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Purpose: To determine whether additional stem extension for stability is necessary, we performed mid-term follow-up of patients who had been managed with 5-mm metal block augmentation for a tibial defect, where tibial prosthesis was fixed using bone cement without stem extension. Also, we evaluated clinical and radiologic results including survival rate of patients without stem extension. Methods: We retrospectively analyzed patients with tibial bone defect, had undergone primary total knee arthroplasty, and had been treated with 5-mm metal block augmentation without stem extension between March 2003 and September 2013. Among 74 patients (80 cases), 47 patients (52 cases) were followed up for at least 5 years. Results: Mean flexion contracture improved from 8.8° (0–40°) preoperatively to 0.4° (−5° to 15°) at final follow-up (P < 0.01), but there was no significant change in the mean angle of great flexion: 124.6° (75–150°) preoperatively and 126.2° (90–145°) at final follow-up (P = 0.488). Mean range of motion improved from 115.8° (35–150°) preoperatively to 125.5° (90–145°) at final follow-up (P < 0.01). Mean knee score improved from 38.7 points (0–66 points) preoperatively to 93.2 points (79–100 points) at final follow-up (P < 0.01), and mean functional score also improved from 50.4 points (10–70 points) preoperatively to 81.8 points (15–100 points) at final follow-up (P < 0.01). The mean postoperative Western Ontario and McMaster University osteoarthritis score was 19.5 points (0–66.0 points). The mean femorotibial angle was corrected from 9.0° varus (23.0° varus–6.3° valgus) preoperatively to 5.5° valgus (2.2° varus–11.1° valgus) at final follow-up (P < 0.01). There was no change in the mean β-angle, which was 90.7° (87.2–94.9°) immediately postoperative and 90.8° (87.2–94.9°) at final follow-up (P = 0.748) and in the mean δ-angle, which was 86.2° (81.3–90.0°) immediately postoperative and 87.2° (83.1–96.5°) at final follow-up (P = 0.272). Radiolucent lines (RLL) were observed in ten cases (26.3%), and the mean RLL scores at final follow-up were 0.34 points (0–3 points) in the anteroposterior view and 0.42 points (0–6 points) in the lateral view. Scores for the RLL were ≤ 4 points in 36 cases, 5–9 points in two cases. Revision surgery due to aseptic loosening (three cases) is rarely required, and the Kaplan–Meier survival rate at 10 postoperative years was 96.4% Conclusion: When performing 5-mm metal block augmentation for a proximal tibial defect, no additional tibial stem extension can be a good surgical option for the stability of tibial prosthetic construct and mid-term clinical and radiologic results. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Background: Human adipose-derived stem cells (hADSCs) have been used in various fields of tissue engineering because of their promising therapeutic efficacy. However, the stemness of hADSCs cannot be maintained for long durations, and their therapeutic cellular functions, such as paracrine factor secretion decrease during long-term cell culture. To facilitate the use of long-term-cultured hADSCs (L-ADSCs), we designed a novel therapeutic anti-senescence ion-delivering nanocarrier (AIN) that is capable of recovering the therapeutic properties of L-ADSCs. In the present study, we introduced a low-pH-responsive ion nanocarrier capable of delivering transition metal ions that can enhance angiogenic paracrine factor secretion from L-ADSCs. The AINs were delivered to L-ADSCs in an intracellular manner through endocytosis. Results: Low pH conditions within the endosomes induced the release of transition metal ions (Fe) into the L-ADSCs that in turn caused a mild elevation in the levels of reactive oxygen species (ROS). This mild elevation in ROS levels induced a downregulation of senescence-related gene expression and an upregulation of stemness-related gene expression. The angiogenic paracrine factor secretion from L-ADSCs was significantly enhanced, and this was evidenced by the observed therapeutic efficacy in response to treatment of a wound-closing mouse model with conditioned medium obtained from AIN-treated L-ADSCs that was similar to that observed in response to treatment with short-term-cultured adipose-derived stem cells. Conclusions: This study suggests a novel method and strategy for cell-based tissue regeneration that can overcome the limitations of the low stemness and therapeutic efficacy of stem cells that occurs during long-term cell culture. [ABSTRACT FROM AUTHOR]

