Lymphangiogenesis after nonvascularized lymph node transplantation: Lymphangiographic findings in mice and minipigs.

The establishment of new connections after NVLNT (non-vascularized lymph node transplantation) is still poorly understood. The purpose of this study was to investigate lymphatic connections after NVLNT using lymphangiography. In a mice model, 40 mice were allocated to undergo NVLNT or sham surgery. On day 21 after NVLNT, the lymphatic vessels were observed on near-infrared fluorescence imaging with indocyanine green. In a minipig model, 12 minipigs underwent NVLNT. On day 14 after NVLNT, the transplanted lymph node and donor site were checked by ultrasound, and minipigs with viable transplanted LNs were allocated to lipiodol lymphangiography or MR lymphangiography groups. Transplanted LN engraftment was examined with immunohistochemical staining. After NVLNT in mice, the signal intensities in the popliteal region at 3 minutes and 5 minutes were higher in the transplanted side than the control side (21.3 ± 8.1 vs. 11.0 ± 4.6 at 3 minutes, 26.7 ± 6.8 vs. 19.7 ± 5.9 at 5 minutes), while in the sham group, there were no significant differences between sides. In minipigs, lipiodol lymphangiography (n = 5) showed Lipiodol accumulation in transplanted LNs with innumerable newly formed lymphatic vessels and lymphovenous shunts. MR lymphangiography (n = 5) showed higher enhancement on the transplanted side compared to the control side. Histology showed successful engraftment of transplanted LNs in 16 out of 20 (80%) mice and 9 out of 12 (75%) minipigs. Omnidirectional lymphangiogenesis forming a dense lymphatic network and spontaneous formation of lymphovenous shunts were shown after NVLNT.

Effect of group sand play therapy on psychopathologies of adolescents with delinquent behaviors.

Prior research has established adolescent vulnerability to delinquent behavior. This single-arm, noninterventional, observational study investigated the effect of sand play therapy on the psychopathologies of adolescents with delinquent behavior. A total of 68 adolescents participated in the study. Participants were treated with 8 weekly sessions of sand play therapy, lasting 50 minutes each and conducted in groups of 3 to 4 members. The psychopathologies of depression, anxiety, self-esteem, impulsiveness, characteristics of attention-deficit hyperactivity disorder (ADHD), and impulsiveness were measured using self-reporting scales. Following therapy, depression (t = 3.28; P = .002; ES = 0.399) and anxiety (t = 4.00; P < .001; ES = 0.485) decreased significantly with moderate effect size. ADHD characteristics (t = 2.73; P = .008) and impulsiveness (t = 2.73; P = .009) also decreased significantly with effect size of 0.330 and 0.327, respectively. Self-esteem (t = -2.06, P = .043; ES = 0.251) was found to have significantly increased. The high-risk group within each psychopathology showed significantly higher improvement than the low-risk group. Results showed that group sand play therapy is effective in improving internalizing problems such as depression and anxiety, as well as externalizing problems of ADHD features and impulsiveness among adolescents with deviant behaviors.

Effects of school sandplay group therapy on children victims of cyberbullying.

Cyberbullying among children is increasing every year, leading to serious public health problems. Victims suffer serious aftereffects such as depression and suicidal ideation; therefore, early and appropriate psychological intervention and the role of schools are emphasized. This study investigated the effects of school sandplay group therapy (SSGT) on children affected by cyberbullying. This study was designed as a parallel-group non-randomized controlled trial. The study subjects were 139 elementary school students (mean age 11.35 years; standard deviation, 0.479; age range 12-13 years) residing in Cheonan City, Korea, who were assigned to the intervention and comparison groups. The intervention group received 10 sessions of therapy on a weekly basis, for 40 minutes per session. No therapy was administered in the control group. The effectiveness of the intervention was assessed using the Children Depression Inventory, Suicidal Ideation Questionnaire-Junior, and Rosenberg Self-Esteem Scale. The assessment for the comparison group was performed concurrently with that of the intervention group. Data were analyzed using multivariate analysis of variance. In this study, the SSGT group showed a significant decrease in depression and suicidal ideation compared to the control group after sandplay group therapy (SGT), and a significant increase in self-esteem. It was confirmed that SSGT can mitigate the negative consequences of cyberbullying and strengthen protective factors. This suggests that the SSGT can be successfully used for crisis counseling.

Deep-Learning-Based Detection of Vertebral Fracture and Osteoporosis Using Lateral Spine X-Ray Radiography.

