Search

The medical metaverse can be defined as a virtual spatiotemporal framework wherein higher-dimensional medical information is generated, exchanged, and utilized through communication among medical personnel or patients. This occurs through the integration of cutting-edge technologies such as augmented reality (AR), virtual reality (VR), artificial intelligence (AI), big data, cloud computing, and others. We can envision a future neurosurgical operating room that utilizes such medical metaverse concept such as shared extended reality (AR/VR) of surgical field, AI-powered intraoperative neurophysiological monitoring, and real-time intraoperative tissue diagnosis. The future neurosurgical operation room will evolve into a true medical metaverse where participants of surgery can communicate in overlapping virtual layers of surgery, monitoring, and diagnosis.

Background: Accurate motor timing requires the coordinated control of actions in response to external stimuli. Over the past few years, several studies have investigated the effect of sensory input on motor timing; however, the evidence remains conflicting. The purpose of this study was to examine the impact of sensory modality and tempo on the accuracy of timed movements and explore strategies for enhancing motor timing., Methods: Participants ( n  = 30) performed synchronization and adaptation circle drawing tasks in virtual reality. In Experiment 1, participants synchronized circle drawing with repeated stimuli based on sensory modalities (auditory, visual, tactile, audio-visual, audio-tactile, and visual-tactile) and tempos (20, 30, and 60 bpm). In Experiment 2, we examined timing adaptation in circle drawing tasks under conditions of unexpected tempo changes, whether increased or decreased., Results: A significant interaction effect between modality and tempo was observed in the comparison of timing accuracy. Tactile stimuli exhibited significantly higher timing accuracy at 60 bpm, whereas auditory stimuli demonstrated a peak accuracy at 30 bpm. The analysis revealed a significantly larger timing error when adapting to changes in the tempo-down condition compared with the tempo-up condition., Discussion: Through Experiment 1, we found that sensory modality impacts motor timing differently depending on the tempo, with tactile modality being effective at a faster tempo and auditory modality being beneficial at a moderate tempo. Additionally, Experiment 2 revealed that adapting to changes by correcting timing errors is more challenging with decreasing tempo than with increasing tempo. Our findings suggest that motor timing is intricately influenced by sensory modality and tempo variation. Therefore, to enhance the motor timing, a comprehensive understanding of these factors and their applications is imperative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeong, Nam and Seo.)

Background: The aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections., Methods: An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1)., Results: RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNFα signaling via NFκB (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months., Conclusion: The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Radio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC 50 ) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log 2 (FC) of MGLL = -0.13, log 2 (FC) of acylglycerol lipase = -1.35, log 2 (FC) of glycerol = -0.81), glycolysis (log 2 (FC) of EGLN1 = 0.16, log 2 (FC) of EGLN1 = 0.62, log 2 (FC) of glucose = -0.76, log 2 (FC) of lactate = -0.81), and kynurenine pathway (log 2 (FC) of KYNU = 0.29, log 2 (FC) of kynureninase = 0.55, log 2 (FC) of alanine = 0.72). Additionally, proline metabolism (log 2 (FC) of PYCR1 = -0.17, log 2 (FC) of proline = -0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log 2 (FC) of CCN1 = -0.15, log 2 (FC) of CCN family member 1 = -1.02) and Rap 1 signaling pathway (log 2 (FC) of PARD6B = -0.28, log 2 (FC) of PAR6B = -3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to enhance performance, identify additional predictors, and improve the interpretability of biopsychosocial machine learning models for low back pain (LBP). Using survey data from a 6-year nationwide study involving 17,609 adults aged ≥50 years (Korea National Health and Nutrition Examination Survey), we explored 119 factors to detect LBP in individuals who reported experiencing LBP for at least 30 days within the previous 3 months. Our primary model, model 1, employed eXtreme Gradient Boosting (XGBoost) and selected primary factors (PFs) based on their feature importance scores. To extend this, we introduced additional factors, such as lumbar X-ray findings, physical activity, sitting time, and nutrient intake levels, which were available only during specific survey periods, into models 2 to 4. Model performance was evaluated using the area under the curve, with predicted probabilities explained by SHapley Additive exPlanations. Eleven PFs were identified, and model 1 exhibited an enhanced area under the curve .8 (.77-.84, 95% confidence interval). The factors had varying impacts across individuals, underscoring the need for personalized assessment. Hip and knee joint pain were the most significant PFs. High levels of physical activity were found to have a negative association with LBP, whereas a high intake of omega-6 was found to have a positive association. Notably, we identified factor clusters, including hip joint pain and female sex, potentially linked to osteoarthritis. In summary, this study successfully developed effective XGBoost models for LBP detection, thereby providing valuable insight into LBP-related factors. Comprehensive LBP management, particularly in women with osteoarthritis, is crucial given the presence of multiple factors. PERSPECTIVE: This article introduces XGBoost models designed to detect LBP and explores the multifactorial aspects of LBP through the application of SHapley Additive exPlanations and network analysis on the 4 developed models. The utilization of this analytical system has the potential to aid in devising personalized management strategies to address LBP., Competing Interests: Disclosures This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (2019R1C1C1007663), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2020R1F1A1068423), and the Promotion of Innovative Businesses for Regulation-Free Special Zones funded by the Ministry of SMEs and Startups (MSS, Korea) (P0020272). The authors declare that they have no conflict of interest., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Our primary purpose in this study was to determine whether trained dancers differed from untrained non-dancers in their ability to accurately control motor timing during finger and heel tapping tasks, both with and without slow isochronous auditory stimuli. Dancers and non-dancers were instructed to synchronize their taps with isochronous auditory stimuli under three conditions: 30, 40, and 50 BPM. After the synchronization phase, participants were asked to continue tapping without the auditory sequences. On the synchronization task, the tapping onset of both groups lagged behind the stimulus onset in all tempo conditions. In all conditions, dancers showed more accurate and stable beat synchronization and continuation than non-dancers. As the tempo condition slowed down (from 50 to 30 BPM), synchronization accuracy decreased while synchronization and continuation variability increased. Unlike for novices, dancers showed no difference between the finger and heel tapping synchronization tasks. During the continuous tasks, their timing accuracy was higher for heel than for finger tapping. Collectively, these findings suggest that dance training, which involves synchronizing bodily movements based on rhythm, may lead to an accumulation of experience that enhances specific sensorimotor skills related to synchronizing movements with external stimuli or continuing rhythmic movements temporally., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The aim of this study is to identify and classify the different attributes that contribute to peak performance among professional dancers, and to understand how these attributes change over time. We conducted an analysis using inductive content analysis on open-ended survey data collected from 42 formally trained professional dancers. Additionally, we analyzed interview data from seven professional dancers who demonstrated outstanding achievements in the field among the survey participants. The main themes that emerged were related to various temporal events of peak performance experience: pre-stage, on-stage, and post-stage. During the on-stage, peak performance was perceived by both internal and external factors. During the pre-stage, emphasis was placed on technical, cognitive, and artistic strategies during practice, whereas just before going on the stage, attention shifted to psychological and physical strategies. During the post-stage, dancers reported immediate changes in their psychological and physical states following the peak performance experience, and thereafter, the peak performance experience was noted to influence psychological, technical, and cognitive aspects. These findings provide valuable insights into the key characteristics that emerge throughout a series of peak performance experiences and are consistent with previous research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nam, Park and Kim.)

