RPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination.

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.

The synaptonemal complex central region modulates crossover pathways and feedback control of meiotic double-strand break formation.

The synaptonemal complex (SC) is a proteinaceous structure that mediates homolog engagement and genetic recombination during meiosis. In budding yeast, Zip-Mer-Msh (ZMM) proteins promote crossover (CO) formation and initiate SC formation. During SC elongation, the SUMOylated SC component Ecm11 and the Ecm11-interacting protein Gmc2 facilitate the polymerization of Zip1, an SC central region component. Through physical recombination, cytological, and genetic analyses, we found that ecm11 and gmc2 mutants exhibit chromosome-specific defects in meiotic recombination. CO frequencies on a short chromosome (chromosome III) were reduced, whereas CO and non-crossover frequencies on a long chromosome (chromosome VII) were elevated. Further, in ecm11 and gmc2 mutants, more double-strand breaks (DSBs) were formed on a long chromosome during late prophase I, implying that the Ecm11-Gmc2 (EG) complex is involved in the homeostatic regulation of DSB formation. The EG complex may participate in joint molecule (JM) processing and/or double-Holliday junction resolution for ZMM-dependent CO-designated recombination. Absence of the EG complex ameliorated the JM-processing defect in zmm mutants, suggesting a role for the EG complex in suppressing ZMM-independent recombination. Our results suggest that the SC central region functions as a compartment for sequestering recombination-associated proteins to regulate meiosis specificity during recombination.

Effect of Postoperative Femoral Neck Shaft Angle on Femoral Head Sphericity Following Proximal Femoral Osteotomy in Legg-Calve-Perthes Disease.

BACKGROUND: Herein, we aimed to examine the relationship between the postoperative neck shaft angle (NSA) and the Stulberg outcome at skeletal maturity in patients with Legg-Calvé-Perthes disease (LCPD) who underwent proximal femoral varus osteotomy (PFVO) and to determine the optimal angle of varization. METHODS: In this retrospective study, we analyzed the data of 90 patients aged older than 6 years at the time of diagnosis with LCPD who underwent PFVO at our institution between 1979 and 2014. Univariate and multivariate logistic regression analyses were used to examine the effects of variables on the sphericity of the femoral head at skeletal maturity, including the age at onset, sex, stage at operation, extent of epiphyseal involvement and epiphyseal collapse, presence of specific epiphyseal, metaphyseal, and acetabular changes, and postoperative NSA. The sphericity of the femoral head on the final plain follow-up radiographs of the hip joint at skeletal maturity was assessed using the Stulberg classification. Cases of spherical femoral head (Stulberg I or II) were rated as good, whereas those of ovoid or flat femoral head (Stulberg III, IV, or V) were rated as bad. RESULTS: The mean age at diagnosis was 7.93 (range, 6.0-12.33) years. The average follow-up period was 10.11 (range, 5.25-22.92) years. The pre and postoperative mean NSAs were 137.31±6.86 degrees (range, 115.7-158 degrees) and 115.7±9.83 degrees (range, 88.6-137.6 degrees), respectively. The age at diagnosis, lateral pillar classification, and postoperative NSA were found to be closely related to the sphericity of the femoral head at skeletal maturity. Patients with a postoperative NSA of <105 degree or more than 125 degree were less likely to have a spherical femoral head. CONCLUSIONS: Our study showed that patients with a postoperative NSA between 105 and 125 degrees were more likely to have a spherical femoral head. When performing PFVO in patients with LCPD, reasonable varus angulation of PFVO should be taken into consideration for the success of the operation. LEVEL OF EVIDENCE: Level III retrospective cohort study.

The logic and mechanism of homologous recombination partner choice.

