Risk factors for fracture by same-level falls among workers across sectors: a cross-sectional study of national open database of the occupational injuries in Japan.

OBJECTIVES: The hospitalisation rate for work-related injuries among older workers is double that of younger workers; however, the risk factors for same-level fall fractures sustained during industrial accidents remain unclear. This study aimed to estimate the influence of worker age, time of day and weather conditions on the risk of same-level fall fractures in all industrial sectors in Japan. STUDY DESIGN: This was a cross-sectional study. METHODS: This study used the population-based national open database of worker death and injury reports in Japan. In total, 34,580 reports of occupational same-level falls between 2012 and 2016 were used in this study. Multiple logistic regression analysis was performed. RESULTS: In primary industries, workers aged ≥55 years had a 1.684 times greater risk of fracture (95% confidence interval [CI]: 1.167-2.430) compared with workers aged ≤54 years. In tertiary industries, relative to the odds ratio (OR) of injuries recorded at 0:00-2:59 a.m., the ORs recorded at 6:00-8:59 p.m., 6:00-8:59 a.m., 9:00-11:59 p.m. and 0:00-2:59 p.m. were 1.516 (95% CI: 1.202, 1.912), 1.502 (95% CI: 1.203-1.876), 1.348 (95% CI: 1.043-1.741) and 1.295 (95% CI: 1.039-1.614), respectively. The risk of fracture increased with a 1-day increase in the number of snowfall days were per month in secondary (OR = 1.056, 95% CI: 1.011-1.103) and tertiary (OR = 1.034, 95% CI: 1.009-1.061) industries. The risk of fracture decreased with every 1-degree increase in the lowest temperature in primary (OR = 0.967, 95% CI: 0.935-0.999) and tertiary (OR = 0.993, 95% CI: 0.988-0.999) industries. CONCLUSIONS: With the increasing number of older workers and changing environmental conditions, the risk of falls in the tertiary sector industries is increasing, particularly just before and just after shift change hours. These risks may be associated with environmental obstacles during work migration. It is also important to consider the weather-associated risks of fracture.

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.

Vascularized Tissue-Engineered Model for Studying Drug Resistance in Neuroblastoma.

Neuroblastoma is a vascularized pediatric tumor derived from neural crest stem cells that displays vasculogenic mimicry and can express a number of stemness markers, such as SOX2 and NANOG. Tumor relapse is the major cause of succumbing to this disease, and properties attributed to cancer stem-like cells (CSLC), such as drug-resistance and cell plasticity, seem to be the key mechanisms. However, the lack of controllable models that recapitulate the features of human neuroblastoma limits our understanding of the process and impedes the development of new therapies. In response to these limitations, we engineered a perfusable, vascularized in vitro model of three-dimensional human neuroblastoma to study the effects of retinoid therapy on tumor vasculature and drug-resistance. METHODS: The in vitro model of neuroblastoma was generated using cell-sheet engineering and cultured in a perfusion bioreactor. Firstly, we stacked three cell sheets containing SKNBE(2) neuroblastoma cells and HUVEC. Then, a vascular bed made of fibrin, collagen I and HUVEC cells was placed onto a collagen-gel base with 8 microchannels. After gelling, the stacked cell sheets were placed on the vascular bed and cultured in the perfusion bioreactor (perfusion rate: 0.5 mL/min) for 4 days. Neuroblastoma models were treated with 10µM isotretionin in single daily doses for 5 days. RESULTS: The bioengineered model recapitulated vasculogenic mimicry (vessel-like structure formation and tumor-derived endothelial cells-TECs), and contained CSLC expressing SOX2 and NANOG. Treatment with Isotretinoin destabilized vascular networks but failed to target vasculogenic mimicry and augmented populations of CSLCs expressing high levels of SOX2. Our results suggest that CSLCs can transdifferentiate into drug resistant CD31+-TECs, and reveal the presence of an intermediate state STEC (stem tumor-derived endothelial cell) expressing both SOX2 and CD31. CONCLUSION: Our results reveal some roles of SOX2 in drug resistance and tumor relapse, and suggest that SOX2 could be a therapeutic target in neuroblastoma.

Plasma phylloquinone, menaquinone-4 and menaquinone-7 levels and coronary artery calcification.

Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 < CAC score < 400; n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P < 0·001), creatinine, collagen type 1 cross-linked N-terminal telopeptide (NTX, P = 0·03), pulse wave velocity (P < 0·001) and osteoprotegerin (P < 0·001). However, CAC did not have a significant correlation with plasma levels of PK, MK-4 or MK-7. In conclusion, plasma MK-7, MK-4 or PK level did not show significant correlation with CAC despite the association between plasma vitamin K levels and vitamin K-dependent proteins such as ucOC or PIVKA-2.

Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

UNLABELLED: Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. INTRODUCTION: Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. METHODS: We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. RESULTS: Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (ß = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. CONCLUSIONS: Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.

High prevalence of vitamin D deficiency in patients with xeroderma pigmetosum-A under strict sun protection.

BACKGROUND/OBJECTIVES: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by defective repair of ultraviolet (UV) irradiation-induced DNA damage and high risk of skin cancer. Thus, these patients require strict photoprotection. Considering the importance of UV-mediated cutaneous vitamin D production, such rigorous photoprotection would cause vitamin D deficiency. Then, we have studied the vitamin D status in patients with XP-A, a group requiring the most strict photoprotection. SUBJECTS/METHODS: Twenty-one patients with XP-A (aged 6-25) were evaluated for their vitamin D intake, serum levels of 25-hydroxy-vitamin D (25OHD) and parathyroid hormone (PTH). Vitamin D intake was assessed by a 2-day food weighing method. RESULTS: Median dietary intake of vitamin D was 4.1 µg/day, and the median concentrations of serum 25OHD and PTH were 7.7 and 49.9 pg/ml, respectively. In 76% of the patients, serum 25OHD level was lower than 10 ng/ml, indicating vitamin D deficiency. Vitamin D intake and serum 25OHD level were significantly lower in patients under enteral nutrition (EN) than those with oral intake (OI). Multivariate analyses revealed that EN was a significant predictor of decreased serum 25OHD level (ß coefficient=-0.59, P=0.03). CONCLUSIONS: Vitamin D deficiency is highly prevalent in XP-A patients, and supplementation should be considered to avoid unfavorable skeletal consequences in these patients. In addition, determination of dietary vitamin D requirement has been a difficult work issue in the decision of dietary reference intakes (DRIs) because of its cutaneous production. Data from XP patients would yield useful information for the determination of DRIs for vitamin D.

Studies of the humoral factors produced by layered chondrocyte sheets.

The authors aimed to repair and regenerate articular cartilage with layered chondrocyte sheets, produced using temperature-responsive culture dishes. The purpose of this study was to investigate the humoral factors produced by layered chondrocyte sheets. Articular chondrocytes and synovial cells were harvested during total knee arthroplasty. After co-culture, the samples were divided into three groups: a monolayer, 7 day culture sheet group (group M); a triple-layered, 7 day culture sheet group (group L); and a monolayer culture group with a cell count identical to that of group L (group C). The secretion of collagen type 1 (COL1), collagen type 2 (COL2), matrix metalloproteinase-13 (MMP13), transforming growth factor-ß (TGFß), melanoma inhibitory activity (MIA) and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA). Layered chondrocyte sheets produced the most humoral factors. PGE2 expression declined over time in group C but was significantly higher in groups M and L. TGFß expression was low in group C but was significantly higher in groups M and L (p<0.05). Our results suggest that the humoral factors produced by layered chondrocyte sheets may contribute to cartilaginous tissue repair and regeneration.

Development of automated 3-dimensional tissue fabrication system Tissue Factory - Automated cell isolation from tissue for regenerative medicine.

We have developed a new automated cell isolation system as one of the modules of automated cell sheet production system named Tissue-Factory (T-Factory). This system enables isolation of the target cells from tissue. Using this new system, we successfully isolated skeletal myoblast from skeletal muscle tissue. The cell isolation system makes us stably prepare cell suspension from each tissue automatically and safely. Isolation of skeletal myoblasts will contribute to labor-saving cell cultivation and operational stability, and lead further process in tissue engineering and regenerative medicine.

Image quality assessment of three cone beam CT machines using the SEDENTEXCT CT phantom.

