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PURPOSE Developmental disabilities often result in decreased physical fitness and problematic behaviors. Participating in regular physical activity and exercise is one of the main ways to improve problems associated with developmental disabilities. In this study, we aimed to develop an evidence-based exercise program tailored to the characteristics, disability level, and functional level of children with developmental disabilities. METHODS The development process is composed of the following nine steps: preliminary literature review, survey of physical activity participation, first expert group discussion, development of the first exercise program, feasibility study, focus group interview, second expert group discussion, development of the evidence-based exercise program, the validation of the developed exercise program. RESULTS Participating in the evidence-based exercise program developed in this study was found to significantly improve cardiovascular fitness (6-minute walk), agility (standing long jump), and muscular function (sit-ups), but did not yield significant results in terms of flexibility (sit-and-reach). Additionally, the exercise program showed significant results in terms of reducing problem behaviors. The parents of children with developmental disabilities were all satisfied with the exercise program and its outcomes. CONCLUSIONS The evidence-based exercise program developed in this study had positive effects on the physical fitness and behavior of children with developmental disabilities. This study provides a basis for the development of exercise programs through a safe and effective means for children with developmental disabilities.

Abstract Background This study aimed to investigate the prescription of traditional herbal medicines for the treatment of unexplained female infertility in Korea. By analyzing the relationships among the prescriptions and between the prescriptions and treatment outcomes, we aimed to confirm the utilization of standardized prescriptions and the effectiveness of this standardization. Methods The data were derived from the “support projects” of the local government for infertile women to receive Korean medical treatments. The presciption data of 453 participants from 2017 to 2018 were analyzed. Data preprocessing, frequency analysis, and network analysis were conducted. For network analysis, the characteristics of the herbal medicine prescriptions were used to calculate the degree centrality, closeness centrality and eigenvector centrality. Modularity clustering was also performed for cluster analysis. Results Fifty different prescriptions were used, among which only 22 were used for participants who became pregnant. The recommended standard prescriptions for support projects were used frequently. “BaeranChacksangBang” showed the highest level of in-degree centrality. Among the prescriptions for participants who became pregnant, “JogyeongJongokTang” and “BaeranChacksangBang” were the most influential nodes. “BaeranChacksangBang”, “AnjeonYicheonTang”, “YukLinZu” and “JogyeongJongokTang” had high closeness centrality among the prescriptions for participants who became pregnant. Clustering analysis of the prescriptions for participants who became pregnant revealed that the prescriptions showed the best modularity when divided into five groups. Conclusions These findings depict the utilization of Korean herbal medicine in the real world and the dynamics underlying the herbal medicine prescription patterns for infertile women.

Low fertility is a critical social problem worldwide, and infertility has a prevalence of 15%. This cross-sectional study aimed to understand the factors affecting the usage and satisfaction of Korean medicine (KM) in subfertile women. An online survey was conducted from 3 November to 8 November 2021. The survey collected basic information, KM treatment experience, and satisfaction from women who experienced poor pregnancy. The t-test and chi-square test (χ2-test) were used to determine the overall characteristics of the subjects and factors affecting the utilization and satisfaction of KM treatment. Of the total of 29,465 people, 4922 read the survey email, and 601 responded. After excluding 51 respondents with questionable response patterns, 550 respondents were included in the final analysis. Of these, 43.1% (n = 237) had experience with conventional treatment, and 16.5% (n = 91) had received KM treatment. The group that received both KM treatment and CM treatment (n = 59, 24.9%) was significantly more prevalent than the group that received KM treatment alone (n = 32, 10.2%) (p = 0.00). Women who had given birth more than once or held a master’s degree were significantly more willing to participate in the ‘KM Support Project for Subfertility’ program. Our findings suggest that subfertile patients prefer integrated treatment that combines KM and CM treatments. Further studies are needed to assess the status of integrative medicine treatment, satisfaction with each KM intervention, factors for low satisfaction, and patient requirements.

Background: In 30–40% of papillary thyroid cancer patients, central neck lymph node metastasis occurs. As a result, prophylactic central neck lymph node dissection is performed. The extent of lymph node dissection and prophylactic central neck lymph node dissection is still debatable. The incidence of central neck lymph node metastasis and related factors were investigated in this study, and also the necessity of both central neck lymph node dissections. Methods: Between December 2017 and December 2019, 482 patients had thyroidectomy at Pusan National University Yangsan Hospital. A retrospective study of 186 patients who had a thyroidectomy with bilateral central neck lymph node dissection for unilateral thyroid carcinoma was done. Results: Ipsilateral and contralateral central neck lymph node metastasis were identified in 40.9% (76/186) and 19.3% (36/186), respectively. Male (p 1 cm (p = 0.047), extrathyroidal extension (p = 0.002), central neck lymph node metastases >5 (p

