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IntroductionChildren who have experienced the coronavirus disease 2019 (COVID-19) pandemic are at an increased risk of adverse neurologic developmental outcomes. Limited data exist on the environmental influences of during the COVID-19 pandemic on preterm infant development. This study aimed to investigate whether COVID-19 exposure affects the neurodevelopmental outcomes in preterm children up to 3 years of age.MethodsThis prospective cohort study included all very low birth weight (VLBW) infants from the Korean Neonatal Network who had undergone a neurodevelopmental assessment between January 2015, and May 2022. The neurodevelopmental outcomes along with the scores on the Bayley Scales of Infant and Toddler Development (BSID) and the Korean Developmental Screening Test for Infants and Children of pediatric patients aged 18–24 and 33–39 months who were exposed to COVID-19 were compared with those of VLBW children born and tested before the pandemic.ResultsThe cohort included 1,683 VLBW infants. The pandemic group had significantly lower language scores on the BSID-III at ages 18–24 months (p = 0.021) and 33–39 months (p = 0.023) than the pre-pandemic group after adjusting for gestational age, morbidity, and environmental factors. At 2nd follow-up period, the pandemic group showed significantly lower scores in the cognitive (p = 0.026) domains with a mean difference of 7 points and had a significantly higher percentage of ≤−1SD in the gross motor domain (p

The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs’ efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.

Background/Aims Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Abstract In a nationwide prospective cohort of Korean infants with very low birthweights (VLBW, birth weight

Objectives Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Abstract Background Thrombotic microangiopathy (TMA), a rare but serious complication of systemic lupus erythematosus (SLE), is associated with poor outcomes to conventional immunosuppressive therapy. Recently, eculizumab, a humanised monoclonal antibody that blocks the complement factor 5, has been known to effectively treat atypical haemolytic uremic syndrome (aHUS). Here, we report a case of aHUS co-existing with lupus nephritis that was successfully treated with eculizumab. Case presentation A 23-year-old man presented with abdominal pain and diarrhoea. Initial laboratory tests have shown thrombocytopaenia, microangiopathic haemolytic anaemia, and acute kidney injury. Immunologic tests were consistent with SLE. Kidney biopsy have revealed lupus nephritis class IV-G with TMA. Genetic analysis have shown complement C3 gene mutations, which hints the co-existence of lupus nephritis with aHUS, a form of complement-mediated TMA. Although initial treatment with haemodialysis, plasma exchange, and conventional immunosuppressive therapy (steroid and cyclophosphamide) did not appreciably improve kidney function and thrombocytopaenia, the patient was able to respond to eculizumab therapy. Conclusions Due to the similar features of TMA and SLE, clinical suspicion of aHUS in patients with lupus nephritis is important for early diagnosis and prompt management. Timely administration of eculizumab should be considered as a treatment option for aHUS in lupus nephritis patients to yield optimal therapeutic outcomes.

Caragana sinica (CS; family Legume) was used as a medicinal material to treat neuralgia and arthritis in folk remedies and has been shown to have antioxidant, neuroprotective, and anti-apoptotic effects. However, CS is unknown for its biological activities related to skin. The present study explored the effects of CS flower absolute (CSFAb) on skin repair responses, viz., wound healing and anti-wrinkle-related responses using keratinocytes. CSFAb was extracted using hexane, and its composition was analyzed by GC/MS. The effects of CSFAb on human keratinocytes (HaCaT cells) were evaluated using Boyden chamber, sprouting, water-soluble tetrazolium salt, 5-bromo-2′-deoxyuridine incorporation, ELISA, zymography, and immunoblotting assays. GC/MS detected 46 components in CSFAb. In addition, in HaCaT cells, CSFAb increased the proliferation, migration, and sprout outgrowth and the phosphorylation of ERK1/2, JNK, p38 MAPK, and AKT, and also increased collagen type I and IV synthesis, reduced TNF-α-increased MMP-2 and MMP-9 activities, and upregulated hyaluronic acid (HA) and HA synthase-2 levels. These effects of CSFAb on wound healing and anti-wrinkle-related responses in keratinocytes suggest its potential use for skin repair and care preparations.