Background and Objectives: The role of bypass surgery in intracranial atherosclerotic steno-occlusive diseases (ICADs) remains controversial. We aimed to analyze the surgical outcomes of bypass surgery in patients with the ICADs in a single tertiary institution., Methods: Among 1018 cases of low-flow bypass surgery between 2003 and 2022, 215 patients with the ICAD refractory to medical treatment were finally enrolled in this study. Clinical and radiological outcomes were retrospectively evaluated, with survival analyses., Results: All strokes, cerebral infarctions, and intracranial hemorrhages occurred in 12.1% (n = 26), 9.8% (n = 21), and 2.3% (n = 5), respectively, during the clinical follow-up of 54.6 ± 47.6 months (range, 0.6-237.8 months). Among all stroke events, 84.6% (n = 22) occurred within 30 postoperative days. The 2-year and 5-year cumulative risks of all strokes were 12.1% each. The mean modified Rankin Scale scores were 1.6 ± 1.1 (range, 0-5) preoperatively and 0.8 ± 1.2 (range, 0-6) at last (P < .01). The patency of direct bypass was 99.1% (n = 213) just before discharge and 96.3% (n = 184 of 191 patients with available tests) at the last angiographic follow-up of 27.0 ± 27.3 months (range, 2.3-97.3 months). All the patients with available data (n = 190) showed hemodynamic improvement on acetazolamide-challenged single-photon emission computed tomography with 99mTc-hexamethylpropyleneamine oxime during the follow-up of 38.6 ± 36.7 months (range, 2.3-158.6 months)., Conclusion: Low-flow bypass surgery showed acceptable treatment outcomes in the prevention of recurrent stroke., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

This in vitro study aimed to evaluate the feasibility of quantitative light-induced fluorescence (QLF) technology for detecting the presence and severity of microleakage of pit and fissure sealants. The areas of interest (AOIs) were 160 pits and fissures of 40 extracted permanent teeth. Fluorescent images were acquired using a QLF device, and the maximum fluorescence loss ΔF max of each AOI was analyzed. After staining and cross-sectioning of the teeth, histological dye penetration was scored on a scale of 0 to 3. The relationship between ΔF max and microleakage depth was analyzed, and the areas under the curve (AUCs) were calculated. The │ΔF max │ increased as microleakage depth increased. The ΔF max values of microleakage areas showed a strong significant correlation with the histological scores of dye penetration (r = - 0.72, P = 0.001). AUC analysis showed a high diagnostic accuracy for microleakage depth (AUC = 0.83-0.91). The highest AUC of 0.91 was found when differentiating the outer half microleakage of the sealant (histological score 0 vs. 1-3). QLF technology is effective in assessing the presence and severity of microleakage, suggesting its potential for noninvasive detection and monitoring of sealant microleakage in clinical settings., (© 2024. The Author(s).)

The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up., (© 2024. The Author(s).)

Background: : This study aimed to identify exact anatomical landmarks and ideal injection volumes for safe adductor canal blocks (ACB)., Methods: : Fifty thighs from 25 embalmed adult Korean cadavers were used. The measurement baseline was the line connecting the anterior superior iliac spine (ASIS) to the midpoint of the patellar base. All target points were measured perpendicular to the baseline. The relevant cadaveric structures were observed using ultrasound (US) and confirmed in living individuals. US-guided dye injection was performed to determine the ideal volume., Results: : The apex of the femoral triangle was 25.3 ± 2.2 cm distal to the ASIS on the baseline and 5.3 ± 1.0 cm perpendicular to that point. The midpoint of the superior border of the vasto-adductor membrane (VAM) was 27.4 ± 2.0 cm distal to the ASIS on the baseline and 5.0 ± 1.1 cm perpendicular to that point. The VAM had a trapezoidal shape and was connected as an aponeurosis between the medial edge of the vastus medialis muscle and lateral edge of the adductor magnus muscle. The nerve to the vastus medialis penetrated the muscle proximal to the superior border of the VAM in 70% of specimens. The VAM appeared on US as a hyperechoic area connecting the vastus medialis and adductor magnus muscles between the sartorius muscle and femoral artery., Conclusions: : Confirming the crucial landmark, the VAM, is beneficial when performing ACB. It is advisable to insert the needle obliquely below the superior VAM border, and a 5 mL injection is considered sufficient.

Wound healing involves a complex and dynamic interplay among various cell types, cytokines, and growth factors. Macrophages and transforming growth factor-β1 (TGF-β1) play an essential role in different phases of wound healing. Cold atmospheric plasma has a wide range of applications in the treatment of chronic wounds. Hence, we aimed to investigate the safety and efficacy of a custom-made plasma device in a full-thickness skin defect mouse model. Here, we investigated the wound tissue on days 6 and 12 using histology, qPCR, and western blotting. During the inflammation phase of wound repair, macrophages play an important role in the onset and resolution of inflammation, showing decreased F4/80 on day 6 of plasma treatment and increased TGF-β1 levels. The plasma-treated group showed better epidermal epithelialization, dermal fibrosis, collagen maturation, and reduced inflammation than the control group. Our findings revealed that floating electrode-dielectric barrier discharge (FE-DBD)-based atmospheric-pressure plasma promoted significantly faster wound healing in the plasma-treated group than that in the control group with untreated wounds. Hence, plasma treatment accelerated wound healing processes without noticeable side effects and suppressed pro-inflammatory genes, suggesting that FE-DBD-based plasma could be a potential therapeutic option for treating various wounds., Competing Interests: Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Korean Society of Medical and Biological Engineering 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Developmental Coordination Disorder (DCD), also known as Dyspraxia, is characterized by movement difficulties in individuals without discernible neurological disorders or identifiable medical conditions. Previous studies from various countries have highlighted disparities in anthropometric, physical activity, and psychological characteristics between children diagnosed with DCD and their typically developing (TD) peers. These differences are influenced by sociocultural norms and geographical locations. However, little attention has been given to scrutinizing analogous differences in adult populations, particularly within Republic of Korea. This study aims to address this knowledge gap by employing a battery of questionnaires to assess anthropometric, physical activity, and psychological traits in a cohort of 377 Korean adults, encompassing those with DCD ( n = 54) alongside TD counterparts ( n = 323). It was hypothesized that Korean adults with DCD would exhibit higher body mass index and lower ratings in physical activity and psychological characteristics than TD, consistent with the previous studies performed in other countries on children. The results showed no statistically significant differences between the DCD and TD groups in anthropometric characteristics such as weight (kg), height (cm), and body mass index. The prevalence of walking and biking for daily commuting in daily routines within Korean society might have contributed to the mitigation of anthropometric among individuals with/without DCD. Statistically significant differences were found in physical activity levels at work and recreational settings, as shown in physical activity scores and duration. The DCD group also displayed lower scores across several psychological characteristics, including exercise adherence, intrinsic motivation, self-efficacy, physical self-concept, exercise expectations, and intrinsic regulation. These findings underscore the necessity of incorporating sociocultural dynamics when investigating anthropometric, physical activity, and psychological characteristics in adults with DCD. Their perceived difficulties in fine motor skills were also significantly poor than TD. Future research studies are warranted to elucidate the underlying mechanisms driving the observed patterns in this study, thus contributing to a more nuanced comprehension of how DCD manifests within specific sociocultural contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Kim, Nam, Kim, Park, Park and Shim.)

