Influence of Different Undercut Depths of Clasp Fabricated by Selective Laser Melting on Retentive Force.

INTRODUCTION: The purpose of this study was to investigate the influence of undercut depths on abutment teeth regarding the retentive force of clasps fabricated through selective laser melting (SLM), and to compare them with conventional cast clasps. METHODS: Akers clasps made of cobalt chromium alloy were fabricated using the SLM method (SLM), and the retentive forces were compared with clasps made with the conventional cast method (Cast). Three undercut amounts (0.25 mm, 0.15 mm, and 0 mm) were applied on the abutment tooth. The specimens were subjected to 10,000 repetitive insertion/removal cycles. RESULTS: SLM-0.15 showed slightly lower initial retentive force than the Cast specimens, it remained within an acceptable range. During insertion/removal test, the SLM-0.15 specimen showed a significant difference between the initial retentive force and the retentive force after 5,000 cycles, indicating that SLM-0.15 was the least likely to change in retentive force within the parameters established in this study. The inner clasp surface on the SLM groups had higher surface roughness before testing compared to the Cast specimen. CONCLUSIONS: Akers clasps fabricated by SLM demonstrated optimal initial retentive forces with smaller undercuts than conventional Cast clasps, and the retentive forces changed less with repetitive insertion/removal.

Automatic detection of early gastric cancer in endoscopic images using a transferring convolutional neural network.

Endoscopic image diagnosis assisted by machine learning is useful for reducing misdetection and interobserver variability. Although many results have been reported, few effective methods are available to automatically detect early gastric cancer. Early gastric cancer have poor morphological features, which implies that automatic detection methods can be extremely difficult to construct. In this study, we proposed a convolutional neural network-based automatic detection scheme to assist the diagnosis of early gastric cancer in endoscopic images. We performed transfer learning using two classes (cancer and normal) of image datasets that have detailed texture information on lesions derived from a small number of annotated images. The accuracy of our trained network was 87.6%, and the sensitivity and specificity were well balanced, which is important for future practical use. We also succeeded in presenting a candidate region of early gastric cancer as a heat map of unknown images. The detection accuracy was 82.8%. This means that our proposed scheme may offer substantial assistance to endoscopists in decision making.

Experimental and theoretical studies of Si-Cl and Ge-Cl σ-bond activation reactions by iridium-hydride.

We report the iridium hydride-mediated Si-Cl and Ge-Cl σ-bond activation in a low-polarity toluene solution owing to diphosphine-chelation, in which the Si-Cl and Ge-Cl σ-bonds are readily cleaved through an SN2-type pathway via the formation of a free chloride anion.

Quantitative real-time PCR (qPCR)--based tool for detection and quantification of Cordyceps militaris in soil.

A quantitative real-time PCR using a primer pair CM2946F/CM3160R was developed for specific detection and quantification of Cordyceps militaris from soil. Standard curves were obtained for genomic DNA and DNA extracts from autoclaved soil with a certain dose of C. militaris suspension. C. militaris was detected from two forest soil samples out of ten that were collected when fruit bodies of C. militaris were found. This method seemed effective in detection of C. militaris in the soil and useful for rapid and reliable quantification of C. militaris in different ecosystems.

Population pharmacokinetic analysis of meropenem in Japanese adult patients.