Since its discovery, polymerase chain reaction (PCR) has emerged as an important technology for the diagnosis and identification of infectious diseases. It is a highly sensitive and reliable nucleic acids (NA) detection tool for various sample types. However, stool, which carries the most abundant micro-organisms and physiological byproducts, remains to be the trickiest clinical specimen for molecular detection of pathogens. Herein, we demonstrate the novel application of hydrogel microparticles as carriers of viral RNA from stool samples without prior RNA purification for real-time polymerase chain reaction (qPCR). In each microparticle of primer-incorporated network (PIN) as a self-sufficient reaction compartment, immobilized reverse transcription (RT) primers capture the viral RNA by hybridization and directly initiate RT of RNA to generate a pool of complementary DNA (PIN-cDNA pool). Through a simple operation with a portable thermostat device, a PIN-cDNA pool for influenza A virus (IAV) was obtained in 20 min. The PIN-cDNA pools can be stored at room temperature, or directly used to deliver cDNA templates for qPCR. The viral cDNA templates were freely released in the subsequent qPCR to allow amplification efficiency of over 91%. The assay displayed good linearity, repeatability, and comparable limit of detection (LoD) with a commercialized viral RNA purification kit. As a proof of concept, this technology carries a huge potential for onsite application to improve human and animal infectious disease surveillance activities using stool samples without the need for a laboratory or centrifuge for sample preparation.

Impatiens textori Miq. (ITM; family Balsaminaceae) is a traditional medicinal plant with many biological activities, which include anti-allergic, anti-inflammatory, and anti-pruritic properties. However, it remains to be determined whether ITM affects biological activities in the skin. Thus, we investigated the effects of ITM flower absolute (ITMFAb) extract on the biological activities of skin, especially those related to skin wound repair and whitening. ITMFAb was extracted with hexane, and its composition was determined through GC/MS. The biological activities of ITMFAb on HaCaT keratinocytes and B16BL6 melanoma cells were analyzed using a water-soluble tetrazolium salt, 5-bromo-2′-deoxyuridine incorporation, a Boyden chamber, an ELISA, a sprouting assay, and by immunoblotting. These analyses were performed in a range of ITMFAb concentrations that did not inhibit the viability of the cells (HaCaT, ≤400 µg/mL; B16BL6, ≤200 µg/m). Forty components were identified in ITMFAb. ITMFAb stimulated proliferation, migration, sprout outgrowth, and type I and IV collagen synthesis and upregulated the activations of ERK1/2, JNK, p38 MAPK, and AKT in HaCaT cells. In addition, ITMFAb attenuated the serum-induced proliferation of B16BL6 cells. ITMFAb inhibited melanin synthesis, tyrosinase activity, and expressions of MITF and tyrosinase in α-MSH-exposed B16BL6 cells. These findings indicate that ITMFAb has beneficial effects on wound repairing and whitening-linked responses in the skin and suggest the potential use of ITMFAb as a natural material for the development of skin wound repair and whitening agents.

Background As the indications for postmastectomy radiotherapy expand, innovative solutions are required to reduce operative complications and reconstructive failure after prosthetic breast reconstruction. In this study, we investigated the effectiveness of acellular dermal matrix (ADM) inlay grafts in preventing postoperative wound dehiscence of irradiated breasts in the context of prosthetic breast reconstruction. Methods A retrospective analysis was conducted of 45 patients who received two-stage prosthetic reconstruction and radiotherapy following mastectomy. An ADM graft was placed beneath the incisional site during the second-stage operation in 19 patients using marionette sutures, whereas the control group did not receive the ADM reinforcement. Patient demographics and complications such as wound dehiscence, capsular contracture, peri-prosthetic infection, cellulitis, and seroma were compared between the two groups. Results During an average follow-up period of 37.1 months, wound dehiscence occurred significantly less often in the ADM-reinforced closure group (0%) than in the non-ADM group (23.1%) (P=0.032). There was no significant difference between the two groups in relation to other complications, such as capsular contracture, postoperative infection, or seroma. Conclusions The ADM inlay graft is a simple and easily reproducible technique for preventing incisional dehiscence in the setting of radiotherapy after prosthetic breast reconstruction. The ADM graft serves as a buttress to offload tension during healing and provides a mechanical barrier against pathogens. Application of this technique may serve to reduce complications in prosthetic breast reconstruction after radiotherapy.