Background: Melanoma is one of the most aggressive and metastatic skin cancers. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, and breast cancer, their expression and functions in melanoma remain unknown., Objective: This study aims to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma., Methods: Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells with small interfering RNA (siRNA) was performed., Results: We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo . Inhibition of Dock180 or Elmo1 following siRNA in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE (+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulation of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase-3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib decreased cell viability in concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability., Conclusion: Our results suggest that both Dock180 and Elmo1 may be associated with cancer progression, and can be potential targets for treatment of melanoma., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: The vestibulocerebellar tract (VCT) is responsible for maintaining balance, spatial orientation, and coordination. Damage to the vestibular system is accompanied by symptoms of balance disorder or ataxia. This study aimed to compare cerebellar dysfunction according to VCT damage in patients with cerebellar stroke., Methods: Six patients with cerebellum injury were recruited. This study measured ataxia and hand function related to visuomotor integration and manual dexterity using the Purdue pegboard test. The primary and bilateral secondary VCTs were reconstructed to investigate the integrity of pathways using diffusion tensor imaging (DTI)., Results: The ataxia sign was positive in five patients (83%) at onset. In the result of the pegboard test, all patients had hand dysfunction in the dominant hand (100%). Likewise, all patients also had non-dominant hand dysfunction (100%). On the DTI tractography, the left and right primary VCTs of the patients demonstrated a 25% injury rate. Furthermore, the injury rates of ipsilateral and contralateral secondary VCTs were 50% and 58%., Conclusions: Ataxia is related to secondary VCTs, and hand dysfunction is also related to VCTs. Therefore, we believe that the current study will be helpful in evaluating and providing a clinical intervention strategy for patients with ataxia and hand dysfunction following cerebellar injury.

Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.

Background and Objectives : This study aimed to evaluate the effectiveness of a wheelchair skills training program (WSTP) in improving sitting balance and pulmonary function in patients with chronic tetraplegia resulting from cervical spinal cord injury (cSCI). Materials and Methods : Twenty-four patients were randomly divided into WSTP and control groups. The WSTP group participated in the WSTP for eight weeks, while the control group underwent conventional physical therapy for the same eight-week period. Sitting balance was evaluated using the activity-based balance level evaluation (ABLE) scale, and pulmonary function was evaluated using forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Results : The WSTP group showed significant improvements in both sitting balance and pulmonary function during the intervention period ( p < 0.05), whereas the control group did not show any significant changes. A strong positive correlation was found between ABLE scores and all three pulmonary function parameters across all time points. Conclusions : Our results suggest that the WSTP significantly improves sitting balance and specific aspects of lung function in patients with tetraplegia.

