A multi-layered network model identifies Akt1 as a common modulator of neurodegeneration.

The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy.

BACKGROUND: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes. OBJECTIVE: Examine the impact of melanoma subtypes on cirAE onset and survival among ICI recipients. METHODS: Retrospective multi-institutional cohort study. Multivariate time-series regressions were utilized to assess relationships between melanoma subtype, cirAE development, and survival. RESULTS: Among 747 ICI recipients, 236 (31.6%) patients developed a cirAE. Patients with acral melanoma were less likely to develop a cirAE (hazard ratio [HR] = 0.41, P = .016) compared to patients with nonacral cutaneous melanoma. Across all melanoma subtypes, cirAEs were associated with reduced mortality (HR = 0.76, P = .042). Patients with acral (HR = 2.04, P = .005), mucosal (HR = 2.30, P < .001), and uveal (HR = 4.09, P < .001) primaries exhibited the worst survival. LIMITATIONS: Retrospective cohort study. CONCLUSION: This is the first study to demonstrate differences in cirAE development among melanoma subtypes. The presence of cirAEs was associated with better survival. Further, the lower incidence of cirAEs may be a marker of immunotherapy response, which is reflected in the association between acral melanoma and mortality.

The conserved microRNA miR-8-3p coordinates the expression of V-ATPase subunits to regulate ecdysone biosynthesis for Drosophila metamorphosis.

The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the underlying mechanisms of ecdysone-mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis-associated microRNAs (miRNAs) and their potential targets by cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR-8-3p targeted five Vha genes encoding distinct subunits of vacuolar H+ -ATPase (V-ATPase), which has a vital role in the organellar acidification. The expression of ecdysone-responsive miR-8-3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR-8-3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR-8-3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR-8-3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone-deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR-8-3p/miR-200 family and V-ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V-ATPase subunits by miR-8-3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis.

Ecdysone-responsive microRNA-252-5p controls the cell cycle by targeting Abi in Drosophila.

The steroid hormone ecdysone has a central role in the developmental transitions of insects through its control of responsive protein-coding and microRNA (miRNA) gene expression. However, the complete regulatory network controlling the expression of these genes remains to be elucidated. In this study, we performed cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 (Ago1) protein, the core effector of the miRNA pathway, in Drosophila S2 cells. We found that regulatory interactions between miRNAs and their cognate targets were substantially altered by Ago1 in response to ecdysone signaling. Additionally, during the larva-to-adult metamorphosis, miR-252-5p was up-regulated via the canonical ecdysone-signaling pathway. Moreover, we provide evidence that miR-252-5p targets Abelson interacting protein ( Abi) to decrease the protein levels of cyclins A and B, controlling the cell cycle. Overall, our data suggest a potential role for the ecdysone/miR-252-5p/Abi regulatory axis partly in cell-cycle control during metamorphosis in Drosophila.-Lim, D.-H., Lee, S., Han, J. Y., Choi, M.-S., Hong, J.-S., Seong, Y., Kwon, Y.-S., Lee, Y. S. Ecdysone-responsive microR-252-5p controls the cell cycle by targeting Abi in Drosophila.

Impact of acute kidney injury in expanded criteria deceased donors on post-transplant clinical outcomes: multicenter cohort study.

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

Generic uniform search grid generation algorithm for far-field source localization.

In this letter, a generic search grid generation algorithm for far-field source localization (SL) is proposed. Since conventional uniform regular grid structures only consider the resolution of the distribution, it is difficult to control the number of grid points to be distributed. The proposed algorithm generates a search grid by distributing a desired number of points evenly, depending on the target criterion, in either direction of arrival or time difference of arrival domain. The experimental results show that the proposed algorithm provides optimally distributed grid points given the number of desired points and the corresponding domain for SL processing.

Prediction of clinical outcomes after kidney transplantation from deceased donors with acute kidney injury: a comparison of the KDIGO and AKIN criteria.