A common complication of cisplatin-based chemotherapy is hearing loss. Here, Park et al. show that glutathione transferase α4 (GSTA4) contributes to reducing cisplatin toxicity in the inner ear of female mice by removing 4-hydroxynonenal (4-HNE).

Although ulcerative colitis (UC) is confined to colonic and rectal mucosa in a continuous fashion, recent studies have also demonstrated the involvement of upper gastrointestinal tract as diagnostic endoscopy becomes more available and technically advanced. The pathogenesis of UC is not well established yet. It might be associated with an inappropriate response of host mucosal immune system to gut microflora. Although continuous and symmetric distribution of mucosal inflammation from rectum to colon is a typical pattern of UC, clinical feature and course of atypically distributed lesions in UC might also help us understand the pathogenesis of UC. Herein, we report a case of duodenal involvement of UC which successfully remitted after infliximab therapy. Endoscopic and pathologic findings before and after administration of anti-tumor necrosis factor suggest that the pathogenesis of upper gastrointestinal involvement of UC may be similar to that of colon involvement.

BackgroundEmerging radiation technologies are expected to provide a positive impact on the reduction in postoperative complications in patients receiving prosthetic breast reconstruction. This study aimed to determine whether hypofractionated radiation therapy(RT) with volumetric modulated arc therapy(VMAT) is superior to conventional RT in the setting of prosthetic reconstruction.MethodsFrom retrospective data collections, postoperative complications were compared for all patients with mastectomy and staged prosthetic reconstruction without RT, with hypofractionation using 40 Gy in 15 fractions with VMAT (Hypo-VMAT) or conventional RT (50 Gy over 5 weeks). After harvesting subpectoral capsules from patients with informed consents, histologic analysis including immunohistochemistry and immunofluorescence for collagen type I, α-smooth muscle actin, CD34 and CD31 expression was performed.ResultsA total of 288 reconstructions without RT, 55 reconstructions with Hypo-VMAT, and 29 reconstructions with conventional RT were examined. During average follow-up period of 34.8 months, rates of overall complications were 6.3% in the no-radiation group, 18.2% in Hypo-VMAT group and 44.8% in conventional-RT group with significant differences (no-RT vs Hypo-VMAT: p=0.006; Hypo-VMAT vs conventional-RT: p=0.012). Levels of myofibroblasts and tissue fibrosis were lower in the Hypo-VMAT group than in conventional-RT group (p=0.016 and p=0.040, respectively), while those of progenitor cells and microvessel density were higher in the Hypo-VMAT group than in conventional-RT group (p

Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown.Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD.Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD.Results:FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8–4.8, P = 6.5 × 10−6]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9–10.3, P = 7.88 × 10−9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction.Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings.

Salix koreensis Anderss (SKA) has been used traditionally to treat inflammation, pain, and edema. SKA has anti-inflammatory and antioxidant effects, but no study has examined its effects on skin wound healing. Here, we aimed to investigate the effects of the absolute extracted from SKA flower (SKAFAb) on skin wound healing-associated responses in keratinocytes. SKAFAb was produced using a solvent extraction method and its chemical composition was analyzed by gas chromatography/mass spectrometry. The effects of SKAFAb on HaCaT cells (a human epidermal keratinocyte cell line) were investigated using a Boyden chamber and 5-bromo-2′-deoxyuridine incorporation, sprout outgrowth, immunoblotting, enzyme-linked immunosorbent, and water-soluble tetrazolium salt assays. Sixteen constituents were identified in SKAFAb. SKAFAb promoted HaCaT cell proliferation, migration, and type I and IV collagen productions. SKAFAb increased sprout outgrowth and increased the phosphorylations of serine/threonine-specific protein kinase (Akt), c-Jun NH2-terminal kinase, extracellular signal-regulated kinase1/2, and p38 mitogen-activated protein kinase (MAPK) in HaCaT cells. These results indicate that SKAFAb promotes keratinocyte proliferation and migration, probably by activating Akt and MAPK signaling pathways, and induces collagen synthesis in keratinocytes. SKAFAb may be a promising material for promoting skin wound healing.