Purpurin, an anthraquinone, has potent anti-oxidant and anti-inflammatory effects in various types of brain damage. In a previous study, we showed that purpurin exerts neuroprotective effects against oxidative and ischemic damage by reducing pro-inflammatory cytokines. In the present study, we investigated the effects of purpurin against D-galactose-induced aging phenotypes in mice. Exposure to 100 mM D-galactose significantly decreased cell viability in HT22 cells, and purpurin treatment significantly ameliorated the reduction of cell viability, formation of reactive oxygen species, and lipid peroxidation in a concentration-dependent manner. Treatment with 6 mg/kg purpurin significantly improved D-galactose-induced memory impairment in the Morris water maze test in C57BL/6 mice and alleviated the reduction of proliferating cells and neuroblasts in the subgranular zone of the dentate gyrus. In addition, purpurin treatment significantly mitigated D-galactose-induced changes of microglial morphology in the mouse hippocampus and the release of pro-inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. In addition, purpurin treatment significantly ameliorated D-galactose-induced phosphorylation of c-Jun N-terminal kinase and cleavage of caspase-3 in HT22 cells. These results suggest that purpurin can delay aging by reducing the inflammatory cascade and phosphorylation of the c-Jun N-terminal in the hippocampus., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Screening for chronic kidney disease (CKD) requires an estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) from a blood sample and a proteinuria level from a urinalysis. We developed machine-learning models to detect CKD without blood collection, predicting an eGFR less than 60 (eGFR60 model) or 45 (eGFR45 model) using a urine dipstick test., Materials and Methods: The electronic health record data (n = 220 018) obtained from university hospitals were used for XGBoost-derived model construction. The model variables were age, sex, and 10 measurements from the urine dipstick test. The models were validated using health checkup center data (n = 74 380) and nationwide public data (KNHANES data, n = 62 945) for the general population in Korea., Results: The models comprised 7 features, including age, sex, and 5 urine dipstick measurements (protein, blood, glucose, pH, and specific gravity). The internal and external areas under the curve (AUCs) of the eGFR60 model were 0.90 or higher, and a higher AUC for the eGFR45 model was obtained. For the eGFR60 model on KNHANES data, the sensitivity was 0.93 or 0.80, and the specificity was 0.86 or 0.85 in ages less than 65 with proteinuria (nondiabetes or diabetes, respectively). Nonproteinuric CKD could be detected in nondiabetic patients under the age of 65 with a sensitivity of 0.88 and specificity of 0.71., Discussion and Conclusions: The model performance differed across subgroups by age, proteinuria, and diabetes. The CKD progression risk can be assessed with the eGFR models using the levels of eGFR decrease and proteinuria. The machine-learning-enhanced urine-dipstick test can become a point-of-care test to promote public health by screening CKD and ranking its risk of progression., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Submucous cleft palate (SMCP) is a subgroup of cleft palate that can present as velopharyngeal insufficiency due to muscle displacement. The pharyngeal flap and Furlow palatoplasty have been introduced to correct SMCP patient with velopharyngeal insufficiency. However, pharyngeal flap and Furlow palatoplasty can occur various complications. We consider the overlapping intravelar veloplasty (IVVP) can overcome these complications. Therefore, we present the speech outcomes of overlapping IVVP for the treatment of patients with SMCP., Methods: We retrospectively reviewed 12 patients with SMCP underwent overlapping IVVP between April 2016 and October 2018. The patients who underwent speech evaluation, nasometry, and nasoendoscopy before and after surgery and who were followed up for >18 months were enrolled in this study., Results: The average age of the patients was 5 years (range, 3-11 years) and the postoperative follow-up period ranged from 18 to 24 months (mean, 20 months). The preoperative perceptual speech evaluation was moderate and the postoperative evaluation was normal ( P < 0.01). The preoperative and postoperative nasalance scores obtained using a nasometer were 37.00 and 12.50, respectively, ( P < 0.01). Preoperative and postoperative velopharyngeal movements were grades 3 and 0, respectively, ( P < 0.01)., Conclusions: Our study showed that overlapping IVVP could provide successful correction of velopharyngeal insufficiency in patients with SMCP, including relatively old patients., Competing Interests: Conflicts of interest: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study is to report rare anatomical variations of the cephalic vein (CV) in a 77-year-old Korean male cadaver., Case Report: On the right upper arm, the CV located lateral to the deltopectoral groove passed anterior to the clavicle at the lateral one-fourth of the clavicle without anastomosis to the axillary vein. It was connected to the transverse cervical and suprascapular veins by two communicating branches in the middle of its course at the neck, and opened into the external jugular vein at its junction with the internal jugular veins. The suprascapular and anterior jugular veins were flowed into the subclavian vein at the jugulo-subclavian venous confluence, and were connected by a short communicating branch., Conclusion: Detailed knowledge of the variations in the CV is expected to be helpful in decreasing unpredicted injuries and possible postoperative complications when invasive venous access is performed through the CV., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Engineering approaches using antibody drug conjugates (ADCs) and bispecific antibodies (bsAbs) are designed to overcome the limitations of conventional chemotherapies and therapeutic antibodies such as drug resistance and non-specific toxicity. Cancer immunotherapies have been shown to be clinically successful with checkpoint blockade and chimeric antigen receptor T cell therapy; however, overactive immune systems still represent a major problem. Given the complexity of a tumor environment, it would be advantageous to have a strategy targeting two or more molecules. We highlight the necessity and importance of a multi-target platform strategy against cancer. Approximately 400 ADCs and over 200 bsAbs are currently being clinically developed for several indications, with promising signs of therapeutic activity. ADCs include antibodies that recognize tumor antigens, linkers that stably connect drugs, and powerful cytotoxic drugs, also known as payloads. ADCs have direct therapeutic effects by targeting cancers with a strong payload. Another type of drug that uses antibodies are bsAbs, targeting two antigens by linking to antigen recognition sites or bridging cytotoxic immune cells to tumor cells, resulting in cancer immunotherapy. Three bsAbs and one ADC have been approved for use by the FDA and the EMA in 2022. Among these, two of the bsAbs and the one ADC are used for cancers. We introduced that bsADC, a combination of ADC and bsAbs, has yet to be approved and several candidates are in the early stages of clinical development in this review. bsADCs technology helps increase the specificity of ADCs or the internalization and killing ability of bsAbs. We also briefly discuss the application of click chemistry in the efficient development of ADCs and bsAbs as a conjugation strategy. The present review summarizes the ADCs, bsAbs, and bsADCs that have been approved for anti-cancer or currently in development. These strategies selectively deliver drugs to malignant tumor cells and can be used as therapeutic approaches for various types of cancer., (© 2023. The Pharmaceutical Society of Korea.)

Drugs produce pharmaceutical and adverse effects that arise from the complex relationship between drug targets and signatures; by considering such relationships, we can begin to understand the cellular mechanisms of drugs. In this study, we selected 463 genes from the DSigDB database corresponding to targets and signatures for 382 FDA-approved drugs with both protein binding information for a drug-target score (KDTN, i.e., the degree to which the protein encoded by the gene binds to a number of drugs) and microarray signature information for a drug-sensitive score (KDSN, i.e., the degree to which gene expression is stimulated by the drug). Accordingly, we constructed two drug-gene bipartite network models, a drug-target network and drug-signature network, which were merged into a multidimensional model. Analysis revealed that the KDTN and KDSN were in mutually exclusive and reciprocal relationships in terms of their biological network structure and gene function. A symmetric balance between the KDTN and KDSN of genes facilitates the possibility of therapeutic drug effects in whole genome. These results provide new insights into the relationship between drugs and genes, specifically drug targets and drug signatures., (© 2023. The Author(s).)