OBJECTIVES: The SEDENTEXCT Project proposed quality assurance (QA) methods and introduced a QA image quality phantom. A new prototype was recently introduced that may be improved according to previous reports. The purpose of this study is to evaluate image quality in various protocols of three cone beam CT (CBCT) machines using the proposed QA phantom. METHODS: Using three CBCT machines, nine image quality parameters, including image homogeneity (noise), uniformity, geometrical distortion, pixel intensity value, contrast resolution, spatial resolution [line pair (LP) chart, point spread function (PSF) and modulation transfer function (MTF)] and metal artefacts, were evaluated using a QA phantom proposed by SEDENTEXCT. Exposure parameters, slice thickness and field of view position changed variously, and the number of total protocols was 22. RESULTS: Many protocols showed a uniform gray value distribution except in the minimum slice thickness image acquired using 3D Accuitomo 80 (Morita, Kyoto, Japan) and Veraviewepocs 3Df (Morita). Noise levels differed among the protocols. There was no geometric distortion, and the pixel intensity values were correlated with the CT value. Low contrast resolution differed among the protocols, but high contrast resolution performed well in all. Many protocols showed that the maximum line pair was larger than 1 LP mm(-1) but smaller than 3 LP mm(-1). PSF and MTF did not correlate well with the pixel size. The measured metal artefact areas varied for each device. CONCLUSIONS: We studied the image quality of three CBCT machines using the SEDENTEXCT phantom. Image quality varied with exposure protocols and machines.

Perioperative haemostatic management of haemophilic mice using normal mouse plasma.

Intense haemostatic interventions are required to avoid bleeding complications when surgical procedures are performed on haemophilia patients. The objective of this study was to establish an appropriate protocol for perioperative haemostatic management of haemophilic mice. We assessed the prophylactic haemostatic effects of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap procedure and a laparotomy. When 500 µL of NMP was administered to the mice, plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at 2.7% 6 h after subcutaneous administration. Administering 500 µL of NMP via IP or IV 30 min in advance enabled the skin flap procedure to be performed safely without any complications. After the laparotomy procedure, several mice in the IP administration group exhibited lethal bleeding, but all mice survived in the IV administration group. Anti-mouse FIX inhibitors did not develop, even after repetitive administrations of NMP. However, human FIX concentrates, especially plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results show that administering 500 µL of NMP via IV or IP 30 min in advance enables surgical procedures to be safely performed on HB mice, and that IV administration is more desirable than IP if the procedure requires opening of the abdominal wall.

Topographical arrangement of α- and ß-cells within neo-islet tissues engineered by islet cell sheet transplantation in mice.

BACKGROUND: We established a procedure to engineer therapeutic neo-islets in subcutaneous spaces in mice by transplanting contiguous layers of islet cell sheets. In this study, we investigated the cellular arrangements of α and ß within these engineered neo-islets in vivo as a function of time after sheet transplantation. METHODS AND RESULTS: Temperature-responsive culture dishes optimized for dispersed islet cell culture were prepared by covalently immobilizing a temperature-responsive polymer poly(N-isopropylacrylamide) (PIPAAm) on plastic dishes followed by laminin-5 coating. Dispersed islet cells obtained from Lewis rats were plated onto the PIPAAm dishes. After reaching confluence at day 2, islet cells were harvested as uniformly spread islet cell sheets by lowering the culture temperature from 37°C to 20°C for 20 minutes. Islet sheet transplantation was performed to creat neo-islet tissues in the subcutaneous spaces of SCID mice with streptozotocin-induced diabetes. This neo-islet engineering approach successfully lowered mouse blood glucose levels, achieving euglycemia at day 5 and thereafter. Histologic analyses of samples obtained at day 4 revealed that neo-islet tissues in the subcutaneous spaces showed heterogeneous cellular alignment of α and ß cells. In contrast, analyses of samples at days 14 and 60 revealed α and ß cells predominantly located at the peripheral and central parts of the engineered tissues, respectively. CONCLUSIONS: Reassembly of α and ß cells occurred in neo-islet tissues engineered by sheet transplantation. The unique cellular arrangements in neo-islet tissues, which were similar to those in naïve pancreatic islets, may contribute to their longevity and long-term function.

Dose indices in dental cone beam CT and correlation with dose-area product.

