Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression.

Genetic or congenital hearing loss still has no definitive cure. Among genes related to genetic hearing loss, the potassium voltage-gated channel subfamily Q member 4 (KCNQ4) is known to play an essential role in maintaining ion homeostasis and regulating hair cell membrane potential. Variants of the KCNQ4 show reductions in the potassium channel activity and were responsible for non-syndromic progressive hearing loss. KCNQ4 has been known to possess a diverse variant. Among those variants, the KCNQ4 p.W276S variant produced greater hair cell loss related to an absence of potassium recycling. Valproic acid (VPA) is an important and commonly used histone deacetylase (HDAC) inhibitor for class I (HDAC1, 2, 3, and 8) and class IIa (HDAC4, 5, 7, and 9). In the current study, systemic injections of VPA attenuated hearing loss and protected the cochlear hair cells from cell death in the KCNQ4 p.W276S mouse model. VPA activated its known downstream target, the survival motor neuron gene, and increased acetylation of histone H4 in the cochlea, demonstrating that VPA treatment directly affects the cochlea. In addition, treatment with VPA increased the KCNQ4 binding with HSP90ß by inhibiting HDAC1 activation in HEI-OC1 in an in vitro study. VPA is a candidate drug for inhibiting late-onset progressive hereditary hearing loss from the KCNQ4 p.W276S variant.

Protective Effect of Avenanthramide-C on Auditory Hair Cells against Oxidative Stress, Inflammatory Cytokines, and DNA Damage in Cisplatin-Induced Ototoxicity.

Cisplatin-induced ototoxicity leads to hearing impairment, possibly through reactive oxygen species (ROS) production and DNA damage in cochlear hair cells (HC), although the exact mechanism is unknown. Avenanthramide-C (AVN-C), a natural, potent antioxidant, was evaluated in three study groups of normal adult C57Bl/6 mice (control, cisplatin, and AVN-C+cisplatin) for the prevention of cisplatin-induced hearing loss. Auditory brainstem responses and immunohistochemistry of outer hair cells (OHCs) were ascertained. Cell survival, ROS production, Phospho-H2AX-enabled tracking of DNA damage-repair kinetics, and expression levels of inflammatory cytokines (TNF-α, IL-1ß, IL6, iNOS, and COX2) were assessed using House Ear Institute-Organ of Corti 1 (HEI-OC1 Cells). In the in vivo mouse model, following cisplatin-induced damage, AVN-C decreased the hearing thresholds and sheltered all cochlear turns' OHCs. In HEI-OC1 cells, AVN-C preserved cell viability and decreased ROS production, whereas cisplatin enhanced both ROS levels and cell viability. In HEI-OC1 cells, AVN-C downregulated IL6, IL-1ß, TNF-α, iNOS, and COX2 production that was upregulated by cisplatin treatment. AVN-C attenuated the cisplatin-enhanced nuclear H2AX activation. AVN-C had a strong protective effect against cisplatin-induced ototoxicity through inhibition of ROS and inflammatory cytokine production and DNA damage and is thus a promising candidate for preventing cisplatin-induced sensorineural hearing loss.

Advanced patient transfer assist device with intuitive interaction control.

This research aims to improve patient transfers by developing a new type of advanced robotic assist device. It has multiple actuated degrees of freedom and a powered steerable base to maximize maneuverability around obstacles. An intuitive interface and control strategy allows the caregiver to simply push on the machine in the direction of desired patient motion. The control integrates measurements of both force and proximity to mitigate any potential large collision forces and provides operators information about obstacles with a form of haptic feedback. Electro-hydraulic pump controlled actuation provides high force density for the actuation. Nineteen participants performed tests to compare transfer operations (transferring a 250-lb mannequin between a wheelchair, chair, bed, and floor) and interaction control of a prototype device with a commercially available patient lift. The testing included a time study of the transfer operations and subjective rating of device performance. The results show that operators perform transfer tasks significantly faster and rate performance higher using the prototype patient transfer assist device than with a current market patient lift. With further development, features of the new patient lift can help facilitate patient transfers that are safer, easier, and more efficient for caregivers.

Theory of mind in children with cochlear implants: Comparison with age- and sex-matched children with normal hearing.

