Validation of the Utility of the Genetically Shared Regions of Chromosomes (GD-ICS) Measuring Method in Identifying Complicated Genetic Relatedness.

BACKGROUND: Relatives share more genomic regions than unrelated individuals, with closer relatives sharing more regions. This concept, paired with the increased availability of high-throughput single nucleotide polymorphism (SNP) genotyping technologies, has made it feasible to measure the shared chromosomal regions between individuals to assess their level of relation to each other. However, such techniques have remained in the conceptual rather than practical stages in terms of applying measures or indices. Recently, we developed an index called "genetic distance-based index of chromosomal sharing (GD-ICS)" utilizing large-scale SNP data from Korean family samples and demonstrated its potential for practical applications in kinship determination. In the current study, we present validation results from various real cases demonstrating the utility of this method in resolving complex familial relationships where information obtained from traditional short tandem repeats (STRs) or lineage markers is inconclusive. METHODS: We obtained large-scale SNP data through microarray analysis from Korean individuals involving 13 kinship cases and calculated GD-ICS values using the method described in our previous study. Based on the GD-ICS reference constructed for Korean families, each disputed kinship was evaluated and validated using a combination of traditional STRs and lineage markers. RESULTS: The cases comprised those A) that were found to be inconclusive using the traditional approach, B) for which it was difficult to apply traditional testing methods, and C) that were more conclusively resolved using the GD-ICS method. This method has overcome the limitations faced by traditional STRs in kinship testing, particularly in a paternity case with STR mutational events and in confirming distant kinship where the individual of interest is unavailable for testing. It has also been demonstrated to be effective in identifying various relationships without specific presumptions and in confirming a lack of genetic relatedness between individuals. CONCLUSION: This method has been proven effective in identifying familial relationships across diverse complex and practical scenarios. It is not only useful when traditional testing methods fail to provide conclusive results, but it also enhances the resolution of challenging kinship cases, which suggests its applicability in various types of practical casework.

Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.

Comparison of Two Variant Analysis Programs for Next-Generation Sequencing Data of Whole Mitochondrial Genome.

BACKGROUND: With advance of next-generation sequencing (NGS) techniques, the need for mitochondrial DNA analysis is increasing not only in the forensic area, but also in medical fields. METHODS: Two commercial programs, Converge Software (CS) and Torrent Variant Caller for variant calling of NGS data, were compared with a considerable amount of sequence data of 50 samples with a homogeneous ethnicity. RESULTS: About 2,300 variants were identified and the two programs showed about 90% of consistency. CS, a dedicated analysis program for mitochondrial DNA, showed some advantages for forensic use. By additional visual inspection, several causes of discrepancy in variant calling results were identified. Application of different notation rules for mitochondrial sequence and the minor allele frequency close to detection threshold were the two most significant reasons. CONCLUSION: With prospective improvement of each program, researchers and practitioners should be aware of characteristics of the analysis program they use and prepare their own strategies to determine variants.

High Risk of Neck-liner Impingement and Notching Observed with Thick Femoral Neck Implants in Ceramic-on-ceramic THA.