OBJECTIVES: In the 2011 project "Safety and efficacy of a new and emerging dental X-ray modality (SEDENTEXCT)", it was suggested that dose index (DI) and dose-area product (DAP) could be easily measured and used as diagnostic reference levels (DRLs), which would help in the management of radiation doses to patients in optimum exposure settings. Such indices could be directly related to effective dose. The purposes of this study, therefore, were to measure and calculate the DI and DAP in cone beam CT (CBCT) machines and to evaluate the correlation between the two. METHODS: Dose measurements were performed on three-dimensional cone beam CT (3D-CBCT) machines [3D Accuitomo (J. Morita Mfg. Corp., Kyoto, Japan), Veraviewepocs (J. Morita Mfg. Corp.) and CS9300 (Carestream, New York, NY)] by exposing a cylindrical poly-methyl methacrylate (PMMA) phantom using a CT ionization chamber. These dose measurements were used for the calculation of Dose Indices 1 and 2, according to the methodology suggested by SEDENTEXCT. The DAP was measured using a DAP meter that was attached to the detector to cover the entire irradiated area. RESULTS: The DI1 ranged from 53.6 mR to 216.6 mR, the DI2 ranged from 77.1 mR to 325.0 mR and the DAP ranged from 101.1 mGy cm(2) to 457.9 mGy cm(2), depending on the machines and exposure settings. Index 2 had a better correlation with the DAP than Index 1. CONCLUSIONS: The DIs and DAP proposed by SEDENTEXCT may be useful for establishing DRLs for dental CBCT machines; however, further studies are necessary to determine which of these indices provide accurate dose estimates proportionally relating to the effective dose.

TNF-α modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells.

OBJECTIVES: To study the effect of tumour necrosis factor (TNF)-α, responsible for the inflammation and circadian rhythm of rheumatoid arthritis (RA), on the expression of circadian clock genes in primary cultured human rheumatoid synovial cells. METHOD: The expression of circadian clock genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt-like protein-1 (Bmal1), period (Per)1/2, and cryptochrome (Cry)1/2, and the proline and acidic amino acid-rich basic leucine zipper (PAR bZip) genes, a transcriptional activator of Per2, including D site of albumin promoter binding protein (Dbp), hepatic leukaemia factor (Hlf), and thyrotroph embryonic factor (Tef), and a transcriptional repressor of Per2, E4-binding protein 4 (E4bp4), in TNF-α-stimulated synovial cells was determined by real-time polymerase chain reaction (PCR). The D-box motifs in the Per2 promoter were mutated by site-directed mutagenesis, and the promoter activity of the Per2 gene was examined using the luciferase assay. RESULTS: TNF-α enhanced the mRNA expression of Bmal1 and Cry1 but did not affect that of Clock, Per1, or Cry2. However, TNF-α inhibited the mRNA expression of the Per2 gene, as well as Dbp, Hlf, and Tef, but enhanced the mRNA expression of E4bp4. Furthermore, TNF-α inhibited the transcriptional activity of the wild-type Per2 gene in a manner dependent on the D-box 1 and D-box 2 motifs in the Per2 promoter. CONCLUSIONS: TNF-α modulates the expression of the Per2 gene through the D-box binding proteins DBP, HLF, TEF, and E4BP4, in rheumatoid synovial cells, and thereby may contribute to the pathogenesis of RA.

A preliminary study to determine the diagnostic reference level using dose-area product for limited-area cone beam CT.

OBJECTIVES: The aim of this study was to measure the dose-area product (DAP) of limited-area cone beam CT (CBCT) units used by dental offices, and to evaluate the rationale of the DAP with an aid of optically stimulated luminescence (OSL) dosemeter in measuring radiation dose. METHOD: The DAPs of 21 CBCT units used in the dental offices of Tokyo and the surrounding areas from five different manufacturers were measured using OSL nanoDot dosemeter. An assembly of OSL dosemeters with an X-ray film was exposed by CBCT units at exposure parameters commonly used in each dental office. DAP values were then calculated as expressed in mGy cm(2). RESULTS: DAP values ranged from 126.7 mGy cm(2) to 1476.9 mGy cm(2), depending on the units used. CONCLUSION: OSL dosemeter coupled with film can be utilized for a large-scale study to measure DAP. The DAP values for individual CBCT units depend not only on the field of view, but also on the exposure parameters adapted by the dental offices.

Requirement of integrin ß3 for iron transportation during enamel formation.