OBJECTIVES/HYPOTHESIS: Theory of mind (ToM) is a crucial ability for maintaining normal social interaction and is directly related to language ability. This study was performed to compare ToM between children with congenital hearing loss who have received cochlear implantation (CI) and those with normal hearing (NH). STUDY DESIGN: Case-control study design. METHODS: One hundred children, aged 2-12 years, participated: 50 children who received CI before 36 months of age (CI group) and one-to-one age- and sex-matched children with normal hearing (NH group). All children underwent tests to examine receptive language ability and ToM. Receptive language was measured using the Receptive and Expressive Vocabulary Test, and ToM was measured using the Theory of Mind Task Battery (ToM-TB). The scores of the two tests were compared between the CI and NH groups. RESULTS: The ToM-TB score in the CI group correlated positively with age and receptive language score. ToM-TB scores did not differ significantly between children in the CI group who achieved normal receptive language and the NH group. However, these children in the CI group scored lower than those in the NH group on some advanced ToM tasks that require the ability to understand second-order emotion, message-desire discrepancy, or second-order false belief. CONCLUSIONS: This case-control study found that children with CI who achieve normal receptive language ability have ToM that is similar to that in children with NH. However, these children exhibited weakness in advanced ToM skills. Interventions to facilitate the development of advanced ToM are needed for children with CI.

Utilization of mixed reality tools in the design of wireless assistive products.

The focus of this paper is on the use of mixed reality tools, specifically augmented reality (AR) andtangible augmented reality (TAR), for evaluating design concepts and soliciting feedback in the design of assistive products. AR and TAR are tools that allow a person to look at an environment where computer-generated elements are dynamically shown alongside real objects. In the context of product development, it allows a 3D model of a product (such as an appliance on a countertop) to be viewed within a real environment. Additionally, it can allow a user to a user to move, operate and interact with the virtual product. Technologies such as AR and TAR have become more accessible to regular users as computing power has become smaller and more powerful. While use by consumers is still somewhat limited, AR is already finding uses in design. This paper will present the current challenges that must be addressed related to using AR including implementation and use of AR by designers, the level of validity in representing a product to users with disabilities, and ability of users to use the technology to provide useful/accurate feedback on a concept compared to manufactured physical prototypes.

Development of Sound Field Audiometry System for Small Audiometric Booths and Comparison of Its Equivalence With Traditional System.

OBJECTIVES: Sound field (SF) audiometry tests are usually conducted in audiometric booths measuring greater than 2×2 m in size. However, most private ENT clinics carry about 1×1-m-sized audiometric booths, making SF audiometry testing difficult to perform. The aims of this study were to develop an SF audiometry system for use in smaller audiometric booths and compare its performance with traditional system. METHODS: The newly developed SF audiometry system can yield an SF signal at a distance of about 30 cm from the subject's ears. Its height can be adjusted according to the subject's head height. We compared SF hearing results between the new SF system and the traditional SF audiometry system in 20 adults with normal hearing (40 ears) and 24 adults with impaired hearing levels (38 ears) who wore hearing aids. Comparative parameters included warble tone audiometry threshold, a speech reception threshold (SRT), and a speech discrimination score (SDS). For statistical analysis, paired t-test was used. The equivalence of both SF systems was tested using two one-sided test (TOST) with a margin of 5 dB (normal hearing participants) and 10 dB (hearing aids wearing participants). RESULTS: Among participants with normal hearing, warble tone hearing thresholds of 0.5, 1, 2, and 4 kHz, average values of these four frequencies, and SRT were similar between the two systems (all P>0.05). Participants with hearing aids showed similar warble tone threshold and SRT (P>0.05) in both systems except for threshold of 4 kHz (P=0.033). SDS was significantly higher in the newly developed system (P<0.05). TOST results showed equivalent SF audiometry results using either system. CONCLUSION: Audiometric results of the newly developed SF audiometry system were equivalent to those of a traditional system. Therefore, the small SF audiometry system can be used at small audiometric booths present in most private ENT clinics.

Teaching Universal Design in the Early Stages of a Design Curriculum: Involving End Users in a Student Project.