BACKGROUND: Recently, impingement between the femoral stem and ceramic liner, which appears as a notch in the stem neck on radiographs, has emerged as a new complication. However, the proportion of impingement, potential risk factors, and related complications are poorly elucidated. QUESTION/PURPOSES: In patients who underwent ceramic-on-ceramic (CoC) THA and had at least 10 years of follow-up, we asked: (1) What proportion had radiographic evidence of stem neck-ceramic liner impingement (notching of the stem), and what implant design, implantation factors, or complications such as ceramic fracture or metallosis are associated with impingement? (2) How common are the complications of noise and ceramic fracture? (3) What are the radiologic changes (including fixation of femoral and acetabular components, osteolysis, and heterotopic ossification) and clinical outcomes as determined by the modified Harris hip score (mHHS) for this cohort? (4) What is the survivorship with implant revision as the endpoint and with reoperation for any reason as the endpoint after CoC THA using a thick-neck stem design? METHODS: Between May 2003 and April 2010, 643 patients underwent primary THA at a tertiary referral hospital. After excluding patients with metal-on-polyethylene and with ceramic-on-polyethylene implants, 621 patients were considered eligible for this study. All patients received the same hemispherical titanium cup, a standard-length tapered titanium stem, and a CoC bearing. Of those, 19% (115) were lost to follow-up before 10 years, and 8% (50) were excluded because they died before the minimum follow-up duration of 10 years, leaving 73% (456) for analysis. Patients had a mean age of 50 ± 14 years and were followed for a median (range) of 13 years (10 to 17). The mean cup abduction was 38° ± 5°, and the mean cup anteversion was 26° ± 7°. To determine the proportion of patients with the neck-liner impingement, we analyzed the plain radiographs of every patient during follow-up to detect notches around the stem. The detection of stem neck notches on the radiographs was reliable (intraobserver reliability: κ = 0.963; p < 0.001 and interobserver reliability: κ = 0.975; p < 0.001). To evaluate factors related to notching, we compared the possible confounding factors including gender, age, BMI, implant position, neck length, and head diameter. Complications such as ceramic fracture, noise, dislocation, and periprosthetic joint infection were recorded. Noise was evaluated via interview and with the Hip Noise Assessment Questionnaire, which assessed the noise qualitatively. For clinical outcome, we assessed the mHHS, which includes pain and function scales (0 [worst] to 100 [best]), every visit. Tilting of at least 4° or migration of at least 4 mm was the criteria for cup loosening; subsidence more than 3 mm, any change in position, or a continuous radiolucent line greater than 2 mm was the criteria for stem loosening. To evaluate osteolysis, we performed CT scans in 57% (262 of 456) of patients. Kaplan-Meier survivorship analysis was performed using the endpoints of survivorship free from implant revision and survivorship free from reoperation for any cause. RESULTS: The proportion of stem neck notching was 11% (49 of 456). There were no differences in cup abduction and anteversion between hips with notches and those without notches. Notched hips were more likely to have 28-mm than 32-mm heads (90% [44 of 49] versus 70% [285 of 407]; odds ratio 3.77 [95% CI 1.46 to 9.73]; p = 0.004). None of the 49 notched hips had a ceramic head or liner fracture or evidence of metallosis. A ceramic head fracture was reported in 2% (9 of 456); all fractures occurred in 28-mm short neck heads. A ceramic liner fracture occurred in 0.2% (1 of 456), and noise was noted in 6% (27 of 456). Acetabular osteolysis developed in 2% (7 of 456). The mHHS was 91 ± 12 points at the final follow-up. The survivorship free from implant revision was 97% (95% CI 96% to 99%), and the survivorship free from reoperation for any cause was 96% (95% CI 95% to 98%) at 13 years. CONCLUSION: The proportion of stems with neck-ceramic liner impingement and ceramic component fracture were unacceptably high after the use of a thick-neck stem design, especially when a 28-mm head was used. We have discontinued the use of this stem design and we recommend that such stems should not be used when CoC bearings are used. As these findings might be generalized to other bearing couples, further studies focused on polyethylene liner wear and local metallosis due to thick stem neck are warranted. LEVEL OF EVIDENCE: Level III, therapeutic study.

Incarcerated diaphragmatic hernia after right hepatectomy: an autopsy case with a review of 45 previous cases.

An iatrogenic diaphragmatic hernia after major hepatic resection is a rare complication. Incarceration of the abdominal organ through a diaphragmatic defect can have a fatal prognosis. Here, we report a case of incarcerated diaphragmatic hernia after right hepatectomy, which was diagnosed only after the autopsy. The deceased, who had right hepatectomy 1 year previously, complained of severe chest pain, and 4 days later was found dead. Localized decomposition in his chest and abdomen suggested a late complication of the surgery because the location was consistent with the prior surgical area. In the autopsy, there was a small defect in his right diaphragm, resulting in the herniation and incarceration of the small intestine. Gross and microscopic findings of the herniated small intestine were consistent with ischemic enteritis. Different from our case, most of the previously reported cases showed a good prognosis after surgical repair, except one lethal one. Even though its overall incidence is very low, an incarcerated diaphragmatic hernia is one of the critical complications of major hepatic resection. The clinicians should warn the patients to avoid preventable morbidity and mortality. Reviewing this fatal complication would be also helpful for forensic pathologists and death investigators.

