Replication of Caucasian loci associated with bone mineral density in Koreans

Summary

Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs.

Introduction

Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples.

Methods

A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5?×?10^?8) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5?×?10^?5. After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis.

Results

Of the 535 GWS SNPs, 276 from 25 loci were replicated (p?<?0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p?<?0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0?×?10^?5, 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta).

Conclusion

Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.     

Dose-related effect of urinary cotinine levels on bone mineral density among Korean females

Summary

To evaluate the dose-dependent relationship between smoking and bone mineral density (BMD), the present study used the BMD dataset of the Korean National Health and Nutrition Examination Survey IV (KNHANES IV). The linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females.

Introduction

It is well established that smoking is an important lifestyle risk factor for bone health (bone loss, osteoporosis, and fracture). However, several studies demonstrated conflicting evidence for a dose-dependent relationship between smoking and bone health. To evaluate the dose-dependent relationship between smoking and BMD, the present study estimated dose-related effects of smoking (urinary cotinine level) on BMD at various sites (femur neck, total femur, and lumbar spine) in females with controlling menopausal status.

Methods

The present study used the BMD dataset of the KNHANES IV, which was performed in 2008 and 2009. A total of 4,260 pre- and postmenopausal females were included in the present study. Dose–response relationships between BMD and urinary cotinine levels were estimated using analysis of covariance in pre-menopausal females and postmenopausal females, respectively.

Results

In postmenopausal females, the regression coefficients for BMD with urinary cotinine levels were ?0.006, ?0.006, and ?0.008 (g/cm² per ng/ml) at femur neck, total femur, and lumbar spine, respectively (p value?<?0.05). Thus, the linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females.

Conclusion

Our findings suggested a significant dose-related effect of urinary cotinine level with BMD at femur neck, total femur, and lumbar spine among postmenopausal females.     

Effects of rod stiffness and fusion mass on the adjacent segments after floating mono-segmental fusion: a study using finite element analysis

Purpose

The aims of the present study were to compare the biomechanical effects on the adjacent segments after mono-segmental floating fusion with posterior semi-rigid or rigid stabilization, and to evaluate the effect of the amount of fusion mass on the biomechanical differences.

Methods

A detailed, nonlinear L1–S1 finite element model had been developed and validated. Then five models were reconstructed by different fixation techniques on the L3–L4 level: rigid fixation with an interbody spacer (Ti + IS), rigid fixation with a large interbody spacer (Ti + IS_all), semi-rigid fixation with an interbody spacer (PEEK + IS), semi-rigid fixation with a large interbody spacer (PEEK + IS_all), and semi-rigid fixation only (PEEK). Analyses were conducted for the case of erect standing position, flexion, and extension motion.

Results

At L1–L2 and L2–L3, PEEK + IS demonstrated less inter-segmental rotation and nucleus pressure increments from the intact model compared with Ti + IS. The L4–L5 and L5–S1 levels showed slightly higher values with PEEK + IS, but these differences among the instrumented models were not significant. The motion difference based on the fusion mass at the adjacent levels was at most 3 %. All instrumentation cases generated a 55 % higher facet contact force at the lower adjacent level (L4–L5) compared to that of the intact model during 26° extension and the largest increment was detected at the upper adjacent level (L2–L3) in the Ti + IS. Instrumentation with Ti + IS markedly increased the stress in the intervertebral disk at the upper adjacent level, while the stress with PEEK + IS appeared largest at the lower adjacent level.

Conclusions

Posterior instrumentation with semi-rigid rods may lower the incidence of disk and facet degeneration in the upper adjacent segment compared to rigid rods. On the other hand, the possibility of facet degeneration will be similar for all instrumentation devices in the lower adjacent segment in the long-term. The stiffness difference between rigid and semi-rigid rods on the changes in the adjacent motion segments was more crucial than amount of fusion mass.     