Introducing Universal Design (UD) early in the design curriculum provides design students with a basic foundational understanding of the Universal Design principles and processes. Additionally, by guiding students on the application of the UD principles and process in designing a solution to a real-world need, students experienced the challenges and tradeoffs such design requires. In Spring 2016, teams of Sophomore-level Industrial Design students were assigned an educational exercise to solve a real-world problem of barriers experienced by people with disabilities during grocery shopping. Students employed the UD process in designing a shopping device enhanced with mobile/wireless enabled features that would be usable by a wide range of users. The shopping device had to function effectively and meet the needs of the general public (men, women, tall, short, etc) while simultaneously meeting the needs of users who have other physical and perceptual limitations such as mobility limitations and visual impairments. In this paper, we discuss the key steps of the educational exercise, as well as lessons learned for improving the exercise for future courses.

Potential barriers in adoption of a medication compliance neckwear by elderly population.

This paper presents results of a study to understand potential barriers of geriatric population with chronic illnesses towards adoption of a wireless wearable medication compliance system in the form of a neckwear. The neck being a critical part of the body can serve as a good source to collect a range of health related information on an individual. The primary research question we investigate here is this: for individuals with chronic illnesses especially amongst the elderly population how willing are they to adopt a neckwear system if it can monitor and mitigate health complications? Elderly patients deal with constant prescription changes over time and this further degrades medication compliance and thereby complicates an already wavering health status. A semi-structured interview was conducted to better understand medication adherence, regimen and issues encountered using reminder devices with the goal of informing the design of a new compliance monitoring system. Results show that preserving health is one of the primary concerns of people living with chronic illnesses therefore there is a promising potential for seamless adoption of a neckwear medication compliance system with additional capabilities to monitor general health status.

Expression of vascular endothelial growth factor (VEGF) and its soluble receptor-1 in endometriosis.

The aim of this study is to evaluate the expression of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) in peritoneal fluid (PF), peritoneal endometriotic lesions and eutopic endometrial tissues of patients with endometriosis. Peritoneal fluid, peritoneal endometriotic lesions and eutopic endometrial samples from patients with endometriosis, and peritoneal fluid, peritoneal tissue and endometrial samples from patients without endometriosis were obtained during an operative laparoscopy. The mean PF concentrations of VEGF and sFlt-1 were significantly higher in patients with endometriosis than in the controls. In the peritoneal tissue, the expressions of VEGF and sFlt-1 were significantly higher, where the expression of sFlt-1 in endometrium was significantly lower in patients with endometriosis. These findings indicate that not only abnormal expressions of angiogenic factors, but also aberrant expressions of antiangiogenic factors in the peritoneal and endometrial environment seem to be involved in the pathogenesis of endometriosis.

Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of red ginseng (RG) on menopausal symptoms and cardiovascular risk factors in postmenopausal women. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted with postmenopausal women between the ages of 45 and 60 years. A total of 72 women were randomly assigned to either an RG group (supplemented with 3 g of RG, including 60 mg of ginsenosides, per day) or a placebo group for 12 weeks. We analyzed changes in menopausal symptoms (the Kupperman index and the menopause rating scale), cardiovascular risk factors (lipid profiles, high-sensitivity C-reactive protein, and carotid intima-media thickness), and serum estradiol levels from baseline to 12 weeks. RESULTS: Significant improvements in the Kupperman index (P = 0.032) and in the menopause rating scale (P = 0.035) scores were observed in the RG group compared with the placebo group. Total cholesterol (P = 0.009) and low-density lipoprotein cholesterol (P = 0.015) significantly decreased in the group receiving RG. The RG group also showed a significant decrease in carotid intima-media thickness (P = 0.049). Serum estradiol levels were not influenced by RG supplementation. CONCLUSIONS: RG could be an attractive herbal dietary supplement for relieving menopausal symptoms and conferring favorable effects on markers of cardiovascular disease in postmenopausal women.

Transcriptome analysis of the effects of gomisin a on the recovery of carbon tetrachloride-induced damage in rat liver.

Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230 down-regulated genes due to the effects of gomisin A on recovery of carbon tetrachloride-induced rat liver damage. For functional characterization of these genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biochemical pathways analyses were performed. Many up-regulated or down-regulated genes were related to cell cycle or focal adhesion and cell death genes, respectively. Our microarray experiment indicated that the liver repair mechanism induced by gomisin A was strongly associated with increased gene expressions related to cell cycle and suppression of the gene expression related in cell death.

Pap smear screening for small cell carcinoma of the uterine cervix: a case series and review of the literature.