BACKGROUND: Acute kidney injury (AKI) is frequently detected in deceased donors (DDs), and it could be associated with adverse clinical outcomes in corresponding kidney transplant recipients (KTRs). In this regard, we sought to identify which criteria is better between the KDIGO and AKIN criteria for the diagnosis of AKI in DDs in the prediction of clinical outcomes after kidney transplantation (KT). METHODS: Two hundred eighty-five cases of deceased donor kidney transplantation (DDKT) were included. We divided them into three groups; the non-AKI by both KDIGO and AKIN criteria group (n = 120), the AKI by KDIGO only group (n = 61), and the AKI by both criteria group (n = 104) according to the diagnosis of AKI using the KDIGO and AKIN criteria in the corresponding 205 DDs. We compared the development of delayed graft function (DGF), the change in allograft function, the allograft survival among the three groups. RESULTS: The incidence of DGF was significantly higher in the AKI by KDIGO only and the AKI by both criteria groups than in the non-AKI by both criteria group (P < 0.05 each). But no difference was detected between the AKI by KDIGO only group and the AKI by both criteria group (P > 0.05). Therefore, the KDIGO criteria had a better predictive value for DGF occurrence than the AKIN criteria (Area under the curve = 0.72 versus 0.63, P < 0.05) in Receiver Operation Characteristic analysis. On comparison of allograft function, the AKI by KDIGO only and the AKI by both criteria groups showed a significantly deteriorating pattern by 6 months after KT in comparison with the non-AKI by both criteria group (P < 0.05). However, the differences disappeared at 1 year from KT and long-term allograft survival did not differ among the three groups. AKI stage either by KDIGO or AKIN in DDs did not affect long-term allograft survival in corresponding KTRs as well. CONCLUSIONS: The KDIGO criteria may be more useful for predicting DGF than the AKIN criteria. However, AKI or AKI stage by either criteria in DDs failed to affect long-term allograft outcomes in KTRs.

Cameroon public health sector: shortage and inequalities in geographic distribution of health personnel.

INTRODUCTION: Cameroon is classified by the World Health Organization (WHO) as having a critical shortage of health personnel. This is further complicated by the geographic distributional inequalities of the national health workforce. This shortfall impedes Cameroons' progress of improving the human resources for health (HRH) to meet up with the Millennium Development Goals (MDGs) by 2015. However, it is unknown whether the health workforce of Cameroon is distributed equally across geographic regions. Additionally, indicators other than population levels have not been used to measure health care needs. This study aimed to assess the adequacy, evenness of distribution and challenges faced by the health workforce across the different regions of Cameroon. METHODS: National health personnel availability and distribution were assessed by use of end-of-year census data for 2011 obtained from the MoPH data base. The inequalities and distribution of the workforce were estimated using Gini coefficient and Lorenz curve and linear regression was used to determine the relation between health personnel density and selected health outcomes. Alternative indicators to determine health care needs were illustrated using concentration curves. RESULTS: Significant geographic inequalities in the availability of health workforce exist in Cameroon. Some regions have a higher number of physicians (per person) than others leading to poor health outcomes across the regions. 70 % of regions have a density of health personnel-to-population per 1,000 that is less than 1.5, implying acute shortage of health personnel. Poor working and living conditions, coupled with limited opportunities for career progress accounted for some documented 232 physicians and 205 nurses that migrated from the public sector. Significant distributional inequality was noticed when under-five infant mortality and malaria prevalence rate were used as indicators to measure health care needs. CONCLUSION: Our results show an absolute shortage of public health personnel in Cameroon that is further complicated by the geographic distributional inequalities across the regions of the nation. Cameroon aims to achieve universal health coverage by 2035; to realize this objective, policies targeting training, recruitment, retention and effective deployment of motivated and supported health workforce as well as the development and improvement of health infrastructures remain the major challenge.

Asthma and allergic diseases in preschool children in Korea: findings from the pilot study of the Korean Surveillance System for Childhood Asthma.