Background: Megakaryocytes (MKs) are platelet precursors, which arise from hematopoietic stem cells (HSCs). While MK lineage commitment and differentiation are accompanied by changes in gene expression, many factors that modulate megakaryopoiesis remain to be uncovered. Replication initiation determinant protein (RepID) which has multiple histone-code reader including bromodomain, cryptic Tudor domain and WD40 domains and Cullin 4-RING E3 ubiquitin ligase complex (CRL4) recruited to chromatin mediated by RepID have potential roles in gene expression changes via epigenetic regulations. We aimed to investigate whether RepID-CRL4 participates in transcriptional changes required for MK differentiation. Methods: The PCR array was performed using cDNAs derived from RepID-proficient or RepID-deficient K562 erythroleukemia cell lines. Correlation between RepID and DAB2 expression was examined in the Cancer Cell Line Encyclopedia (CCLE) through the CellMinerCDB portal. The acceleration of MK differentiation in RepID-deficient K562 cells was determined by estimating cell sizes as well as counting multinucleated cells known as MK phenotypes, and by qRT-PCR analysis to validate transcripts of MK markers using phorbol 12-myristate 13-acetate (PMA)-mediated MK differentiation condition. Interaction between CRL4 and histone methylation modifying enzymes were investigated using BioGRID database, immunoprecipitation and proximity ligation assay. Alterations of expression and chromatin binding affinities of RepID, CRL4 and histone methylation modifying enzymes were investigated using subcellular fractionation followed by immunoblotting. RepID-CRL4-JARID1A-based epigenetic changes on DAB2 promoter were analyzed by chromatin-immunoprecipitation and qPCR analysis. Results: RepID-deficient K562 cells highly expressing MK markers showed accelerated MKs differentiation exhibiting increases in cell size, lobulated nuclei together with reaching maximum levels of MK marker expression earlier than RepID-proficient K562 cells. Recovery of WD40 domain-containing RepID constructs in RepID-deficient background repressed DAB2 expression. CRL4A formed complex with histone H3K4 demethylase JARID1A in soluble nucleus and loaded to the DAB2 promoter in a RepID-dependent manner during proliferation condition. RepID, CRL4A, and JARID1A were dissociated from the chromatin during MK differentiation, leading to euchromatinization of the DAB2 promoter. Conclusion: This study uncovered a role for the RepID-CRL4A-JARID1A pathway in the regulation of gene expression for MK differentiation, which can form the basis for the new therapeutic approaches to induce platelet production. EhctJ7T1-GG5oU5fji2odB Video Abstract [ABSTRACT FROM AUTHOR]

Background: Breast cancer brain metastasis (BCBM) is a growing therapeutic challenge and clinical concern. Stromal cancer-associated fibroblasts (CAFs) are crucial factors in the modulation of tumorigeneses and metastases. Herein, we investigated the relationship between the expression of stromal CAF markers in metastatic sites, platelet-derived growth factor receptor-beta (PDGFR-β), and alpha-smooth muscle actin (α-SMA) and the clinical and prognostic variables in BCBM patients. Methods: Immunohistochemistry (IHC) of the stromal expression of PDGFR-β and α-SMA was performed on 50 cases of surgically resected BCBM. The expression of the CAF markers was analyzed in the context of clinico-pathological characteristics. Results: Expression of PDGFR-β and α-SMA was lower in the triple-negative (TN) subtype than in other molecular subtypes (p = 0.073 and p = 0.016, respectively). And their expressions were related to a specific pattern of CAF distribution (PDGFR-β, p = 0.009; α-SMA, p = 0.043) and BM solidity (p = 0.009 and p = 0.002, respectively). High PDGFR-β expression was significantly related to longer recurrence-free survival (RFS) (p = 0.011). TN molecular subtype and PDGFR-β expression were independent prognostic factors of recurrence-free survival (p = 0.029 and p = 0.030, respectively) and TN molecular subtype was an independent prognostic factor of overall survival (p < 0.001). Conclusions: Expression of PDGFR-β in the stroma of BM was associated with RFS in BCBM patients, and the clinical implication was uniquely linked to the low expression of PDGFR-β and α-SMA in the aggressive form of the TN subtype. [ABSTRACT FROM AUTHOR]

Background: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family. Methods: In this study, we tested genetic predispositions by analyzing the family-specific variants in familial breast cancer. Using exome sequencing, we analyzed three families and 22 probands with BRCAx (BRCA-negative) familial breast cancer. Results: We observed the presence of family-specific, novel, deleterious germline variants in each family. Of the germline variants identified, many were shared between the disease-affected family members of the same family but not found in different families, which have their own specific variants. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation. Conclusions: Our study demonstrates that the predispositions for many BRCAx familial breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect many new predispositions. [ABSTRACT FROM AUTHOR]