OBJECTIVE: Small cell carcinoma of the uterine cervix (SMCC) is extremely rare, and an aggressive disease that proliferates rapidly. It was often reported that the diagnostic accuracy of cytologic smears in diagnosing SMCC was low. This is a report of the Severance Hospital experience with the patients suffering from SMCC. METHODS: Twenty-seven patients with small cell carcinoma of the uterine cervix were diagnosed and treated at the Severance Hospital from November 1991 to January 2010. The data were analyzed retrospectively, based on the available charts and pathology reports. Various fields, such as chief complaints and symptoms present at first clinic visit, age, International Federation of Obstetrics and Gynecology (FIGO) clinical stage, treatment modality, the 5-year overall survival rate, and recurrence rate were investigated. RESULTS: Among the 27 patients diagnosed with small cell carcinoma of the uterine cervix, 18 of them (66.7%) presented with symptoms, including vaginal bleeding, at the first clinic visit, and the remaining 9 patients (33.3%) showed abnormal Pap smear screening in the process of their routine health check-up. The median age of the patients was 54 years (range, 24 to 77 years). FIGO stage IIB was the most common stage (11 of 27 patients). The 5-year overall survival rate of 21 patients, who could be followed up, was 57.2%. Six patients showed recurrence after remission, and the mean disease free interval of them was 9.2 months (range, 6 to 11 months). Abnormal Pap smear screening results of 9 patients was investigated, and the diagnostic accuracy of the cytologic findings was 22.2%. CONCLUSION: Our study was consistent with the concept that Pap smear screening might not be helpful in early diagnosis of SMCC considering its low diagnostic accuracy. Further large-scale multicenter prospective studies are definitely needed in order to produce abundant information about optimal therapy and diagnosis.

Single port transumbilical laparoscopic surgery for adnexal lesions: a single center experience in Korea.

OBJECTIVES: The purpose of this study was to demonstrate the feasibility of single port transumbilical laparoscopic surgery (SPLS) for the treatment of adnexal lesions. METHODS: We have performed SPLS to treat adnexal lesions using a single three-channel port system with a wound retractor and surgical glove since October 2008. All patients who underwent SPLS for adnexal lesions between October 2008 and September 2009 were included in the study. We retrospectively reviewed their medical records and analyzed demographic data and surgical outcomes including age, medico-surgical illness, surgical indications, operative times and pathologic results. RESULTS: Eighty-six patients underwent SPLS for adnexal lesions. The median age of the patients was 31 years (range 14-78 years), the median body mass index was 21.0 kg/m(2) (range 16.7-32.2 kg/m(2)), and the median operation time was 64.5 min (range 21-176 min). The median blood loss was 10 ml (range 10-300 ml). The median length of postoperative hospital stay was 2 days (range 1-7 days). Endometriosis was the most frequently diagnosed etiology (34.9%). Other laparoscopic approaches were employed in two cases (2.3%). There were four cases (4.7%) with complications: three with pelvic infections and one with postoperative hemorrhage. CONCLUSIONS: SPLS is a feasible approach for the treatment of adnexal lesions.

Asian plantain (Plantago asiatica) essential oils suppress 3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase expression in vitro and in vivo and show hypocholesterolaemic properties in mice.

Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82.5 %, w/w), measured using GC-MS. Incubation of 0-200 microg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0.2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0.05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( - 37 %; P < 0.05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0.05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( - 46 and - 11 %, respectively; P < 0.05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits.

Anopheles kleini, Anopheles pullus, and Anopheles sinensis: potential vectors of Plasmodium vivax in the Republic of Korea.