Background: Nasal bone fractures are the most common type of facial fracture. Nasal bone fractures often occur in combination with septal cartilage fractures, because the nasal septal cartilage acts as a vertical strut and provides structural support for the nose and bilateral nasal airway. However, the treatment for nasal septal cartilage fracture remains controversial, and if untreated, nasal septal cartilage fracture can lead to various complications, such as nasal obstruction and posttraumatic nasal and septal deformity. This study aimed to evaluate the effectiveness and safety of our procedure in which septal cartilage fractures were treated with septoplasty using an absorbable plate as an internal splint., Methods: Between January 2017 and November 2020, 21 patients with nasal septal cartilage fractures were treated with septoplasty using an absorbable plate as an internal splint. The severity of the septal cartilage fracture was graded from 0 to 3 according to the computed tomography septal grading system. The numeric graded scale of nasal septal cartilage fracture was evaluated preoperatively and 6 months postoperatively using a computed tomography scan., Results: Of 21 patients with septal cartilage fractures, 12 were treated with a polycaprolactone (PCL) mesh plate, and 9 were treated with a polydioxanone (PDS) plate. In the PDS plate group, the preoperative numeric scale of nasal septal cartilage fracture was 2.50 (2.00-3.00), whereas the postoperative numeric scale was 1.00 (1.00-1.25, P = 0.023). In the PCL mesh plate group, the preoperative numeric scale of nasal septal cartilage fracture was 2.00 (2.00-3.00), whereas the postoperative numeric scale was 1.00 (1.00-1.50, P = 0.034). The effectiveness of the PCL mesh plate and that of the PDS plate group according to the septal grading scale were 1.45 (SD, 0.522) and 1.18 (SD, 0.603), respectively. However, these differences were not statistically significant., Conclusions: Our study shows that septoplasty using absorbable plates provides satisfactory and safe clinical outcomes in patients with nasal septal cartilage fractures., Competing Interests: Conflicts of interest and sources of funding: This work was supported by the Basic Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2021R1I1A3048885) and the Soonchunhyang University Research Fund., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Molecular subgrouping of medulloblastoma has become important due to its impact on risk group stratification. Immunohistochemistry (IHC) has been widely used but it has innate limitations. The NanoString assay has been proposed as an alternative method. This study aims to present the characteristics of medulloblastoma subgrouped by the NanoString assay and to compare the subgrouping results with the IHC method., Methods: Pediatric patients with histological diagnosis of medulloblastoma who underwent surgery from 2007 to 2021 were included. Clinical characteristics, pathological findings were reviewed. Molecular subgrouping was performed by IHC and by NanoString nCounter Elements TagSets assay. Test for concordance between two methods was made., Results: Among a total of 101 patients analyzed, subgrouping using the NanoString assay resulted in 14 (13.8%) WNT, 20 (19.8%) SHH, 18 (17.8%) Group 3, and 39 (38.6%) Group 4 subgroup cases. Survival analysis revealed the following from best to worse prognosis: WNT, Group 4, SHH, and Group 3. In SHH subgroup the large cell/anaplastic histology was present in 30% of cases. Seventy-one cases were analyzed for concordance between NanoString and IHC. Cohen's kappa value indicated moderate agreement but identification of Groups 3 and 4 with IHC using NPR3 and KCNA1 markers exhibited poor results., Conclusions: The NanoString assay of Korean medulloblastoma patients revealed a more aggressive clinical course in the SHH subgroup which may be explained by a higher proportion of large cell/anaplastic histology being present in this subgroup. IHC did not distinguish Group 3 or 4 accurately. The NanoString assay may represent a good alternative method for practical use in the clinical field., (© 2022. The Author(s).)

The forward shoulder posture (FSP) results from shoulders being pulled forward by shortened anterior shoulder girdle muscles. The objective of this study was to investigate the short-term effectiveness of the reverse plank exercise on parascapular muscle thickness and forward shoulder angle (FSA) in patients with FSP. Participants were divided into the FSP and non-FSP (NFSP) groups based on the observed angle between the horizontal line of the C7 spinous process and the acromion process. All participants performed a total of five sets of reverse plank exercises at 30 s per set. FSA and muscle thickness of the pectoralis major (PM), serratus anterior (SA), upper trapezius (UT), and lower trapezius (LT) were measured before and after the reverse plank exercise. The muscle thicknesses of the SA and LT, and the FSA, were significantly increased after exercise in the FSP group (p < 0.05). Muscle thickness of the PM and UT significantly decreased after the exercise. In the NFSP group, muscle thickness of the LT was significantly increased, and muscle thickness of the PM and UT were significantly reduced after exercise (p < 0.05). Upon using between-group analysis, there were significant differences between the FSA, SA, UT, and LT groups (p < 0.05). The reverse plank exercise has the short-term benefit of correcting and preventing FSP by increasing SA and LT thickness while decreasing PM and UT thickness. We believe that the reverse plank exercise significantly improved the ability to prevent FSP in FSP-related muscles and was beneficial in achieving optimal postural alignment.

Objective: Frontonasal dysplasia (FND) is a rare congenital condition. Its major features include hypertelorism, a large and bifid nasal tip, and a broad nasal root. We present our technique of septal L-strut reconstruction using costal cartilage., Design: Retrospective review from June 2008 and August 2017., Methods: Under general anesthesia, 6 patients with FND underwent septal reconstruction using costal cartilage via open rhinoplasty. We reconstructed the nasal and septal cartilaginous framework by placing columellar struts and cantilever-type grafts., Results: The patients ranged in age from 6 to 13 years old. All were female. The follow-up period ranged from 8 months to 2 years; we encountered no postoperative complications (infection, nasal obstruction, or recurrence). All patients were satisfied with their nasal appearance., Conclusions: Although the results were not entirely satisfactory from an esthetic point of view, we found that FND can be treated via septal reconstruction with costal cartilage and that the clinical outcomes are reliable and satisfactory. Our approach is a useful option for FND patients.

Background: This study was conducted to address the potential of combining porous biocompatible scaffolds with primary cells or autologous diced cartilage in cartilage tissue engineering in the animal model. The purpose of this study is an experimental evaluation of polycaprolactone (PCL) scaffold cell-based nasal implant using three-dimensional (3D) printing., Methods: In this study, we applied hollow PCL cage scaffolds with 200 and 400 µm pore sizes. The scaffolds were divided into three groups (n = 4 for each group): (1) PCL cage scaffolds loaded with agarose gel and chondrocytes; (2) PCL cage scaffolds loaded with agarose gel and fibroblasts, and (3) PCL cages loaded with autologous diced cartilage. In each group, chondrocytes and fibroblasts were seeded into the agarose gel at the density of 5 × 10 6 cells/mL., Results: All implants showed sufficient integration into the surrounding tissue. It was revealed that chondrocytes were proliferated and differentiated better in the "400 µm" scaffolds than in the "200 µm" group. However, a pore size of 200 µm was optimal for fibroblasts' proliferation. In addition, the results of our study showed that the use of PCL-based scaffolds can achieve the desirable stable augmentation effect with almost none of the changes of contour., Conclusion: In this study, both groups: (1) PCL cage scaffolds loaded with agarose gel and chondrocytes and (2) PCL cages loaded with autologous diced cartilage demonstrated chondrogenic potential with scaffolds with 400 µm pore size. The PCL cage scaffolds loaded with agarose gel and fibroblasts demonstrated potential in cartilage tissue formation within the pore size of 200 µm., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

This study investigated the differences of anticipatory postural adjustments (APAs) in a one-leg stance (OLS) that appear according to lower-extremity dominance and dual-task interference. Thirteen young, healthy, male volunteers performed the OLS task under the following six conditions: (1) dominant leg (DL), single-task; (2) DL, dual-task, with a low level of cognitive load (DT1/2); (3) DL, dual-task, with a high level of cognitive load (DT + 1); (4) non-dominant leg (NDL), single-task; (5) NDL, DT1/2; and (6) NDL, DT + 1. In order to measure the subjects' APA, we used the medial-lateral displacement of their centers of pressure and gravity from the force plate and the time-series data of joint angular motions, recorded using a 3D motion analysis system. In the NDL under the dual-task condition, the onset of APA was delayed and the amplitude declined, which resulted in an increase in the duration of the APA period. The number of components identified by principal component analysis differed according to the dominant foot, and the change caused by cognitive load was found only in the NDL. As the cognitive load increased, the variance of the principal component decreased. These findings show that dual-task interference asymmetrically influences APA according to limb dominance, which reorganizes the coordination strategy of joints' angular motion.

