Stochastic chromatin packing of 3D mitotic chromosomes revealed by coherent X-rays.

DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints. However, its three-dimensional (3D) structure remains elusive with challenges in observing native structures of specimens at tens-of-nanometers resolution. Here, using cryogenic coherent X-ray diffraction imaging, we succeeded in obtaining nanoscale 3D structures of metaphase chromosomes that exhibited a random distribution of electron density without characteristics of high-order folding structures. Scaling analysis of the chromosomes, compared with a model structure having the same density profile as the experimental results, has discovered the fractal nature of density distributions. Quantitative 3D density maps, corroborated by molecular dynamics simulations, reveal that internal structures of chromosomes conform to diffusion-limited aggregation behavior, which indicates that 3D chromatin packing occurs via stochastic processes.

Development and validation of a sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method for quantitative analysis of bambermycin in livestock and aquatic products: Implications for food safety control and regulatory enforcement.

A sensitive and accurate analytical method was developed and validated to detect bambermycin, a commonly used antibiotic in animal feed and livestock. The presence of bambermycin residues in food products can pose health risks to consumers, emphasizing the need for a sensitive and accurate analytical method. A reversed-phase analytical column was utilized with a mobile phase comprising 0.005 mol/L ammonium acetate in 5% acetonitrile (A) and 0.005 mol/L ammonium acetate in 95% acetonitrile (B) to achieve effective chromatographic separation. Quantitative determination of bambermycin in various samples, including beef, pork, chicken, milk, eggs, flatfish, eel, and shrimp, was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Sample extraction involved a mixture of methanol and a 25% ammonium hydroxide solution, followed by low-temperature purification and phospholipid removal utilizing a Phree cartridge. The method exhibited a satisfactory recovery rate ranging from 69% to 100%. Validation results demonstrated the reliability, robustness, and accuracy of the method, exhibiting good linearity, precision, and recovery. This validated method can be applied for routine analysis of bambermycin residues, assisting in the development of effective monitoring and control measures to ensure the safety of livestock and aquatic products.

The 30-day unplanned readmission rate and hospital volume: a national population-based study in South Korea.

OBJECTIVE: To examine the association between hospital volume and the unplanned 30-day readmission rate as a quality measure. DESIGN: A retrospective cross-sectional study. SETTING: The Korea healthcare system is operated by a single payer under the National Health Insurance Service. PARTICIPANTS: Using national health claims data of the Health Insurance Review and Assessment in South Korea, we examined 1 296 275 adult discharges (≥18 years old) from 90 hospitals (≥500 beds) in the 2013 calendar year. MAIN OUTCOME MEASURES: We analysed the 30-day, unplanned, observed-to-expected standardized readmission rate for hospitals and for five specialty cohorts: medicine, surgery/gynaecology, cardiovascular, cardiorespiratory, and neurology. We assessed the association between hospital volume by tertiles and the 30-day standardized readmission rates with and without adjustment for hospital characteristics. RESULTS: The rate for the lowest-volume hospitals was 6.10 compared with 6.20 for the highest-volume hospitals. We observed the standardized readmission rates did not differ significantly between the lowest- and highest-volume groups, except for the neurology cohort, which remained significant after adjusting for hospital characteristics. CONCLUSIONS: The standardized readmission rates were not associated with hospital volume, except for the neurology cohort, in which the standardized readmission rate was significantly higher in the highest-volume hospitals than in lowest- and intermediate-volume hospitals, which was not consistent with the typical association of greater hospital volume with better outcomes. This association was independent of hospital characteristics. Therefore, the rate of readmissions should be used with caution when gauging the quality of hospital care according to hospital volume.

Medical security and catastrophic health expenditures among households containing persons with disabilities in Korea: a longitudinal population-based study.

BACKGROUND: Although persons with disabilities need access to comprehensive and consistent healthcare services, a significant number of the poor with disabilities do not receive Medical-Aid due to the conditions of eligibility. We aimed to compare the financial burden of healthcare services between two groups of poor persons with disabilities: those not enrolled in Medical-Aid and Medical-Aid enrollees. METHODS: This study used the 1st-8th data (2008-2014 year) of Panel Survey of Employment for the Disabled (PSED) conducted by the Korea Employment Agency for the Disabled. We classified adults who did not exceed 100 % of the poverty level into two groups (N = 3,010). The first group consisted of enrollees in Medical-Aid (n = 1,259) and the second group comprised those not enrolled in Medical-Aid (n = 1,325). We applied generalized estimating equations (GEEs) to assess the independent effect of enrollment in Medical-Aid on catastrophic health expenditures (CHE). RESULTS: We found that about 4.2 % of the poor not enrolled in the Medical-Aid experienced CHE and the poor not enrolled in Medical-Aid were 2.1 times more likely to experience CHE than Medical-Aid enrollees after applying multivariate models adjusted for several covariates. CONCLUSIONS: Given the additional expenses for treatment and rehabilitation caused by disability-related health problems, persons with disabilities are more likely to face barriers to needed medical services. Thus, policy makers need to expand the number of people receiving Medical-Aid by loosening the strict criteria for those with disabilities.

