Effect of coordinator-based osteoporosis intervention on quality of life in patients with fragility fractures: a prospective randomized trial.

We examined the effects of the coordinator-based intervention on quality of life (QOL) in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL. The coordinator-based interventions mitigated the decrease in QOL. Secondary fracture after primary fracture, however, was a significant predictor of lower QOL. PURPOSE: This study aimed to determine the effects of the coordinator-based intervention on QOL in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL, in an Asian population. METHODS: Patients with new fractures in the intervention group received the coordinator-based intervention by a designated nurse certified as a coordinator, within 3 months of injury. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scale  before the fracture (through patient recollections) and at 0.5, 1, and 2 years after the primary fracture. RESULTS: Data for 141 patients were analyzed: 70 in the liaison intervention (LI) group and 71 in the non-LI group. Significant intervention effects on QOL were observed at 6 months after the fracture; the QOL score was 0.079 points higher in the LI group than in the non-LI group (p=0.019). Further, the LI group reported significantly less pain/discomfort at 2 years after the fracture, compared to the non-LI group (p=0.037). In addition, secondary fractures were found to significantly prevent improvement and maintenance of QOL during the recovery period (p=0.015). CONCLUSION: Short-term intervention effects were observable 6 months after the primary fracture, with the LI group mitigated the decrease in QOL. Few patients in the LI group reported pain/discomfort 2 years after the fracture, but there is uncertainty regarding its clinical significance. Secondary fracture after initial injury was a significant predictor of lower QOL after a fracture.

Efficiency of coordinator-based osteoporosis intervention in fragility fracture patients: a prospective randomized trial.

We examined the effectiveness of coordinators' interventions to prevent secondary fractures in patients with fragility fractures. These coordinator-based interventions improved bone density assessment implementation and treatment rates, and enhanced treatment persistence rates in the early stages following fractures. INTRODUCTION: This study aimed to determine the efficiency of coordinator-based osteoporosis intervention in fragility fracture patients during a 2-year period. METHODS: A prospective intervention randomized control study was conducted at seven medical facilities from January 2015 to March 2017. Postmenopausal women and men over 50 years old with fragility fractures were randomly divided into the coordinator intervention (LI; 70 patients) and without intervention (non-LI; 71 patients) groups. The osteoporosis treatment rate, osteoporosis treatment persistence rate, fall rate, fracture incidence rate, and bone density measurement rate 3 months, 6 months, 1 year, and 2 years after registration were compared between the two groups. Non-parametric tests were used to analyze data at each inspection period. RESULTS: The osteoporosis treatment initiation rate was significantly higher in the LI group than in the non-LI group (85.7% vs. 71.8%; p = 0.04). The LI group had significantly higher bone density assessment implementation rates than the non-LI group at the time of registration (90.0% vs. 69.0%; p = 0.00) and 6 months after registration (50.0% vs. 29.6%; p = 0.01), but not 1 or 2 years after registration. In addition, no significant differences in fall or fracture incidence rates were found between the two groups. CONCLUSION: The coordinator-based interventions for fragility fractures improved bone density assessment implementation and treatment rates and enhanced treatment persistence rates in the early stages following bone fractures. The findings suggest that liaison intervention may help both fracture and osteoporosis physicians for the evaluation of osteoporosis and initiation and continuation of osteoporosis medication.

Airborne particle dispersion around the feet of surgical staff while walking in and out of a bio-clean operating theatre.