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

PURPOSE The prevalence of sarcopenia, which can lead to disability, hospitalization, and death, is increasing among older populations. Resistance exercise training (RT) is currently the most effective strategy for combating sarcopenia by stimulating hypertrophy and increasing strength. This review describes the underlying mechanisms of aging skeletal muscle and whether RT attenuates aging-related loss of muscle function and mass. METHODS We reviewed and summarized previous research using PubMed, Science Direct, and Google Scholar databases. RESULTS Load-induced muscle growth is a complex phenomenon that depends on various physiological systems and signaling pathways. Muscle growth occurs through signaling events arising from mechanical stress and consequent muscle protein turnover controlled by the balance between protein synthesis and degradation, which is negatively affected by aging. The authors used the myonuclear domains mediated by muscle satellite cells to explain the molecular machinery of exercise-induced muscle growth and recovery in aging muscles. CONCLUSIONS Despite a blunted molecular response to an exercise bout, aging muscle cells demonstrated remarkable plasticity, with substantial improvements in myofibril size and strength during RT. More studies are necessary to elucidate the specific mechanisms by which RT activates muscle satellite cells and mitogenic and myogenic signaling in aged muscles.

PURPOSE Genes had selectively evolved to enhance the motivation for physical movement in human during the Paleolithic era. To prepare for a potential forthcoming food deficiency, high physical activity was essential for survival in the environment where hunting wild animals and gathering plants. In modern society, however, developing technology and engineering has made human life easier to accomplish tasks with not much movement and effort, resulting in a profound deficiency in physical activity (i.e., physical inactivity). METHODS In this review, the authors summarized previous studies searched by the PubMed, Google Scholar, and Science Direct databases. RESULTS Reduced physical activity is significantly associated with the high prevalence of various diseases including metabolic syndrome, obesity, sarcopenia, and cancer. Unfortunately, in women, menopause negatively impacts their body and physiology mainly due to the loss of estrogens, which also contributes to behavioral changes such as a significant reduction of physical activity levels during menopausal transition. In this review, the author focused to describe the underlying brain mechanism by which menopause results in reduced levels of physical activity through estrogens, estrogen receptors, and dopamine signaling in the nucleus accumbens, the main controller for exercise motivation. CONCLUSIONS Estrogen receptor, specifically ERα, and dopamine receptors are the main controllers for voluntary physical activity. Furthermore, high running motivation is associated with enhanced dopamine activity. More studies are needed to verify whether enhanced dopamine activity can protect against menopause-associated reduction in physical activity.

Abstract Background The aim of this study was to investigate the effects of muscle strength and BMI (body Mass Index) on Metabolic syndrome (MetS) risk factors and prevalence in Korean adult women, using data from the Korea National Health and Nutrition Examination Survey. Methods A total of 3189 Korean adults women participated in the cross-sectional study. Participants were measured BMI, MetS risk factors including waist-circumference (WC), fasting glucose (FG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and handgrip strength as muscle strength. Results As a result ‘high BMI & Low muscle strength’, ‘low BMI & low muscle strength’, and ‘high BMI & high muscle strength’ groups had a significantly higher prevalence of Mets [OR (Odd ratio): 1.49, 95% CI (confidence interval): 1.01 2.20; OR: 5.77, 95% CI: 4.32 7.17; OR: 10.46, 95% CI: 8.05 13.59] than ‘low BMI & high muscle strength’ group; and after adjusting smoking, menstruation status, and drinking rate, the OR were 1.07 (95% CI: 0.71–1.61), 4.89 (95% CI: 3.60–6.55), and 7.38 (95% CI: 5.63–9.68), respectively. Conclusions These findings indicated that increasing muscle strength and lowering BMI through regular physical activity and exercise are effective methods to reduce the prevalence of risk factors for Mets.

This study aims to analyze the types and cost of infertility care provided in a clinical setting to examine the changes of healthcare utilization for infertility after the 2017 launch of assisted reproductive technology (ART) health insurance coverage in South Korea. Health Insurance Review Assessment-National Patient Sample data from 2016 and 2018 were analyzed comparatively. Data related to receiving medical service under the International Classification of Diseases 10th revision code N97 (female infertility) or N46 (male infertility) at least once were analyzed, including patients' characteristics and healthcare utilization (type of healthcare facility and treatment approach). Between 2016 and 2018, the percentage of patients aged 30-34 receiving infertility care dropped; the percentages of patients in older age groups increased. The number of female patients remained comparable, whereas the number of male patients increased by 23%. Average visits per patient increased by about 1 day from 2016 to 2018. Total annual infertility care claim cost increased from $665,391.05 to $3,214,219.48; the per-patient annual cost increased from $114.76 to $522.38. The number of claims and cost of treatment and surgery increased markedly, as did the number of claims and cost of gonadotropins. With its focus on health insurance coverage of ART and results demonstrating increases in medical services, medications, cost, and patient utilization, this study reveals the significant effects of national health policies on the treatment, cost, and management of infertility.

