Development of an optimal relief method for the palatal plate by stress analysis

Background Plate dentures cannot be easily modified after fabrication; therefore, the sites and magnitude of relief must be effectively assessed at the time of fabrication. However, a considerable variation exists in the magnitude of optimal relief and relief range, and there are no guidelines that present these clearly, leading the dentists to decide subjectively. Thus, this study aims to develop an optimal relief method to improve the stress bearing capacity of the palatal mucosa. Methods The objective of this study, namely, the borderline, was set in steps. A three-dimensional finite element model for the pseudopalatal plate was created and used to evaluate the changes in stress distribution in the palatal mucosa due to the selective relief of stresses above the borderline. The resulting data were used to develop the optimal relief method. Results In the relief model with a borderline of 0.04 MPa or higher, the distribution volume at which a high stress of 0.20 MPa or higher is generated was approximately 800% of that with the no-relief model, and in the relief model with a borderline of 0.06 MPa or higher, the respective ratio was approximately 280%. On the other hand, the relief models with a borderline of 0.14 MPa or higher were approximately 60%. In the mid-palatal relief model, the distribution volume at which a stress of 0.20 MPa or higher was generated was 180% of that in the relief model. Conclusions The supportive strength of plates can be increased by selectively applying optimal relief rather than standard relief, allowing for easier and more effective plate-denture treatment.

Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose

Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

Development of an Optimal Relief Method for the Palatal Plate by Stress Analysis

Background: A maxillary-palate-shaped device for simultaneous measurement of bite force and palatal mucosal subsidence at the time of pain onset in dentate persons has been developed. However, palatal mucosal stress analysis in a simulation based on three-dimensional finite element analysis is effective for objective and efficient evaluation of various types of denture-supporting mucosa. Recently plate dentures are not easily modified after the completion of these dentures , so it is essential to effectively assess the sites and magnitude of relief at the time of preparation. However, there is considerable variation in the magnitude of optimal relief and relief range, and there are no guidelines that present these clearly, leading the surgeon to decide subjectively. Thus, this study aimed to develop an optimal relief method to improve the stress bearing capacity of the palatal mucosa.Objectives: The objective of this study, the borderline was set in steps. The changes in stress distribution in the palatal mucosa due to the selective relief of stresses above the borderline were evaluated using a three-dimensional finite element simulation. The purpose of this study was to develop an optimal relief method to improve the bearing capacity of the palatal mucosa.Methods: The objective of this study, the borderline, was set in steps. A three-dimensional finite element model for the pseudopalatal plate was prepared and used to evaluate the changes in stress distribution in the palatal mucosa due to the selective relief of stresses above the borderline. The resulting data were used to develop the optimal relief method.Results: In the relief model with a borderline of 0.04 MPa or higher, the distribution volume at which high stress of 0.20 MPa or higher is generated was approximately about 800%％ of that with the no-relief model, and in the relief model with a borderline of 0.06 MPa or higher, the respective ratio was approximately about 280％%. On the other hand, the relief models with borderline of 0.14 MPa or higher were about 60%. In the mid-palatal relief model, the distribution volume at which stress of 0.20 MPa or higher was generated was 180% of that in the relief model.Conclusions: The supportive strength of plates can be increased by selectively applying optimal relief rather than standard relief, allowing for easier and more effective plate-denture treatment.

A Customer Clustering Algorithm for Power Logistics Distribution Network Structure and Distribution Volume Constraints

Customer clustering technology for distribution process is widely used in location selection, distribution route optimization and vehicle scheduling optimization of power logistics distribution center. Aiming at the problem of customer clustering with unknown distribution center location, this paper proposes a clustering algorithm considering distribution network structure and distribution volume constraint, which makes up for the defect that the classical Euclidean distance does not consider the distribution road information. This paper proposes a logistics distribution customer clustering algorithm, which improves CLARANS algorithm to make the clustering results meet the constraints of customer distribution volume. By using the single vehicle load rate, the sufficient conditions for logistics distribution customer clustering to be solvable under the condition of considering the ubiquitous and constraints are given, which effectively solves the problem of logistics distribution customer clustering with sum constraints. The results state clearly that the clustering algorithm can effectively deal with large-scale spatial data sets, and the clustering process is not affected by isolated customers, The clustering results can be effectively applied to the distribution center location, distribution cost optimization, distribution route optimization and distribution area division of vehicle scheduling optimization.

Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy

Background: Current risk assessment approaches fail to identify the majority of patients at risk of sudden cardiac arrest (SCA). Noninvasive imaging of the cardiac sympathetic nervous system using single-photon emission computed tomography and positron emission tomography offers the potential for refining SCA risk assessment. While various [ 11 C]meta-hydroxyephedrine quantification parameters have been proposed, it is currently unknown whether regional denervation or global innervation yields greater SCA risk discrimination. The aim of the study was to determine whether the global innervation parameters yield any independent and additive prognostic value over the regional denervation alone. Methods: In a post hoc competing-risks analysis of the PAREPET trial (Prediction of Arrhythmic Events With Positron Emission Tomography), we compared global innervation and regional denervation parameters using the norepinephrine analog [ 11 C]meta-hydroxyephedrine for SCA risk discrimination. Patients with ischemic cardiomyopathy (n=174) eligible for an implantable cardioverter-defibrillator for the primary prevention of SCA were recruited into the trial. [ 11 C]meta-hydroxyephedrine uptake and clearance rates were measured to assess global (left ventricle mean) retention index and volume of distribution. Regional defects were quantified as the percentage of the left ventricle having values <75% of the maximum. Results: During a median follow-up of 4.2 years, there were 56 cardiac-related deaths, of which 26 were SCAs. For any given regional denervation volume, there was substantial heterogeneity in global innervation scores. Global retention index and distribution volume did not decrease until regional defects exceeded 40% left ventricle. Global scale parameters, retention index, and distribution volume (area under the curve=0.61, P =0.034, P =0.046, respectively), yielded inferior SCA risk discrimination compared to regional heterogeneity (area under the curve=0.74). Conclusions: Regional denervation volume has superior cause-specific mortality prediction for SCA versus global parameters of sympathetic innervation. These results have widespread implications for future cardiac sympathetic imaging, which will greatly simplify innervation analysis. REGISTRATION: URL: ClinicalTrials.gov Identifier: NCT01400334 https://clinicaltrials.gov/ct2/show/NCT01400334