Improved STR analysis of degraded DNA from human skeletal remains through in-house MPS-STR panel.

DNA analysis of degraded samples and low-copy number DNA derived from skeletal remains, one of the most challenging forensic tasks, is common in disaster victim identification and genetic analysis of historical materials. Massively parallel sequencing (MPS) is a useful technique for STR analysis that enables the sequencing of smaller amplicons compared with conventional capillary electrophoresis (CE), which is valuable for the analysis of degraded DNA. In this study, 92 samples of human skeletal remains (70+ years postmortem) were tested using an in-house MPS-STR system designed for the analysis of degraded DNA. Multiple intrinsic factors of DNA from skeletal remains that affect STR typing were assessed. The recovery of STR alleles was influenced more by DNA input amount for amplification rather than DNA degradation, which may be attributed from the high quantity and quality of libraries prepared for MPS run. In addition, the higher success rate of STR typing was achieved using the MPS-STR system compared with a commercial CE-STR system by providing smaller sized fragments for amplification. The results can provide constructive information for the analysis of degraded sample, and this MPS-STR system will contribute in forensic application with regard to skeletal remain sample investigation.

A case of 46,XX/46,XX chimerism in a phenotypically normal woman.

Chimerism is the presence of two genetically different cell lines within a single organism, which is rarely observed in humans. Usually, chimerism in the human body is revealed by the finding of an abnormal phenotype during a medical examination or is unexpectedly detected in routine genetic analysis. However, the incidence or underlying mechanism of chimerism remains unclear due to the lack of information on this infrequent biological event. A phenotypically normal woman with a 46,XX karyotype and atypical short tandem repeat (STR) allelic patterns observed in DNA analysis was investigated with various genetic testing methods, including STR typing based on capillary electrophoresis and massively parallel sequencing, genome-wide SNP array, and a differentially methylated parental allele assay (DMPA). The proband's parents were not available for testing to discriminate the parental allelic contribution, but the parents' alleles were recovered from testing the proband's siblings. Based on the results consistently found in multiple analyses using STR and single nucleotide polymorphism (SNP) polymorphism markers, dispermic fertilization was suggested as the underlying mechanism. The application of various molecular genetic testing methods was used to elucidate the chimerism observed in the proband in this study. In the future, the development of novel genetic markers or techniques, such as DMPA, may have potential use in the investigation of chimerism.

The diagnostic value of SPECT/CT in predicting the occurrence of osteonecrosis following femoral neck fracture: a prospective cohort study.

BACKGROUNDS: One of the most significant complications after a femoral neck fracture is osteonecrosis of the femoral head (ONFH). The concomitant use of single-photon emission computed tomography (SPECT) with computed tomography (CT) increases the sensitivity for detecting the anatomic location and severity of ONFH. In this study, we evaluated the diagnostic value of SPECT/CT for the occurrence of ONFH by quantifying the perfusion status of the femoral head. METHODS: A total of 30 patients who had multiple pinnings for femur neck fractures were included in this study. We classified the perfusion status into three groups: normal perfusion, decreased perfusion, and avascular groups, and compared the occurrence of femoral head necrosis between them. For quantitative analysis, we evaluated the uptake ratio of both femur heads (head-to-head uptake ratio). If the patient's contralateral hip was incomparable, we measured the uptake ratio from the superior dome of the ipsilateral acetabulum (head-to-acetabulum uptake ratio). RESULTS: Twenty-four patients out of 30 achieved bone union, whereas the others developed ONFH. When the population was divided into intact and defective perfusion groups on scintigraphy, the sensitivity, specificity, and accuracy of the test were 83.3, 75.0, and 76.7%, respectively. The mean head-to-head uptake ratio value with a 95% confidence interval (CI) was 1.10 (95% CI: 0.85-1.36). In the osteonecrosis group, the mean value of the head-to-head uptake ratio was 0.33 (95% CI: 0.28-0.38). In contrast, the ratio was 1.30 (95% CI: 1.03-1.57) in the non-osteonecrosis group, demonstrating a significant difference in the uptake ratio (P < 0.001). When the cutoff value of the uptake ratio was set to 0.5, both the sensitivity and specificity were 100%. There was also a significant difference in the head-to-acetabulum uptake ratio between the two groups (P <  0.001). CONCLUSIONS: SPECT/CT was useful in evaluating the perfusion status of the femoral head, showing high accuracy in predicting the occurrence of avascular necrosis. To demonstrate the reliability and validity of SPECT/CT, further prospective studies on a larger scale are warranted.