Purpose Laparoscopic posterior retroperitoneal adrenalectomy (LPRA) is a surgical method that accesses the adrenal gland through the back. The aim of this study was to report initial experience of LPRA and evaluate possibilities for surgical application. Methods From March 2018 to December 2019, a total of 30 consecutive patients diagnosed with adrenal tumor underwent surgical treatment at Pusan National University Hospital were enrolled. Clinicopathologic features and various peri- and postoperative parameters were analyzed by retrospective medical record review. The mean age of the patients was 48.20±13.66 years. Results The mean body mass index (BMI) was 25.50±4.30 kg/m2. Primary hyperaldosteronism was the most frequently preoperative diagnosed disease (n=13, 43.4%), followed by adrenal incidentaloma (n=8, 26.6%), Cushing syndrome (n=5, 16.6%) and pheochromocytoma (n=4, 13.3%). The mean size of postoperative adrenal tumor was 2.72±1.76 cm. The mean operating time was 162±58.14 minutes. Among the 30 patients, 28 patients underwent total adrenalectomy (93.3%) and two patients underwent cortical sparing adrenalectomy (6.7%). When LPRA was performed for patients with BMI >23.16 kg/m2, the operating time was longer than the average (P=0.016). Conclusion LPRA was suitable and safe for patients with benign adrenal tumors. BMI, retroperitoneal fat density and postoperative adrenal weight may be related to the operating time, so they should be considered when deciding on a surgical method for adrenalectomy.

Purpose There are many studies on sentinel lymph node (SLN) biopsy in thyroid carcinoma but SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) remains open to debate. Therefore in this retrospective study, the usefulness of SLNB in thyroid carcinoma patients who had micro-PTC without cervical lymphadenopathy was assessed. Methods SLNB was performed in 114 patients who were diagnosed with micro-PTC in a single lobe without palpable or ultrasound-detected lymph node at the tertiary center between January 2012 and December 2013. After SLNB, all patients underwent total thyroidectomy and central neck dissection or thyroid lobectomy and central neck dissection of the single side. Results SLNs were identified in 112 of 114 patients with 41 positive SLNs and 71 negative SLNs on intraoperative frozen sections. However, eight negative patients were found to be positive in the final pathology. Sentinel node identification rate and false negative value of SLNB were 98.2% and 11.3%, respectively. In the univariate analysis, higher lymph node metastasis was detected in men than in women. Higher detection number of SLN showed higher probability of lymph node metastasis. Conclusion SLNB may be helpful in papillary thyroid cancer, especially in male patients. Also, it is useful for the staging of nodal status and clearance of persistent disease.

Background: Hominis placenta pharmacopuncture is widely used for climacteric symptoms. This study examined the efficacy and safety of pharmacopuncture with PLC (the extract of Hominis placenta) on hot flashes for perimenopausal and postmenopausal women. Methods: This study was a randomized placebo-controlled single-blind trial, which recruited 128 perimenopausal and postmenopausal women, randomly assigned to receive pharmacopuncture with PLC or normal saline (NS) for eight weeks. The primary outcome was the mean changes in the hot flash score (HFS) and the secondary outcomes were the mean changes in the Menopause Rating Scale (MRS), follicle-stimulating hormone (FSH) levels, and estradiol (E2) levels from baseline to eight weeks. Missing values were imputed using the last-observation-carried-forward method. Results: After treatment (week 9), the HFS decreased significantly in both groups (p = 0.000). The residual HFS was 47.09 ± 41.39% and 56.45 ± 44.92 % in the PLC and control groups, respectively (p = 0.262). One month after the treatment (week 13), the score of the PLC group was reduced, but the score increased in the control group (p = 0.077). There were no statistically significant differences in the mean changes in MRS, FSH, and E2 between the two groups. No serious adverse events related to this trial were noted. Conclusion: In this study, Hominis placenta extract pharmacopuncture did not differ significantly from NS in reducing the hot flash score. While this therapy appears safe, the potential for long-term effect of PLC extract needs to be examined in a large randomized controlled trial with appropriate controls. Trial registration: Clinical Research Information Service, Republic of Korea, KCT0 0 03533.

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Abstract There have been substantial efforts in using deep learning (DL) to diagnose cancer from digital images of pathology slides. Existing algorithms typically operate by training deep neural networks either specialized in specific cohorts or an aggregate of all cohorts when there are only a few images available for the target cohort. A trade-off between decreasing the number of models and their cancer detection performance was evident in our experiments with The Cancer Genomic Atlas dataset, with the former approach achieving higher performance at the cost of having to acquire large datasets from the cohort of interest. Constructing annotated datasets for individual cohorts is extremely time-consuming, with the acquisition cost of such datasets growing linearly with the number of cohorts. Another issue associated with developing cohort-specific models is the difficulty of maintenance: all cohort-specific models may need to be adjusted when a new DL algorithm is to be used, where training even a single model may require a non-negligible amount of computation, or when more data is added to some cohorts. In resolving the sub-optimal behavior of a universal cancer detection model trained on an aggregate of cohorts, we investigated how cohorts can be grouped to augment a dataset without increasing the number of models linearly with the number of cohorts. This study introduces several metrics which measure the morphological similarities between cohort pairs and demonstrates how the metrics can be used to control the trade-off between performance and the number of models.

