc1, which play a role in osteoclast differentiation. Conclusions SME suppressed the loss of trabecular bone via suppressing bone resorption and osteoclast differentiation both in OVX and NM mice. SME is likely to be developed as a therapeutic agent for osteoporosis.

Background A few reported studies have documented psychotic syndromes secondary to a middle fossa arachnoid cyst (AC). However, the association between middle fossa ACs and psychopathological symptoms remains to be determined. The present study investigated the psychopathological effects of middle fossa ACs in young men. Methods We reviewed military personal inventory test profiles and baseline demographic data of 19-year-old conscription examinees from February 2013 to December 2016. In total, 132 examinees with middle fossa ACs and 350 examinees with normal findings were enrolled in the present study. Two separate comparisons were performed. First, we compared the middle fossa AC group with the control group. Second, the middle fossa AC group was divided into 2 groups according to cyst size and compared with the control group. Results Faking bad response behavior, infrequency, inconsistency, depression, schizophrenia, paranoia, and personality disorder cluster A scales were significantly associated with the presence of a middle fossa AC. Abnormal responses to the military personal inventory were significantly and positively correlated with cyst size. The prediction rate to show abnormal psychological results with the presence of an AC was estimated to be 60.7%–68.8%. Conclusions The presence of ACs and cyst size were associated with psychopathology in this select group of young men. The size-dependent psychopathological effects of ACs appear to result from a local mass effect on the brain.

Three-dimensional printer technology can produce the personalized orthosis in various forms.To develop a personalized wrist orthosis using a three-dimensional scanner and three-dimensional printer for patients with wrist pain.A preliminary, prospective, randomized, open-label study.A total of 22 patients with wrist pain were randomly assigned to the control and experimental groups. The control group wore a cock-up orthosis and the experimental group wore a three-dimensional-printed wrist orthosis for 1 week. The Patient-Rated Wrist Evaluation, Jebsen Hand Function Test, and Orthotics and Prosthetics Users' Survey were checked before and 1 week after the application.The Patient-Rated Wrist Evaluation showed significant pain relief in both groups. Two items of the 28 Orthotics and Prosthetics Users' Survey questions, "Put toothpaste on brush and brush teeth" and "Dial a touch tone phone," showed high satisfaction scores, with statistically significant difference in the experimental group ( p = 0.036 and 0.004).The three-dimensional-printed wrist orthosis was superior to the cock-up orthosis for two items of the Orthotics and Prosthetics Users' Survey. Wrist pain was reduced in the group wearing the three-dimensional-printed wrist orthosis as well as the group wearing the cock-up orthosis, so the three-dimensional-printed wrist orthosis could possibly play the same role as the cock-up orthosis.A three-dimensional-printed wrist orthosis can be a substitute for a conventional ready-made wrist orthosis for patients with wrist pain with more satisfaction.

Ojjective The aim of this study was to find peripheral biomarkers and central metabolites affecting neuroinflammation in complex regional pain syndrome (CRPS) patients using [11C]-(R)-PK11195 positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Methods Using MRS and PET, we measured associations between neurometabolites and neuroinflammation in 12 CRPS patients and 11 healthy controls. Also, we investigated various peripheral parameters that may affect neuroinflammation in CRPS. Results We found positive correlations of Lipid (Lip)13a/total creatine (tCr) and Lip09/tCr with neuroinflammation, the distribution volume ratio (DVR) of [11C]-(R)-PK11195 in the right and left insula in CRPS patients. However, these correlations were not found in controls. High hemoglobin levels correlated with decreased neuroinflammation (the DVR of [11C]-(R)-PK11195) in the right thalamus and left insula in healthy controls. We found that high levels of glucose and pH correlated with increased neuroinflammation, but high levels of CO2, basophil, and creatinine were associated with decreased neuroinflammation in the left thalamus and the right and left insula in CRPS patients. Conclusions This is the first report indicating that elevated neuroinflammation levels are associated primarily with lipids in the brain and pH, glucose, CO2, basophil, and creatinine in the peripheral parameters in CRPS patients. Our results suggest that characterizing the peripheral biomarkers and central metabolites affecting neuroinflammation is essential to understanding the pathophysiology of CRPS.

Pancreatic neuroendocrine microadenomas (NEMAs) are non-functioning neuroendocrine tumors

Atherosclerosis is a major cause of coronary heart disease. As a result of the development of atherosclerotic lesions, the walls of blood vessels become thicker and inhibit blood circulation. Atherosclerosis is caused by a high-fat diet and vascular injury. Chronic arterial inflammation plays an important role in the pathogenesis of atherosclerosis. In particular, secretion of the pro-atherogenic cytokine tumor necrosis factor-α induces expression of endothelial adhesion molecules including P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1), which mediate attachment of circulating monocytes and lymphocytes. In this study, we examined the anti-atherosclerotic effect of sorghum, which is known to have anti-oxidant and anti-inflammatory activity. A 50% ethanol extract of Sorghum bicolor L. Moench fermented with Aspergillus oryzae NK (fSBE) was used for experiments. In vitro expression of endothelial adhesion molecules VCAM-1 and ICAM-1 and pro-inflammatory factor cyclooxygenase-2 was significantly decreased and that of the anti-atherogenic factor heme oxygenase-1 significantly increased by fSBE (P