Objective To replace camera-based three-dimensional motion analyzers which are widely used to analyze body movements and gait but are also costly and require a large dedicated space, this study evaluates the validity and reliability of inertial measurement unit (IMU)-based systems by analyzing their spatio-temporal and kinematic measurement parameters. Methods The investigation was conducted in three separate hospitals with three healthy participants. IMUs were attached to the abdomen as well as the thigh, shank, and foot of both legs of each participant. Each participant then completed a 10-m gait course 10 times. During each gait cycle, the hips, knees, and ankle joints were observed from the sagittal, frontal, and transverse planes. The experiments were conducted with both a camerabased system and an IMU-based system. The measured gait analysis data were evaluated for validity and reliability using root mean square error (RMSE) and intraclass correlation coefficient (ICC) analyses. Results The differences between the RMSE values of the two systems determined through kinematic parameters ranged from a minimum of 1.83 to a maximum of 3.98 with a tolerance close to 1%. The results of this study also confirmed the reliability of the IMU-based system, and all of the variables showed a statistically high ICC. Conclusion These results confirmed that IMU-based systems can reliably replace camera-based systems for clinical body motion and gait analyses.

Background: The geographical origin of Panax ginseng Meyer, a valuable medicinal plant, is important to both ginseng producers and consumers in the context of economic profit and human health benefits. We, therefore, aimed to discriminate between the cultivation regions of ginseng using the stable isotope ratios of C, N, O, and S, which are abundant bioelements in living organisms. Methods: Six Korean ginseng cultivars (3-yr-old roots) were collected from five different regions in Korea. The C, N, O, and S stable isotope ratios in ginseng roots were measured by isotope ratio mass spectrometry, and then these isotope ratio profiles were statistically analyzed using chemometrics. Results: The various isotope ratios found in P. ginseng roots were significantly influenced by region, cultivar, and the interactions between these two factors (p ≤ 0.001). The variation in δ15N and δ13C in ginseng roots was significant for discriminating between different ginseng cultivation regions, and δ18O and δ34S were also affected by both altitude and proximity to coastal areas. Chemometric model results tested in this study provided discrimination between the majority of different cultivation regions. Based on the external validation, this chemometric model also showed good model performance (R2 = 0.853 and Q2 = 0.738). Conclusion: Our case study elucidates the variation of C, N, O, and S stable isotope ratios in ginseng root depending on cultivation region. Hence, the analysis of stable isotope ratios is a suitable tool for discrimination between the regional origins of ginseng samples from Korea, with potential application to other countries. Keywords: geographical origin, Panax ginseng, PCA, PLS-DA, stable isotope ratio