Cold acclimation refers to a phenomenon in which plants become more tolerant to freezing after exposure to non-lethal low temperatures. Aulacomnium turgidum (Wahlenb.) Schwaegr is a moss found in the Arctic that can be used to study the freezing tolerance of bryophytes. To improve our understanding of the cold acclimation effect on the freezing tolerance of A. turgidum, we compared the electrolyte leakage of protonema grown at 25 °C (non-acclimation; NA) and at 4 °C (cold acclimation; CA). Freezing damage was significantly lower in CA plants frozen at −12 °C (CA-12) than in NA plants frozen at −12 °C (NA-12). During recovery at 25 °C, CA-12 demonstrated a more rapid and greater level of the maximum photochemical efficiency of photosystem II than NA-12, indicating a greater recovery capacity for CA-12 compared to NA-12. For the comparative analysis of the transcriptome between NA-12 and CA-12, six cDNA libraries were constructed in triplicate, and RNA-seq reads were assembled into 45,796 unigenes. The differential gene expression analysis showed that a significant number of AP2 transcription factor genes and pentatricopeptide repeat protein-coding genes related to abiotic stress and the sugar metabolism pathway were upregulated in CA-12. Furthermore, starch and maltose concentrations increased in CA-12, suggesting that cold acclimation increases freezing tolerance and protects photosynthetic efficiency through the accumulation of starch and maltose in A. turgidum. A de novo assembled transcriptome can be used to explore genetic sources in non-model organisms.

Abstract Background BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model. Methods In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues. Results BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. Conclusion These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.

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Background: This study was conducted to demonstrate the effectiveness and safety of herbal medicine and acupuncture treatment in unexplained infertile females. Methods: One hundred patients were recruited from 3 Korean Medicine hospitals in Korea and they voluntarily signed informed consent agreements. Participants took the Onkyeong-tang (120cc) twice daily between menstrual cycle day (MCD) 3 and 12, and herbal medicine for ovulation and implantation (120cc) twice daily between MCD 13 and 28. They also received acupuncture and moxibustion treatment during 4 menstrual cycles. After the 4 menstrual cycle treatment period, there were 3 menstrual cycle observation periods. The primary outcome is signified by clinical pregnancy rates (CPR) and the secondary outcomes were implantation rates (IR), ongoing pregnancy rates (OPR), and live birth rates. Results: 90 patients completed the study. 13 of the 90 subjects became pregnant. The CPR and IR was 14.44%. 7 of 13 pregnant subjects had continuing pregnancy for over 12 weeks, so that the OPR was 53.85%. The birth rate was 7.78%. All 7 pregnant patients gave birth to their babies and all the babies were live singletons and healthy. There were no serious adverse events. Conclusions: The findings of this study may provide the possibility of effectiveness and safety of Korea medicine treatment for unexplained infertile women. Further study is required due to lack of control and small sample size in this study.

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Although sarcopenia has been dealt with in several studies, the standardized guidelines for preventing sarcopenia resulting from increased life expectancy are still insufficient. Therefore, this study evaluated the effects of daily resistance exercise and the intake of leucine-rich protein supplements daily for 12 weeks on the body composition and physical function of healthy adults aged >50 years living in Korea. The study analyzed 50 healthy people without medical conditions, who were randomly assigned to two groups (taking either protein powder or placebo powder) twice a day for 12 weeks. All participants performed resistance exercises regularly that could be repeated 8–12 times using a TheraBand for 12 weeks. A total of 41 participants completed the study. When measured via bioimpedance analysis (BIA), body fat mass (kg) and body fat (%) significantly decreased, and lean body mass (LBM) (kg) and skeletal muscle mass (SMM) (kg) significantly increased, in both groups. However, when measured via dual-energy X-ray absorptiometry (DXA), LBM was significantly increased only in the protein powder group. The LBM and SMM change measured via BIA was significantly greater in the protein powder group than in the placebo powder group (LBM: 0.95 ± 0.91 kg in the protein powder group vs. 0.38 ± 1.06 kg in the placebo powder group, p = 0.043; SMM: 0.69 ± 0.58 kg in the protein powder group vs. 0.29 ± 0.65 kg in the placebo powder group, p = 0.039, respectively). In the senior fitness test (SFT), significant functional improvement was found within the two groups, but no significant difference was found between the groups in the degree of improvement. In conclusion, in older people aged >50, to prevent sarcopenia, is more effective to combine resistance exercise and leucine-rich protein supplementation than to simply perform resistance exercise.