Recombinational repair of spontaneous double-strand breaks (DSBs) exhibits sister bias. DSB-initiated meiotic recombination exhibits homolog bias. Physical analysis in yeast reveals that, in both cases, the recombination reaction intrinsically gives homolog bias. From this baseline default, cohesin intervenes to confer sister bias, likely independent of cohesion. In meiosis, cohesin's sister-biasing effect is counteracted by RecA homolog Rad51 and its mediators, plus meiotic RecA homolog Dmc1, which thereby restore intrinsic homolog bias. Meiotic axis complex Red1/Mek1/Hop1 participates by cleanly switching recombination from mitotic to meiotic mode, concomitantly activating Dmc1. We propose that a Rad51/DNA filament at one DSB end captures the intact sister, creating an anchor pad. This filament extends across the DSB site on the intact partner, precluding intersister strand exchange, thus forcing use of the homolog. Cohesin and Dmc1 interactively modulate this extension, with program-appropriate effects. In accord with this model, Rad51-mediated recombination in vivo requires the presence of a sister.

The added prognostic value of radiological phenotype combined with clinical features and molecular subtype in anaplastic gliomas.

PURPOSE: To determine whether radiological phenotype can improve the predictive performance of the risk model based on molecular subtype and clinical risk factors in anaplastic glioma patients. METHODS: This retrospective study was approved by our institutional review board with waiver of informed consent. MR images of 86 patients with pathologically diagnosed anaplastic glioma (WHO grade III) between January 2007 and February 2016 were analyzed according to the Visually Accessible Rembrandt Images (VASARI) features set. Significant imaging findings were selected to generate a radiological risk score (RRS) for overall survival (OS) and progression-free survival (PFS) using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The prognostic value of RRS was evaluated with multivariate Cox regression including molecular subtype and clinical risk factors. The C-indices of multivariate models with and without RRS were compared by bootstrapping. RESULTS: Eight VASARI features contributed to RRS for OS and six contributed to PFS. Multifocality or multicentricity was the most influential feature, followed by restricted diffusion. RRS was significantly associated with OS and PFS (P < .001), as well as age and molecular subtype. The multivariate model with RRS demonstrated a significantly higher predictive performance than the model without (C-index difference: 0.074, 95% confidence interval [CI]: 0.031, 0.148 for OS; C-index difference: 0.054, 95% CI: 0.014, 0.123 for PFS). CONCLUSION: RRS derived from VASARI features was an independent predictor of survival in patients with anaplastic gliomas. The addition of RRS significantly improved the predictive performance of the molecular feature based model.

Rad61/Wpl1 (Wapl), a cohesin regulator, controls chromosome compaction during meiosis.

Meiosis-specific cohesin, required for the linking of the sister chromatids, plays a critical role in various chromosomal events during meiotic prophase I, such as chromosome morphogenesis and dynamics, as well as recombination. Rad61/Wpl1 (Wapl in other organisms) negatively regulates cohesin functions. In this study, we show that meiotic chromosome axes are shortened in the budding yeast rad61/wpl1 mutant, suggesting that Rad61/Wpl1 negatively regulates chromosome axis compaction. Rad61/Wpl1 is required for efficient resolution of telomere clustering during meiosis I, indicating a positive effect of Rad61/Wpl1 on the cohesin function required for telomere dynamics. Additionally, we demonstrate distinct activities of Rad61/Wpl1 during the meiotic recombination, including its effects on the efficient processing of intermediates. Thus, Rad61/Wpl1 both positively and negatively regulates various cohesin-mediated chromosomal processes during meiosis.

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure.

Rec8 is a prominent component of the meiotic prophase chromosome axis that mediates sister chromatid cohesion, homologous recombination and chromosome synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show here that such cleavage plays no detectable role for chromosomal events of prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24 or 29 alanine substitutions. A distinct 'separation of function' phenotype is revealed. In the mutants, axis formation and recombination initiation are normal, as is non-crossover recombination; in contrast, crossover (CO)-related events are defective. Moreover, the severities of these defects increase coordinately with the number of substitution mutations, consistent with the possibility that global phosphorylation of Rec8 is important for these effects. (iii) We have analyzed the roles of three kinases that phosphorylate Rec8 during prophase. Timed inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8 phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not. Our results suggest that Rec8's prophase function, independently of cohesin cleavage, contributes to CO-specific events in conjunction with the maintenance of homolog bias at the leptotene/zygotene transition of meiotic prophase.

MGEScan: a Galaxy-based system for identifying retrotransposons in genomes.