OBJECTIVE: This article was intended to introduce the Korean Surveillance System for Childhood Asthma (KSSCA) and also to determine the factors that increase the risk for the development of asthma and allergic diseases in preschool children in Korea based on the study results. METHODS: The KSSCA pilot study was a web-based, cross-sectional survey that sampled 1002 parents with a biological child aged 2-6 years that visited the website and participated in the survey. This website consisted of a questionnaire designed to measure the history and prevalence of asthma and allergic diseases, the characteristics of dwelling, lifestyle, and the socioeconomic status of the subjects. Using logistic regression analysis, odds ratios (ORs) and 95% confidence intervals (CIs) between each risk factor and disease development were calculated. RESULTS: The rate of a family where a child had asthma was 7.4%, while 34.7% and 35.9% for allergic rhinitis and atopic dermatitis, respectively. The OR (95% CI) that a child whose parents had an allergic disease and was also diagnosed with an allergic disease was 2.86 (2.20-3.72). Children who lived in the first floor or basement of apartments had a higher risk of atopic dermatitis, as well as children from socioeconomically vulnerable families. Upon analysis of allergic reaction tests and disease development, it was found that asthma was associated with the positive reaction of cockroaches and food, allergic rhinitis with mites, and atopic dermatitis with mold and food. CONCLUSION: The study indicated that genetic and some environmental or socioeconomic factors might be important in the development of asthma and allergic diseases among preschool children in Korea through the web-survey.

Polycyclic aromatic hydrocarbons exposure in residents living near a cement factory with kilns.

PURPOSE: This study was performed to investigate polycyclic aromatic hydrocarbons (PAHs) exposure in the area around a cement factory with kilns using waste, including refuse plastic fuel. METHODS: Atmospheric total suspended particulates (TSPs) for each of an exposed area and a non-exposed area were collected. Similarly, urine samples were collected from 330 subjects in the exposed area and 126 subjects in the non-exposed area. Gas chromatography with mass spectrometry was used to analyze PAHs in the collected TSP samples and the PAH metabolites, urinary 2-naphthol (2-NAP) and 1-hydroxypyrene (1-OHP), of the residents. The concentrations of urinary 2-NAP and 1-OHP were adjusted by creatinine concentrations. RESULTS: The atmospheric concentrations of PAHs, including naphthalene and pyrene, were higher in the exposed area than those in the non-exposed area. The geometric means (GMs) of the urinary 2-NAP concentrations in the exposed and non-exposed groups without work experience were 4.06 and 1.55 µg/g creatinine, respectively. The GMs of the urinary 1-OHP concentrations were 0.26 and 0.14 µg/g creatinine, respectively. The results showed that the concentrations of PAH metabolites were significantly higher in the exposed group than those in the non-exposed group (p < 0.001). Multiple linear regression analysis with the log-transformed urinary 2-NAP and 1-OHP concentrations and other variables indicated a strong correlation of residence in the exposed area and smoking with an increase in the urinary 2-NAP and 1-OHP concentrations. CONCLUSIONS: In addition to the known risk factors, this study indicated that living near a cement factory with kilns is also a risk factor for PAH exposure.

Discrimination of metal contaminant sources in river sediments influenced by mining and smelting activities using stable Pb and Zn isotopes.

To determine the sources and pathways of lead (Pb) and zinc (Zn) in river sediments contaminated with metals from mining and smelting activities, metal concentrations and Pb and Zn isotope ratios were measured in river water and sediment, and potential metal contaminant samples (imported Zn concentrates, smelting wastes, soils around the smelter, mine ores, and riverside tailings). Zn and cadmium (Cd) concentrations in river water and sediment samples were 30- and 11-25-fold higher, respectively, near the smelter than upstream, while a 6-fold increase in sediment Pb concentrations was detected over the same region. Sediment samples near the smelter (207Pb/206Pb = 0.8638 and 208Pb/206Pb = 2.0960) were observed to have a different Pb isotopic composition from upstream of the smelter (207Pb/206Pb = 0.8322 and 208Pb/206Pb = 2.0502), with δ66Zn values increasing from -0.01 to 0.82‰. Analysis of Pb and Zn isotopes and concentrations revealed that dust-contaminated soils were a major Pb source, and baseline sediments were found to be contaminated by regional mining tailings. For Zn in sediments, the main Zn sources were groundwater-derived Zn (δ66Zn = 1.02 ± 0.43‰, n = 4), dust-contaminated soils (δ66Zn = -0.18 ± 0.08‰, n = 3), and tailings-contaminated sediments (δ66Zn = 0.01 ± 0.07‰, n = 10). Endmember mixing model results showed that dust-contaminated soils contributed 78% and 64% of sediment Pb and Zn, respectively, within 2 km of the Zn smelter, decreasing to negligible levels after 47.1 km downstream. Downstream of the smelter, groundwater-derived Zn contributed 54% of sediment Zn, whereas tailings contaminated sediments contributed 70% and 25% of Pb and Zn, respectively.