Background: Acupuncture and herbal medicine have been used as additional treatments for infertility or as an adjuvant treatment of assisted reproductive technology (ART) in infertility. Many systematic reviews (SRs) and meta-analyses (MA) have been published. This paper reviews the SRs and MA of acupuncture and herbal medicine on infertility to provide evidence for clinical decision making. Methods: A comprehensive literature search of SRs and MA for the effects of acupuncture and herbal medicine on infertility was conducted using nine databases. Two independent reviewers extracted the data of the selected SR and MA and evaluated their methodological quality using the ‘Assessment of multiple systematic reviews 2 (AMSTAR2)’. Results: Twenty-one studies were included in this analysis. Eight studies were published in China, and three studies each were published in the USA, UK, and Australia. Conflicting evidence on the efficacy of acupuncture for infertile women has been reported. Herbal medicine for infertile women undergoing ART, women with anovulation, and women with polycystic ovary syndrome helped improve the clinical pregnancy rate. The methodological quality of SRs and MAs evaluated by AMSTAR 2 was low or very low because the protocol or list of excluded studies were omitted. Conclusion: Herbal medicine tended to be effective in infertility, but acupuncture had low evidence of an effect on infertility. The methodological quality of the published SRs and MAs was underestimated because AMSTAR2 is a more rigorous assessment tool than the previous version.

Background: This study aimed to obtain the symptom, prescription and therapeutic patterns for the treatment of patients with menopausal syndrome in major Korean medicine (KM) hospitals. Methods: We used a retrospective chart review of climacteric disorder and postmenopausal syndrome patients by examining medical records (ICD-10, menopausal and female climacteric states: N95.1, Menopausal and perimenopausal disorder, unspecified: N95.9) from eight university KM hospitals in South Korea. Results: The main symptoms of 1,682 patients with menopausal disorders visiting 8 college-affiliated oriental medicine hospitals were hot flush, hyperhidrosis, fatigue, insomnia, and chest tightness. Guipi-tang (decoction), Siwu Guipi-tang (decoction), Qingxin Lianzi-yin (decoction), Jiawei Xiaoyao-san (powder) and Guipi Wendan-tang (decoction) were the most commonly prescribed herbal medicines for menopausal disorders. Patients were most often treated with a combination of herbal medicine and acupuncture. Conclusion: Our study shows that the current prescribed herbal medicines were used for treating menopausal disorders in Korean medicine hospitals. However, the objectivity of the efficacy assessment should be studied further.

Characterizing the subsurface flow in karstic areas is challenging due to distinct flow paths coexisting, and lithologic heterogeneity makes it more difficult. A combined use of hydrochemical, environmental isotopic, and hydrograph separation study was performed to understand the subsurface flow in a karst terrain where Ordovician carbonate rocks overlie Jurassic sandstone and shale along thrusts. Spring water collected was divided into Type Ⅰ (n = 11) and Ⅱ (n = 30) based on flow patterns (i.e., low and high discharge, respectively). In addition, groundwater (n = 20) was examined for comparison. Three Type Ⅱ springs were additionally collected during a storm event to construct hydrographs using δ18O and δD. As a result, Type Ⅱ had higher electrical conductivity, Mg2+, HCO3−, and Ca2+/(Na+ + K+) than Type Ⅰ and was mostly saturated with calcite, similar to deep groundwater. The hydrochemical difference between Types Ⅰ and Ⅱ was opposite to the expectation that Type Ⅱ would be undersaturated given fast flow and small storage, which could be explained by the distinct geology and water sources. Most Type Ⅱ springs and deep groundwater occurred in carbonate rocks, whereas Type Ⅰ and shallow groundwater occurred in various geological settings. The carbonate rocks seemed to provide conduit flow paths for Type Ⅱ given high solubility and faults, resulting in 1) relatively high tritium and NO3− and Cl−via short-circuiting flow paths and 2) the similar hydrochemistry and δ18O and δD to deep groundwater via upwelling from deep flow paths. The deep groundwater contributed to 83–87% of the discharge at three Type Ⅱ springs in the dry season. In contrast, Type Ⅰ showed low Ca2+ + Mg2+ and Ca2+/(Na+ + K+) discharging diffuse sources passing through shallow depths in a matrix in mountain areas. Delayed responses to rainfall and the increased concentrations of contaminants (e.g., NO3−) during a typhoon at Type Ⅱ implied storage in the vadose zone. This study shows that hydrochemical and isotopic investigations are effective to characterize flow paths, when combined with hydrograph separation because the heterogenous geology affects both flow paths and the hydrochemistry of spring water passing through each pathway.

Differentiated thyroid cancer (DTC) originating from thyroid tissue is affected by thyrotropin (TSH). TSH suppression therapy is usually recommended after thyroidectomy in cases of DTC. A 57-year-old woman who harbored a very huge recurred lymph node underwent TSH suppression therapy because of the risk of surgical complications. After TSH suppression, the huge neck lymph node exhibited a response and decreased in size. She had been followed up for 144 months. TSH suppression therapy could be considered as an alternative treatment option in a recurred DTC patient with a high perioperative risk.