BACKGROUND: Bacterial contamination by airborne particles is one of the most important factors in the pathogenesis of surgical-site infections. AIM: This study aimed to identify the generation and behaviour of airborne particles around the feet of surgical staff while walking in and out of an operating theatre. METHODS: Two physicians and two nurses walked in and out of a bio-clean theatre under laminar airflow, either individually or as a group. The generation and behaviour of airborne particles was filmed using a fine-particle visualization system, and the number of airborne particles per 2.83 m3 of air was counted using a laser particle counter. Each action was repeated five times, and particle counts were evaluated statistically. FINDINGS: Airborne particles were generated from the floor and by the shoes and gown hems of the participants, whether walking individually or as a group. Numerous airborne particles were generated by the group, and significantly more particles, especially those measuring 0.3-0.5 µm, were carried up to the level of the operating table by the group than by individuals (P<0.01). CONCLUSIONS: The results of this study provide a clearer picture of the dispersion and distribution of airborne particles around the feet of staff walking in and out of an operating theatre. The findings suggest that to reduce the incidence of bacterial contamination and risk of surgical site infections, surgical staff should walk calmly and independently, if possible, near sterile areas.

An objective tool to measure the effect of botulinum toxin in blepharospasm and hemifacial spasm.

BACKGROUND AND PURPOSE: It is challenging to assess patients with blepharospasm (BSP) and hemifacial spasm (HFS) as these patients exhibit a wide range of amplitudes of eyelid movements. In order to quantify these movements, a mathematical algorithm, i.e. Fast Fourier Transform, can be employed to convert the signal from the time domain to the frequency domain. The result of this quantification represents the energy generated during the eyelid movements. In order to objectively assess the therapeutic effects of botulinum toxin (BoNT) in these patients, we evaluated the energy generated by the upper eyelid during spontaneous eyelid movements before and after treatment. METHODS: A total of 39 patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinum toxin A injections. A high-speed camera and micro light-emitting diodes were used to register the spontaneous eyelid movements. The result of the quantification obtained using Fast Fourier Transform permitted assessment of the activity associated with the eyelid movements. RESULTS: We studied 78 eyelids. The total energy generated during spontaneous eyelid movements was significantly reduced after treatment in the patients with BSP (P = 0.0018) and on the affected side in the patients with HFS (P = 0.0058). CONCLUSIONS: The assessment of the energy generated by the upper eyelid during spontaneous eyelid movements enabled us to measure the therapeutic effects of BoNT in patients with these conditions. The use of this system could enable customized and fine adjustments to BoNT doses based on each patient's needs.

Simple clinical predictors of stroke outcome based on National Institutes of Health Stroke scale score during 1-h recombinant tissue-type plasminogen activator infusion.

BACKGROUND AND PURPOSE: An index for predictors of stroke outcome was determined based on the National Institutes of Health Stroke Scale (NIHSS) scores during 1-h intravenous administration of recombinant tissue-type plasminogen activator (rt-PA). METHODS: Stroke patients with baseline NIHSS score ≥8 and occlusion at the internal carotid or middle cerebral arteries (ICA, MCA) were retrospectively studied from a prospective single-center registry. NIHSS scores and inverse change from baseline scores (ΔNIHSS) were assessed at 30 min and 1 h after rt-PA infusion. Patients were divided into two groups according to arterial occlusion sites: group P, ICA or proximal M1; and group D, distal M1 or M2. A modified Rankin Scale score of 2-6 at 3 months was defined as an unfavorable outcome. RESULTS: In all 108 patients, the cutoff NIHSS score predicting unfavorable outcome was ≥12 and cutoff ΔNIHSS scores were ≤2 at both 30 min and 1 h. In group P (n = 36), the cutoff NIHSS score was ≥14 at both 30 min and 1 h and cutoff ΔNIHSS scores were ≤1 at 30 min and ≤2 at 1 h. Unfavorable outcome was seen in all patients with NIHSS1 h ≥ 14, ΔNIHSS30 min ≤ 1 and ΔNIHSS1 h ≤ 2. In group D (n = 72), the cutoff NIHSS scores were ≥12 at both 30 min and 1 h, and cutoff ΔNIHSS scores were ≤2 at 30 min and ≤7 at 1 h; 90% of patients with unfavorable outcome showed ΔNIHSS1 h ≤ 7. CONCLUSION: NIHSS and ΔNIHSS during 1-h rt-PA infusion seemed predictive of 3-month outcome when the site of arterial occlusion was identified prior to rt-PA.