UNLABELLED: : MGEScan-long terminal repeat (LTR) and MGEScan-non-LTR are successfully used programs for identifying LTRs and non-LTR retrotransposons in eukaryotic genome sequences. However, these programs are not supported by easy-to-use interfaces nor well suited for data visualization in general data formats. Here, we present MGEScan, a user-friendly system that combines these two programs with a Galaxy workflow system accelerated with MPI and Python threading on compute clusters. MGEScan and Galaxy empower researchers to identify transposable elements in a graphical user interface with ready-to-use workflows. MGEScan also visualizes the custom annotation tracks for mobile genetic elements in public genome browsers. A maximum speed-up of 3.26× is attained for execution time using concurrent processing and MPI on four virtual cores. MGEScan provides four operational modes: as a command line tool, as a Galaxy Toolshed, on a Galaxy-based web server, and on a virtual cluster on the Amazon cloud. AVAILABILITY AND IMPLEMENTATION: MGEScan tutorials and source code are available at http://mgescan.readthedocs.org/ CONTACT: hatang@indiana.edu or syoh@ajou.ac.kr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Feasibility of 3D navigator-triggered magnetic resonance cholangiopancreatography with combined parallel imaging and compressed sensing reconstruction at 3T.

PURPOSE: To assess the feasibility of 3D navigator-triggered magnetic resonance cholangiopancreatography (MRCP) with combined parallel imaging (PI) and compressed sensing (CS). MATERIALS AND METHODS: With Institutional Review Board approval, 30 consecutive patients who underwent MRCP for suspected pancreaticobiliary disease were prospectively recruited. All patients underwent 3D navigator-triggered MRCP with conventional PI alone, and with combined PI and CS using a 3T machine. The acquisition time and relative duct-to-periductal contrast ratios (RCs) at three biliary segments were quantitatively compared between the two MRCP methods. Qualitative image parameters were independently evaluated by two blinded radiologists, and were compared between two methods using the Wilcoxon signed-rank test. RESULTS: The mean acquisition time of MRCP with combined PI and CS (131.87 ± 33.60 sec) was significantly shorter compared with that of MRCP with PI (253.63 ± 56.08 sec; P < 0.001). The RC obtained using MRCP with combined PI and CS at two segments was slightly lower compared to that obtained using MRCP with PI (P = 0.007 and 0.002). Both reviewers found no significant differences in duct visualization, overall image quality, and degree of artifacts between the two methods (P ≥ 0.063; P = 0.637; and P = 0.752, respectively). Lesion conspicuity and confidence in duct abnormalities were comparable between two MRCP methods in both readers (P = 0.564 and P > 0.999). CONCLUSION: Combined PI and CS reconstruction is feasible for 3D navigator-triggered MRCP, providing image quality comparable to that of MRCP with PI alone, in about half the acquisition time. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1289-1297.

Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion.

OBJECTS: To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. METHODS: We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. RESULTS: The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. CONCLUSION: Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. KEY POINTS: • Accuracy of fusion MRI was 79.0% for T stage ≥2 in bladder cancer. • AUC of fusion MRI was 0.793 for T stage ≥2 in bladder cancer. • Diagnostic performance of fusion MRI was comparable with T2WI plus DWI. • As a non-contrast MRI technique, fusion MRI is useful for bladder cancer.

Lack of anti-tumor activity by anti-VEGF treatments in hepatic hemangiomas.

Recently, anti-vascular endothelial growth factor (anti-VEGF) agents have been described in the literature as a valid treatment option for symptomatic liver hemangiomas, but only limited evidence supports this notion. The purpose of this study was to elucidate whether or not the administration of anti-VEGF agents can reliably achieve a size reduction in liver hemangiomas. We examined patients with incidental hemangiomas who received anti-angiogenic agents for the treatment of other malignancies. Our study population consisted of 17 colorectal cancer patients and one lung cancer patient carrying 21 hemangiomas who received bevacizumab, and seven renal cell carcinoma patients carrying nine hepatic hemangiomas who received sunitinib. We have measured the liver hemangioma volume on both the pre-treatment and post-treatment computed tomography images and then calculated the volume alteration rates. No statistically significant difference (P = 0.365) in the volume of the liver hemangiomas was observed before (1.1-168.8 cm(3); mean ± SD 19.8 ± 39.7 cm(3)) or after (1.2-163.6 cm(3); 19.3 ± 38.0 cm(3)) bevacizumab treatment. The volume reduction rate ranged from -35.0 to 11.2 % (mean ± SD -1.3 ± 10.8 %). The sunitinib treatment group also showed no statistically significant difference (P = 0.889) in hemangioma volume before (1.2-6.5 cm(3); 3.0 ± 1.8 cm(3)) or after (1.2-6.0 cm(3); 3.0-1.7 cm(3)) treatment. The volume reduction rate ranged from -13.3 to 7.7 % (median: mean ± SD -2.5 ± 6.6 %). We did not observe liver hemangioma shrinkage after bevacizumab or sunitinib treatment. Our data do not support the application of anti-VEGF agents for the treatment of hepatic hemangiomas.