Abstract: The skin redraping method for medial epicanthoplasty is characterized by some shortcomings which warrants modification. In this study, clinical data of 193 patients who underwent medial epichanthoplasty by the modified skin redraping technique or the classic skin redraping technique were reviewed retrospectively. The patients underwent operation between May 2018 and June 2020 and were followed up for not less than 6 months. Interepicanthal distance, interpupillary distance, patient satisfaction, and postoperative complications were evaluated. In terms of interepicanthal distance/inter-pupillary distance ratio ( P > 0.05) and satisfaction score ( P = 0.759), the modified skin redraping technique and the classic skin redraping technique were similar. In the classic skin redraping group, there were 3 cases of visible scarring in the lower eyelid, corresponding to significantly more cases than in the modified skin redraping group (n = 0, P < 0.001). There were more out-fold cases in the modified skin redraping group (76/90) than in the classic skin redraping group (17/88) ( P < 0.001). Utilizing the modified skin redraping medial epicanthoplasty can prevent medial hooding of the upper eyelid, reduce the probability of visible scarring, and produce more out-fold with concurrent double eyelidplasty compared with classic skin redraping epicanthoplasty. Level of evidence: IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Among numerous cosmetic procedures for face rejuvenation performed all over the world, botulinum toxin type A (BoNT-A) for wrinkles is one of the most widely practiced procedures. However, for severe frowns, the application of botulinum toxin is often insufficient. In this study, the effects of hyaluronic acid filler combination therapy and the BoNT-A alone were evaluated., Methods: Forty subjects with 2 or higher points (moderate to severe) of a facial wrinkle scale (FWS) when frowning in the glabellar area were assigned to 2 group: Botulinum toxin type A monotherapy group and a combination regimen of the toxin and hyaluronic acid filler group. Subjects visited outpatient department every 4 weeks until 28 weeks after the injection, and the assessment of the efficacy using FWS, subject satisfaction at both resting and maximum frowning and safety analysis were performed., Results: Subjects of both group was administered 18U of BoNT-A and the subjects of the combination group received additional 0.45mL of hyaluronic acid filler regimen. Both at rest and maximum frown, the combination group scored lower FWS than the toxin and showed significance in the week-20 and week-28. And at final visit, subject satisfaction score of the combination was higher than that of toxin group., Conclusion: For patients with moderate to severe glabellar frown, the combined administration of BoNT-A and hyaluronic acid filler could be a considerable treatment for improving wrinkles., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Most preconditioning techniques before fat grafting require external manipulation. Since nutrition is the main factor maintaining the balance of lipogenesis and lipolysis, we hypothesized that fasting before undergoing autologous fat grafting may increase lipolysis and reduce adipocyte size, thereby improving the fat graft survival rate., Methods: C57BL/6 mice were divided into 24 h starved or fed groups. Adipose tissue lipolysis, adipogenesis, and angiogenesis-related gene expression, in fat from both groups, were analyzed. The volume and weight of the grafted fat at 4-8 weeks postoperatively were measured using micro-computed tomography. Immunohistochemistry staining and mRNA expression analysis were also performed to evaluate the effect of fasting on fat graft survival., Results: Fasting decreased adipocyte size by inducing adipose tissue lipolysis. Adipogenesis-related genes were remarkably downregulated while lipolysis-related genes and angiogenesis inducer genes were significantly upregulated in the starved adipose tissue. The mice grafted with the fat from the 24 h starved group had approximately 20% larger volumes and considerably heavier weights than those from the fed group. Increased viable adipocytes and vessels, and reduced macrophages in the fat grafts obtained from the 24 h starved group were also observed., Conclusions: Fasting for 24 h before harvesting fat increased the retention volume of fat graft by increasing angiogenesis via VEGF induction. Therefore, fasting would be a novel and reliable preconditioning strategy to improve graft survival in autologous fat grafting., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Velopharyngeal insufficiency involving a large velopharyngeal gap and poor lateral wall movement is referred to as a "black hole" and remains a challenging problem for cleft surgeons. The effect of the pharyngeal flap on this form of velopharyngeal insufficiency is still debatable because a wide pharyngeal flap is associated with a high incidence of airway obstruction. The present study aimed to evaluate the speech outcomes of combined overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty for the treatment of velopharyngeal insufficiency., Methods: Between March 2016 and June 2019, 15 patients with velopharyngeal insufficiency were treated with a combination of overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty. Preoperative speech evaluation was performed on the basis of perceptual speech evaluation, nasometry, and nasoendoscopy. Postoperative speech evaluation using the same approach as that used preoperatively was performed after completion of speech therapy., Results: All 15 patients achieved satisfactory velopharyngeal port closure and speech phonation after completion of speech therapy. No additional procedures were performed to improve velopharyngeal port closure and speech production. The preoperative and postoperative results of perceptual speech evaluation, nasometry, and nasoendoscopy evaluation were significantly different (P < 0.01)., Conclusion: Combined treatment with overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty can correct the velopharyngeal insufficiency "black hole" with highly reliable results and minimal risk of airway obstruction., Competing Interests: Conflicts of interest and sources of funding: The authors declare no conflict of interest. This work was supported by the Soonchunhyang University Research Fund., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Visual cue deprivation is the instability of head control is increased. The purpose of this study is to investigate the effects of visual cue deprivation balance training by applying head control feedback to the balance and gait ability of stroke patients. Materials and Methods : The study was conducted on 41 patients diagnosed with hemiplegia due to stroke. Subjects were randomly assigned to any of the following groups: the experimental group I, the experimental group II or the control group. The randomization method used a simple randomization method. To evaluate changes in balance function, a LOS (Limit of Stability) and a BBS (Berg Balance Scale) were performed. In addition, to evaluate changes in ST (stride time), SL (stride length), and cadence, a LEGSys were performed. Results: A two-way repeated ANOVA was conducted to analyze the differences between groups. There were significant differences between groups in all variables for the balance function. There were significant differences between groups in all variables for the balance function. There were significant differences between groups in SL and cadence for the gait function. Conclusions: Visual cue deprivation balance training applying head control feedback is effective in improving dynamic balance ability and cadence. It is necessary to constantly maintain the head orientation by feedback and to properly control the head movement.