Inflammatory bowel disease (IBD) is caused by chronic inflammation of the gastrointestinal tract. The pathogenesis of IBD remains unclear. The inflammation is associated with activation of T helper (Th) lymphocytes and chronic production of inflammatory cytokines. Ro60 suppresses the expression of tumor necrosis factor α, interleukin (IL)-6, and interferon α by inhibiting Alu transcription; control of Ro60 mRNA expression may thus be therapeutically useful. However, few studies have evaluated the anti-inflammatory activity of Ro60. The Ro60 level is decreased in IBD patients; we thus hypothesized that Ro60 was involved in the development of this autoimmune disease. We subjected mice with dextran sodium sulfate (DSS)-induced colitis to gene therapy using a vector that overexpressed Ro60 threefold. We scored IBD progression by repeatedly weighing the mice. Ro60 ameliorated colitis severity and reduced the levels of tumor necrosis factor α, IL-6, IL-17, IL-8, and vascular endothelial growth factor. Ro60 overexpression decreased the levels of α-smooth muscle actin (a marker of activated myofibroblasts) and type I collagen. The anti-inflammatory and anti-fibrotic activities of Ro60 ameliorated the severity of DSS-induced colitis in mice by repressing inflammation, fibrosis, angiogenesis, and the production of reactive oxygen species.

Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n=6; p<0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n=6; p<0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n=6; p<0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.

Sorghum [

Agrimonia eupatoria L. has been shown to protect against liver injury due to its lipid lowering and antioxidant activities. The aim of this research was to evaluate the effect of A. eupatoria L. aqueous extract (AEE) on 80 subjects with elevated alanine transaminase (ALT) levels in a randomized, double-blind, placebo-controlled, 8-week study. This trial was conducted between January 2013 and July 2013 at the Oriental Medical Hospital (Jecheon) of Semyung University. The trial included subjects aged 20 years or older who were diagnosed with mildly to moderately elevated ALT levels (between 45 and 135 IU/L). Subjects received two capsules of placebo or AEE twice a day for 8 weeks. Adverse events were recorded. Eighty subjects were randomized to placebo or AEE groups who had similar baseline characteristics. During the 8 weeks of treatment, 11 subjects were excluded from the analysis for protocol violation or consent withdrawal; efficacy of treatment was, therefore, evaluated in 69 subjects (placebo = 35, AEE = 34). The AEE group showed a significant reduction in ALT and serum triglyceride (TG) at 8 weeks compared with the placebo group (ALT P = .044, TG P = .020). Significant group and time interactions were found in ALT (P = .038), aspartate aminotransferase (P = .040), and TG (P = .010). Alkaline phosphatase, total bilirubin, and gamma-glutamyl transferase levels were not different between the two groups. There were no reported severe adverse events during this study, and total protein, albumin, blood urea nitrogen, creatine, and total cholesterol levels were normal in both groups. AEE consumption was safe and generally well tolerated without severe adverse events.

Cucurbitacin E (CuE) is a biochemical compound found in plants that are members of the family CuE has been studied for its roles in anti-inflammation and the inhibition of angiogenesis as well as for its properties as an antioxidant. CuE is a new agent that was identified as a selective inhibitor of the signal transducer and activator of transcription 3 (STAT3)-related pathway. STAT3, a pivotal transcription factor for Th17 differentiation, is critical for T cell alloactivation in acute graft-versus-host disease (aGvHD). We investigated whether CuE attenuates the development of aGvHD through the suppression of Th17 cells. The alloreactive proliferation of mouse and human T cells was reduced by CuE treatment. CuE also decreased pro-inflammatory cytokines, such as IL-17 and IFN-γ, in alloreactive T cells. STAT3-responsive and IL-17A-promoter activities were also suppressed by CuE treatment, confirming that activated STAT3 was decreased by CuE treatment. To construct an aGvHD-induced mouse line, splenocytes and bone marrow cells from C57BL/6 mice were transplanted into BALB/c mice with complete mis-matched major histocompatibility complex molecules. CuE was administered to aGvHD animals 3 days per week via intraperitoneal injection. CuE attenuated the severity of aGvHD disease-related scores compared to the vehicle group. CuE inhibited skin inflammation and fibrosis, as evidenced by the expression of α-Sma and Col-I in aGvHD mice compared to the vehicle group. Additionally, aGvHD mice treated with CuE showed improved histopathological features in the small and large intestines, whereas the vehicle group showed collapsed villi in the small intestine and cryptic structures in the large intestine. We also observed a marked reduction of pro-inflammatory cytokines in the intestinal tissue. Collectively, our data suggest that CuE could serve as a therapeutic agent for patients with aGvHD.

Background Context Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. Objective The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. Study design Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. Methods We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. Results In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p Conclusions Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.