Rodent incisors exhibit pigmentation on their labial surfaces. Although previous studies have shown that this pigment is composed of iron, the existence of other elements has not been investigated. This study found that the lower incisors of CD61, also known as integrin ß3, null mice (CD61(-/-)) lacked pigmentation. Although ameloblasts differentiated and formed enamel normally, no ferric ion accumulation was observed in maturation-stage ameloblasts in CD61(-/-) mice. Surface elements of control and CD61-/- lower incisors were compared by x-ray photoelectron spectroscopy (XPS). XPS analysis detected C, Ca, N, O, and P on the labial surfaces of lower incisors of both mice, whereas Fe was detected only in control samples. No peak of non-ferrous metal or other element was detected in either group. Quantitative RT-PCR analysis of 18 iron-transportation-related genes with mRNA from maturation-stage ameloblasts and ALC, a pre-ameloblastic cell line, was performed. The results suggested that CD61 regulates the expressions of Slc11a2 and Slc40a1, both of which are involved in iron transportation in epithelial tissues. These results suggested that the pigment on the labial surface of mouse incisors is composed of Fe and that both anemia and reduction of iron-transporting proteins may cause the loss of pigmentation in CD61(-/-) mice.

Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules.

BACKGROUND: Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cß. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. RESULTS: We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. CONCLUSION: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules.

Characterization of optically stimulated luminescence dosemeters to measure organ doses in diagnostic radiology.

OBJECTIVE: The aim of this study was to assess the characteristics of an optically stimulated luminescence dosemeter (OSLD) for use in diagnostic radiology and to apply the OSLD in measuring the organ doses by panoramic radiography. METHODS: The dose linearity, energy dependency and angular dependency of aluminium oxide-based OSLDs were examined using an X-ray generator to simulate various exposure settings in diagnostic radiology. The organ doses were then measured by inserting the dosemeters into an anthropomorphic phantom while using three panoramic machines. RESULTS: The dosemeters demonstrated consistent dose linearity (coefficient of variation<1.5%) and no significant energy dependency (coefficient of variation<1.5%) under the applied exposure conditions. They also exhibited negligible angular dependency (≤ 10%). The organ doses of the X-ray as a result of panoramic imaging by three machines were calculated using the dosemeters. CONCLUSION: OSLDs can be utilized to measure the organ doses in diagnostic radiology. The availability of these dosemeters in strip form proves to be reliably advantageous.

Production of islet cell sheets using cryopreserved islet cells.

BACKGROUND: To establish novel islet-based therapies, our group has recently developed technologies to create a contiguous, monolayered sheet made from freshly dispersed islet cells. Islet cell sheets generated from freshly isolated cells are easily transplantable for engraftment into subcutaneous sites in rodents. The use of a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), grafted culture dishes with laminin-5 coating is an important feature of this process. To expand the utility of this protocol, the present study was performed to assess whether sheets generated using cryopreserved islet cells maintained viability and normal cellular phenotypes. METHODS: Dispersed islet cells obtained from Lewis rats were, cryopreserved using University of Wisconsin solution and 10% dimethyl sulfoxide. Specially coated plastic dishes were prepared by covalently immobilizing PIPAAm onto the culture plastic, followed by a coating of rat laminin-5. After 1 month of cryopreservation, the thawed cells were plated onto the PIPAAm-coated dishes. RESULTS: Viability of the thawed islet cells as assessed by trypan blue exclusion test was 86% ± 5%. Thawed dispersed islet cells favorably attached to PIPAAm dishes could be harvested as a contiguous cell sheet using a simple change in culture temperature conditions. Electron microscopy showed the harvested islet cell sheet to retain cell-cell connections and numerous secretion granules. CONCLUSIONS: The present data indicated that dispersed islet cells, which were appropriately frozen and thawed, represent another viable cells source to create functional islet sheets for tissue engineering and potential clinical applications.

Pre-clinical evaluation of a new dental panoramic radiographic system based on tomosynthesis method.

OBJECTIVES: The purpose of the study was to compare the image generated by a classic panoramic machine equipped with a cadmium telluride sensor capable of digital tomosynthesis and special software with images produced by other popular panoramic X-ray machines using a charge-coupled device and native software for image capture. METHODS: Panoramic images were made using a phantom of a human skull on Planmeca ProMax, Planmeca EC Proline, Kodak 8000 and PC-1000. With the last machine we used the PanoACT® software to adjust the entire arch and to adjust the image in selected regions of interest (ROIs). Ten viewers evaluated the images and provided the viewer data. ANOVA for repeated measures was used to compare the means by pairwise comparisons of means. RESULTS: The image of the entire arch adjusted by the PanoACT® software was statistically superior to the images produced by other machines. The images generated and individually adjusted by PanoACT® were statistically superior to all other images. CONCLUSIONS: The image generated by the cadmium telluride sensor has great potential and can be processed to create superior images to those taken with other machines. Furthermore, the ROI individual images enhanced by the PanoACT® were superior to the entire arch adjusted by the same software.