Objectives: We aimed to evaluate diagnosis and management of an ectopic pregnancy developing in a previous cesarean scar. Materials and methods: Between March 2003 and October 2015, total 64 cases of cesarean scar pregnancy (CSP) were retrospectively reviewed. The cliniscal characteristics, diagnosis, various methods of treatment and clinical outcomes were analyzed. Results: The mean gestational age at diagnosis was 6.5 ± 1.1 weeks and the number of previous cesarean section was 1.6 ± 0.6. The main ultrasonographic findings included anterior implantation of gestational sac within the previous CS scar and thinning of anterior myometrium (average: 3.0 ± 2.0 mm). Excluding 6 cases that were lost to follow up after diagnosis, 58 patients underwent first line treatment. The treatment was successful with first line therapy alone in 32 patients (55.2%). Emergency hysterectomy was necessary in 4 cases during following up of first line treatment. In 22 patients who underwent second line treatment, all of them were successfully treated with no additional treatment. Conclusions: MTX treatment alone as first line treatment showed low success rate (41.3%). Wedge resection (100%) and hysteroscopy (66.7%) were relatively safe and they were the most successful treatment modalities in this study. Dilatation and curettage as first and second line treatment had about 20% and 16.7% risk of emergency hysterectomy due to severe hemorrhage respectively. Therefore, surgical modalities with direct visualization excluding dilatation and curettage seem to be more safe and successful than medical treatment using MTX alone. Early precise diagnosis and management of CSP will be very important to minimize the extent of treatment and thus improve clinical outcomes of the patients. Keywords: Cesarean scar pregnancy, Cesarean section, Methotrexate, Treatment, Surgery

Background Mesenchymal stem cells (MSCs) attenuate injury in various lung injury models through paracrine effects. We hypothesized that intratracheal transplantation of allogenic MSCs could attenuate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, mediated by anti-inflammatory responses. Methods Six-week-old male mice were randomized to either the control or the ALI group. ALI was induced by intratracheal LPS instillation. Four hours after LPS instillation, MSCs or phosphate-buffered saline was randomly intratracheally administered. Neutrophil count and protein concentration in bronchoalveolar lavage fluid (BALF); lung histology; levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein-2; and the expression of proliferation cell nuclear antigen (PCNA), caspase-3, and caspase-9 were evaluated at 48 hours after injury. Results Treatment with MSCs attenuated lung injury in ALI mice by decreasing protein level and neutrophil recruitment into the BALF and improving the histologic change. MSCs also decreased the protein levels of proinflammatory cytokines including IL-1β, IL-6, and TNF-α, but had little effect on the protein expression of PCNA, caspase-3, and caspase-9. Conclusions Intratracheal injection of bone marrow-derived allogenic MSCs attenuates LPS-induced ALI via immunomodulatory effects.

Hennekam syndrome is a rare autosomal recessive disorder resulting from malformation of the lymphatic system. The characteristic signs of Hennekam syndrome are lymphangiectasia, lymph edema, facial anomalies, and mental retardation. This is a case in which a patient presented with left-arm lymphedema, facial-feature anomalies, and multiple organ lymphangiectasia consistent with symptoms of Hennekam syndrome. There is no curative therapy at this time, but rehabilitative treatments including complete decongestive therapy for edema control appeared to be beneficial.

ObjectiveTo investigate the general characteristics of video display terminal (VDT) workers with lower extremity pain, to identify the risk factors of work-related lower extremity pain, and to examine the relationship between work stress and health-related quality of life.MethodsA questionnaire about the general characteristics of the survey group and the musculoskeletal symptom was used. A questionnaire about job stress used the Korean Occupational Stress Scale and medical outcome study 36-item Short Form Health Survey (SF-36) to assess health-related quality of life.ResultsThere were 1,711 subjects in the lower extremity group and 2,208 subjects in the control group. Age, sex, hobbies, and feeling of loading affected lower extremity pain as determined in a crossover analysis of all variables with and without lower extremity pain. There were no statistically significant difference between the two groups in terms of job stress and SF-36 values of the pain and control groups.ConclusionJob stress in VDT workers was higher than average, and the quality of life decreased as the stress increased. Factors such as younger age, women, hobbies other than exercise, and feeling of loading influenced lower extremity pain of workers. Further long-term follow-up and supplementary studies are needed to identify risk factors for future lower extremity pain, taking into account ergonomic factors such as worker's posture.