Femoral head deformity and severity of acetabular dysplasia of the hip.

Patients with acetabular dysplasia commonly undergo peri-acetabular osteotomy after skeletal maturity to reduce the risk of the late development of osteoarthritis. Several studies have suggested that deformity of the femoral head influences the long-term outcome. We radiologically examined 224 hips in 112 patients with acetabular dysplasia and early-stage osteoarthritis. There were 103 women and nine men with a mean age of 37.6 years (18 to 49). A total of 201 hips were placed in the acetabular dysplasia group and 23 in a normal group. The centre-edge angle and acetabular head index were significantly smaller (both p < 0.001), and the acetabular angle, acetabular roof angle and roundness index were significantly greater in the acetabular dysplasia group than those in the normal group (all p < 0.001). There were significant correlations between the roundness index and other parameters. Femoral head shape may be influenced by the severity of the acetabular dysplasia.

Associations of vertebral deformities and osteoarthritis with back pain among Japanese women: the Hizen-Oshima study.

UNLABELLED: We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain. INTRODUCTION: Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan. METHODS: Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren-Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain. RESULTS: Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5-6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0--0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1-2.9), independent of other covariates including age and deformities. CONCLUSION: Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.

Beneficial effect of risedronate for preventing recurrent hip fracture in the elderly Japanese women.

SUMMARY: A 36-month observational study compared the incidence of unaffected side hip fracture in Japanese female osteoporosis patients with a history of hip fracture between 173 patients receiving risedronate and 356 risedronate-untreated controls. New hip fractures were significantly less frequent in the risedronate group, suggesting a preventive effect in high-risk patients. INTRODUCTION: The purpose of this study was to investigate the preventive effect of risedronate on second hip fracture immediately following a first hip fracture in Japanese female osteoporosis patients with unilateral hip fracture. METHODS: We conducted a prospective matched cohort study in 184 patients treated with risedronate and 445 patients not receiving risedronate after discharge from hospital. Both groups were followed-up for 36 months, and the incidence of unaffected side hip fracture and the frequency of adverse events were assessed. RESULTS: Efficacy could be investigated in 173 patients from the risedronate group and 356 patients from the control group. Hip fracture was detected in 5 and 32 patients, respectively. Kaplan-Meier estimates of the 36-month fracture incidence were 4.3% in the risedronate group and 13.1% in the control group (P = 0.010, log-rank test). The hazard ratios (95% confidence intervals) obtained by univariate and multivariate analysis were 0.310 (0.121-0.796) and 0.218 (0.074-0.639), respectively, indicating a significantly lower incidence of unaffected side hip fracture in the risedronate group. Adverse events occurred in 38 patients (48 events) from the risedronate group and 94 patients (108 events) from the control group, with serious adverse events in 21 patients (26 events) and 78 patients (88 events), respectively. CONCLUSIONS: No significant differences were observed between the two groups. The incidence of unaffected side hip fracture was significantly lower in the risedronate group. Accordingly, risedronate may have a preventive effect on hip fracture in high-risk Japanese female osteoporosis patients for fracture with a history of unilateral hip fracture.

Proteomic analysis of secreted proteins from aseptically grown rice.

Plants are known to secrete a variety of compounds into the rhizosphere. These compounds are thought to play important roles in the regulation of soil chemical properties and soil microorganisms. To determine the composition of proteins secreted from rice roots, aseptic hydro culture was performed, and the collected proteins were analyzed. Over 100 proteins were identified; most were identified using the rice database (RAP-DB), and about 60% of the identified proteins were suspected to have a signal peptide. Functional categorization suggested that most were secondary metabolism- and defense-related proteins. Pathogenesis- and stress-related proteins were the major proteins found in the bathing solution under aseptic conditions. Thus, we propose that rice plants constitutively secrete a large variety of proteins to protect their roots against abiotic and/or biotic stresses in the environment.