The Effect of Povidone-Iodine Lavage in Preventing Infection After Total Hip and Knee Arthroplasties: Systematic Review and Meta-Analysis.

BACKGROUND: Dilute povidone-iodine (PI) lavage, a simple disinfection method, could reduce postoperative infection risk. However, there is no clinical consensus regarding its efficacy in total joint arthroplasties (TJAs). This systematic review and meta-analysis evaluated PI lavage's efficacy in preventing infection after TJA. METHODS: MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before November 22, 2019, that compared postoperative infection rates in patients who underwent TJA with or without PI lavage before wound closure. Subgroup analyses were designed to identify the differences in infection site (overall or deep), type of surgery (total hip arthroplasty or total knee arthroplasty), time until diagnosis of infection (3 or 12 months postoperatively), and primary/aseptic revision arthroplasties. RESULTS: We included 7 studies with 31,213 TJA cases, comprising 8861 patients who received PI lavage and 22,352 who did not. Pooled odds ratio for overall infection rate for the PI and non-PI lavage groups was 0.67 (95% confidence interval, 0.38-1.19, P = .17) and for the deep infection rate was 0.90 (95% confidence interval, 0.27-2.98, P = .86). Subgroup analyses revealed no differences in postoperative infection rates between the PI and non-PI lavage groups in terms of total hip arthroplasty and total knee arthroplasty, diagnosis of infection at 3 and 12 months postoperatively, or primary and aseptic revision arthroplasties. CONCLUSION: We detected no differences in the overall postoperative infection rates between the PI and non-PI lavage groups before wound closure in TJA including all studies in the subgroup analyses.

Low skeletal muscle mass and radiographic osteoarthritis in knee, hip, and lumbar spine: a cross-sectional study.

BACKGROUND: Although several studies have shown that low skeletal muscle mass is correlated with knee osteoarthritis, no studies have investigated the correlation between skeletal muscle mass and hip and lumbar spine osteoarthritis (OA). AIM: This study aimed to delineate the relationship between low skeletal muscle mass and radiographic OA (ROA) of the knee, hip, and lumbar spine. METHODS: This is a cross-sectional study using the public data obtained from the Fifth Korean National Health and Nutrition Examination Survey (2010-2011). We included subjects aged ≥ 50 years who completed the surveys (3813 subjects). ROA was assessed by knee, hip, and lumbar spine radiographs and defined as Kellgren/Lawrence (KL) grade of at least 2 in the knee and lumbar spine, whereas KL grade ≥ 1 in the hip. Multivariate logistic regression analyses were performed to evaluate the effects of low skeletal muscle mass on radiographic joint degeneration. RESULTS: Appendicular skeletal muscle mass (ASM) was higher in subjects with healthy joints than in subjects with knee and lumbar spine ROA (18.9 ± 0.1 kg vs. 17.1 ± 0.2 kg, P < 0.0001 and 18.6 ± 0.1 kg vs. 17.4 ± 0.2 kg, P < 0.0001, respectively), whereas it was higher in those with ROA than in those with healthy hip (17.9 ± 0.1 kg vs. 19.1 ± 0.2 kg P < 0.0001). On multivariate logistic regression analysis, lower skeletal muscle mass independently associated with knee ROA [odds ratio (OR) 1.348; 95% confidence interval (CI) 1.037-1.752]. However, it was inversely associated with lumbar spine ROA (OR 0.786; 95% CI 0.623-0.991). CONCLUSION: Low skeletal muscle mass was independently associated with knee ROA alone, whereas it was inversely associated with lumbar spine ROA. These opposite results might originate from measuring the area of ASM.