ObjectiveTo explore the incidence, characteristics, complications and socioeconomic impacts associated with falls in community-dwelling elderly.MethodsFrom September 1, 2015 to October 12, 2015, a questionnaire-based survey was conducted involving a total of 2,012 elderly who lived in Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), Yangpyeong-gu (Gyeonggi-do), Dalseong-gu (Daegu), and Jung-gu (Daegu). The subjects were interviewed using a structured questionnaire to obtain demographic characteristics and comprehensive falling histories. The socioeconomic cost related to falls was estimated using the statistical data provided by the Health Insurance Review and Assessment Service.ResultsFalls were recorded in 666 out of the 2,012 subjects (33.1%) during the past year. Frequent falls occurred during December, in the afternoons, when the floor was slippery. The most common injuries included the low back and the most common injury type was sprain. The total direct costs related to falls involving the 2,012 subjects were 303,061,019 KRW (Korean won). The average medical cost related to falls in the 2,012 subjects was 150,627 KRW and the average medical cost of 666 subjects who experienced falls was 455,047 KRW. Estimates of the total population over the age of 60 years showed that the annual direct costs associated with falls in Korea over the age of 60 years were about 1.378 trillion KRW.ConclusionThis study was conducted to explore the incidence, characteristics, complications, and socioeconomic impacts of falls in community-dwelling elderly. This study is expected to be used as a source of basic data for the establishment of medical policy for the elderly and the development of a fall prevention program for the elderly in Korea.

Optimizing flowering time in crop plants is critical for maximizing yield and quality under target environments. While there is a wide range of heading date variation in Korean rice cultivars, the underlying gene mechanisms are unclear. Here, we sequenced the protein coding regions of Hd1, the major rice heading date gene, from 293 Korean rice cultivars and investigated the associations between Hd1 allele types and major agronomic traits under four different environments. There were four functional Hd1 and five nonfunctional hd1 alleles distributed among the 293 Korean rice cultivars. The effects of the Hd1 allele types were highly significant for days to heading in all four environments, explaining 51.4–65.8% of the phenotypic variation. On average, cultivars carrying nonfunctional hd1 headed 13.7 days earlier than those carrying functional Hd1. While the Hd1 allele types exhibited highly significant effects on culm length and protein content under all four environments, the differences between cultivars carrying Hd1 and hd1 were minimal. The effects of the Hd1 allele types on amylose content were significant in only one of the four environments. Our results provide useful information for fine-tuning rice heading dates by utilizing different Hd1 alleles in rice breeding programs.

Angelica polymorpha Maxim. (APM) is used in traditional medicine to treat chronic gastritis, rheumatic pain, and duodenal bulbar ulcers. However, it is not known whether APM has epidermis-associated biological activities. Here, we investigated the effects of APM flower absolute (APMFAb) on responses associated with skin wound healing and whitening using epidermal cells. APMFAb was obtained by solvent extraction and its composition was analyzed by GC/MS. Water-soluble tetrazolium salt, 5-bromo-2′-deoxyuridine incorporation, Boyden chamber, sprouting, and enzyme-linked immunosorbent assays and immunoblotting were used to examine the effects of APMFAb on HaCaT keratinocytes and B16BL6 melanoma cells. APMFAb contained five compounds and induced keratinocyte migration, proliferation, and type IV collagen synthesis. APMFAb also induced the phosphorylations of ERK1/2, JNK, p38 mitogen-activated protein kinase, and AKT in keratinocytes. In addition, APMFAb decreased serum-induced B16BL6 cell proliferation and inhibited tyrosinase expression, melanin contents, and microphthalmia-associated transcription factor expression in α-melanocyte-stimulating hormone-stimulated B16BL6 cells. These findings demonstrate that APMFAb has beneficial effects on skin wound healing by promoting the proliferation, migration, and collagen synthesis of keratinocytes and on skin whitening by inhibiting melanin synthesis in melanoma cells. Therefore, we suggest that APMFAb has potential use as a wound healing and skin whitening agent.