Background: BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability. Methods: Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members. Results: We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo. Conclusion: Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western population. Although genetic factors are considered to contribute to CLL etiology, at present genomic aberrations identified in CLL are limited compared with those identified in other types of leukemia, which raises the question of the degree of genetic influence on CLL. We performed a high-resolution genome scanning study to address this issue. Findings: Using the restriction paired-end-based Ditag Genome Scanning technique, we analyzed three primary CLL samples at a kilobase resolution, and further validated the results in eight primary CLL samples including the two used for ditag collection. From 51,632 paired-end tags commonly detected in the three CLL samples representing 5% of the HindIII restriction fragments in the genomes, we identified 230 paired-end tags that were present in all three CLL genomes but not in multiple normal human genome reference sequences. Mapping the full-length sequences of the fragments detected by these unmapped tags in seven additional CLL samples confirmed that these are the genomic aberrations caused by small insertions and deletions, and base changes spreading across coding and non-coding regions. Conclusions: Our study identified hundreds of loci with insertion, deletion, base change, and restriction site polymorphism present in both coding and non-coding regions in CLL genomes, indicating the wide presence of small genomic aberrations in chronic lymphocytic leukemia. Our study supports the use of a whole genome sequencing approach for comprehensively decoding the CLL genome for better understanding of the genetic defects in CLL. [ABSTRACT FROM AUTHOR]

Background: Colloid cyst (CC) is a rare and benign cyst found in the third ventricle near the foramen of Monro. Although the role of surgical resection is well established in symptomatic large-sized CC, it remains debatable whether surgical removal of CC with no symptoms or minimal symptoms is necessary.Case Presentation: A 49-year-old male patient visited our institute for incidentally detected intracranial mass. MRI demonstrated typical, 12 mm-sized CC located in the third ventricle. It was noticed that the cyst spontaneously decreased in size from 12 mm to 4 mm on MRI at 18 months after the first visit.Conclusion: Although spontaneous regression is a very rare phenomenon in CC, regular imaging study and frequent neurologic examination can be an alternative option for well-selected, asymptomatic cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the objective and subjective long-term clinical outcomes of tendon transfer and tendon graft for extensor tendon ruptures in rheumatoid hands.Methods: We evaluated the long-term clinical outcomes of tendon transfer and tendon graft for extensor tendon ruptures in rheumatoid hands of 37 patients (43 hands) followed up for a mean of 14 years (range, 10-21 years).Results: The mean time from rupture to surgery was 13.1 weeks (range, 3-48 weeks). The mean extension lag of the metacarpophalangeal joint was 8.7° (range, 0-40°), the mean pulp-to-palm distance was 0.4 cm (range, 0-3 cm), and the mean overall satisfaction rate was 86.5 (range, 70-100). There were no significant differences in clinical outcomes between tendon transfers and tendon grafts. There was a significant correlation between extension lag of the metacarpophalangeal joint and overall satisfaction rate (R2 = 0.155; p = 0.009). Time to surgery was significantly correlated with extension lag of the metacarpophalangeal joint (R2 = 0.437; p = 0.001) in the tendon graft group.Conclusions: Both tendon transfer and tendon graft for extensor tendon ruptures in rheumatoid hands achieve satisfactory results that are maintained for an average of 14 years. In cases of tendon graft, the time to surgery should be considered, and there is concern over extension lag of MP joint.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Background: To compare the dosimetric profiles of volumetric modulated arc therapy (VMAT) plans using the fast-rotating O-ring linac (the Halcyon system) based on a dual-layer stacked multi-leaf collimator and helical tomotherapy (HT) for nasopharyngeal cancer (NPCa).Methods: For 30 NPCa patients, three sets of RT plans were generated, under the same policy of contouring and dose constraints: HT plan; Halcyon VMAT plan with two arcs (HL2arc); and Halcyon VMAT plan with four arcs (HL4arc), respectively. The intended dose schedule was to deliver 67.2 Gy to the planning gross target volume (P-GTV) and 56.0 Gy to the planning clinical target volume (P-CTV) in 28 fractions using the simultaneously integrated boost concept. Target volumes and organ at risks dose metrics were evaluated for all plans. Normal tissue complication probabilities (NTCP) for esophagus, parotid glands, spinal cord, and brain stem were compared.Results: The HT plan achieved the best dose homogeneity index for both P_GTV and P_CTV, followed by the HL4arc and L2arc plans. No significant difference in the dose conformity index (CI) for P_GTV was observed between the HT plan (0.80) and either the HL2arc plan (0.79) or the HL4arc plan (0.83). The HL4arc plan showed the best CI for P_CTV (0.88), followed by the HL2arc plan (0.83) and the HT plan (0.80). The HL4arc plan (median, interquartile rage (Q1, Q3): 25.36 (22.22, 26.89) Gy) showed the lowest Dmean in the parotid glands, followed by the HT (25.88 (23.87, 27.87) Gy) and HL2arc plans (28.00 (23.24, 33.99) Gy). In the oral cavity (OC) dose comparison, the HT (22.03 (19.79, 24.85) Gy) plan showed the lowest Dmean compared to the HL2arc (23.96 (20.84, 28.02) Gy) and HL4arc (24.14 (20.17, 27.53) Gy) plans. Intermediate and low dose regions (40-65% of the prescribed dose) were well fit to the target volume in HL4arc, compared to the HT and HL2arc plans. All plans met the dose constraints for the other OARs with sufficient dose margins. The between-group differences in the median NTCP values for the parotid glands and OC were < 3.47% and < 1.7% points, respectively.Conclusions: The dosimetric profiles of Halcyon VMAT plans were comparable to that of HT, and HL4arc showed better dosimetric profiles than HL2arc for NPCa. [ABSTRACT FROM AUTHOR]