Quantitative ultrasound and radiographic absorptiometry are associated with vertebral deformity in Japanese Women: the Hizen-Oshima study.

UNLABELLED: We evaluated the ability of heel quantitative ultrasound (QUS) and metacarpal radiographic absorptiometry (RA) to identify subjects with vertebral deformities in Japanese women aged ≥40. Both QUS and RA were associated with vertebral deformities, and the estimated prevalence at each T-score widely varied with age. INTRODUCTION: Heel QUS and metacarpal RA have been used for screening patients to evaluate risk of osteoporotic fractures. The aim of this study was to evaluate the ability of QUS and RA to identify women with vertebral deformities in 570 Japanese women aged ≥40, and to estimate the prevalence of vertebral deformity at each T-score. METHODS: Calcaneal QUS and metacarpal RA were performed. Radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. RESULTS: The receiver operating characteristic analysis showed that both calcaneal stiffness index (SI) and metacarpal bone mineral density (BMD) were associated with vertebral deformities. Using the T-score of -2.5 as a cutoff value, the specificity and sensitivity for identifying individuals with vertebral deformities was 65% and 83% for calcaneal SI, and 40% and 88% for metacarpal BMD, respectively. The prevalence of vertebral deformity was estimated using age-adjusted logistic regression models. Women with calcaneal SI T-score of -2.5 had a 2% estimated probability of vertebral deformity at age 40, and 22% at age 80. For metacarpal BMD T-score of -2.5, estimated probability was less than 1% at age 40, and 27% at age 80. CONCLUSION: Both calcaneal SI and metacarpal BMD were associated with prevalence of vertebral deformity. Furthermore, the prevalence widely varied with age at any given bone value.

In vivo structural analysis of subchondral trabecular bone in osteoarthritis of the hip using multi-detector row CT.

OBJECTIVE: With developments in clinical computed tomography (CT), in vivo analysis of patients' bone microstructure has become increasingly possible. We analyzed the subchondral trabecular bone of hip osteoarthritis (OA) patients using multi-detector row CT (MDCT) to closely examine the structural changes that occur as OA progresses. DESIGN: 47 female hip joints were studied: 20 with OA secondary to hip dysplasia (11 advanced OA, nine early-moderate OA), seven with hip dysplasia without OA, and 20 normal. The images' maximal spatial resolution was 280 × 280 × 500 µm. Regions of interest (ROIs) were the subchondral trabecular bones of the acetabulum and femoral head. Measurement parameters were bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structure model index (SMI), trabecular bone pattern factor (TBPf), Euler's number, and degree of anisotropy (DA). Relationships between joint space volume and these parameters were analyzed. RESULTS: With decreasing joint space, Tb.Th and BV/TV increased, and Tb.Sp, Tb.N, SMI, TBPf, and DA decreased significantly. The microstructures were significantly different between the early to advanced OA groups and the normal and dysplasia groups; there was no significant difference between the normal and dysplasia groups. CONCLUSIONS: Changes of subchondral trabecular bone structure in OA could be evaluated using MDCT, despite imperfect spatial resolution and limited accuracy. Trabecular bone thickening and associated structural changes may be closely related to OA. Changes were observed in early to advanced OA, but not in dysplasia. This method may help to further elucidate OA pathogenesis, determine the therapeutic strategy, and evaluate therapy.

Refined human artificial chromosome vectors for gene therapy and animal transgenesis.

Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance, and the ability to carry large gene inserts. We previously developed HAC vectors from the normal human chromosomes using a chromosome engineering technique. However, endogenous genes were remained in these HACs, limiting their therapeutic applications. In this study, we refined a HAC vector without endogenous genes from human chromosome 21 in homologous recombination-proficient chicken DT40 cells. The HAC was physically characterized using a transformation-associated recombination (TAR) cloning strategy followed by sequencing of TAR-bacterial artificial chromosome clones. No endogenous genes were remained in the HAC. We demonstrated that any desired gene can be cloned into the HAC using the Cre-loxP system in Chinese hamster ovary cells, or a homologous recombination system in DT40 cells. The HAC can be efficiently transferred to other type of cells including mouse ES cells via microcell-mediated chromosome transfer. The transferred HAC was stably maintained in vitro and in vivo. Furthermore, tumor cells containing a HAC carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were selectively killed by ganciclovir in vitro and in vivo. Thus, this novel HAC vector may be useful not only for gene and cell therapy, but also for animal transgenesis.

Use of a dual priming oligonucleotide system to detect multiple sexually transmitted pathogens in clinical specimens.

AIMS: To evaluate a new dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) assay for detection of six sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum and Trichomonas vaginalis. METHODS AND RESULTS: Using 130 clinical specimens, the results obtained by the multiplex PCR, previously established in-house PCR and COBAS Amplicor PCR assays were compared. The specimens frequently contained multiple pathogens (34/130 specimens). The multiplex PCR assay had an overall sensitivity of 96% and specificity of 100% compared to the in-house PCR assay at >20 microg ml(-1) of DNA concentrations in samples and there was no cross-reaction with nonpathogenic Neisseria species that cause the majority of false-positive results with the COBAS Amplicor PCR assay. CONCLUSIONS: The DPO-based multiplex PCR assay detected the six sexually transmitted pathogens in clinical specimens with a high sensitivity and specificity, although its sensitivity was dependent on the DNA content of the samples. SIGNIFICANCE AND IMPACT OF THE STUDY: It is the first report about the new DPO-based technique to detect multiple sexually transmitted pathogens in a single assay, which has considerable potential to diagnose the infections accurately and rapidly.

MicroRNAs as biomarkers and therapeutic drugs in human cancer.

MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, noncoding small RNAs that act as post-transcriptional gene regulators. Experimental evidence has shown that miRNAs can play roles as oncogenes or tumor suppressor genes, suggesting their contribution to cancer development and progression. Expression profiles of human miRNAs demonstrated that many miRNAs are deregulated in cancers and are differentially expressed in normal tissues and cancers. Therefore, miRNA profiling is used to create signatures for a variety of cancers, indicating that the profile will help further establish molecular diagnosis, prognosis and therapy using miRNAs. This paper introduces the aberrant expression of miRNAs in human cancer, and discusses the potential of these miRNAs as biomarkers and targets/molecules for molecular therapy.

Correction of a genetic defect in multipotent germline stem cells using a human artificial chromosome.

Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including regulatory elements. Multipotent germline stem (mGS) cells have a great potential for gene therapy because they can be generated from an individual's testes, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we herein report the functional restoration of a genetic deficiency in mouse p53-/- mGS cells, using a HAC with a genomic human p53 gene introduced via microcell-mediated chromosome transfer. The p53 phenotypes of gene regulation and radiation sensitivity were complemented by introducing the p53-HAC and the cells differentiated into several different tissue types in vivo and in vitro. Therefore, the combination of using mGS cells with HACs provides a new tool for gene and cell therapies. The next step is to demonstrate functional restoration using animal models for future gene therapy.

Rotational acetabular osteotomy for advanced osteoarthritis secondary to developmental dysplasia of the hip.

We evaluated the results of rotational acetabular osteotomy in 44 hips (42 patients) with advanced osteoarthritis secondary to developmental dysplasia. The mean age of the patients at surgery was 43.4 years (30 to 59) and the mean follow-up was 12.1 years (8 to 19). The mean Merle d'Aubigné clinical score improved from 10.8 points (8 to 15) pre-operatively to 13.5 points (6 to 18) at follow-up. Radiologically, this procedure produced adequate improvement regarding cover of the femoral head. At follow-up, the osteoarthritic stage assessed using the Japanese Orthopaedic Association grading, was improved in 11 hips (25%), unchanged in 22 (50%) and had progressed in 11 (25%). The mean pre-operative roundness index of the femoral head was significantly different in the 33 hips which had improved or maintained their osteoarthritic stage compared with the 11 which had progressed (53.7% vs 63.7%; p < 0.001). Osteoarthritis with a round femoral head is considered to be an indication for rotational acetabular osteotomy, even in advanced stages of the disease.