Osteoporosis and vertebral fractures (VFs) remain underdiagnosed. The addition of deep learning methods to lateral spine radiography (a simple, widely available, low-cost test) can potentially solve this problem. In this study, we develop deep learning scores to detect osteoporosis and VF based on lateral spine radiography and investigate whether their use can improve referral of high-risk individuals to bone-density testing. The derivation cohort consisted of patients aged 50 years or older who underwent lateral spine radiography in Severance Hospital, Korea, from January 2007 to December 2018, providing a total of 26,299 lateral spine plain X-rays for 9276 patients (VF prevalence, 18.6%; osteoporosis prevalence, 40.3%). Two individual deep convolutional neural network scores to detect prevalent VF (VERTE-X pVF score) and osteoporosis (VERTE-X osteo score) were tested on an internal test set (20% hold-out set) and external test set (another hospital cohort [Yongin], 395 patients). VERTE-X pVF, osteo scores, and clinical models to detect prevalent VF or osteoporosis were compared in terms of the areas under the receiver-operating-characteristics curves (AUROCs). Net reclassification improvement (NRI) was calculated when using deep-learning scores to supplement clinical indications for classification of high-risk individuals to dual-energy X-ray absorptiometry (DXA) testing. VERTE-X pVF and osteo scores outperformed clinical models in both the internal (AUROC: VF, 0.93 versus 0.78; osteoporosis, 0.85 versus 0.79) and external (VF, 0.92 versus 0.79; osteoporosis, 0.83 versus 0.65; p < 0.01 for all) test sets. VERTE-X pVF and osteo scores improved the reclassification of individuals with osteoporosis to the DXA testing group when applied together with the clinical indications for DXA testing in both the internal (NRI 0.10) and external (NRI 0.14, p < 0.001 for all) test sets. The proposed method could detect prevalent VFs and osteoporosis, and it improved referral of individuals at high risk of fracture to DXA testing more than clinical indications alone. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Higher red cell distribution width and poorer hospitalization-related outcomes in elderly patients.

BACKGROUND: Red cell distribution width (RDW), an index for variation of red blood cell (RBC) size, has been proposed as a potential marker for poorer outcomes in several aging-related diseases and conditions. We tested whether greater variability of RBC size, presented as a higher RDW value, predicts poor prognoses among hospitalized patients over 60 years old. METHODS: We retrospectively collected data from older hospitalized patients aged ≥60 years between January 2013 to December 2017 at Sutter Health, a large integrated health system in Northern California. The RDW was measured during hospital admission and categorized with 1% intervals (≤13.9, 14.0-14.9, 15.0-15.9, 16.0-16.9, 17.0-17.9 and ≥18.0%). The primary outcome was the rate of in-hospital mortality and secondary outcomes included 30-day re-admission rate and length of hospital stay (in days). RESULTS: A total of 167,292 admissions from 94,617 patients were included. The overall in-hospital mortality rate was 6.3%. As the RDW value increased, the rate of in-hospital mortality gradually increased from 2.7% for the lowest RDW category to 12.2% in the highest category (p-trend <0.001). The overall 30-day re-admission rate after discharge was 12.5% and the rate of 30-day re-admission also increased with increasing RDW categories (7.4% in the lowest group vs. 15.8% in the highest group, p-trend <0.001). Patients with the highest RDW values at admission stayed 1.5-2.0 times longer in the hospital than patients with lower RDW values who were admitted for the same causes. CONCLUSIONS: Greater variability of RBC size is significantly associated with worse prognosis in hospitalized elderly patients, indicating higher mortality, greater risk of early re-admission, and longer hospital stay days. Risk stratification strategies for hospitalized elderly should include RDW value.

Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice.

CONTEXT: Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking. OBJECTIVE: This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury. MATERIALS AND METHODS: C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay. RESULTS: SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and -9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group. DISCUSSION AND CONCLUSIONS: SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.

Mustard Seed (Brassica nigra) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion.

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.

Korean Society for Bone and Mineral Research Task Force Report: Perspectives on Intermittent High-dose Vitamin D Supplementation.

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

Cytotoxicity, Intestinal Transport, and Bioavailability of Dispersible Iron and Zinc Supplements.

Iron or zinc deficiency is one of the most important nutritional disorders which causes health problem. However, food fortification with minerals often induces unacceptable organoleptic changes during preparation process and storage, has low bioavailability and solubility, and is expensive. Nanotechnology surface modification to obtain novel characteristics can be a useful tool to overcome these problems. In this study, the efficacy and potential toxicity of dispersible Fe or Zn supplement coated in dextrin and glycerides (SunActive FeTM and SunActive ZnTM) were evaluated in terms of cytotoxicity, intestinal transport, and bioavailability, as compared with each counterpart without coating, ferric pyrophosphate (FePP) and zinc oxide (ZnO) nanoparticles (NPs), respectively. The results demonstrate that the cytotoxicity of FePP was not significantly affected by surface modification (SunActive FeTM), while SunActive ZnTM was more cytotoxic than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive FeTM were significantly higher than those of its counterpart material, which was in good agreement with enhanced oral absorption efficacy after a single-dose oral administration to rats. These results seem to be related to dissolution, particle dispersibility, and coating stability of materials depending on suspending media. Both SunActiveTM products and their counterpart materials were determined to be primarily transported by microfold (M) cells through the intestinal epithelium. It was, therefore, concluded that surface modification of food fortification will be a useful strategy to enhance oral absorption efficiency at safe levels.

Hepatic arterial damage after transarterial chemoembolization for the treatment of hepatocellular carcinoma: comparison of drug-eluting bead and conventional chemoembolization in a retrospective controlled study.