Background: Human adipose-derived stem cells (hADSCs) have been widely used for regenerative medicine because of their therapeutic efficacy and differentiation capacity. However, there are still limitations to use them intactly due to some difficulties such as poor cell engraftment and viability after cell transplantation. Therefore, techniques such as photobiomodulation (PBM) are required to overcome these limitations. This study probed improved preclinical efficacy of irradiated hADSCs and its underlying molecular mechanism. Methods: hADSCs were irradiated with green organic light-emitting diodes (OLEDs). Treated cells were analyzed for mechanism identification and tissue regeneration ability verification. Expression levels of genes and proteins associated with photoreceptor, cell proliferation, migration, adhesion, and wound healing were evaluated by performing multiple assays and immunostaining. Excision wound models were employed to test in vivo therapeutic effects. Results: In vitro assessments showed that Opsin3 (OPN3) and OPN4 are both expressed in hADSCs. However, only OPN4 was stimulated by green OLED irradiation. Cell proliferation, migration, adhesion, and growth factor expression in treated hADSCs were enhanced compared to control group. Conditioned medium containing paracrine factors secreted from irradiated hADSCs increased proliferation of human dermal fibroblasts and normal human epidermal keratinocytes. Irradiated hADSCs exerted better wound healing efficacy in vivo than hADSCs without OLED irradiation. Conclusions: Our study introduces an intracellular mechanism of PBM in hADSCs. Our results revealed that photoreceptor OPN4 known to activate Gq-protein and consequently lead to reactive oxygen species production responded to OLED irradiation with a wavelength peak of 532 nm. In conclusion, green OLED irradiation can promote wound healing capability of hADSCs, suggesting that green OLED has potential preclinical applications. [ABSTRACT FROM AUTHOR]

FKBP5 encodes the FK506 binding protein 5, a glucocorticoid receptor (GR) binding protein known to play an important role in the physiological stress response. However, results from previous studies examining the association between common variants of FKBP5 and stress have been inconsistent. To investigate whether the loss of FKBP5 affects the stress response, we examined the behavior of mice following the induction of chronic restraint stress between homozygous wild-type and Fkbp5 knock-out mice. After 21 days of exposure to restraint stress, WT mice showed anhedonia, a core symptom of depression, which could be measured by a sucrose preference test. However, Fkbp5-deficient mice did not exhibit significant depressive-like behavior compared to the WT after exposure to chronic restraint stress. To investigate the molecular mechanism underlying stress resilience, we performed RNA sequencing analysis. The differentially expressed gene (DEG) analysis showed that chronic stress induced changes in various biological processes involved in cell-cell adhesion and inflammatory response. Weighted gene co-expression network analysis identified 60 characteristic modules that correlated with stress or the FKBP5 genotype. Among them, M55 showed a gene expression pattern consistent with behavioral changes after stress exposure, and the gene ontology analysis revealed that this was involved in nervous system development, gland morphogenesis, and inflammatory response. These results suggest that FKBP5 may be a crucial factor for the stress response, and that transcriptomic data can provide insight into stress-related pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). Methods: Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis. Results: High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175–2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC. Conclusions: Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation. [ABSTRACT FROM AUTHOR]

Background: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family.Methods: In this study, we tested genetic predispositions by analyzing the family-specific variants in familial breast cancer. Using exome sequencing, we analyzed three families and 22 probands with BRCAx (BRCA-negative) familial breast cancer.Results: We observed the presence of family-specific, novel, deleterious germline variants in each family. Of the germline variants identified, many were shared between the disease-affected family members of the same family but not found in different families, which have their own specific variants. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation.Conclusions: Our study demonstrates that the predispositions for many BRCAx familial breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect many new predispositions. [ABSTRACT FROM AUTHOR]

Background: BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability.Methods: Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members.Results: We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo.Conclusion: Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells. [ABSTRACT FROM AUTHOR]

Background: The burden of rare diseases on society and patients' families has increased in Korea. However, because of the infrequency of rare diseases, there is a lack of resources and information to address these cases and inadequate funding for the management of these patients. We investigated the average annual cumulative incidence of rare diseases and the trends in annual cumulative incidence from 2011 to 2015 in Korea by using nationwide administrative data from the Korean National Health Insurance Service (NHIS) database for patients registered with the co-payment assistance policy for rare and incurable diseases. Annual cumulative incidence per 10,000,000 was calculated as the total number of newly enrolled patients with the Korean Standard Classification of Diseases (KCD)-7 code in the register, divided by the number of residents with health insurance coverage during each year. We employed simple linear regression analysis to evaluate the trends in annual cumulative incidence/10,000,000 population per year for each rare disease.Results: Overall, national support was provided for patients with 415 KCD codes listed among the targeted rare diseases. The total number of newly enrolled patients with rare diseases was 53,831 in 2011, 52,658 in 2012, 52,955 in 2013, 71,530 in 2014, and 70,559 in 2015. The number of rare diseases with an average annual cumulative incidence of 100/10,000,000 and above was 22 (5.30%), while there were 227 (54.70%) and 148 (35.66%) with an average cumulative incidence between 1/10,000,000 and 100/10,000,000 and less than 1/10,000,000, respectively. The trends in the annual cumulative incidence for 43 rare diseases were statistically significant (p-value < 0.05). The rare diseases for which the incremental trend per year was statistically significant were sarcoidosis (D86, D86.0, D86.1, D86.2, D86.3, D86.8, D86.9), Parkinson's disease (G20), Guillain-Barré syndrome (G61.0), primary biliary cirrhosis (K74.3) and Sjogren's syndrome (M35.0).Conclusions: The number of rare diseases showing an increasing trend in annual cumulative incidence was higher than the number of diseases showing a decreasing trend in annual cumulative incidence. Given that the definition and diagnosis vary based on country and that there is difficulty in identifying valid cases, further detection strategies are needed to establish the incidence of each rare disease considering the importance of establishing a health policy based on the actual incidence of the targeted diseases. [ABSTRACT FROM AUTHOR]

Background: Epithelial-mesenchymal transition (EMT), principally involving an E-cadherin to N-cadherin shift, linked to tumor invasion or metastasis, and therapeutic resistance in various human cancer. A growing body of recent evidence has supported the hypothesis that EMT play a crucial role in the invasive phenotype of gliomas. To evaluate the prognostic connotation of EMT traits in glioma, expression of E-cadherin and N-cadherin was explored in a large series of glioma patients in relation to patient survival rate.Methods: Expressions of E- and N-cadherin were examined using immunohistochemical analysis in 92 glioma cases diagnosed at our hospital. These markers expressions were also explored in 21 cases of fresh frozen glioma samples and in glioma cell lines by Western blot analysis.Results: Expression of E-cadherin was observed in eight cases (8.7%) with weak staining intensity in the majority of the immunoreactive cases (7/8). Expression of N-cadherin was identified in 81 cases (88.0%) with high expression in 64 cases (69.5%). Fresh frozen tissue samples and glioma cell lines showed similar results by Western blot analysis. There was no significant difference in either overall survival (OS) or progression-free survival (PFS) according to E-cadherin expression (P > 0.05). Although the OS rates were not affected by N-cadherin expression levels (P = 0.138), PFS increased in the low N-cadherin expression group with marginal significance (P = 0.058). The survival gains based on N-cadherin expression levels were significantly augmented in a larger series of publicly available REMBRANDT data (P < 0.001).Conclusions: E- and N-cadherin, as representative EMT markers, have limited prognostic value in glioma. Nonetheless, the EMT process in gliomas may be compounded by enhanced N-cadherin expression supported by unfavorable prognostic outcomes. [ABSTRACT FROM AUTHOR]