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Abstract Background Hot flashes are the most frequent symptoms of the menopause, with 10–20% of all postmenopausal women reporting nearly intolerable occurrences. Although pharmacopuncture with hominis placenta extract is one of the new acupuncture therapies popular in East Asian medicine with a known efficacy in treating facial flushing, there has been little research on the efficacy and safety of this extract. This study, therefore, aims to evaluate the efficacy and safety of pharmacopuncture with hominis placenta extract (PLC) compared to injections of normal saline, in perimenopausal and postmenopausal women in Korea. Methods/design This study is a randomized placebo-controlled single-blind multi-center parallel-design trial. In total, 128 perimenopausal or postmenopausal women who meet the inclusion criteria will be recruited. The treatment group will receive PLC pharmacopuncture twice a week, for a total of 18 sessions over 9 weeks. The control group will receive injections of normal saline at the same acupoints during the same period. The post-treatment follow-up assessment will occur 4 weeks after the participant has completed the treatment. Discussion We believe that this trial will provide evidence for the efficacy and safety of PLC pharmacopuncture as a treatment for hot flashes in perimenopausal and postmenopausal women. Trial registration Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0003533, Registered on 20 February 2019.

Beige adipocytes, which consume energy mainly in an uncoupling protein 1 (UCP1)-dependent manner, are risen in white adipose tissue (WAT) depots. Since beige adipocyte development is gaining attention as a potential strategy for conquering obesity, worldwide researchers are making efforts to study its biological aspects. However, assessing UCP1 protein levels in beige adipocytes is challenging because of the high level of lipid contaminants in WAT. This study showed that an acetone precipitation method had advantages over conventional methods for eliminating lipid contaminants, achieving clear Western blot bands for WAT proteins, especially UCP1. Our results suggest that the acetone precipitation cleaning method could be useful for the clear analysis and precise evaluation of WAT proteins.

The pineal hormone, melatonin, plays important roles in circadian rhythms and energy metabolism. The hepatic peptide hormone, hepcidin, regulates iron homeostasis by triggering the degradation of ferroportin (FPN), the protein that transfers cellular iron to the blood. However, the role of melatonin in the transcriptional regulation of hepcidin is largely unknown. Here, we showed that melatonin upregulates hepcidin gene expression by enhancing the melatonin receptor 1 (MT1)-mediated c-Jun N-terminal kinase (JNK) activation in hepatocytes. Interestingly, hepcidin gene expression was increased during the dark cycle in the liver of mice, whereas serum iron levels decreased following hepcidin expression. In addition, melatonin significantly induced hepcidin gene expression and secretion, as well as the subsequent FPN degradation in hepatocytes, which resulted in cellular iron accumulation. Melatonin-induced hepcidin expression was significantly decreased by the melatonin receptor antagonist, luzindole, and by the knockdown of MT1. Moreover, melatonin activated JNK signaling and upregulated hepcidin expression, both of which were significantly decreased by SP600125, a specific JNK inhibitor. Chromatin immunoprecipitation analysis showed that luzindole significantly blocked melatonin-induced c-Jun binding to the hepcidin promoter. Finally, melatonin induced hepcidin expression and secretion by activating the JNK-c-Jun pathway in mice, which were reversed by the luzindole treatment. These findings reveal a previously unrecognized role of melatonin in the circadian regulation of hepcidin expression and iron homeostasis.

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Abstract Background It has been recognized that alternate day calorie restriction (ADCR) or exercise has positive effects on cardio-metabolic risk factors. It is unclear whether the combined effect of ADCR and exercise (aerobic + resistance training) influences risk. We investigated effects of an 8-week ADCR and exercise program (aerobic + resistance training) on cardio-metabolic risk factors in overweight and obese adults. Methods This study randomized 45 overweight or obese but healthy adults (F = 26, M = 19; aged about 32 to 40 years) into 4 groups: ADCR (n = 13), exercise (n = 10), exercise plus ADCR (n = 12), and control (n = 10) for 8 weeks. Body composition, blood lipids profile, and insulin resistance were measured. The intention to treat (ITT) method was used to analyze all participants that were randomized. Results A total of 35 participants completed the trial (78%). Body weight, body mass index, waist circumference, fat mass and percent body fat were reduced in the exercise plus ADCR group (− 3.3 ± 2.4 kg, p

Abstract Background Electroacupuncture has been used for treatment in patients with overactive bladder. This study was conducted to evaluate the efficacy and safety of electroacupuncture for treating overactive bladder of postmenopausal women. Methods/design This is a multicenter, randomized controlled, parallel clinical trial. Two hundred ninety participants with overactive bladder syndrome will be recruited from Dongguk University Bundang Oriental Hospital and Cheonan Korean Medicine Hospital of Daejeon University and randomly allocated into one of two groups in a 1:1 ratio. One group will receive electroacupuncture (EA) and the other acupuncture (AC). The allocation will be concealed from both participants and assessors. The study period will be about 10 weeks, including 6 weeks of electroacupuncture or acupuncture treatment and a four week follow-up period. Both EA group and AT group will undergo acupuncture at 7 fixed points, and the EA group will undergo electronic stimulation at 6 points. The primary outcome will be the average number of micturitions per 24 h based on a 3-day bladder diary. The secondary outcome will comprise the 3-day bladder diary, the overactive bladder symptom score and the results of the King’s health questionnaire. Discussion The results of this trial will provide information regarding the efficacy and safety of electroacupuncture for treating overactive bladder in postmenopausal women. Trial registration ClinicalTrials.gov, NCT03260907. Registered on 24 August 2017.