Disruption of srtA gene in Streptococcus suis results in decreased interactions with endothelial cells and extracellular matrix proteins.

Streptococcus suis, a major pathogen of swine, is an emerging zoonotic agent which causes meningitis and septic shock. In this study, we investigated the ability of S. suis mutant strain (SRTDeltaA) lacking the sortase A gene (srtA) to interact with host cells and extracellular matrix (ECM) proteins, as well as its virulence in a mouse infection model. We demonstrated that mutant SRTDeltaA had reduced capacity to adhere to and invade porcine brain microvascular endothelial cells compared to the wild-type strain. In addition, mutant SRTDeltaA also showed significantly less adherence to plasma fibronectin, cellular fibronectin and collagen type I. However, disruption of srtA had little effect on the virulence of S. suis in a mouse intraperitoneal model of infection. These results indicate that surface proteins anchored by sortase A are required for a normal level of bacterial binding. However, other factors may also be important for S. suis virulence and interaction with host tissues.

Rotational acetabular osteotomy with a resection of the lateral edge of the acetabulum for the treatment of advanced coxarthrosis.

INTRODUCTION: We compared the functional and radiological results of a rotational acetabular osteotomy (RAO) with and without a resection of the lateral edge of the acetabulum. The purpose of the resection was to obtain good joint congruency. MATERIALS AND METHODS: RAO was performed on 71 hips to treat advanced coxarthrosis caused by acetabular dysplasia. RAO without a resection (non-resection group) was performed in 54 patients (57 hips) with a median age of 43.1 years. The remaining 14 patients (14 hips), who had a median age of 44.6 years, received RAO with a resection of the lateral edge of the acetabulum (resection group). RESULTS: The average postoperative total hip joint score was better than the average preoperative score in the non-resection group (P < 0.001), but not in the resection group. In the resection group, all hips displayed progressive osteoarthritic change and ten hips had chondrolysis of the hip joint and a collapse of the transferred acetabulum within 3 years. In the non-resection group, 15 hips showed progressive osteoarthritic change, 24 hips had no change, and 18 hips showed a decrease in the osteoarthritic stage. CONCLUSION: Our findings demonstrated that resection of the lateral edge of the acetabulum is not a useful adjunct to the RAO procedure for the treatment of advanced coxarthrosis.

Anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course: clinical profile and approach to management in the pediatric population.

An anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course (interarterial coronary artery [IACA]) is a rare congenital anomaly associated with sudden cardiac death. The cardiac and surgical databases at a single pediatric institution were reviewed for a description of the clinical profiles and associated risk factors of this coronary anomaly. From 1994 to 2006, IACA was diagnosed for 31 patients with a median age of 6.2 years (range, birth to 16 years). The symptoms for 6 (19%) of the 10 patients (32%) presenting with symptoms were deemed to be cardiac in origin. The symptoms for the remaining 21 patients (68%) were incidental findings. Of the 31 patients, 29 (94%) had normal resting electrocardiograms (ECG). A total of 17 patients underwent dobutamine stress echo. None had wall motion abnormalities, but two had ECG changes indicating ischemia, and 4 had abnormal coronary flow, as detected by Doppler echocardiography. Seven patients, with either acute symptoms or testing suggestive of ischemia, underwent surgery. All seven had an interarterial left main coronary artery. There was one cardiac-related death. No sudden death was found in either the surgery or nonsurgery group during the mean follow-up period of 23 and 58 months, respectively. Whether surgical intervention modifies the natural history of the anomaly or not remains to be determined.

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress.

We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein. We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5'untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis.