Association between ambient air pollution and pregnancy rate in women who underwent IVF.

STUDY QUESTION: Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? SUMMARY ANSWER: Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. WHAT IS KNOWN ALREADY: Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. STUDY DESIGN, SIZE, DURATION: Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. LIMITATIONS, REASONS FOR CAUTION: The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Novel proteins that regulate cell extension formation in fibroblasts.

Cell extensions are critical structures that enable matrix remodeling in wound healing and cancer invasion but the regulation of their formation is not well-defined. We searched for new proteins that mediated cell extension formation over collagen by tandem mass tagged mass spectrometry analysis of purified extensions in 3T3 fibroblasts. Unexpectedly, importin-5, ENH isoform 1b (PDLIM5) and 26 S protease regulatory subunit 6B (PSMC4) were more abundant (> 10-fold) in membrane-penetrating cell extensions than cell bodies, which was confirmed by immunostaining and immunoblotting and also observed in human gingival fibroblasts. After siRNA knockdown of these proteins and plating cells on grid-supported floating collagen gels for 6 h, formation of cell extensions and collagen remodeling were examined. Knockdown of importin-5 reduced collagen compaction (1.9-fold), pericellular collagen degradation (~ 1.8-fold) and number of cell extensions (~ 69%). Knockdown of PSMC4 reduced collagen compaction (~ 1.5-fold), pericellular collagen degradation (~ 1.7-fold) and number of cell extensions (~ 42%). Knockdown of PDLIM5 reduced collagen compaction (~ 1.6-fold) and number of cell extensions (~ 21%). Inhibition of the TGF-ß RI kinase, Smad3 or ROCK-II signaling pathways reduced the abundance of PDLIM5 in cell extensions but PSMC4 and importin-5 were reduced only by Smad3 or ROCK-II inhibitors. We conclude that these novel proteins are required for cell extension formation and their recruitment into extensions involves the Smad3 and ROCK signaling pathways.

Effects of female sex hormones on folic acid-induced anti-angiogenesis.

AIM: Pregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti-angiogenic activity. As angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the foetus to escape from the FA-induced anti-angiogenesis. This study was designed to investigate the effect of female sex hormones on the FA-induced anti-angiogenic activity. METHODS: The protein levels and protein-protein interaction were examined by Western blot analysis and immunoprecipitation assay respectively. The cell proliferation and migration were examined by MTT assay and wound healing assay respectively. The in vivo angiogenesis was evaluated by Matrigel angiogenesis assay. RESULTS: In human umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy levels of progesterone (P4) or oestradiol (E2) prevented FA-induced inhibitions of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA-induced anti-angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited the signalling pathways involved in FA-induced inhibitions of proliferation and migration in HUVEC. CONCLUSION: Female sex hormones interrupt the FA-induced anti-angiogenic action through receptor-receptor interaction.

Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies.

In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Parental preferences with regards to disclosure following adverse events occurring in relation to medication use or diagnosis in the care of their children - perspectives from Malaysia.

INTRODUCTION: Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action. METHODS: We translated and contextualised a questionnaire developed from a previous study. The questionnaire consisted of four case vignettes that described the following: medication error with a lifelong complication; diagnostic error with a lifelong complication; diagnostic error without lifelong effect; and medication error without lifelong effect. Each case vignette was followed by a series of questions examining the subject's perception on the above areas. We also determined the content validity of the questionnaire. We invited parents of Malaysian children admitted to the paediatric wards of Tuanku Jaafar Hospital to participate in the study. RESULTS: One hundred and twenty-three parents participated in the study. The majority of parents wanted to be told regarding the event. As the severity of the case vignettes increased, the desire for information, remedial action, acknowledgement of responsibility, compensation, punishment, legal action, and reporting to a higher agency also increased. The findings did not have strong evidence of a relationship with subject's demographics. CONCLUSION: This study gives insights into previously unexplored perspectives and preferences of parents in Malaysia regarding open disclosure. It also highlights the opportunity for more research in this area with potentially broad applications.

A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas.

BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.

RAS status in Korean patients with stage III and IV colorectal cancer.

BACKGROUND: KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship to clinical, pathologic, and molecular features remains unclear. METHODS: We evaluated 130 colorectal tumors for mutations in KRAS and NRAS gene. We tested for mutations in codons 61 and 146 of KRAS and codons 12, 13, 59, 61 and 146 of NRAS. Mutation status was determined by targeted dideoxy sequencing. RESULTS: Among the analyzed primary tumors, 36.2% had KRAS mutation. Of the 83 KRAS codon 12 and 13 wild-type patients, 7.2% had KRAS codon 61, 146 or NRAS. 40.7% harbored any RAS mutation. CONCLUSION: The frequency of other RAS (NRAS and KRAS exon 3, 4) activating mutations in colorectal cancers is relatively low in Korean colorectal cancer patients.