We developed a machine-learning-based model that could predict a decrease in one-year graft function after kidney transplantation, and investigated the risk factors of the decreased function. A total of 4317 cases were included from the Korean Organ Transplant Registry (2014−2019). An XGBoost model was trained to predict the recipient’s one-year estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 using 112 pre- and peri-transplantation variables. The network of model factors was drawn using inter-factor partial correlations and the statistical significance of each factor. The model with seven features achieved an area under the curve of 0.82, sensitivity of 0.73, and specificity of 0.79. The model prediction was associated with five-year graft and rejection-free survival. Post-transplantation hospitalization >25 days and eGFR ≥ 88.0 were the prominent risk and preventive factors, respectively. Donor age and post-transplantation eGFR < 59.8 were connected to multiple risk factors on the network. Therefore, careful donor−recipient matching in older donors, and avoiding pre-transplantation risk factors, would reduce the risk of graft dysfunction. The model might improve long-term graft outcomes by supporting early detection of graft dysfunction, and proactive risk factor control.

Background: Several materials for medial orbital wall reconstruction have been mentioned in the literature. Our main purpose was to investigate postoperative enophthalmos and diplopia after medial orbital wall reconstruction with polydextro- and polylevolactic (poly- L / DL ) acid (P[ L / DL ]LA) mesh plates and porous polyethylene plates., Methods: Using a retrospective study design, we enrolled a cohort of isolated medial blowout fracture patients treated during a 58-month interval. The predictor variable was medial orbital wall reconstruction materials (P( L / DL )LA mesh plate and porous polyethylene plate. The main outcome variables included the occurrence of postoperative enophthalmos and diplopia at 1 week, 1, 3, 6, and 12 months post-surgery. Appropriate descriptive, uni- and bivariate statistics were computed, and P < 0.05 was considered significant., Results: Three hundred-two isolated medial blowout fracture patients were included (24.5% females, 67% treated with P( L / DL )LA mesh plate). Exophthalmos measured highest in both groups 1 week after surgery and decreased steadily for 6 months postoperatively. Statistically significant differences were observed between both groups at 1 week, 1 month, and 3 months after surgery, with a higher incidence of exophthalmos observed in the P( L / DL )LA mesh plate group (P < 0.001). No significant differences were observed at 6 and 12 months after surgery., Conclusion: The occurrence of enophthalmos after medial blowout fracture reconstruction with P( L / DL )LA mesh plate is comparable with the use of porous polyethylene plate. Both P( L / DL )LA mesh and porous polyethylene plates are, therefore, reliable implants for medial orbital wall reconstruction., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/objectives: Various sodium reduction policies have been implemented. However, there are limitations in the aspect of actual field applicability and efficiency. For effective sodium reduction, cooperation with the field is required and consumer preference must be considered. Thus, this study aimed to develop a low-sodium burger considering field applicability and consumer preference., Materials/methods: Focus group interviews and in-depth interviews on the sodium reduction measures were conducted with nine professionals in related fields to discuss practical methods for sodium reduction from September 7 to 21, 2018. By reflecting the interview results, a burger using a low-sodium sauce was developed, and preference analysis for sodium in the burger sauces and finished products was performed. The consumer preference for low-sodium burgers was evaluated on 51 college students on November 12, 2018., Results: The results of the professional interview showed that it is desirable to practice sodium reduction gradually, and by reflecting this, the burger sauce was prepared by adjusting the ratio of refined salt to 15%, 30%, and 50%. The sodium content of the burger using low-sodium sauce was 399 mg/100 g in the control group, 362 mg/100 g in the H1 group, and 351.5 mg/100 g in the H2 group, showing a 9.3-11.9% decrease in sodium in the H1 and H2 groups. The preference evaluation on the low-sodium burgers showed a higher preference for burgers with 9.3-11.9% sodium reduction, which did not affect the overall taste., Conclusions: This study examined the potential for sodium reduction in the franchise foodservice industry. An approximate 10% sodium reduction resulted in an increase in consumer preference without affecting the strength of the taste. Thus, if applied gradually, sodium reduction at practical levels could increase the consumer preference without changing the taste or quality and could be applied in the franchise foodservice industry., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2022 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Objective: To establish a preoperative evaluation procedure by measuring the volume of dead space using MRI in patients with ischial pressure injuries., Methods: Patients with spinal cord injury and ischial pressure injuries who underwent treatment between August 2016 and November 2019 were included in the study. Preoperative MRI scan was conducted on all patients. The volume estimation and three-dimensional (3D) reconstruction were performed based on MRI data using a 3D Slicer. Based on the resulting volume, a muscle flap that could fit the dead space was selected. Surgery was performed with the selected muscle flap, and a fasciocutaneous flap was added, if necessary., Results: A total of eight patients with ischial pressure injuries were included in the study. The mean patient age was 59.0 ± 11.0 years. The mean body mass index was 26.62 ± 3.89 kg/m2. The mean volume of dead space was 104.75 ± 81.05 cm3. The gracilis muscle was the most selected muscle flap and was used in four patients. In five of eight cases, a fasciocutaneous flap was used as well. The mean follow-up period was 16 months, and by that point, none of the patients evinced complications that required surgery., Conclusions: To the authors' knowledge, this is the first report on volumetric evaluation of dead space in ischial pressure injuries. The authors believe that the 3D reconstruction process would enable adequate dead space obliteration in ischial pressure injuries. The authors propose that preoperative MRI scans in patients with ischial pressure injury should become an essential part of the process., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.

We report on the design, construction, and performance of a custom apparatus built to measure the frequency- and temperature-dependent absorptivity of millimeter-wave light by cosmic analog dusts. We highlight the unique challenges faced as well as a few key innovations that are part of the instrument. Among those is an ultra-compact Fourier transform spectrometer. We have measured its effective frequency range and FWHM resolution to be 150-2100 GHz and ∼45 G H z , respectively. Another innovation is a cold sample positioner whose temperature can be controlled within the range of 3.7-50 K. The use of a pulse-tube cryocooler results in a pulse-synchronous signal that dominates the detector (bolometer) signal. Methods used to address that challenge are also presented.

Objectives: Prostaglandin E2 E-prostanoid 2 receptor (PGE2 EP2), downstream of cyclooxygenase-2 (COX-2), plays an important role in inflammatory responses, but there are some reports about synaptic functions of COX-2 and PGE2 EP2 in the hippocampus., Materials and Methods: C57BL/6J mice were sacrificed at postnatal days (P) 1, 7, 14, 28, and 56 for immunohistochemical staining for EP2 and doublecortin as well as western blot for EP2. In addition, COX-2 knockout and its wild-type mice were euthanized for immunohistochemical staining for EP2., Results: EP2 immunoreactivity was observed in the majority of the cells in the dentate gyrus at P1 and P7, while at P14, it was detected in the outer granule cell layer and was confined to its subgranular zone at P28 and P56. EP2 protein levels in the hippocampal homogenates were also highest at P7 and lowest at P56. EP2 immunoreactivity was partially colocalized, with doublecortin (DCX)-immunoreactive neuroblasts appearing in the mid-zone of the granule cell layer at P14 and in the subgranular zone of the dentate gyrus at P28. Co-localization of EP2 and DCX was significantly decreased in the dentate gyrus in the P28 group compared with that in the P14 group. In COX-2 knockout mice, EP2 immunoreactivity was significantly decreased in the hippocampal CA1 region ( P =0.000165) and dentate gyrus ( P =0.00898)., Conclusion: EP2 decreases with age, which is expressed in DCX-immunoreactive neuroblasts in the dentate gyrus. This suggests that EP2 is closely linked to structural lamination and adult neurogenesis in the dentate gyrus.