Anopheles sinensis Wiedemann (63.3%) was the most abundant Anopheles mosquito captured at cowshed resting collections in malaria high-risk areas (northern Gyeonggi Province) near the demilitarized zone (DMZ) in Korea during 2005, followed by Anopheles kleini Rueda (24.7%) and Anopheles pullus M. Yamada (8.7%). At cowshed resting collections in malaria low-risk areas (Jeonnam and Gyeongnam provinces), An. sinensis accounted for 96.8% of all Anopheles spp. collected, followed by An. kleini Rueda (2.7%), whereas no An. pullus were collected. Three species, An. kleini (50.9%), An. pullus (29.0%), and An. sinensis (13.8%), accounted for nearly all of the 224 Anopheles spp. captured by New Jersey light trap near the DMZ. In addition, An. pullus and An. kleini captured by New Jersey light trap near the DMZ and assayed by enzyme linked immunosorbent assay for Plasmodium vivax circumsporozoite antigen concentrations were higher than An. sinensis sensu stricto (s.s.), indicating higher levels of sporozoites. In laboratory studies of four concurrent artificial membrane feedings on malaria-infected blood from patients, F1 progeny of An. kleini and An. pullus had higher infection rates (8.8 and 7.5%, respectively) than An. sinensis s.s. (4.2%). These data suggest that An. kleini and An. pullus and An. sinensis are vectors of malaria in Korea. Further studies are required to determine the role of these species in the transmission of P. vivax in the Republic of Korea.

Ligation of centrocyte/centroblast marker 1 on Epstein-Barr virus--transformed B lymphocytes induces cell death in a reactive oxygen species--dependent manner.

After primary infection of B cells with Epstein-Barr virus (EBV), infected B cells express several viral homologs of human genes that promote activation (LMP1 and CD40) or survival (BHRF and BCL2). EBV-infected B cells also express germinal center phenotype markers, such as CD77, PNA, CD95, and CD38. This transformation of B cells by EBV infection resembles normal B-cell activation and differentiation arising in the germinal center. In the present study, we found that EBV-transformed B cells expressed centrocyte/centroblast marker 1 (CM1), a possible marker of GC B cells and an inducer of their apoptosis. Moreover, ligation of CM1 on EBV-transformed B cells by immobilized anti-CM1 monoclonal antibody induced cell death. The ligation of CM1 immediately increased the generation of intracellular reactive oxygen species (ROS) and disrupted the mitochondrial membrane potential. Pretreatment with N-acetyl cystein (an ROS inhibitor) almost completely blocked this cell death, but Z-VAD-fmk (a caspase inhibitor) did not. We further investigated whether apoptosis-inducing factor (AIF) and endonuclease G (EndoG), which are both related to caspase-independent cell death, would be translocated to the nucleus during the ligation of CM1. We found that AIF and EndoG were released to the cytosplam but not translocated to the nucleus. Moreover, cytochalasin D, a cytoskeleton disruptor, rescued the cells from CM1-mediated cell death and blocked ROS generation. Therefore, it is conceivable that CM1 signaling might provoke cytoskeleton polymerization and trigger ROS generation. Taking these observations together, we conclude that the ligation of CM1 on EBV-transformed B cells can cause cell death via the ROS produced by F-actin polymerization in a caspase-independent manner, although this cell death might be unrelated to AIF and EndoG release from the mitochondria.

Delayed allograft rejection by the suppression of class II transactivator.

(CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenicity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.

Coagulation parameters and plasma total homocysteine levels in Behcet's disease.

Behcet's disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis in addition to systemic manifestations. However, the mechanism of hypercoagulability is not known. We evaluated the coagulation and fibrinolytic activities and the plasma total homocysteine levels of Korean BD patients in two cross-sectional studies. In the first study regarding coagulation and fibrinolytic activities, the levels of fibrinogen and von Willebrand factor (vWF) antigen were significantly higher in the BD patients than in the healthy controls (387.7+/-24.3 versus 240.6+/-8.8 mg/dl, p<0.001, and 131.9+/-8.8 versus 105.2+/-0.3%, p<0.01, respectively). The level of antithrombin III (AT III) was significantly lower in the BD patients (92.8+/-3.2 versus 106.3+/-2.6%, p<0.005). No differences were observed in the levels of plasminogen, protein C, or protein S activities. Activated protein C (APC) resistance was not observed in any BD patients. In the second study, the plasma total homocysteine levels of patients with a history of thrombosis (11.9+/-3.0 micromol/l) or disease activity (12.5+/-3.8 micromol/l) were found to be significantly higher than those of the controls (9.2+/-2.6 micromol/l, p<0.05, both). The plasma homocysteine concentrations in the thrombosis patients were positively correlated with plasma vWF levels; a relationship which suggests injury of the vascular endothelium (Spearman coefficient=0.857, p<0.01). Therefore, coagulation abnormality did not contribute to thrombotic complications, and higher levels of homocysteine may play a role in the hypercoagulablity of BD patients.