Assessment of mitochondrial DNA heteroplasmy detected on commercial panel using MPS system with artificial mixture samples.

Mitochondrial DNA (mtDNA) heteroplasmy is a potential genetic marker for forensic mtDNA analysis as well as phylogenic studies. Frequency of mtDNA heteroplasmy has been investigated in different populations through massively parallel sequencing (MPS) analysis, revealing various levels of frequency based on different MPS systems. For accurate heteroplasmy identification, it is essential to explore reliable detection threshold on various MPS systems. In addition, software solutions and pipelines need to be evaluated to analyze data effectively. In this study, heteroplasmy analysis was conducted on a commercially available mtDNA analysis system developed for forensic caseworks with artificially mixed DNA samples known for ratios and variant positions for assessment. mtDNA heteroplasmy > 10% was detectable with Torrent Variant Caller (TVC) while lower levels were identified using GeneMarker® HTS specialized software for minor variant detection. This study implies that analytical parameters and tools need to be optimized and evaluated for low-level heteroplasmy identification. Automated system with simple and efficient workflow is needed for forensic caseworks.

Detection of Innate and Artificial Mitochondrial DNA Heteroplasmy by Massively Parallel Sequencing: Considerations for Analysis.

BACKGROUND: Mitochondrial heteroplasmy, the co-existence of different mitochondrial polymorphisms within an individual, has various forensic and clinical implications. But there is still no guideline on the application of massively parallel sequencing (MPS) in heteroplasmy detection. We present here some critical issues that should be considered in heteroplasmy studies using MPS. METHODS: Among five samples with known innate heteroplasmies, two pairs of mixture were generated for artificial heteroplasmies with target minor allele frequencies (MAFs) ranging from 50% to 1%. Each sample was amplified by two-amplicon method and sequenced by Ion Torrent system. The outcomes of two different analysis tools, Torrent Suite Variant Caller (TVC) and mtDNA-Server (mDS), were compared. RESULTS: All the innate heteroplasmies were detected correctly by both analysis tools. Average MAFs of artificial heteroplasmies correlated well to the target values. The detection rates were almost 90% for high-level heteroplasmies, but decreased for low-level heteroplasmies. TVC generally showed lower detection rates than mDS, which seems to be due to their own computation algorithms which drop out some reference-dominant heteroplasmies. Meanwhile, mDS reported several unintended low-level heteroplasmies which were suggested as nuclear mitochondrial DNA sequences. The average coverage depth of each sample placed on the same chip showed considerable variation. The increase of coverage depth had no effect on the detection rates. CONCLUSION: In addition to the general accuracy of the MPS application on detecting heteroplasmy, our study indicates that the understanding of the nature of mitochondrial DNA and analysis algorithm would be crucial for appropriate interpretation of MPS results.

Influence of immunologic status on age prediction using signal joint T cell receptor excision circles.

Age estimation based on quantifying signal joint T cell receptor excision circle (sjTREC) in T cells has been established to be a promising approach in forensic practice and demonstrated in different ethnic groups. Considering that the homeostasis of T cells carrying sjTRECs is closely related to the immunologic status of a person, it is important to investigate the influence of various immunologic statuses on the age estimation model. In this study, quantification of sjTREC contents was performed for groups of people with various immune system statuses, and the result showed less correlation with chronological age (r 2 = 0.424) than in the healthy group (r 2 = 0.648). The simulation model indicated that this influence could increase the range of prediction in the age estimation model, and the mean absolute deviation (MAD) between chronological age and predicted age. Through this study, it was demonstrated that immunologic status is a factor that affects the accuracy of age prediction using sjTREC quantification.

Entire Mitochondrial DNA Sequencing on Massively Parallel Sequencing for the Korean Population.

Mitochondrial DNA (mtDNA) genome analysis has been a potent tool in forensic practice as well as in the understanding of human phylogeny in the maternal lineage. The traditional mtDNA analysis is focused on the control region, but the introduction of massive parallel sequencing (MPS) has made the typing of the entire mtDNA genome (mtGenome) more accessible for routine analysis. The complete mtDNA information can provide large amounts of novel genetic data for diverse populations as well as improved discrimination power for identification. The genetic diversity of the mtDNA sequence in different ethnic populations has been revealed through MPS analysis, but the Korean population not only has limited MPS data for the entire mtGenome, the existing data is mainly focused on the control region. In this study, the complete mtGenome data for 186 Koreans, obtained using Ion Torrent Personal Genome Machine (PGM) technology and retrieved from rather common mtDNA haplogroups based on the control region sequence, are described. The results showed that 24 haplogroups, determined with hypervariable regions only, branched into 47 subhaplogroups, and point heteroplasmy was more frequent in the coding regions. In addition, sequence variations in the coding regions observed in this study were compared with those presented in other reports on different populations, and there were similar features observed in the sequence variants for the predominant haplogroups among East Asian populations, such as Haplogroup D and macrohaplogroups M9, G, and D. This study is expected to be the trigger for the development of Korean specific mtGenome data followed by numerous future studies.

A collaborative exercise on DNA methylation based body fluid typing.

A collaborative exercise on DNA methylation based body fluid identification was conducted by seven laboratories. For this project, a multiplex methylation SNaPshot reaction composed of seven CpG markers was used for the identification of four body fluids, including blood, saliva, semen, and vaginal fluid. A total of 30 specimens were prepared and distributed to participating laboratories after thorough testing. The required experiments included four increasingly complex tasks: (1) CE of a purified single-base extension reaction product, (2) multiplex PCR and multiplex single-base extension reaction of bisulfite-modified DNA, (3) bisulfite conversion of genomic DNA, and (4) extraction of genomic DNA from body fluid samples. In tasks 2, 3 and 4, one or more mixtures were analyzed, and specimens containing both known and unknown body fluid sources were used. Six of the laboratories generated consistent body fluid typing results for specimens of bisulfite-converted DNA and genomic DNA. One laboratory failed to set up appropriate conditions for capillary analysis of reference single-base extension products. In general, variation in the values obtained for DNA methylation analysis between laboratories increased with the complexity of the required experiments. However, all laboratories concurred on the interpretation of the DNA methylation profiles produced. Although the establishment of interpretational guidelines on DNA methylation based body fluid identification has yet to be performed, this study supports the addition of DNA methylation profiling to forensic body fluid typing.

Geijigajakyak decoction inhibits the motility and tumorigenesis of colorectal cancer cells.

BACKGROUND: Recent studies report that inflammatory diseases of the large intestine are associated with colorectal cancer. Geijigajakyak Decoction (GJD) has antispasmodic and anti-inflammatory effects on the gastrointestinal tract. Thus, in light of the connection between chronic bowel inflammation and colorectal cancer (CRC), we asked whether GJD inhibits colorectal tumorigenesis. METHODS: The effects of GJD on the viability and proliferation of CRC cells were evaluated using MTT and BrdU assays, respectively. The motility of CRC cells was examined by a Transwell migration/invasion assay and immunoblot analysis was used to examine the signaling pathways associated with migration. A syngeneic Balb/c mice allograft model, in which CT26 cells were injected into the dorsum, was used to evaluate the anti-tumor effects of GJD in vivo. RESULTS: GJD had no cytotoxic effects against HCT116 CRC cells, although it did inhibit their proliferation. GJD inhibited the migration of HCT116 cells, and suppressed the invasion of HCT116, Caco2, and CSC221 CRC cells. In addition, GJD downregulated the expression of p-JNK and p-p38 MAPK, which are downstream signaling molecules associated with invasiveness. Furthermore, oral administration of GJD (333 mg/kg, twice a day) inhibited tumor growth in a mouse xenograft model. CONCLUSIONS: GJD inhibited the motility of human CRC cells and suppressed tumorigenesis in a mouse model. These results suggest that GJD warrants further study as a potential adjuvant anti-cancer therapy.