PAK1 is involved in sensing the orientation of collagen stiffness gradients in mouse fibroblasts.

Migrating cells sense variations of stiffness in connective tissue matrices but how cells detect and respond to stiffness orientation is not defined. We examined cell extension formation on collagen with underlying support (vertical stiffness gradient) or on collagen laterally supported by nylon (lateral stiffness gradient). At 6 h after plating, cells plated on laterally-supported collagen exhibited >2-fold more abundant and ~2-fold longer cell extensions than cells plated on collagen with underlying support. We examined whether p21-activated kinase 1 (PAK1) influences extension formation that is dependent on the orientation of support. At 6 h after plating on collagen with underlying support, wild-type cell extensions were 40% shorter than PAK1 knockdown cells. In contrast, on laterally-supported collagen, wild-type cell extensions were 2-fold longer than PAK1 knockdown cells. In cells plated on laterally-supported collagen, there were ~2-fold reductions of collagen fiber alignment and compaction in PAK1 knockdown cells compared with wild-type cells. PAK1 knockdown did not affect collagen fiber alignment or compaction by cells plated on collagen with underlying support. Wild-type cells with lateral support of collagen exhibited 3-fold increases of phospho-myosin staining at 6h, which was 2-fold lower in PAK1 knockdown cells. In contrast, cells on collagen with underlying support showed no increase of phospho-myosin staining at any times. PAK1 knockdown did not affect α2 or ß1 integrin expression or function. We conclude that PAK1 is involved in the ability of cells to sense the orientation of stiffness in collagen substrates and generate contractile forces that affect cell extension formation.

Rice prolamin extract ameliorates acute murine colitis by inhibiting nuclear factor-kappa B and modulating intestinal apoptosis and cell proliferation.

We investigated the impact of rice prolamin extract (RPE) on lipopolysaccharide (LPS)-induced nuclear factor (NF)-κB signalling in intestinal epithelial cells and macrophages, and determined the therapeutic efficacy of RPE in acute murine colitis. The effect of RPE on LPS-induced NF-κB signalling and proinflammatory gene expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in-vivo efficacy of RPE was assessed in mice with 3% dextran sulphate sodium (DSS)-induced colitis. Apoptotic and cellular proliferative activities were evaluated by immunostaining with cleaved caspase-3 and proliferating cell nuclear antigen (PCNA) antibodies. RPE inhibited LPS-induced expression of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha and LPS-induced NF-κB signalling in intestinal epithelial cells and macrophages. RPE-fed, DSS-exposed mice showed less weight loss, longer colon length and lower histological score compared to control diet-fed, DSS-exposed mice. Immunostaining analysis revealed a significant decrease of cleaved caspase-3 positive cells in RPE-fed, DSS-exposed mice compared to DSS-exposed mice. Also, the number of PCNA-positive cells within intact colonic crypts decreased significantly in RPE-fed, DSS-exposed mice compared to control diet-fed, DSS-exposed mice. DSS-induced NF-κB signalling was inhibited by RPE. RPE ameliorates intestinal inflammation by inhibiting NF-κB activation and modulating intestinal apoptosis and cell proliferation in an acute murine colitis.

Differences in omega-3 and fatty acid profiles between patients with endometriosis and those with a functional ovarian cyst.

Endometriosis is a chronic inflammatory gynaecological disease. Problems associated with endometriosis include dysmenorrhoea, dyspareunia and infertility. We evaluated the omega-3 and fatty acid profiles in erythrocytes and tissues in patients with endometriosis (n = 10) or a functional ovarian cyst (n = 12), using a food frequency questionnaire that included questions about 117 food items typical of Korean meals. Erythrocyte levels of 20:5n3 and 22:6n3, the omega-3 index, and n-3 PUFA were significantly higher, and the n-6:n-3 ratio was significantly lower in the endometriosis group than in the functional ovarian cyst group. The functional ovarian cyst group consumed significantly more fruit than the group with endometriosis.

Lack of association between TYK2 and STAT3 genes and Crohn's disease in the Malaysian population.

This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.

Transcriptional profiling with a pathway-oriented analysis in the placental villi of unexplained miscarriage.

INTRODUCTION: Miscarriage is the most common placental-related complication of pregnancy. It has been extensively investigated to discover the underlying mechanism(s) by which miscarriage occurs, but in many cases the etiology still remains unclear. The aim of this study was to analyze genome-wide expression profiles of placental villi (PV) from unexplained miscarriage with a pathway-oriented method for identifying underlying mechanism(s) of unexplained miscarriage. METHODS: We investigated PV of 18 women with unexplained miscarriage and 11 women underwent normal pregnancy. Each PV was obtained through dilatation & evacuation and chorionic villous sampling, respectively. Genome-wide expression profiles of PV were analyzed by Gene Set Enrichment Analysis (GSEA) to find dysregulated signaling pathways in PV of unexplained miscarriage. RESULTS: Unsupervised hierarchical clustering showed heterogeneity of expression profiles between PV of normal developing pregnancy and unexplained miscarriage. GSEA, a supervised analysis, with KEGG pathways revealed that several gene sets associated with mitochondrial function including glutathione metabolism and oxidative phosphorylation are dysregulated in PV from unexplained miscarriage. RT-PCR, real-time RT-PCR and/or immunohistochemistry reinforced that expression of genes constituting these gene sets enriched in normal pregnancy and Cu/Zn-superoxide dismutase was down-regulated in PV of unexplained miscarriage. DISCUSSION: Structural vulnerability of placental villi for reactive oxygen species (ROS), which is caused by systemic down-regulation of mitochondrial pathways involved in mitochondrial redox balance and functions, aggravates oxidative stress with increased ROS production in PV of unexplained miscarriage. CONCLUSION: Systemic vulnerability for ROS in PV could be a major cause of unexplained miscarriage.

Suppression of PU.1-linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis.

BACKGROUND AND PURPOSE: The present study assessed the effects of cilostazol on LPS-stimulated TLR4 signal pathways in synovial macrophages from patients with rheumatoid arthritis (RA). These effects were confirmed in collagen-induced arthritis (CIA) in mice. EXPERIMENTAL APPROACH: Expression of TLR4, PU.1, NF-κB p65 and IκBα on synovial fluid macrophages from RA patients was determined by Western blotting, and cytokines were measured by ELISA. Anti-arthritic effects were evaluated in CIA mice. KEY RESULTS: Intracellular cAMP was concentration-dependently raised by cilostazol (1-100 µM). Cilostazol significantly suppressed LPS-stimulated increase of TLR4 expression by blocking PU.1 transcriptional activity in RA macrophages. In addition, cilostazol decreased LPS-induced myeloid differentiation factor 88 (MyD88) expression, but not that of TNF receptor-associated factor 6 (TRAF6). Cilostazol also suppressed IkBα degradation and NF-κB p65 nuclear translocation. Moreover, LPS-induced increase of cytokine production (TNF-α, IL-1ß) was inhibited by cilostazol, an effect which was accompanied by suppression of IκBα degradation, and NF-κB p65 nuclear translocation. However, expression of anti-inflammatory IL-10 was elevated by cilostazol and forskolin/IBMX. In mice with CIA, post-treatment with cilostazol (30 mg kg⁻¹ day⁻¹) decreased expression of TLR4 in knee joints in association with decreased recruitment of macrophages. Consequently, synovial inflammation, proteoglycan depletion and bone erosion were significantly inhibited by cilostazol treatment. CONCLUSIONS AND IMPLICATIONS: Cilostazol down-regulated LPS-stimulated PU.1-linked TLR4 expression and TLR4/MyD88/NF-κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice.

Expression of p53, p27 and Jab1 protein in epithelial ovarian tumors.

OBJECTIVE: The study aimed to investigate expression of p53, p27 and Jun activation domain-binding protein 1 (Jab1) proteins in epithelial ovarian tumors and the values of these factors as discriminating markers for the transformation of borderline tumors to cancers. METHODS: Forty-seven cases of paraffin-embedded tissues of epithelial ovarian tumors including 22 cases of benign ovarian tumors, nine cases of borderline tumors, and 16 cases of invasive cancers were used to evaluate expression of p53, p27 and Jab1 proteins by immunohistochemical methods. RESULTS: p53 protein was expressed in 13.6% of the benign tumors, 44.4% of the borderline tumors and 62.5% of the malignant tumors and p27 protein was expressed in 95.5% of the benign tumors, 66.7% of the borderline tumors, and 37.5% of the malignant tumors. Expression of Jab1 protein was observed in 22.7% of the benign tumors, 77.8% of the borderline tumors and 62.5% of the malignant tumors. Expressions of p53, p27 and Jab1 proteins in malignant tumors were all higher than in benign tumors and the expression of p27 protein in malignant tumors was lower than in benign tumors (p < 0.05). Expression of Jab1 protein in borderline tumors was significantly higher than in benign tumors (p < 0.05). CONCLUSIONS: Expression of p53, p27 and Jab1 proteins can be used to discriminate between benign and malignant tumors in epithelial ovarian tumors.