Osteoporosis: protein trigger for postmenopausal bone loss identified A protein that helps trigger bone loss in postmenopausal osteoporosis could be a potential therapeutic target. After the menopause, decreases in estrogen hormone levels can lead to bone diseases including osteoporosis. Osteoporosis occurs when the bone remodeling process breaks down, and bone resorption by cells called osteoclasts outweighs bone formation. In a mouse model of postmenopausal osteoporosis, Jong-Hwan Park at Chonnam National University, Gwangju, South Korea and co-workers identified key players in the progression of the disease. The team focused on factors influencing the RANKL protein, a known controller of bone remodeling. They found that RANKL triggers the formation of osteoclasts via interaction with another protein, PRMT1. Suppression of PRMT1 by estrogen appears to inhibit excessive osteoclast formation, suggesting it could be a potential therapeutic target for treating osteoporosis.

Wnts are important for synapse formation and maintenance. Here, the authors show that proline-rich 7 (PRR7) is a Wnt inhibitor that is secreted via exosomes to regulate excitatory synapse numbers.

Abstract Background Appendiceal intussusception is very rare condition with an estimated incidence of 0.01%. Therefore, it is likely to be overlooked. In addition, making the diagnosis before or during surgery is very difficult. Case presentation A 60-year-old male who was referred to our gastroenterology center with cecal inflammation found during a colonoscopy. An abdominal computed tomography (CT) following endoscopy revealed a 5 × 2.5 × 4 cm mass-like lesion in the cecum around the ileocolic (IC) valve and appendiceal orifice. The main lesion seemed to be an inflammatory mass rather than a malignancy because it appeared to be an extraluminal or extramucosal lesion. Ultrasonography revealed diffuse wall thickening of the cecum around the appendiceal orifice that was suspicious for an inflammatory mass or a benign mass. A diagnosis was uncertain. The differential diagnosis included chronic appendicitis, appendiceal neoplasm such as appendiceal mucocele, low grade appendiceal mucinous neoplasm. The patient underwent a laparoscopic partial cecectomy. In the surgical field, there was a large mass in the appendiceal orifice. The cecum was partially resected, with care taken to preserve the IC valve. Final histopathological analysis of the surgical specimen revealed an appendiceal intussusception without any mucosal lesion of the appendix. Narrowing of the terminal ileum with a small bowel obstruction and stenosis of the IC valve occurred postoperatively. Therefore, ileocecectomy was performed via a laparoscopic approach. The patient was discharged 11 days after the second surgery without another significant postoperative complication. Conclusions We report a rare case of appendiceal intussusception that required reoperation due to ileocolic valve stenosis. If the correct diagnosis of appendiceal intussusception is made, we can select an appropriate surgical treatment based on the classification of appendiceal intussusceptions.

Pulse-echo laser ultrasonic propagation imaging is a nondestructive testing technique developed for composite materials and aluminum alloys used in aerospace. Although this method has been in usage for a considerable time, information of the detectable depth and the relationship between ultrasonic frequencies and the acoustic properties of metals is not readily available. Therefore, we investigate the A-scan and C-scan ultrasonic testing data of aluminum alloy, hot rolled steel, stainless steel, and copper alloy, which are used in aircraft bodies, frameworks, and gas pipelines. Experiments are performed with the pulse-width and excitation laser power fixed at 32 ns and approximately 4 W, respectively. The metal specimens include 24 artificial cylindrical defects with a diameter of 5 mm, located at depths of 1–12 mm on the front surface. The A-scan and C-scan data obtained at room temperature indicate the detectable depth for metals via the pulse-echo laser ultrasonic propagation imaging technique.

PURPOSE To examine the association of resting heart rate (RHR) and muscular endurance with prevalence of type 2 diabetes in Korean adults. METHODS A baseline data from a total of 10,704 subjects who participated in the exercise program held at the National Health Promotion Center were analyzed. Participants were divided into tertiles according to their RHR. Participants were further divided into two groups (2-quantile) according to their muscular endurance measured. Statistical methods included frequency analysis, analysis of variance, and logistic regression. RESULTS Fasting glucose levels were significantly higher among participants with higher RHR. Compared with participants in the first RHR tertile, participants in the third RHR tertile are at 2.35 times (95% confidence interval [CI]: 2.16-3.03) higher odds of having type 2 diabetes. When participants were divided into two groups according to muscular strength, participants in the second quantile (less fit) are at 1.32 times (95% CI:1.13-1.54) higher odds of having type 2 diabetes compared with participants in the first quantile. When joint associations of RHR and muscular endurance were analyzed, participants in the highest tertile of RHR with lower muscular endurance have 3.40 times (95% CI: 2.58-4.47) higher odds of having type 2 diabetes compared with those in the lowest tertile of RHR and high muscular endurance after controlling for age, sex and BMI. CONCLUSIONS RHR and muscular endurance were significantly associated with the prevalence of type 2 diabetes. In addition, this study shows that RHR and muscular endurance level are important indicators for the prevalence of type 2 diabetes in Korean adults.