WHAT IS KNOWN AND OBJECTIVE: Meropenem is frequently employed as an empirical treatment for serious infections, but there has been no report on its population pharmacokinetic parameters for Japanese patients. Our aim is to undertake a population pharmacokinetic analysis of meropenem using non-linear mixed effects model (NONMEM). METHODS: Data from 68 patients were analysed via NONMEM with the first-order method. The participants' covariates, including gender, age, actual body weight, serum creatinine, serum albumin, serum total protein and creatinine clearance, were analyzed by the forward inclusion and backward elimination method to identify their potential influence on meropenem pharmacokinetics. The adequacy of the constructed model was assessed by goodness-of-fit plots and the precision of the parameter estimated at each step of the model development. To assess the robustness of the estimated parameter, bootstrap analysis was performed. RESULTS AND DISCUSSION: The data were best described by a one-compartment model. The serum creatinine values modified by the below normal limit in our hospital (mSCR) were an influential covariate for clearance (CL): CL (L/h) = 11·1 × (mSCR/0·7)(-1). The volume of distribution was estimated as 33·6 L. The coefficient of variation of the inter-individual variability of CL and the residual variability were 52·1% and 0·827% µg/mL, respectively. A comparison of the population pharmacokinetic parameters of meropenem in the final model estimated in NONMEM with original data, and 1000 bootstrap samples shows that both sets of estimates were comparable, thereby indicating the robustness of the proposed model. WHAT IS NEW AND CONCLUSION: A population pharmacokinetic model that satisfactorily described the disposition and variability of meropenem in our Japanese population is described. NONMEM analysis showed that the clearance of meropenem depended on modified serum creatinine. The results of this study should help Japanese patients on meropenem by improving the prediction accuracy of dosing using the Bayesian method.

Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation.

Chronic GVHD (cGVHD) of the liver is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-SCT). It is characterized by the destruction of bile duct epithelium followed by progressive cholestasis, which resembles primary biliary cirrhosis (PBC) clinically and histologically. Bezafibrate (BF) is a widely used agent for hyperlipidemia that is also effective in ursodeoxycholic acid (UDCA)-resistant PBC patients. The putative mechanism in cholestasis is that BF upregulates the expression of phosphatidylcholine flippase on bile canaliculi, facilitates phospholipid output into bile and relieves bile duct damage caused by hydrophobic bile salts. Therefore, the effects of BF in patients with cGVHD of the liver were investigated. Of 87 patients with cGVHD who survived more than 100 days after SCT, 8 were given BF to treat liver cGVHD because of a poor therapeutic response to UDCA and immunosuppressants. The serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels decreased significantly within 1 month after initiation of BF therapy compared with those before BF therapy in all patients (ALP, 964.9.0+/-306.9 to 597.8+/-102.5 IU/l, P=0.012; gamma-GTP, 528.8+/-299.0 to 269.0+/-119.9 IU/l, P=0.012). BF was effective in patients with liver cGVHD, including UDCA-resistant patients. BF could be a novel therapeutic option for liver cGVHD that helps to preserve normal immunity with the antileukemic effect of cGVHD.

Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression.

We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19-24 years were more likely to be persistently noncompliant compared to patients aged 24-44 years (aOR 1.49 [1.06-2.10]). Poor (aHR 1.80 [1.52-2.13]) and fair (aHR 1.63[1.37-1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3-year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.

Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma.

BACKGROUND: Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported. METHODS: The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated. RESULTS: Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan-Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test. CONCLUSION: These data showed that p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis.

Population of follicles and luteal structures during the oestrous cycle of mares detected by three-dimensional internal structure microscopy.

The structure of the equine ovary is different from that of other mammals in its extremely large size, the presence of ovarian fossa and the inverted location of its cortex and medulla. A three-dimensional internal structure microscopy (3D-ISM), which consists of a computer-controlled slicer, a CCD camera, a laser disc recorder and a PC, is very useful for the observation of the internal structures in equine ovaries. In addition, the three-dimensional images of follicles and corpus luteum (CL) reconstructed by the segmentation technique can clarify the spatial arrangement in the equine ovary. In this study, to understand the changes in the ovarian internal structures of the mare during the oestrous cycle, the size and numbers of follicles and luteal structures were analysed by 3D-ISM in addition to the concentrations of progesterone (P(4)) and oestradiol-17beta. As a result, many small follicles (<10 mm in diameter) were detected. It was recognized that the luteal structures were distinguished into three types, such as the corpus haemorragicum (CH), which is formed by blood elements at the cavity after ovulation, CL and corpus albican (CA). There were some CHs and CL in the group, which had the concentration of P(4) > 1 ng/ml. CHs were also observed in the group, which had low level of P(4) (P(4) < 1 ng/ml). CAs were found regardless of the P(4) level. In conclusion, 3D-ISM enabled the internal observation of the ovarian structures in detail, and estimation of the stage of the ovarian cycle with complementary physiological information. The findings by 3D-ISM provide basic information for clinical applications.