Exercise intensity of exoskeleton-assisted walking in patients with spinal cord injury (SCI) has been reported as moderate. However, the cardiorespiratory responses to long-term exoskeleton-assisted walking have not been sufficiently investigated. We investigated the cardiorespiratory responses to 10 weeks of exoskeleton-assisted walking training in patients with SCI. Chronic nonambulatory patients with SCI were recruited from an outpatient clinic. Walking training with an exoskeleton was conducted three times per week for 10 weeks. Oxygen consumption and heart rate (HR) were measured during a 6-min walking test at pre-, mid-, and post-training. Exercise intensity was determined according to the metabolic equivalent of tasks (METs) for SCI and HR relative to the HR reserve (%HRR). Walking efficiency was calculated as oxygen consumption divided by walking speed. The exercise intensity according to the METs (both peak and average) corresponded to moderate physical activity and did not change after training. The %HRR demonstrated a moderate (peak %HRR) and light (average %HRR) exercise intensity level, and the average %HRR significantly decreased at post-training compared with mid-training (31.6 ± 8.9% to 24.3 ± 7.3%, p = 0.013). Walking efficiency progressively improved after training. Walking with an exoskeleton for 10 weeks may affect the cardiorespiratory system in chronic patients with SCI.

Introduction: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. Methods: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. Discussion: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Abstract Background Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion that mostly comprises a conventional adenomatous component with a minute proportion of neuroendocrine (NE) component. Although microcarcinoids are well-recognized in the setting of chronic inflammatory disorders of the gastrointestinal tract, large intestinal microcarcinoids associated with intestinal adenoma are exceedingly rare and their clinicopathologic characteristics are yet to be elucidated. This study was performed to clarify their clinicopathologic characteristics and to review the relevant literature. Methods In total, 24 cases of CIAM in which tumors were excised endoscopically (n = 22) or surgically (n = 2) were retrieved from the Department of Pathology, Daehang Hospital. We analyzed their clinicopathologic characteristics and performed immunohistochemical staining for NE markers to determine their endocrine nature. Results CIAM usually developed in middle-aged and elderly patients, with a mean age of 62.0 years (range, 44–81 years). Thirteen patients were men and 11 were women, indicating a nearly equal sex ratio. Unlike classic carcinoid tumors, CIAMs occurred mostly in the colon (83.3% of cases), particularly in the proximal colon. Histologically, the microcarcinoid component consisted of low-grade NE cells arranged in small nests, glands or cords interspersed with glandular elements or less frequently resembled squamous morules. There was no expansile nodular or organoid growth pattern, which is typical of carcinoid tumors. The microcarcinoids were 1–20 mm in size (mean size, 4.7 mm) and were mostly situated in the basal lamina propria with no submucosal layer involvement; none showed desmoplastic reaction or increased proliferative activity. Follow-up data (mean, 23.1 months) were available for 18 patients; all patients are alive and well. Conclusions To the best of our knowledge, ours is the largest series of patients with CIAM in the English-language literature. Microcarcinoids found in CIAMs appear to show favorable clinical outcomes regardless of their size, likely due to the absence of submucosal extension and/or increased proliferative activity. We recommend avoiding additional radical surgeries in patients who have endoscopically undergone complete CIAM excision unless they exhibit ominous histologic features such as submucosal extension or increased proliferative activity.

Abstract Background The relationship between premature birth and early cognitive function as measured by eye-tracking data remains unexplored. The aim of this study was to determine the effect of prematurity on the development of object permanence and attention capacity using eye-tracking measures. Methods We prospectively studied very low birth weight (VLBW

Objective Gait disturbance is the main factor contributing to a negative impact on quality of life in patients with Huntington’s disease (HD). Understanding gait features in patients with HD is essential for planning a successful gait strategy. The aim of this study was to investigate temporospatial gait parameters in patients with HD compared with healthy controls. Methods We investigated 7 patients with HD. Diagnosis was confirmed by genetic analysis, and patients were evaluated with the Unified Huntington’s Disease Rating Scale (UHDRS). Gait features were assessed with a gait analyzer. We compared the results of patients with HD to those of 7 age- and sex-matched normal controls. Results Step length and stride length were decreased and base of support was increased in the HD group compared to the control group. In addition, coefficients of variability for step and stride length were increased in the HD group. The HD group showed slower walking velocity, an increased stance/swing phase in the gait cycle and a decreased proportion of single support time compared to the control group. Cadence did not differ significantly between groups. Among the UHDRS subscores, total motor score and total behavior score were positively correlated with step length, and total behavior score was positively correlated with walking velocity in patients with HD. Conclusion Increased variability in step and stride length, slower walking velocity, increased stance phase, and decreased swing phase and single support time with preserved cadence suggest that HD gait patterns are slow, ataxic and ineffective. This study suggests that quantitative gait analysis is needed to assess gait problems in HD.