Background: The prevalence of idiopathic scoliosis is rapidly increasing in Korean children, but research on the disorder is limited compared to that in other countries. Accordingly, in the present study, we aimed to investigate the relationship between idiopathic scoliosis and body mass index (BMI) levels in Korean children. Methods: This cross-sectional study enrolled elementary school students and middle school first graders in the Capital Area in Korea. The participants underwent body composition measurements and screening for idiopathic scoliosis. Idiopathic scoliosis was defined as a Cobb angle of ≥10°. The students were classified into three groups—the severely underweight (SUW: BMI < 16 kg/m2) group, the underweight group (UW: 16 ≤ BMI < 18.5 kg/m2), and the normal weight group (NW: 18.5 ≤ BMI < 25 kg/m2) to compare the risk of idiopathic scoliosis across BMI levels. Results: The final cohort comprised 1375 participants. The odds ratio (OR) of idiopathic scoliosis was 0.69 (95% confidence interval (CI): 0.50–0.94) and 0.66 (95% CI: 0.49–0.89) for the UW and the NW groups, respectively, with the SUW group as the reference. This shows that the risk decreased significantly by 31% and 34% in the UW and the NW groups, respectively. After controlling for age and sex, the corresponding ORs were 0.72 (95% CI: 0.52–0.98) and 0.70 (95% CI: 0.51–0.96), and the risk significantly decreased by 28% and 30% in the UW and the NW groups, respectively. Conclusions: Low body weight is closely associated with spinal deformity and idiopathic scoliosis.

Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks’ gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.

Mycotic aneurysms of the common carotid artery (CCA) are very rare and warrant surgical treatment to prevent rupture and death. A 89-year-old man who complained of a sore throat and swelling of the right side of neck. He had no history of trauma or neck infection. Physical examination revealed hard and pulsatile mass. Computed tomography showed initially pseudoaneurysm rupture on the right CCA with surrounding inflammation. The emergency operation revealed mycotic aneurysm rupture with CCA necrosis and was successfully done by wide debridement and carotid artery resection with interposition bypass. The resected tissue and blood culture grew growth of Staphylococcus aureus group. We report a rare case of mycotic aneurysm of right CCA that treated by bypass interposition.

Protons are released in pain-generating pathological conditions such as inflammation, ischemic stroke, infection, and cancer. During normal synaptic activities, protons are thought to play a role in neurotransmission processes. Acid-sensing ion channels (ASICs) are typical proton sensors in the central nervous system (CNS) and the peripheral nervous system (PNS). In addition to ASICs, capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channels can also mediate proton-mediated pain signaling. In spite of their importance in perception of pH fluctuations, the regulatory mechanisms of these proton-sensitive ion channels still need to be further investigated. Here, we compared regulation of ASICs and TRPV1 by membrane phosphoinositides, which are general cofactors of many receptors and ion channels. We observed that ASICs do not require membrane phosphatidylinositol 4-phosphate (PI(4)P) or phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for their function. However, TRPV1 currents were inhibited by simultaneous breakdown of PI(4)P and PI(4,5)P2. By using a novel chimeric protein, CF-PTEN, that can specifically dephosphorylate at the D3 position of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), we also observed that neither ASICs nor TRPV1 activities were altered by depletion of PI(3,4,5)P3 in intact cells. Finally, we compared the effects of arachidonic acid (AA) on two proton-sensitive ion channels. We observed that AA potentiates the currents of both ASICs and TRPV1, but that they have different recovery aspects. In conclusion, ASICs and TRPV1 have different sensitivities toward membrane phospholipids, such as PI(4)P, PI(4,5)P2, and AA, although they have common roles as proton sensors. Further investigation about the complementary roles and respective contributions of ASICs and TRPV1 in proton-mediated signaling is necessary.

Lipotoxicity-induced mesangial cell apoptosis is implicated in the exacerbation of diabetic nephropathy (DN). Protein arginine methyltransferases (PRMTs) have been known to regulate a variety of biological functions. Recently, it was reported that PRMT1 expression is increased in proximal tubule cells under diabetic conditions. However, their roles in mesangial cells remain unexplored. Thus, we examined the pathophysiological roles of PRMTs in mesangial cell apoptosis. Treatment with palmitate, which mimics cellular lipotoxicity, induced mesangial cell apoptosis via protein kinase RNA-like endoplasmic reticulum kinase (PERK) and ATF6-mediated endoplasmic reticulum (ER) stress signaling. Palmitate treatment increased PRMT1 expression and activity in mesangial cells as well. Moreover, palmitate-induced ER stress activation and mesangial cell apoptosis was diminished by PRMT1 knockdown. In the mice study, high fat diet-induced glomerular apoptosis was attenuated in PRMT1 haploinsufficient mice. Together, these results provide evidence that lipotoxicity-induced PRMT1 expression promotes ER stress-mediated mesangial cell apoptosis. Strategies to regulate PRMT1 expression or activity could be used to prevent the exacerbation of DN.

We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]). Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41]) was significantly elevated when the effect of moderate drinking (20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.