Background: Chylothorax is a disease that has various causes such as neoplasm, infection, post-surgery trauma, congenital, and venous thrombosis. In approximately 15% of cases of chylothorax, the exact cause is unknown. We report a case of delayed occurrence of right chylothorax in a patient who had multiple segmental ribs fracture on his left side.Case Presentation: A 70-year-old Asian man had a "rollover" accident in which the cultivator he was driving overturned. He presented to our hospital with the main complaint of severe dyspnea. On chest computed tomography, multiple ribs fracture from the first to the eighth rib of the left side of his chest and left-sided hemopneumothorax were presented, but there was no evidence of fracture in the right side of his chest. After closed thoracostomy, an emergency operation for open reduction of fractured ribs was performed. On the fifth postoperative day, tubal feeding was performed. On the next day, a plain chest X-ray image showed pleural effusion of the right side of his chest. After insertion of a small-bore chest tube, 3390 ml of fluid for 24 hours was drained. The body fluid analysis revealed triglycerides levels of 1000 mg/dL, which led to a diagnosis of chylothorax. Although non-oral feeding and total parenteral nutrition were sustained, drain amount was increased on the fifth day. Surgical treatment (thoracoscopic thoracic duct ligation and pleurectomy) was performed in the early phase. The right chest tube was removed on the 14th postoperative day after the effusion completely resolved and he was uneventfully discharged.Conclusions: In this case, as our patient was in old age and had multiple traumas, surgical treatment for chylothorax needed to be performed in the early phase. [ABSTRACT FROM AUTHOR]

Background: Serial interferon-gamma-release-assay (IGRA) result can show variance due to within-subject variation and difference in host immune status, and may be affected by latent tuberculosis infection (LTBI) treatment. We aimed to know the changes in QFT-IT (QuantiFERON-TB Gold In-Tube) results measured at a 4 month interval in end stage renal disease patients and whether these changes were influenced by dialysis method or LTBI treatment.Methods: We prospectively performed serial QFT-IT tests at 4 month interval in 93 end stage renal disease (ESRD) patients on HD (hemodialysis) or PD (peritoneal dialysis). LTBI treatment was given to 18 of 39 patients with initial positive QFT-IT result. Agreement between the two results was estimated for all 93 patients and reversion rates were estimated among the 39 patients with initial positive QFT-IT.Results: Positive QFT-IT at the first and 2(nd) tests were 41.9 and 34.4 %, respectively. The concordance rate between baseline QFT-IT and 2(nd) QFT in 93 ESRD patients was excellent (90.3 %, kappa = 0.80, p < 0.001). Agreement between the first QFT-IT and 2(nd) QFT-IT in HD (95.3 %, kappa = 0.91, p < 0.001) was higher than in PD patients (86.0 %, kappa = 0.69, p < 0.001). Among all ESRD patients, the odds of reversion of QFT-IT was not different in those who were, or were not treated for LTBI [odds ratio = 2.3 (0.5-11.4), p = 0.43].Conclusions: In a group of 93 dialyzed ESRD patients 8.6 % showed reversion of initial positive QFT to negative within 4 months. Reversion seemed not to be associated with LTBI treatment. Further study with larger numbers of patients is needed to investigate the variation of QFT-IT tests in dialyzed ESRD patients. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent evidence suggests that genetic factors are related to the pathogenesis of IgAN. We conducted a genome-wide association study (GWAS) to identify novel genetic susceptibility loci for IgAN in a Korean population. Methods: We enrolled 188 biopsy-confirmed IgAN cases and 455 healthy controls for the discovery stage and explored associations between IgAN and single nucleotide polymorphisms (SNPs) using a customized DNA chip. The significant SNPs from the discovery samples were then selected for replication in an independent cohort with 310 biopsy-confirmed IgAN cases and 438 healthy controls. Results: In the first stage, two SNPs (rs10172700 in LOC105373592 and rs2296136 in ANKRD16) were selected for further association analysis in the next stage. In the replication cohort, rs2296136 in ANKRD16 was significantly associated with IgAN (odds ratio [OR] = 1.40, 95% confidence interval [CI] 0.99–1.98, p = 0.05 in log-additive model, OR = 1.55, 95% CI = 1.06–−2.27, p = 0.02 in dominant model, and OR = 0.70, 95% CI = 0.17–−2.84, p = 0.62 in recessive model). rs2296136 in ANKRD16 also showed a significant association with IgAN in the entire study population combining GWAS and replication study (p = 0.0045 in log-additive model, p = 0.0027 in dominant model, and p = 0.76 in recessive model). Conclusions: The SNPs identified in the present study could be good candidate markers for predicting IgAN in Koreans, although further experimental validation is needed. [ABSTRACT FROM AUTHOR]