Objective To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson’s disease (PD). Methods We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups. Results At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697). Conclusion The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.

Objective Autonomic symptoms are commonly observed in patients with Parkinson’s disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson’s disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients. Methods For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10−14 days. Results The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach’s α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson’s Disease Rating Scale part II) and quality of life [the Korean version of Parkinson’s Disease Quality of Life 39 (K-PDQ39)]. Conclusion The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life.

Usher’s syndrome is the most common combined blindness–deafness disorder with USH1B, caused by mutations in MYO7A, resulting in the most severe phenotype. The existence of numerous, naturally occurring shaker1 mice harboring variable MYO7A mutations on different genetic backgrounds has complicated the characterization of MYO7A knockout (KO) and heterozygote mice. We generated a novel MYO7A KO mouse (Myo7a–/–) that is easily genotyped, maintained, and confirmed to be null for MYO7A in both the eye and inner ear. Like USH1B patients, Myo7a–/– mice are profoundly deaf, and display near complete loss of inner and outer cochlear hair cells (HCs). No gross structural changes were observed in vestibular HCs. Myo7a–/– mice exhibited modest declines in retinal function but, unlike patients, no loss of retinal structure. We attribute the latter to differential expression of MYO7A in mouse vs. primate retina. Interestingly, heterozygous Myo7a+/– mice had reduced numbers of cochlear HCs and concomitant reductions in auditory function relative to Myo7a+/+ controls. Notably, this is the first report that loss of a single Myo7a allele significantly alters auditory structure and function and suggests that audiological characterization of USH1B carriers is warranted. Maintenance of vestibular HCs in Myo7a–/– mice suggests that gene replacement could be used to correct the vestibular dysfunction in USH1B patients. While Myo7a–/– mice do not exhibit sufficiently robust retinal phenotypes to be used as a therapeutic outcome measure, they can be used to assess expression of vectored MYO7A on a null background and generate valuable pre-clinical data toward the treatment of USH1B.

PurposeIntensive care unit (ICU)-related mortality for lung cancer is ranked highest among the solid tumors and little information exists on the role of intensivists on clinical outcomes. This study aimed to elucidate the intensivist's contribution toward clinical outcomes.Materials and methodsData of advanced lung cancer patients, including stage IIIB or IV non-small cell lung cancer and extensive-stage small cell lung cancer, admitted to the ICU from 2005 to 2016 were analyzed. Multivariate logistic regression was performed to determine variables associated with ICU and in-hospital mortality. Autoregressive integrated moving average (ARIMA) for time-series was used to assess the intensivist's impact.ResultsOf 264 patients, 85 (32.2%) were admitted to the ICU before and 179 (67.8%) after organized intensive care introduction in 2011. Before and after 2011, the changes observed were as follows: ICU mortality rate, 43.5% to 40.2%, respectively (p = 0.610); hospital mortality rate, 82.4% to 65. 9% (p = 0.006). The duration of ICU and hospital stay decreased after 2011 (14.5±16.5 vs. 8.3 ± 8.6, p < 0.001; 36.6 ± 37.2 vs. 22.0 ± 19.6, p < 0.001). On multivariate analysis, admission after 2011 was independently associated with decreased hospital mortality (Odds ratio 0.42, 95% confidence interval 0.21-0.77, p = 0.006). In ARIMA models, intensivist involvement was associated with significantly reduced hospital mortality. (Estimate -17.95, standard error 5.31, p = 0.001).ConclusionIn patients with advanced lung cancer, organized intensive care could contribute to improved clinical outcomes.