Outcomes of simultaneous heart-kidney transplant in the US: a retrospective analysis using OPTN/UNOS data.

Simultaneous heart-kidney transplantation (SHK) remains uncommon in the US. We examined outcomes of SHK compared to heart transplant alone (HTA) and deceased donor kidney transplant (DDKT). Data from OPTN/UNOS heart and kidney data bases were used to identify 16,710 HTA, 263 SHK transplants and 68,833 DDK transplants between 1998 and 2007. Outcomes included patient survival (PS), acute cardiac and renal rejection and renal graft survival (rGS). The adjusted risk of death was 44% lower with SHK compared to HTA. Over half of SHK were performed in cases where pretransplant dialysis was not initiated. In these cases, there was no significant difference in the risk of death between SHK and HTA (HR 1.01; 95% CI 0.67-1.50). Recipients of SHK had worse 1-year rGS and PS and had a higher relative risk of overall renal graft loss compared to DDKT recipients. One-year rates of cardiac (14.5%) and renal (6.5%) rejection were lower in SHK compared to HTA and DDKT, respectively. Recipients of SHK had a lower adjusted risk of death compared to HTA recipients, particularly in patients who required pretransplant dialysis. These data suggest that SHK should be considered in heart transplant candidates with renal failure requiring dialysis, whereas the utility of SHK in cases of renal failure not requiring dialysis warrants further study.

Predictive ability of pretransplant comorbidities to predict long-term graft loss and death.

Whether to include additional comorbidities beyond diabetes in future kidney allocation schemes is controversial. We investigated the predictive ability of multiple pretransplant comorbidities for graft and patient survival. We included first-kidney transplant deceased donor recipients if Medicare was the primary payer for at least one year pretransplant. We extracted pretransplant comorbidities from Medicare claims with the Clinical Classifications Software (CCS), Charlson and Elixhauser comorbidities and used Cox regressions for graft loss, death with function (DWF) and death. Four models were compared: (1) Organ Procurement Transplant Network (OPTN) recipient and donor factors, (2) OPTN + CCS, (3) OPTN + Charlson and (4) OPTN + Elixhauser. Patients were censored at 9 years or loss to follow-up. Predictive performance was evaluated with the c-statistic. We examined 25 270 transplants between 1995 and 2002. For graft loss, the predictive value of all models was statistically and practically similar (Model 1: 0.61 [0.60 0.62], Model 2: 0.63 [0.62 0.64], Models 3 and 4: 0.62 [0.61 0.63]). For DWF and death, performance improved to 0.70 and was slightly better with the CCS. Pretransplant comorbidities derived from administrative claims did not identify factors not collected on OPTN that had a significant impact on graft outcome predictions. This has important implications for the revisions to the kidney allocation scheme.

Methodologies for determining the bioavailability and biodegradability of sludges.

The measurement of sludge bioavailability and biodegradability is important to assess the sludge potential as a source of carbon and energy during its biological stabilization. As the majority of biological sludge (secondary sludge) consists of biomass, an increase in sludge bioavailability can be achieved by using different techniques for cell lysis, which is aimed at releasing intracellular organics into the bulk solution and enhancing hydrolysis of particulate organic matter. This paper reviews the main methodologies currently used for cell lysis, which include thermal, ultrasonic and chemical techniques and a combination of these, as well as the analytical procedures that can be employed to assess the degree of lysis and sludge solubilization. In addition, this paper also discusses common techniques that can be used for measuring the biodegradability of sludge under aerobic and anaerobic conditions.