MicroRNA miR-252-5p regulates the Notch signaling pathway by targeting Rab6 in Drosophila wing development.

The Notch signaling pathway plays a central role in the development of various organisms. However, dysregulation of microRNAs (miRNAs), which are crucial regulators of gene expression, can disrupt signaling pathways at all stages of development. Although Notch signaling is involved in wing development in Drosophila, the mechanism underlying miRNA-based regulation of the Notch signaling pathway is unclear. Here, we report that loss of Drosophila miR-252 increases the size of adult wings, whereas the overexpression of miR-252 in specific compartments of larval wing discs leads to patterning defects in the adult wings. The miR-252 overexpression-induced wing phenotypes were caused by aberrant Notch signaling with intracellular accumulation of the full-length Notch receptor during development, which could be due to defects in intracellular Notch trafficking associated with its recycling to the plasma membrane and autophagy-mediated degradation. Moreover, we identified Rab6 as a direct target of miR-252-5p; Rab6 encodes a small Ras-like GTPase that regulates endosomal trafficking pathways. Consistent with this finding, RNAi-mediated downregulation of Rab6 led to similar defects in both wing patterning and Notch signaling. Notably, co-overexpression of Rab6 completely rescued the wing phenotype associated with miR-252 overexpression, further supporting that Rab6 is a biologically relevant target of miR-252-5p in the context of wing development. Thus, our data indicate that the miR-252-5p-Rab6 regulatory axis is involved in Drosophila wing development by controlling the Notch signaling pathway.

Algorithm for environmental risk assessment of cosmetics to reduce their environmental impact.

Cosmetics, especially rinse-off personal care products (PCPs), such as shampoo, facial cleanser, and body wash, are composed of various chemicals and are one of the sources of chemicals released into aquatic ecosystems. Therefore, the cosmetic industry strives to reduce the impact of their products on the aquatic environment. In this study, we proposed an algorithm based on persistence, bioaccumulation potential, and toxicity (PBT) for the environmental risk assessment of cosmetics. PBT features are generally used in the evaluation of the environmental impact of chemicals. Based on the PBT assessment, it is possible to predict the short- and long-term effects of chemicals on the environment. Our algorithm derives substance and product scores from PBT features, allowing for the risk assessment of each ingredient in the product. Furthermore, we proposed a criterion for the environmental impact grade through which each component can be classified. We intend to use this grade and factors determined through the algorithm to manufacture products with low environmental impact.

A comparison of triamcinolone acetonide and fibrin glue for seroma prevention in a rat mastectomy model.

BACKGROUND: Seroma formation is one of the most common complications after flap surgery during the postoperative period. Various methods have been developed to overcome this problem, but none of them have been used successfully. Authors used topical triamcinolone acetonide to reduce seroma formation in a rat mastectomy model and compared its effectiveness with fibrin glue. METHODS: In the rat mastectomy model, the authors administered triamcinolone acetonide (experimental group I, n=12), fibrin glue (experimental group II, n=12), and saline (control group, n=12) beneath the skin flap just before closure of the skin. Seroma collections were aspirated and quantified after 7 days, and histologic analysis of the skin flaps and chest walls of the rats was performed. RESULTS: The experimental group I had a reduced mean seroma volume of 1.79±1.32 mL, whereas the experimental group II and control group had mean seroma volumes of 4.04±1.43 mL and 8.51±2.60 mL, respectively (P<0.05). In semiquantitative analysis of inflammation, inflammatory cell count in experimental group I was significantly fewer than in the other 2 groups (P<0.001). In addition, seroma capsule formation did not occur. CONCLUSIONS: Seroma prevention using triamcinolone acetonide is simpler, more economical, and more effective than fibrin glue. In proper concentrations, triamcinolone acetonide can be used to prevent seroma formation in clinical practice.

Development of self-microemulsifying tablets containing dutasteride for enhanced dissolution and pharmacokinetic profile.

This study aimed to develop self-microemulsifying tablets containing the hydrophobic drug dutasteride for easy administration and high in vivo absorption. The candidate lipids and surfactants were formulated into a self-microemulsifying drug delivery system (SMEDDS), and their mean droplet size upon dilution was evaluated. The SMEDDS containing Capmul® MCM, Captex® 355, and Cremophor® EL showed improved dissolution in the gastric medium when compared to the dissolution of the conventional product (Avodart®) and the raw drug. Among the various porous silicon microparticles for solidifying SMEDDS, Neusilin® US2 showed favorable properties in terms of maximum adsorption capacity, powder flow, and compaction. However, the amount of drug released from the solidified SMEDDS after the adsorption process was lower than that of liquid SMEDDS, indicating incomplete desorption. After observing the effect of the solid-to-liquid ratio and pre-filling the pores with blank SMEDDS, complete desorption was obtained when the pores were first adsorbed with polyvinylpyrrolidone. The self-microemulsifying tablets exhibited improved bioavailability (29.9% and 15.2%) compared to the conventional soft gelatin product. Therefore, the proposed system could successfully solubilize the hydrophobic drug while maintaining rapid and complete desorption from the solid carrier, resulting in enhanced in vivo performance.

Prediction of early-stage melanoma recurrence using clinical and histopathologic features.

Prognostic analysis for early-stage (stage I/II) melanomas is of paramount importance for customized surveillance and treatment plans. Since immune checkpoint inhibitors have recently been approved for stage IIB and IIC melanomas, prognostic tools to identify patients at high risk of recurrence have become even more critical. This study aims to assess the effectiveness of machine-learning algorithms in predicting melanoma recurrence using clinical and histopathologic features from Electronic Health Records (EHRs). We collected 1720 early-stage melanomas: 1172 from the Mass General Brigham healthcare system (MGB) and 548 from the Dana-Farber Cancer Institute (DFCI). We extracted 36 clinicopathologic features and used them to predict the recurrence risk with supervised machine-learning algorithms. Models were evaluated internally and externally: (1) five-fold cross-validation of the MGB cohort; (2) the MGB cohort for training and the DFCI cohort for testing independently. In the internal and external validations, respectively, we achieved a recurrence classification performance of AUC: 0.845 and 0.812, and a time-to-event prediction performance of time-dependent AUC: 0.853 and 0.820. Breslow tumor thickness and mitotic rate were identified as the most predictive features. Our results suggest that machine-learning algorithms can extract predictive signals from clinicopathologic features for early-stage melanoma recurrence prediction, which will enable the identification of patients that may benefit from adjuvant immunotherapy.

Prevalence of electrocardiographic findings suggestive of sudden cardiac death risk in 10,867 apparently healthy young Korean men.

BACKGROUND: The objective of this study was to determine the prevalence of electrocardiographic (ECG) findings suggestive of sudden cardiac death risk in apparently healthy young Korean men. METHODS: We administered questionnaires that elicited personal and family histories and performed ECGs on 10,867 male subjects (mean age, 20.9 years). The subjects with abnormal ECG findings underwent echocardiography, a treadmill test, Holter monitoring, a flecainide provocation test, or an electrophysiologic study (EPS) according to the ECG findings and histories. RESULTS: Of the subjects, 5.95% had left ventricular hypertrophy on ECG, but no subjects had hypertrophic cardiomyopathy by echocardiography. The percentage of subjects with a Brugada ECG pattern was 0.90%. We identified one subject with a positive result on the flecainide provocation test. The percentage of subjects with a preexcitation ECG was 0.17%. In two of the subjects, supraventricular tachycardia was induced in the EPS. Of the subjects, 0.05% had epsilon waves, but there were no subjects with arrhythmogenic right ventricular dysplasia/cardiomyopathy by echocardiography. The percentage of subjects with long QT intervals was 0.02%, but there were no arrhythmias on the treadmill test or Holter monitoring. CONCLUSIONS: The prevalence of a Brugada ECG pattern in apparently healthy young men is higher in Korea than other countries.

Daily intakes of naturally occurring radioisotopes in typical Korean foods.

The concentrations of naturally occurring radioisotopes ((232)Th, (228)Th, (230)Th, (228)Ra, (226)Ra, and (40)K) in typical Korean foods were evaluated. The daily intakes of these radioisotopes were calculated by comparing concentrations in typical Korean foods and the daily consumption rates of these foods. Daily intakes were as follows: (232)Th, 0.00-0.23; (228)Th, 0.00-2.04; (230)Th, 0.00-0.26; (228)Ra, 0.02-2.73; (226)Ra, 0.01-4.37 mBq/day; and (40)K, 0.01-5.71 Bq/day. The total daily intake of the naturally occurring radioisotopes measured in this study from food was 39.46 Bq/day. The total annual internal dose resulting from ingestion of radioisotopes in food was 109.83 muSv/y, and the radioisotope with the highest daily intake was (40)K. These values were same level compiled in other countries.

Skin irritation and sensitization potential of oxidative hair dye substances evaluated with in vitro, in chemico and in silico test methods.

Permanent oxidative hair dyes are widely used but their toxicity is not well-established. Here we aimed to evaluate the skin sensitization and irritation of nine hair dye substances (MAP, MRP-N, RS, PAOX, 2,4-DAPE, 2,6-PYR, PPD, Grey HED and PM) permitted for use in EU and Korea, using in vitro and in chemico and in silico test methods. Skin sensitization was evaluated by the KeratinoSens™ assay, Direct Peptide Reactivity Assay (DPRA) and DEREK. Six of nine dyes tested were determined as sensitizers in common. However, the decision for MAP, RS or PAOX was diverged across assays showing 2 positives and 1 negative. Skin irritation of hair dye substances was assessed with or without 6% H2O2 on a reconstructed human epidermis, Epiderm™, which demonstrated that H2O2 increased the skin irritation potential of some hair dyes. PPD and PM were determined to be irritants with H2O2. Epidermal damages by hair dye and H2O2 could be further confirmed through the histology of tissue remaining after MTT assay. Collectively, our study demonstrated that hair dyes possess potential skin sensitization and irritation issues which could be further aggravated by H2O2.

Polydeoxyribonucleotide improves tendon healing following achilles tendon injury in rats.

Tendon injuries are major musculoskeletal disorders. Polydeoxyribonucleotide activates the adenosine receptor subtype A2A, resulting in tissue growth and neogenesis. This experimental study confirms that polydeoxyribonucleotide can improve secretion of various growth factors, promote collagen synthesis, and restore tensile strength of the Achilles tendon in a rat model with Achilles tendon injury. Thirty-six male Sprague-Dawley rats, aged 7 weeks, were divided into two groups, and the Achilles tendon was transected and repaired using the modified Kessler's method. In the experimental group (n = 18), the rats received daily intraperitoneal administration of polydeoxyribonucleotide (8 mg/kg/day for 1, 2, or 4 weeks). The control groups received the same amount of normal saline. The rats were euthanized at 1, 2, and 4 weeks, and tissues from the repair site were harvested. The cross-sectional area of the tendon was significantly increased at 2 and 4 weeks in polydeoxyribonucleotide group (p = 0.008 and p = 0.017, respectively). Moreover, tendons in the polydeoxyribonucleotide group were more resistant to mechanical stress at 2 and 4 weeks (p = 0.041 and p = 0.041, respectively). The staining levels of collagen type I in the experimental group were significantly stronger at 2 and 4 weeks (p = 0.026 and p = 0.009, respectively). Furthermore, higher expression levels of fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor ß1 were detected in the experimental group at 4 weeks (p = 0.041, p = 0.026, and p = 0.041, respectively). This study confirms that polydeoxyribonucleotide can improve the tensile strength of the rats' Achilles tendon following injury and repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1767-1776, 2018.