Efficacy of fractional microneedle radiofrequency device in the treatment of primary axillary hyperhidrosis: a pilot study.

BACKGROUND: Fractional microneedle radiofrequency (FMR) devices deliver energy to the deep dermis through insulated microneedles without destroying the epidermis. These FMR devices have been shown to be effective for the treatment of wrinkles, acne scars and large pores. In this study it was postulated that FMR energy could specifically affect the sweat glands, preserving the skin surface even if sweat glands were seated in the deep dermis. OBJECTIVE: To evaluate the efficacy and safety of FMR for primary axillary hyperhidrosis (PAH) treatment and to conduct a histological analysis before and after treatment. METHODS: Twenty patients with PAH had 2 sessions of bipolar FMR treatment at 4-week intervals. Clinical improvement was evaluated using a Hyperhidrosis Disease Severity Scale (HDSS) and photographs were taken using the starch-iodine test at every visit and 2 months after the last treatment. The amount of sweat reduction was indirectly assessed using a Tewameter™. Skin biopsies were obtained from 3 of the enrolled patients before and after treatment. The satisfaction and adverse reactions of the research participants were recorded at every follow-up visit. RESULTS: HDSS scores decreased significantly from a baseline of 3.3 to 1.5 and 1.8 after the first and second months of posttreatment follow-up sessions, respectively (p < 0.001). In response to a subjective assessment at 1 month after the second treatment, 75% of patients (n = 15) had an HDSS score of 1 or 2, and 70% of patients (n = 14) expressed more than 50% improvement in their sweating. The starch-iodine reaction was also remarkably reduced in 95% of patients (n = 19) after FMR treatment. Histological findings showed a decrease in the number and size of both apocrine and eccrine glands 1 month after the final treatment. Side effects were minimal and included mild discomfort, transient swelling and postinflammatory hyperpigmentation. CONCLUSION: FMR treatment was effective for the treatment of PAH without significant adverse reactions due to direct volumetric heating of the lower dermis.

Effect of smartphone app-based health care intervention for health management of high-risk mothers: a study protocol for a randomized controlled trial.

BACKGROUND: The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life. METHODS: This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework. DISCUSSION: These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers. TRIAL REGISTRATION: Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows: Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193 . Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022.

The effect of 308nm excimer laser on segmental vitiligo: a retrospective study of 80 patients with segmental vitiligo.

BACKGROUND: Segmental vitiligo (SV), which frequently accompanies poliosis, indicating a poor prognosis that is likely resistant to treatments. OBJECTIVES: In this study, we performed a retrospective analysis to evaluate the treatment response to 308 nm excimer laser in SV patients. METHODS: A retrospective chart and photographic review was performed on 80 SV patients who had been treated with 308nm excimer laser for >3 months. RESULTS: Eighty patients with SV (mean age: 24.0 years ± 15.3, males: 50%) were included in this study. The mean grade of repigmentation was 2.3 after 20.6 months of mean treatment duration; 23.8% of 80 patients showed grade 4, 20% showed grade 3, and 56.2% showed grade 1-2 repigmentation. However, none of them achieved complete repigmentation with excimer laser. The degree of repigmentation was positively correlated with treatment duration (r=0.315, P=0.004) and cumulative ultraviolet (UV) dosage (r=0.366, P=0.001), whereas it was negatively correlated with disease duration (r=-0.265, P=0.017). CONCLUSION: This study suggests that SV has a better repigmentation response when excimer laser is used at earlier stages of the disease and long-term use and high cumulative UV energy of the excimer laser elicit better responses. Additional treatments like surgical procedures in addition to excimer laser should be considered for complete repigmentation.

High-Throughput 3D Ensemble Characterization of Individual Core-Shell Nanoparticles with X-ray Free Electron Laser Single-Particle Imaging.

The structures as building blocks for designing functional nanomaterials have fueled the development of versatile nanoprobes to understand local structures of noncrystalline specimens. Progress in analyzing structures of individual specimens with atomic scale accuracy has been notable recently. In most cases, however, only a limited number of specimens are inspected lacking statistics to represent the systems with structural inhomogeneity. Here, by employing single-particle imaging with X-ray free electron lasers and algorithms for multiple-model 3D imaging, we succeeded in investigating several thousand specimens in a couple of hours and identified intrinsic heterogeneities with 3D structures. Quantitative analysis has unveiled 3D morphology, facet indices, and elastic strain. The 3D elastic energy distribution is further corroborated by molecular dynamics simulations to gain mechanical insight at the atomic level. This work establishes a route to high-throughput characterization of individual specimens in large ensembles, hence overcoming statistical deficiency while providing quantitative information at the nanoscale.

Keratitis caused by Verticillium species.

PURPOSE: To report a case of fungal keratitis caused by Verticillium species. METHODS: A 50-year-old man developed pain, redness, and an infiltrate in his left eye and had no history of trauma. The cornea showed superficial, white, stromal infiltrates and epithelial ulceration with a dendritic margin. The clinical features suggested herpetic keratitis, and the patient was treated with topical antiviral medication. Two weeks later, his condition deteriorated. Examination of the left eye showed stromal infiltrates with a feathery margin and epithelial ulceration with its covering white exudates. Corneal scrapings were taken for direct microscopic examination and culture. RESULTS: Corneal scraping showed the presence of fungal filaments. The fungus was identified as Verticillium species. Topical amphotericin B and systemic fluconazole were started after discontinuing the antiviral treatment. Clinically, the inflammation subsided during the 3 weeks after treatment. CONCLUSION: This is a rare case of infectious keratitis caused by Verticillium species. Rare species of fungal infection should be considered in the differential diagnosis of stromal keratitis refractive to conventional medical treatment.

Expression of cytosolic NADP(+)-dependent isocitrate dehydrogenase in melanocytes and its role as an antioxidant.

BACKGROUND: Cytosolic NADP(+)-dependent ICDH (IDPc) has an antioxidant effect as a supplier of NADPH to the cytosol, which is needed for the production of glutathione. OBJECTIVE: To evaluate the expression of IDPc in melanocytes and to elucidate its role as an antioxidant. METHODS: The knock-down of IDPc expression in immortalized mouse melanocyte cell lines (melan-a) was performed using the short interfering RNA (siRNA)-targeted gene silencing method. After confirming the silencing of IDPc expression with mRNA and protein levels, viability, apoptosis and necrosis, as well as ROS production in IDPc-silenced melanocytes were monitored under conditions of oxidative stress and non-stress. Also, the ratio of oxidized glutathione to total glutathione was examined, and whether the addition of glutathione recovered cell viability, decreased by oxidant stress, was checked. RESULTS: The expression of IDPc in both primary human melanocytes and melan-a cells was confirmed by Western blot and RT-PCR. The silencing of IDPc expression by transfecting IDPc siRNA in melan-a cells was observed by Western blotting and real-time RT-PCR. IDPc knock-down cells showed significantly decreased cell viability and an increased number of cells under apoptosis and necrosis. IDPc siRNA-treated melanocytes demonstrated a higher intensity of DCFDA after the addition of H(2)O(2) compared with scrambled siRNA-treated melanocytes, and a lower ratio of reduced glutathione to oxidized glutathione were observed in IDPc siRNA transfected melanocytes. In addition, the addition of glutathione recovered cell viability, which was previously decreased after incubation with H(2)O(2). CONCLUSIONS: This study suggests that decreased IDPc expression renders melanocytes more vulnerable to oxidative stress, and IDPc plays an important antioxidant function in melanocytes.

Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function.

The root of Panax ginseng C. A. Meyer is one of the most popular natural tonics in oriental countries. In this study, we have isolated polysaccharide fraction of Panax ginseng (ginsan) and examined its effect on the function of murine peritoneal macrophages. When macrophages were treated with ginsan, cytotoxic activity against B16 melanoma cells was significantly induced. In addition, the levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and Interferon-gamma (IFN-gamma) were increased and the production of reactive oxygen/nitrogen components such as nitric oxide (NO) and hydrogen peroxide (H2O2) was enhanced. Moreover, phagocytic activity was induced in ginsan-treated macrophages compared to the control. The expression of CD14 and 1-Ab on murine peritoneal macrophages was increased by the treatment with ginsan, while the expression of CD11b was decreased. Taken together, these results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.