Background Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) frequently causes feeding artery stenosis or occlusion that may interfere with repeated treatment. Purpose To investigate the incidence and predictors of hepatic arterial damage (HAD) after drug-eluting bead-TACE (DEB-TACE) in comparison with conventional TACE (Conv-TACE). Material and Methods We retrospectively analyzed 54 patients who underwent DEB-TACE for HCC as an initial treatment with follow-up angiography and 54 patients who underwent Conv-TACE using doxorubicin-lipiodol mixture and gelfoam particles for comparison. HAD was evaluated after a single session of TACE and graded as follows: grade I, no significant wall irregularity; grade II, overt stenosis; grade III, occlusion. Results The incidence of HAD was significantly higher in the DEB-TACE group than the Conv-TACE group when analyzed per branch (odds ratio [OR], 6.36; P < 0.001) and per patient (OR, 3.15; P = 0.005). For each HAD grade, the mean doxorubicin dose was greater in the DEB-TACE group than in the Conv-TACE group ( P < 0.001, P = 0.053, and P = 0.01 for grades I, II, and III, respectively). In multivariate analysis, risk factors of HAD included mean doxorubicin dose and selective embolization in the Conv-TACE group ( P = 0.03 and P < 0.001, respectively) and mean doxorubicin dose in the DEB-TACE group ( P = 0.004). Conclusion The incidence and grade of HAD were higher after DEB-TACE compared to Conv-TACE with doxorubicin dose as a possible risk factor. HAD was independent of overall survival in both groups.

Calcium and Vitamin D Supplementations: 2015 Position Statement of the Korean Society for Bone and Mineral Research.

Calcium and vitamin D are essential components for bone health, thus calcium and vitamin D supplementation is an important strategy in the management of osteoporosis. However, the benefit of calcium and vitamin D supplementation on bone health is still controversial. Moreover, potentially harmful effects of excessive calcium supplementation on cardiovascular health are recently suggested. Too high a level of vitamin D has been also reported to have several, possibly related, harmful events. Korea is well known for low dietary calcium intake and vitamin D deficiency in its population. This position statement developed the following recommendation for adequate levels of calcium and vitamin D intake in Korean, postmenopausal women and men older than 50 years: Adequate calcium intake and optimal vitamin D level are essential for preventing and treating osteoporosis in postmenopausal women and men older than 50 years. We recommend a daily calcium intake of 800 to 1,000 mg/day. Food remains the best source of calcium; however calcium supplements should be considered when dietary intake of calcium is inadequate. We recommend dietary vitamin D intake of more than 800 IU per day, a level which appears to reduce the risk of fractures. When vitamin D deficiency is suspected, serum 25-hydroxy-vitamin D (25-[OH]D) level should be tested. We suggest that a serum 25-(OH)D level greater than 20 ng/mL is generally appropriate for prevention of osteoporosis. However, a serum 25-(OH)D level greater than 30 ng/mL is probably helpful for management of osteoporosis and prevention of fractures.

The risks and benefits of calcium supplementation.

The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.

Calcium, Is It Better to Have Less?--Global Health Perspectives.

Appropriate calcium intake is necessary for the accrual and maintenance of bone mass. A significant proportion of the world's population does not have adequate calcium intake, and thus, supplementation plays a key role in maintaining bone homeostasis and other aspects of health. Since a series of reports from the Auckland calcium study and meta-analysis indicated that calcium supplementation was associated with an increased risk for adverse cardiovascular events, concern over the safety of calcium supplementation has grown; however, considerable inconsistencies in the reproducibility were found and questions regarding the study methodologies have been raised. In addition, since the increased adverse cardiovascular events by calcium supplementation were observed in calcium-replete subjects, it should be clarified whether the same risk profile would be observed in countries with low calcium intake. Dietary calcium intake varies widely across the world; cardiovascular event risk factors and outcomes also vary and appear to be the opposite of calcium intake levels. Furthermore, the effects of calcium supplementation were shown to depend on dietary calcium intake, with a better bone mineral density response for low calcium intake subjects compared to that in calcium-replete subjects. Based on these evidences, the risk-benefit ratio of calcium supplement is likely to be different in different region of the world. Therefore, accumulation of evidence to establish population-specific guidelines for calcium supplementation is warranted before extrapolating the results obtained from a limited number of studies to the other people with different age, gender, ethnicity and risk profile across the world.

Therapeutic approach of wrist ganglion using electroacupuncture: two case reports.

A ganglion cyst is a relatively common benign tumor on the wrist. Conservative and surgical approaches have been used for its treatment. Various conservative treatment methods have been suggested such as reassurance, aspiration, sclerosant injection, and direct compression. But, there is no acceptable treatment of choice yet because each suggested method has a relatively high recurrence rate. We want to report two cases in which the size of the wrist ganglion was decreased by using electroacupuncture. One patient presented with a chronic ganglion for six years and the other patient presented with a recently occurred acute ganglion. We applied electroacupuncture for 20 minutes once a week for eight weeks to both of them. Afterwards, the size of the wrist ganglion diminished in the follow-up sonography and the accompanying pain was also relieved. Herein we report both cases along with a review of the relevant literature.

The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats.

BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS AND FINDINGS: LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls. CONCLUSIONS: Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.