Internal plug mesh without fixation in laparoscopic total extraperitoneal (TEP) repair of inguinal hernias: a pilot study

Purpose

Mesh fixation is essential in laparoscopic total extraperitoneal (TEP) repair of inguinal hernia; however, fixation sometimes causes post-operative pain. This study investigated a novel method of laparoscopic TEP repair without mesh fixation.

Methods

This study reviewed data from about two-hundred and forty-one laparoscopic TEP repairs on 219 patients, which were performed between December 2004 and October 2005.

Results

There were no statistically significant differences in the recurrence rate, seroma formation, and hospital stay. However, the mean operation time was shorter in the internal plug mesh group than the fixation group (p = 0.009), and post-operative pain only occurred in 4 cases in the internal plug mesh group in comparison to 29 cases in the mesh fixation group (p = 0.014).

Conclusions

An internal plug mesh without fixation might reduce post-operative pain after laparoscopic TEP repair of an inguinal hernia. Internal plug mesh without fixation may be an alternative method in laparoscopic TEP repair, especially for those involving indirect hernias.     

Are the imaging features of the pleomorphic variant of invasive lobular carcinoma different from classic ILC of the breast?

The aim of this study was to evaluate whether pleomorphic invasive lobular carcinoma (PILC) is different from classic invasive lobular carcinoma (CILC) in terms of radiologic and clinicopathologic features.We compared the radiologic and clinicopathologic features of 22 surgically confirmed PILCs in 21 patients from 2004 to 2009 and 47 CILCs from 47 consecutive patients. For all cases, we reviewed the imaging findings, medical records and pathological results.PILC had a higher T stage, N stage, nuclear and histologic grade compared to CILC. PILC was more commonly negative for estrogen receptors and positive for HER2 than CILC (all p < 0.05). However, there were no significant differences in age, symptoms, tumor size, extensive intraductal component, lymphovascular invasion, triple negative profile, or multiplicity between the two groups. PILC was not detected on mammography in 1 (4.5%) of 22 cases, whereas CILC was not detected on mammography in 7 (14.9%) of 47 cases and on MRI in 2 (5.0%) of 40 (p = 0.42 and p = 1.000, respectively). MRI identified more frequent multiplicity than mammography for both PILC and CILC (p < 0.001), but was similar to US (p = 0.066). Most lesions showed a spiculated mass or architectural distortion with or without calcifications on mammography and ultrasound. No differences in mass and/or non-mass lesions or kinetics on MRI were observed between the two groups.PILC shows more pathologically aggressive features, but cannot be differentiated from CILC based on imaging findings.     

Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus cavernosum

The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum (PCC) was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits (2.5–3.0 kg) were precontracted with phenylephrine (Phe, 10 µmol l⁻¹) and then treated with various concentrations of Cuscuta chinensis extract (1, 2, 3, 4 and 5 mg ml⁻¹). The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay (RIA). The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase (NOS) inhibitor (Nω nitro-L-arginine-methyl ester, L-NAME), a guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ), or a protein kinase A inhibitor (KT 5720) did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction (ED), which does not completely respond to sildenafil citrate.     

Effect of chondroitinase ABC on adhesion and behavior of synovial membrane‐derived mesenchymal stem cells in rabbit partial‐thickness chondral defects

Transplanted cells may have difficulty attaching to the surface of partial‐thickness chondral lesions because of the anti‐adhesive properties of the proteoglycan rich matrix. Therefore, the current study attempts to evaluate the effect of chondroitinase ABC (chABC) on the adhesion and behavior of transplanted synovial membrane‐derived mesenchymal stem cells (SDSCs) in rabbit partial‐thickness chondral defects. In ex vivo adhesion experiments, chABC treatment (0.1 U/ml) was increased in SDSC attachment to the cartilage explants, and significantly diminished by pretreatment with neutralizing antibody against fibronectin. In the in vivo experiments, 1 day and 4 weeks after the chABC treatment (0.1 and 1 U/ml), the immunoreactivity (IR) against CS‐56 (intact chondroitin sulfate antibody) was markedly decreased; however, the IR of 2B6 (stub of the chondroitin 4‐sulfate chain), 3B3 (stub of the chondroitin 6‐sulfate chain), and fibronectin was increased. At 12 weeks, this IR returned to normal except in the high‐dose chABC‐treated group (1 U/ml). Furthermore, the attachment of SDSCs to the chondral defects after chABC treatment was increased at 7 days compared with that in the chondral defects pretreated with saline. However, the tissue repaired by SDSCs was negatively stained for type II collagen at 12 weeks. In conclusion, these results showed that the exposure to fibronectin by chABC treatment enhances the attachment of SDSCs to partial‐thickness chondral defects. However, the tissue regenerated by SDSCs showed lack of hyaline cartilage regeneration. Thus, to understand the fate of transplanted MSCs in cartilage defect is very important for successful cell therapies. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1293–1301, 2013     