Background: In epidemiological studies, finding the best subset of factors is challenging when the number of explanatory variables is large., Objective: Our study had two aims. First, we aimed to identify essential depression-associated factors using the extreme gradient boosting (XGBoost) machine learning algorithm from big survey data (the Korea National Health and Nutrition Examination Survey, 2012-2016). Second, we aimed to achieve a comprehensive understanding of multifactorial features in depression using network analysis., Methods: An XGBoost model was trained and tested to classify "current depression" and "no lifetime depression" for a data set of 120 variables for 12,596 cases. The optimal XGBoost hyperparameters were set by an automated machine learning tool (TPOT), and a high-performance sparse model was obtained by feature selection using the feature importance value of XGBoost. We performed statistical tests on the model and nonmodel factors using survey-weighted multiple logistic regression and drew a correlation network among factors. We also adopted statistical tests for the confounder or interaction effect of selected risk factors when it was suspected on the network., Results: The XGBoost-derived depression model consisted of 18 factors with an area under the weighted receiver operating characteristic curve of 0.86. Two nonmodel factors could be found using the model factors, and the factors were classified into direct (P<.05) and indirect (P≥.05), according to the statistical significance of the association with depression. Perceived stress and asthma were the most remarkable risk factors, and urine specific gravity was a novel protective factor. The depression-factor network showed clusters of socioeconomic status and quality of life factors and suggested that educational level and sex might be predisposing factors. Indirect factors (eg, diabetes, hypercholesterolemia, and smoking) were involved in confounding or interaction effects of direct factors. Triglyceride level was a confounder of hypercholesterolemia and diabetes, smoking had a significant risk in females, and weight gain was associated with depression involving diabetes., Conclusions: XGBoost and network analysis were useful to discover depression-related factors and their relationships and can be applied to epidemiological studies using big survey data., (©Sang Min Nam, Thomas A Peterson, Kyoung Yul Seo, Hyun Wook Han, Jee In Kang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 24.06.2021.)

Entacapone, a catechol-O-methyltransferase inhibitor, can strengthen the therapeutic effects of levodopa on the treatment of Parkinson's disease. However, few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice. To investigate the effects of entacapone, a modulator of dopamine, on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus, 60 mice (7 weeks old) were randomly divided into a vehicle-treated group and the groups treated with 10, 50, or 200 mg/kg entacapone. The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition. Immunohistochemical staining results revealed that after entacapone treatment, the numbers of Ki67-positive proliferating cells, doublecortin-positive immature neurons, and phosphorylated cAMP response element-binding protein (pCREB)-positive cells were significantly increased. Western blot analysis results revealed that treatment with tyrosine kinase receptor B (TrkB) receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor (BDNF). Entacapone treatment antagonized the effects of TrkB receptor antagonist. These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway. This study was approved by the Institutional Animal Care and Use Committee of Seoul National University (approval No. SNU-130730-1) on February 24, 2014., Competing Interests: None

Background: Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca 2+ ] i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF., Methods: C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o. ), and GEF100 (GEF 100 mg/kg, p.o. ). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups., Results: NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β 3 -adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels., Conclusion: We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS., Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests., Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits., Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms., Competing Interests: All the authors declare that they have no conflicts of interest., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain., Materials and Methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment., Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425., Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration., Competing Interests: The authors declare no conflict of interest., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a poor prognosis for which no effective therapeutic measures are currently available. The present study aimed to investigate whether interactions with endothelial colony-forming cells (ECFCs) promote aggressive progression of TNBC cells. Herein, using an indirect co-culture system, we showed that co-culture increased the invasive and migratory phenotypes of both MDA-MB-231 TNBC cells and ECFCs. Through a cytokine antibody array and RT-PCR analysis, we revealed that co-culture markedly induced secretion of the chemokine C-C motif ligand (CCL)8 from ECFCs and that of interleukin (IL)-8 from MDA-MB-231 cells. CCL8 was crucial for ECFC-induced IL-8 secretion and invasion of MDA-MB-231 cells as well as for MDA-MB-231-enhanced MMP-2 secretion and angiogenesis of ECFCs. We suggest c-Jun as a transcription factor for CCL8-induced IL-8 expression in MDA-MB-231 cells. IL-8 was important for co-culture-induced CCL8 and MMP-2 upregulation and invasion of ECFCs. Notably, our findings reveal a positive feedback loop between CCL8 and IL-8, which contributes to the aggressive phenotypes of both ECFC and TNBC cells. Using an MDA-MB-231 cell-based xenograft model, we show that tumor growth and metastasis are increased by co-injected ECFCs in vivo. Increased expression of IL-8 was observed in tissues with bone metastases in mice injected with conditioned media from co-cultured cells. High IL-8 levels are correlated with poor recurrence-free survival in TNBC patients. Together, these results suggest that CCL8 and IL-8 mediate the crosstalk between ECFCs and TNBC, leading to aggravation of tumorigenicity in TNBC.

Due to the limited supply of vessels and nerves, acute or chronic tendon injuries often result in significant and persistent complications, such as pain and sprains, as well as the loss of joint functions. Among these complications, tendon adhesions within the surrounding soft tissue have been shown to significantly impair the range of motion. In this study, to elucidate the effects of a hyaluronic acid (HA) injection at the site of tenorrhaphy on tendon adhesion formation, we used a full transection model of a rat's Achilles tendon to investigate the anti-adhesive function of HA. Our initial findings showed that significantly lower adhesion scores were observed in the HA-treated experimental group than in the normal saline-treated control group, as determined by macroscopic and histological evaluations. Hematoxylin and eosin, as well as picrosirius red staining, showed denser and irregular collagen fibers, with the larger number of infiltrating inflammatory cells in the control group indicating severe adhesion formation. Furthermore, we observed that the expression of tendon adhesion markers in operated tendon tissue, such as collagen type I, transforming growth factor-β1, and plasminogen activator inhibitor-1, was suppressed at both the gene and protein levels following HA treatment. These results suggest that HA injections could reduce tendon adhesion formation by significantly ameliorating inflammatory-associated reactions.