A retrospective analysis of immunosuppression compliance, dose reduction and discontinuation in kidney transplant recipients.

We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome. Medicare claims for MMF in 7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards. Pediatric (Age 0-18, Odds ratio = 1.71, 95% CI 1.11-2.63, p = 0.014) and adolescent recipients (19-24, 1.57, 1.23-2.00, p < 0.001) were more likely poorly compliant compared to adults age 25-44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11-1.84, p = 0.005) and low (1.46, 1.13-1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was >50% dose reduction (1.69, 1.15-2.50, p = 0.008) and discontinuation (8.34, 6.85-10.2, p < 0.001). Medication possession ratios lower than the 3-year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance.

Patient and graft survival implications of simultaneous pancreas kidney transplantation from old donors.

We investigated graft and patient survival implications of simultaneous pancreas kidney (SPK) transplant from old donors. Data describing patients with type 1 diabetes mellitus listed for an SPK transplant from 1994 to 2005 were drawn from Organ Procurement and Transplant Network registries. Allograft survival, patient survival and long-term survival expectations among SPK recipients from young (age <45 years) and old (age >/=45 years) donors were modeled by multivariate regression. We also examined predictors of reduced early access to young donor transplants. Of 16 496 eligible SPK candidates, 8850 patients (53.6%) received an SPK transplant and 776 (8.8%) of these transplants were from old donors. Reasonable 5-year, death-censored kidney (77.8 %) and pancreas (71.3%) survivals were achieved with old donors. SPK transplantation from both young and old donors predicted lower mortality compared to continued waiting. An additional expected wait of 1.5 years for a young donor equalized long-term survival expectations to that achieved with use of old donors. Early allocation of young donor transplants declined in the more recent era and varied by region, candidate age, blood type and sensitization. We conclude that old SPK donors should be considered for patients with decreased access to young donor transplants. Prospective evaluation of this practice is needed.

Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients.

BACKGROUND: Previous multicenter, randomized trials, lacking standardized post-transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA, Sandimmune) and demonstrated similar outcomes with some different adverse effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA as the more widely utilized CyA formulation. This is the first 5-year follow-up study of a large, single-center trial (n = 67) under a standardized post-transplant protocol comparing Tac and mCyA. METHODS: Sixty-seven heart transplant patients were randomized to Tac (n = 33) or mCyA (n = 34), both in combination with corticosteroids and azathioprine without cytolytic induction. Five-year end-points included survival, Grade > or = 3A or treated rejection, angiographic cardiac allograft vasculopathy (CAV; any lesion > or = 30% stenosis), renal dysfunction (creatinine > or = 2.0 mg/dl), use of two or more anti-hypertensive medications, percent diabetic and lipid levels. RESULTS: Five-year survival, freedom from Grade > or = 3A or any treated rejection and angiographic CAV, mean cholesterol level and percent diabetic were similar between the two groups. The Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 +/- 34 vs mCyA 175 +/- 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2 +/- 0.5 mg/dl vs mCyA 1.5 +/- 0.4 mg/dl, p = 0.044). There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group (Tac 33% vs mCyA 59%, p = 0.065). CONCLUSIONS: Tac and mCyA appear to be comparable with regard to 5-year survival, freedom from rejection and CAV. However, compared with mCyA, Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications.

Multivariate analysis of the effectiveness of using antibody induction therapy according to the degree of HLA mismatches.