Intra‐operative cardiac arrests during liver transplantation – a retrospective review of the first 15 yr in Asian population

Although many report intra‐operative cardiac arrests (ICAs) in liver transplantation (LT), the incidence, major causes, and outcome remain unclear. We aimed to investigate retrospectively, the incidence, nature, and outcome of ICA in Asian population and to identify risk factors for ICA. Consecutive 1071 LTs in an institution during 1996–2011 (adult 920, pediatric 151/living donor liver transplantation, LDLT 841, deceased donor liver transplantation, DDLT 230) were reviewed. ICA occurred in 14 adult LTs (1.5%), but none in pediatrics. ICA occurred 1.0% and 3.3% in LDLT and DDLT, respectively. Stages of ICA incidence were three at pre‐anhepatic, one at anhepatic, and 10 at neohepatic stage. Post‐reperfusion syndrome (PRS) with hyperkalemia and bleeding were the major causes of ICA. While LDLT showed miscellaneous causes for ICA at various stages, DDLT incurred ICAs at neohepatic stage only. Interestingly, we did not find pulmonary thromboembolism (PTE) to incur ICA. Risk factor analysis showed no association of pre‐operative patient condition, donor types, and intra‐operative parameters. In this review, the incidence of ICA was low in Asian population with LDLT predominance, and while PTE was not the cause of ICA, the neohepatic stage with PRS and bleeding was the most vulnerable period to anticipate ICA.     

The Prognostic Relevance of Psammoma Bodies and Ultrasonographic Intratumoral Calcifications in Papillary Thyroid Carcinoma

Background

Although psammoma bodies (PB) are found in up to 50 % of papillary thyroid carcinomas (PTC), their clinicopathological significance remains uncertain. The aim of the present study was to determine the clinicopathological significance of PB and the correlation between PB and ultrasonographic intratumoral calcification in PTC.

Methods

The clinicopathological parameters, ultrasonographic calcifications, and the presence of PB were evaluated in 258 surgically resected conventional PTC.

Results

Psammoma bodies were found in 141 of 258 PTC (54.7 %). The presence of PB was significantly correlated with tumor multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.009, P = 0.004, and P < 0.001, respectively), but not with the BRAF^V600E mutation. Higher incidences of both intratumoral and extratumoral PB were found in overt PTC (>1 cm) than in papillary microcarcinomas (≤1 cm) (P < 0.001 and P = 0.015, respectively). Extratumoral PB were only identified in 48.9 % of 141 PTC with PB, and PTC with extratumoral PB showed higher incidences of tumor multifocality, extrathyroidal extension, and nodal metastasis compared to PTC with intratumoral PB (P = 0.014, P = 0.005 and P = 0.001, respectively). Ultrasonographic intratumoral calcification corresponded to clusters of intratumoral PB (P < 0.001) and was associated with nodal metastasis (P = 0.026).

Conclusions

The findings of the present study suggest that the presence of PB may be a useful prognostic indicator of aggressive PTC behaviors. In addition, confirmation of ultrasonographic intratumoral calcification would be a useful decision-making criterion when determining the need for preoperative or intraoperative surveillance of nodal metastasis.