The association between mental health, chronic disease and sleep duration in Koreans: a cross-sectional study.

BACKGROUND: Sleep duration holds considerable importance as an indicator of mental/physical health. The objective of this study was to investigate the association between sleep duration, mental health, and chronic disease prevalence in Koreans. METHODS: Of 31,596 subjects eligible for the Korean National Health and Nutrition Examination Survey V (2010-2012), 17,638 participants who answered items on sleep duration (aged ≥ 19 yrs) were analyzed in a cross-sectional study. Association between sleep duration, mental health, and chronic disease prevalence was assessed using logistic regression, and adjusted for various socioeconomic and lifestyle characteristics. RESULTS: Short or long sleep duration showed correlations with mental health, and items of significance showed gender-specific patterns. Women displayed significant associations with stress and depressive symptoms, and men with stress, thoughts of suicide, and psychiatric counseling. While stress was related with short sleep duration in both genders, depressive symptoms showed a relationship with long duration in men, and short duration in women. Prevalence of any chronic disease was associated with ≤ 6 h sleep when adjusted for factors including mental health, and among chronic diseases, cancer and osteoarthritis showed associations with short sleep duration, while diabetes and dyslipidemia were associated with normal sleep duration. CONCLUSIONS: Mental health problems were associated with sleep duration with gender-specific patterns. Associations with osteoarthritis, cancer, diabetes, dyslipidemia and abnormal sleep duration persisted after adjustment for mental health.

A Herbal Formula HT048, Citrus unshiu and Crataegus pinnatifida, Prevents Obesity by Inhibiting Adipogenesis and Lipogenesis in 3T3-L1 Preadipocytes and HFD-Induced Obese Rats.

HT048 is a combination composed of Crataegus pinnatifida leaf and Citrus unshiu peel extracts. This study aimed to investigate potential anti-obesity effect of the combination. The 3T3-L1 adipocytes were treated with different doses of HT048 and triglyceride accumulation, glycerol release and adipogenesis-related genes were analyzed. For in vivo study, male Sprague Dawley rats were divided according to experimental diets: the chow diet group, the high-fat diet (HFD) group, the HFD supplemented with orlistat group, the HFD supplemented with HT048 group (0.2% or 0.4%) for 12 weeks. We measured the body weight, serum lipid levels and the expression of genes involved lipid metabolism. HT048 treatment dose-dependently suppressed adipocyte differentiation and stimulated glycerol release. The expressions of PPARγ and C/EBPα mRNA were decreased by HT048 treatment in adipocytes. HT048 supplementation significantly reduced the body and fat weights in vivo. Serum lipid levels were significantly lower in the HT048 supplemented groups than those of the HFD group. Expression of the hepatic lipogenesis-related genes were decreased and expression of the ß-oxidation-related genes were increased in rats fed HT048 compared to that of animals fed HFD. These results suggest that HT048 has a potential benefit in preventing obesity through the inhibition of lipogenesis and adipogenesis.

Development of a novel PLDLA/ß-TCP composite-based biodegradable anterior cervical plate and screw system.