Ultrasonographic evaluation of costal cartilage fractures unnoticed by the conventional radiographic study and multidetector computed tomography.

INTRODUCTION: Rib fractures are the most common injuries resulting from blunt chest trauma. However, costal cartilage fractures are almost invisible on chest X-rays unless they involve calcified cartilage. The sensitivity of conventional radiography and computed tomography for detecting rib fractures is limited, especially in cases where rib cartilage is involved. Therefore, this study was designed to evaluate the sensitivities of chest wall ultrasonography, clinical findings, and radiography in the detection of costal cartilage fractures. MATERIALS AND METHODS: A total of 93 patients presenting with a high clinical suspicion of rib or sternal fractures were recruited for radiological workup with posterior-anterior (PA) chest radiographs, oblique rib views, sternal views, computed tomography, and chest ultrasound between April 2008 and May 2010. There were 47 men and 46 women, and the mean age of the patients was 51.8 ± 15.9 years (range 17-78 years). These patients with minor blunt chest trauma showed no evidence of rib fractures on conventional radiography and computed tomography, and no evidence of other major fractures. Chondral rib fractures were detected by using ultrasonography on a 7.5-MHz linear transducer. RESULTS: Of the total 93 patients, 64 (68.8%) showed chondral rib fractures, whereas 29 (31.2%) did not. The mean number of chondral rib fracture sites detected in 64 patients was 1.8 ± 0.8 (range 1-5). Subperiosteal hematoma was the most common finding associated with costal cartilage fractures (n = 14, 15.0%), followed by sternal fracture (n = 9, 9.7%). However, subperiosteal hematoma was also noticed in 1 (1.1%) of the patients without costal cartilage fractures, and sternal fractures in 7 patients (7.5%). DISCUSSION: The results of this study suggest that ultrasonography may be a useful imaging method for detecting costal cartilage fractures overlooked on conventional radiographs and computed tomography in patients with minor blunt chest trauma. Early ultrasonographic evaluation can give more accurate information than clinical and radiologic evaluation in detecting costal cartilage fractures and sternal fractures that are overlooked on conventional radiography and computed tomography after minor blunt chest trauma.

Increased immunoreactivity of membrane type-1 matrix metalloproteinase (MT1-MMP) and ß-catenin in high-risk basal cell carcinoma.

BACKGROUND: Although various immunohistological markers have been investigated to assess the aggressive characteristics of basal cell carcinoma (BCC), the role of membrane type-1 matrix metalloproteinase (MT1-MMP) has not been well established. OBJECTIVES: To clarify the precise role of MT1-MMP in BCC, MT1-MMP expression was studied in various histological subtypes of BCC. MATERIALS AND METHODS: High-risk subtypes of BCC were compared by assessing the expression of ß-catenin and MT1-MMP. The tissue microarray technique was used for immunohistochemical staining. Fifty-eight samples were divided into six subtypes (10 nodular, 12 mixed, nine infiltrative, eight morphoeiform, 10 micro-nodular and nine basosquamous). Overall, the 10 nodular BCC samples were classified as low-risk BCC and the remaining 48 samples were classified as high-risk BCCs. RESULTS: ß-Catenin immunoreactivity was increased in the high-risk BCCs compared with the low-risk (nodular) BCC (P < 0·001). Nuclear ß-catenin immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesion (P < 0·01). For the mixed BCC (P < 0·01), infiltrative BCC (P < 0·001), morphoeiform BCC (P < 0·001), micronodular BCC (P < 0·001) and basosquamous (P < 0·001) carcinoma, ß-catenin immunoreactivity was increased at the invading front compared with nodular BCC. MT1-MMP immunoreactivity was increased in the high-risk BCCs compared with the low-risk (nodular) BCC (P < 0·01). The membranous MT1-MMP immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesions (P < 0·01). For the mixed (P < 0·01), infiltrative (P < 0·05), morphoeiform (P < 0·05), micronodular (P > 0·05) and basosquamous (P < 0·05) BCC, MT1-MMP immunoreactivity was also increased at the invading front compared with nodular BCC. CONCLUSIONS: The results of this study suggest that MT1-MMP might be a novel marker for high-risk BCC. In addition, expression of both ß-catenin and MT1-MMP was increased in high-risk BCC tumour cells, indicating that these two proteins may play an important role in locally invasive and highly destructive growth behaviour of high-risk BCCs.