Background: The Sapsaree is a breed of dog (Canis familiaris) native to Korea, which became perilously close to extinction in the mid-1980s. However, with systematic genetic conservation and restoration efforts, this breed was rescued from extinction and population sizes have been gradually increasing over the past few decades. The aim of this study was to ascertain novel information about the genetic diversity, population structure, and demographic history of the Sapsaree breed using genome-wide single nucleotide polymorphism data. We characterized the genetic profile of the Sapsaree breed by comparison with seven foreign dog breeds with similar morphologies to estimate genetic differentiation within and among these breeds. Results: The results suggest that Sapsarees have higher genetic variance compared with the other breeds analyzed. The majority of the Sapsarees in this study share a discrete genetic pattern, although some individuals were slightly different, possibly as a consequence of the recent restoration process. Concordant results from analyses of linkage disequilibrium, effective population size, genetic diversity, and population structural analyses illustrate a relationship among the Sapsaree and the Tibetan breeds Tibetan terrier and Lhasa Apso, and a small genetic introgression from European breeds. The effective population size of the Sapsaree has contracted dramatically over the past generations, and is currently insufficient to maintain long-term viability of the breed's genetic diversity. Conclusions: This study provides novel insights regarding the genetic diversity and population structure of the native Korean dog breed Sapsaree. Our results suggest the importance of a strategic and systematic approach to ensure the genetic diversity and the authenticity of the Sapsaree breed. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aβ) protein. Aβ is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme 'transmembrane aspartyl protease, β-secretase'. Inhibition of β-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with Aβ peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, β-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD.Results: Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets.Conclusion: These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered. [ABSTRACT FROM AUTHOR]

Background: Anterior lumbar interbody fusion (ALIF) followed by pedicle screw fixation (PSF) is used to restore the height of the intervertebral disc and provide stability. Recently, stand-alone interbody cage with anterior fixation has been introduced, which eliminates the need for posterior surgery. We compared the biomechanics of the stand-alone interbody cage to that of the interbody cage with additional PSF in ALIF.Methods: A three-dimensional, non-linear finite element model (FEM) of the L2-5 segment was modified to simulate ALIF in L3-4. The models were tested under the following conditions: (1) intact spine, (2) destabilized spine, (3) with the interbody cage alone (type 1), (4) with the stand-alone cage with anterior fixation (SynFix-LR®; type 2), and (5) with type 1 in addition to PSF (type 3). Range of motion (ROM) and the stiffness of the operated level, ROM of the adjacent segments, load sharing distribution, facet load, and vertebral body stress were quantified with external loading.Results: The implanted models had decreased ROM and increased stiffness compared to those of the destabilized spine. The type 2 had differences in ROM limitation of 8%, 10%, 4%, and 6% in flexion, extension, axial rotation, and lateral bending, respectively, compared to those of type 3. Type 2 had decreased ROM of the upper and lower adjacent segments by 3-11% and 3-6%, respectively, compared to those of type 3. The greatest reduction in facet load at the operated level was observed in type 3 (71%), followed by type 2 (31%) and type 1 (23%). An increase in facet load at the adjacent level was highest in type 3, followed by type 2 and type 1. The distribution of load sharing in type 2 (anterior:posterior, 95:5) was similar to that of the intact spine (89:11), while type 3 migrated posterior (75:25) to the normal. Type 2 reduced about 15% of the stress on the lower vertebral endplate compared to that in type 1. The stress of type 2 increased two-fold compared to the stress of type 3, especially in extension.Conclusions: The stand-alone interbody cage can provide sufficient stability, reduce stress in adjacent levels, and share the loading distribution in a manner similar to an intact spine. [ABSTRACT FROM AUTHOR]