We investigated the effectiveness and safety of a new composite-based biodegradable anterior cervical plate/screw (ACPS) system for the anterior cervical discectomy and fusion (ACDF) fixation. A biocomposite in combination with 30 wt% ß-tricalcium phosphate (ß-TCP; a biodegradable ceramic having osteoconductive ability) and 70 wt% poly-l/d-lactide copolymer (PLDLA; a biodegradable polymer) was developed and used in the ACPS device, comprising one plate and four screws for fixation. Based on a literature review, a clinically required period of performance maintenance was set as 16 weeks, and to verify the performance for a period of 16 weeks or more, the test was conducted for 26 weeks. Following ISO 13781:2017 testing protocols, an in vitro degradation test was performed to verify the performance and evaluate the decomposition characteristics of the biodegradable ACPS system. Using an animal model as a preclinical investigation, the prepared ACPS device was implanted into five mongrel dogs weighing over 30 kg to evaluate the detachment prevention effect of the ACPS system on polyether ether ketone (PEEK) cage after ACDF. By week 26, the molecular weight was decreased by 45.35% for the plate and 52.56% for the screw; the bending strength of the plate was decreased by approximately 26.2% when compared with the initial stage. The torsional yield strength and pullout strength of the screw was increased by 52.31% and 5.3%, respectively by week 2 and then subsequently decreased until week 26. No detachment or dislocation of the inserted PEEK cage was observed for 26 weeks in vivo study. These findings recommend that the ACPS system might be a promising biodegradable tool for the fixation of interbody implants and supporting the fusion in an ACDF model. Furthermore, additional clinical trials are planned for the future.

Bone grafting for periprosthetic bone cysts following total ankle arthroplasty.

Aims: The purpose of this study was to assess the success rate and functional outcomes of bone grafting for periprosthetic bone cysts following total ankle arthroplasty (TAA). Additionally, we evaluated the rate of graft incorporation and identified associated predisposing factors using CT scan. Methods: We reviewed a total of 37 ankles (34 patients) that had undergone bone grafting for periprosthetic bone cysts. A CT scan was performed one year after bone grafting to check the status of graft incorporation. For accurate analysis of cyst volumes and their postoperative changes, 3D-reconstructed CT scan processed with 3D software was used. For functional outcomes, variables such as the Ankle Osteoarthritis Scale score and the visual analogue scale for pain were measured. Results: Out of 37 ankles, graft incorporation was successful in 30 cases. Among the remaining seven cases, four (10.8%) exhibited cyst re-progression, so secondary bone grafting was needed. After secondary bone grafting, no further progression has been noted, resulting in an overall 91.9% success rate (34 of 37) at a mean follow-up period of 47.5 months (24 to 120). The remaining three cases (8.1%) showed implant loosening, so tibiotalocalcaneal arthrodesis was performed. Functional outcomes were also improved after bone grafting in all variables at the latest follow-up (p < 0.05). The mean incorporation rate of the grafts according to the location of the cysts was 84.8% (55.2% to 96.1%) at the medial malleolus, 65.1% (27.6% to 97.1%) at the tibia, and 81.2% (42.8% to 98.7%) at the talus. Smoking was identified as a significant predisposing factor adversely affecting graft incorporation (p = 0.001). Conclusion: Bone grafting for periprosthetic bone cysts following primary TAA is a reliable procedure with a satisfactory success rate and functional outcomes. Regular follow-up, including CT scan, is important for the detection of cyst re-progression to prevent implant loosening after bone grafting.

A dose-dependent bimodal switch by homologous Aux/IAA transcriptional repressors.

Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic cells. However, a dose-dependent functional switch of homologous transcriptional repressors has rarely been reported. Here, we show that SHY2, an Auxin/Indole-3-Acetic Acid (Aux/IAA) repressor, exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcription in Arabidopsis, whereas other Aux/IAA homologs consistently repress the auxin responses. The corepressor (TOPLESS [TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently repressing Aux/IAA. The switch of a single amino-acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and biological roles in auxin responses. Based on these data, we propose a model whereby competition between homologous repressors with different corepressor-binding affinities could generate a bimodal output at the transcriptional and developmental levels.

Long-term dispersion stability and adhesion promotion of aqueous Cu nano-ink for flexible printed electronics.

Aqueous Cu nanoparticles are synthesized using a reducing agent and surface capping molecule which prevents the interparticular agglomeration and surface oxidation. Aqueous conductive nano ink is prepared using the resulting Cu nanoparticles and conductive Cu layers are prepared via a wet coating process. The conductive Cu layers, metalized by annealing at 300 degrees C under vacuum atmosphere, exhibit excellent electrical resistivity, showing values as low as 12 microomega cm. The long-term dispersion stability for three months is monitored through an investigation on the rheological behavior of the conductive nano ink and the resistivity variation of the conductive Cu layer. The adhesion property of the conductive Cu layer is dramatically improved when using a primer-treated polyimide film, whereas the conductive Cu layer completely peels off on a pristine polyimide film. The epoxy-contained primer plays a critical role as an intermediary between the aqueous Cu nano ink and the polyimide film.

Evaluation of poly(lactic-co-glycolic acid) plate and screw system for bone fixation.

In this study, we investigated the efficacy and safety of the recently developed modifiable bioabsorbable plates and screws, which are made of PLGA [poly(lactic-co-glycolic acids)]. An in vitro extract test and a mammalian erythrocyte micronucleus test revealed that neither cytotoxicity nor genotoxicity was observed with the plates and screws tested in this study. An in vivo mandible fracture model in rabbit was introduced to evaluate the in vivo efficacy and of the PLGA-based plates and screws. At 4, 6, 8, and 10 weeks after implantation, tissue specimens were taken from the implanted sites of the rabbits and a histologic analysis was performed for each of the specimens. After 4 weeks, the plate was covered by connective tissues and severe chronic active inflammation in soft tissue was observed. After 6 weeks, the inflammation decreased and some of the specimens exhibited new bone formation around the periosteum. After 8 and 10 weeks, new bone formation was observed with all samples, where almost no severe inflammation was involved, implying the healing of the fracture. Given these, it can be suggested that the biodegradable plate and screw system that we evaluated in this study is effective for treatment of mandible fracture, one of the regions under a high load-bearing condition. The adjustment process and the long-term follow-up study are in progress for clinical application of the plate and screw system introduced in this study.

Evaluation of the effect of particulate matter on construction accidents using relative probability.

PM10 is known to have a great adverse effect on the human body. However, there is a lack of research analyzing the impact of PM10 on the occurrence of accidents. Accordingly, the purpose of this study is to analyze the correlation between PM10 and accidents in the construction industry and to present a new concentration group to manage accidents caused by PM10 in the construction industry. This study was conducted in the following four stages. (i) collection of data, (ii) classification of data, (iii) relative probability analysis, and (iv) modified PM10 group classification. The main results of this study are as follows. When the frequency analysis of the traditional method was conducted, 3,721 accidents occurred at a PM10 concentration of 32 µg/m3. However, as a result of the relative probability analysis presented in this study, it was confirmed that the relative accident probability increased as the PM10 concentration increased. In addition, the current PM10 concentration is presented by the WHO in six groups from a health perspective. However, in this study, the newly proposed PM10 group was classified into three groups from the perspective of the probability of construction accidents. The group proposed in this study is not from a health perspective but a group for managing construction site accidents. The contribution of this study was to confirm that PM10 also affects accidents occurring at construction sites, and the impact of PM10 on accidents was quantitatively analyzed through the relative probability analysis presented in this study.

Mitochondrial Toxic Effects of Antiepileptic Drug Valproic Acid on Mouse Kidney Stem Cells.

Valproic acid (VPA) is a histone deacetylase inhibitor that is used mainly as an antiepileptic and anticonvulsant drug. The side effects of VPA usually appears as hepatic injury and various metabolic disorders. On the other hand, it is rarely reported to cause kidney injury. Despite the many studies on the influence of VPA exposure on the kidneys, the specific mechanism remains unclear. This study examined the changes after VPA treatment to the mouse kidney stem cells (mKSCs). VPA triggers an increase in mitochondrial ROS, but there was no change in either mitochondrial membrane potential or the mitochondrial DNA copy number in mKSCs. The VPA treatment increased the mitochondrial complex III but decreased complex V significantly compared to the DMSO treatment as a control. The inflammatory marker (IL-6) and the expression of the apoptosis markers (Caspase 3) and were increased by VPA. In particular, the expression of the podocyte injury markers (CD2AP) was increased significantly. In conclusion, VPA exposure has adverse effects on mouse kidney stem cells.