Bearing Change to Metal-On-Polyethylene for Ceramic Bearing Fracture in Total Hip Arthroplasty; Does It Work?

We evaluated the short-term to midterm results of reoperation with bearing change to metal-on-polyethylene (MoP) after ceramic bearing fracture in ceramic-on-ceramic total hip arthroplasty. Nine third-generation ceramic bearing fractures (6 heads and 3 liners) were treated with bearing change to MoP. Mean age at reoperation was 52.7 years. Mean follow-up was 4.3 years. During follow-up, 2 of 3 liner-fractured hips and 1 of 6 head-fractured hips showed radiologic signs of metallosis and elevated serum chromium levels. Re-reoperation with bearing rechange to a ceramic head was performed for the hips with metallosis. One liner-fractured hip had periprosthetic joint infection. Dislocation occurred in 3 hips. From our experience, bearing change to MoP is not a recommended treatment option for ceramic bearing fracture in total hip arthroplasty.

Alumina-alumina total hip arthroplasty for the sequelae of Legg-Calve-Perthes disease: A comparative study with adult-onset osteonecrosis.

BACKGROUND: Total hip arthroplasty (THA) for sequelae of Legg-Calve-Perthes disease (LCPD) involves specific concerns for deformity, leg length discrepancy (LLD), and relatively young age. Excellent long-term outcome has been proven after Alumina-Alumina (Al-Al) THA for relatively young patients, however, there was no study for Al-Al THA for LCPD sequelae. The aim of this study is to evaluate the results of Al-Al THA for LCPD sequelae and to compare the results with those for adult-onset ONFH, in which THA is necessitated in relatively young age and excellent long term outcome has been proven after Al-Al THA. METHODS: Between 1997 and 2007, 41 Al-Al THA were performed in 37 patients with LCPD sequelae and followed-up for mean 10.4 years. Mean age at THA was 43.6 years. Using the propensity score matching, 41 THAs in 37 patients were identified from 339 hips in 256 patients with ONFH. The medical record and radiographic data was retrospectively reviewed. RESULTS: During follow-up, no revision was performed in both group. Harris Hip Score increased from 66.7 ± 17.4 points to 96.8 ± 6.8 points in LCPD group and from 47.9 ± 18.4 to 96.6 ± 4.6 in ONFH group. LLD decreased significantly from 2.0 ± 1.2 cm to 0.2 ± 0.9 cm in LCPD group and from 0.5 cm to 0.1 cm in ONFH group. Postoperative LLD showed no difference in both groups. As for complication, rate of intraoperative femoral fracture was significantly higher in LCPD group than in ONFH group. Other postoperative complication showed no difference. CONCLUSIONS: Despite the higher rate of intraoperative femoral crack, outcomes of Al-Al THA for LCPD were comparable to those for ONFH. Similar to ONFH, Al-Al THA may be a reliable treatment option for LCPD.

Kinship Testing Based on SNPs Using Microarray System.

BACKGROUND: Kinship testing using biallelic SNP markers has been demonstrated to be a promising approach as a supplement to standard STR typing, and several systems, such as pyrosequencing and microarray, have been introduced and utilized in real forensic cases. The Affymetrix microarray containing 169 autosomal SNPs developed for forensic application was applied to our practical case for kinship analysis that had remained inconclusive due to partial STR profiles of degraded DNA and possibility of inbreeding within the population. CASE REPORT: 169 autosomal SNPs were typed on array with severely degraded DNA of two bone samples, and the kinship compared to genotypes in a reference database of their putative family members. RESULTS: Two bone samples remained unidentified through traditional STR typing with partial profiles of 10 or 14 of 16 alleles. Because these samples originated from a geographically isolated population, a cautious approach was required when analyzing and declaring true paternity only based on PI values. In a supplementary SNP typing, 106 and 78 SNPs were obtained, and the match candidates were found in each case with improved PI values than using only STRs and with no discrepant SNPs in comparison. CONCLUSION: Our case showed that the utility of multiple SNPs on array is expected in practical forensic caseworks with an establishment of reference database.