OBJECTIVE: HLA mismatches have a strong impact on acute rejection and renal allograft survival. The objective of this study was to evaluate the effectiveness of antibody induction according to the degree of HLA mismatches. METHODS: Of 20,429 deceased donor (DD) transplantations and 12,859 living donor (LD) transplantations reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% of DD and 45% of LD transplant recipients received induction therapy. Propensity scores (PS) were calculated to indicate independent factors associated with the use of induction. Levels of HLA match examined for DD transplant recipients were 0 ABDR (n = 3239), 0 DR (n = 4210), and DR mismatched transplants (n = 12,980), and 0 (n = 1133), 1 (n = 3836), and 2 (n = 7890) haplotype mismatches for LD transplant recipients. Outcome parameters were reported as hazard ratios (HR) for graft loss and odds ratios (OR) for first-year acute rejection. RESULTS: Recipients with HLA mismatches were more likely to receive induction antibody for DR mismatch in DDs (PS = 1.11, 95% confidence interval [CI] 1.04-1.19) and for haplotype mismatch in LDs (PS = 1.36, 95% CI 1.22-1.52). Induction reduced the likelihood of acute rejection for DD transplant recipients regardless of the level of HLA mismatch (OR = 0.70; 95% CI 0.57-0.85 in 0 ABDR MM; OR = 0.76, 95% CI 0.64-0.89 in 0 DR MM; and OR = 0.69, 95% CI 0.62-0.77 in DR MM), and for 2 haplotype mismatched LD transplant recipients (OR = 0.82, 95% CI 0.70-0.96); in other LD transplant recipients, reductions in acute rejection rates were observed but not statistically significant. Induction reduced the risk of graft loss for DR mismatched DD transplant recipients by about 12% (HR = 0.88; 95% CI 0.80-0.97). CONCLUSIONS: Antibody induction resulted in a significant reduction of acute rejection and graft loss for patients with HLA mismatch.

Multivariate analysis of antibody induction therapy and their associated outcomes in deceased donor transplants.

AIMS: The aims of this study were to describe factors associated with the use of overall induction, classes of induction agents, and to evaluate the incidence of acute rejection, short-term graft survival, and patient survival. METHODS: Of 24,901 transplants reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% received induction therapy including Thymoglobulin (T; n = 3090), Simulect (S; n = 6063), or Zenapax (Z; n = 3755). Propensity scores (PS) were calculated to indicate factors associated with use of induction and for each induction agent. Outcome parameters included graft survival (GS), hazard ratio (HR) for graft loss (GL), and odds ratio (OR) for first-year acute rejection (AR). RESULTS: Pediatric (PS = 1.29; 95% confidence interval [CI] 1.12-1.49, vs adults) and retransplanted recipients (PS = 1.36; 1.23-1.49, vs first) were more likely to receive induction. One-year GS (90.1 vs 88.0%; P < .001), GL = 0.92% (0.86-0.98; P = .01), and AR free = 0.74 (P < .001) were superior in patients receiving induction. Using multivariate analysis, the odds of rejection 0.73 (0.68-0.78), GL 0.91 (0.85-0.97), and death 0.90 (0.82-0.98) were lower in those receiving induction. Among patients given induction, those receiving T were more likely sensitized (PS = 1.50%; 1.31-1.71), retransplanted (PS = 1.51; 1.31-1.75), or had delayed graft function (PS = 1.75; 1.58-1.93). T decreased the odds of rejection compared with S or Z (OR = 0.74; 0.69-0.79), but the type of induction agent did not have an impact on graft outcome HR for T = 1.07 (0.96-1.19). CONCLUSIONS: The use of antibody induction was associated with lower risk of rejection and better GS. There were no differences in GS among individual regimens. Comparative safety data were not analyzed but should be taken into consideration when choosing antibody preparations.

Three-dimensional reconstruction of the equine ovary.

The equine ovary has a very unique structure in terms of its extreme large size, the presence of the ovulation fossa and the inverted location of its cortex and medulla. In the previous study, it was recognized that the application of three-dimensional internal structure microscopy (3D-ISM) to observe the mare ovary is very effective. Three-dimensional reconstruction of serially sliced images made by 3D-ISM was successful in this study with the aid of the sophisticated image processing technique. The rotation of the reconstructed ovary has been carried out with and without the application of the transparency technique in the ovarian stromal region. The spatial localization of follicles and corpus luteum was clearly visualized by rotating the reconstructed image of the ovary. The extraction of the images of follicles and corpus luteum was also available and gave a quantifiable understanding of their structure.