A double-blind placebo-controlled trial of minocycline on translocator protein distribution volume in treatment-resistant major depressive disorder

Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO VT), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans. Here, the ability of oral minocycline to reduce TSPO VT was assessed in TRD. To determine whether oral minocycline, as compared to placebo, can reduce prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula TSPO VT in TRD, twenty-one TRD participants underwent two [18F]FEPPA PET scans to measure TSPO VT. These were completed before and after either oral minocycline 100 mg bid or placebo which was administered in a randomized double-blinded fashion for 8 weeks. There was no significant difference between the minocycline and placebo groups on change in TSPO VT within the PFC, ACC, and insula (repeated measures ANOVA, effect of group interaction, PFC: F1,19 = 0.28, P = 0.60; ACC: F1,19 = 0.54, P = 0.47; insula F1,19 = 1.6, P = 0.22). Oral minocycline had no significant effect on TSPO VT which suggests that this dosage is insufficient to reduce gliosis in TRD. To target gliosis in TRD either alternative therapeutics or intravenous formulations of minocycline should be investigated. These results also suggest that across neuropsychiatric diseases in humans, it should be assumed that oral minocycline will not reduce TSPO VT or gliosis unless empirically demonstrated.

MO599COMPARISON OF TOTAL BODY WATER MEASURED BY BIOIMPEDANCE SPECTROSCOPY TO UREA DISTRIBUTION VOLUME ESTIMATED FROM UREA KINETIC MODELING IN HEMODIALYSIS PATIENTS

Background and Aims Monitoring of fluid, body composition and nutritional changes is important in clinical nephrology. The Body Composition Monitor (BCM; Fresenius Medical Care, Bad Homburg, Germany) measures whole-body bioimpedance and determines extracellular and intracellular resistance by using the Cole-model to estimate total body water (TBW-BCM) and its partition into extracellular and intracellular water. Both can then be used to define body composition and separate body weight into lean tissue mass, adipose tissue mass, and fluid overload. Urea kinetic modeling (UKM) allows the estimation of dialysis dose (double-pooled Kt/V), urea distribution volume (V-UKM) and dietary protein intake. We studied the bias between estimated V-UKM to anthropometric and measured TBW-BCM (Vant, TBW-BCM). Method Pre-hemodialysis (HD), electrodes for the BCM assessments were placed on the non-arteriovenous access arm and ipsilateral leg, respectively, with the patient in a supine position. Vant was calculated using the Watson equation. In addition to these assessments we entered the specified values from the most recent urea kinetic modeling (UKM) treatment into the online solute-solver calculator (http://ureakinetics.org). We chose a baseline ratio of modeled/anthropometric volume of 0.6 to 1.3 L to exclude values with data entry errors and/or UKM sampling errors. We calculated the post HD TBW-BCM by subtracting the intradialytic weight loss and adjusted these estimates by the differences in post HD weight between sessions to make both estimates comparable. We depicted the comparison between the estimated V-UKM versus the TBW-BCM in a scatter- and Bland-Altman (BA) plot (Figure). For the purpose of error investigation we studied the computed bias (V-UKM minus TBW-BCM) as a function of body mass index (BMI) and stray capacitance (td) in a BA plot. We then calculated the difference between Vant and V-UKM and illustrated the comparison in a scatter and BA plot. Results In a cross-sectional design, we studied 161 stable prevalent HD patients (61.3±14.7 years, 98 (60.9%) males, height of 167.5±10.7 cm) prior to their treatment. The regression plot showed slight agreement (R2= 0.69) and the Bland-Altman plot no systematic trends or proportional error in the main analysis (Figure 1a and b). Neither BMI or td explained bias and variance in the bias between both estimates. Vant and V-UKM plots showed agreement (R2 of 0.68) with a mean bias of -2.3±5.1 and no proportional error. Conclusion Both TBW-BCM and the V-UKM as the “bronze standard” of TBW estimation seemed to agree reasonably well. Neither body composition measurement or kinetic modeling approach showed any significant influence on the accuracy and precision of the estimate. According to BCM availability, estimated V-UKM or measured TBW-BCM could be used alternatively in practice to support clinical decision when pharmacokinetic considerations are concerned.

Drug Interaction Effect of Ketoprofen and Dexamethasone With Thiopental: A Pharmacokinetics and Anesthetics Study in Male Dogs

There is a growing concern about drug interactions on the pharmacokinetic parameters of anesthetics. The aim of this study was to evaluate the pharmacokinetic effects of thiopental anesthesia under the administration of ketoprofen and dexamethasone in the male dogs. 21 adult healthy male stray dogs weighing 21-23 kg were randomly divided into three groups. The control group received normal saline (0.2 ml/kg) 5 minutes before intravenous administration of thiopental (17 mg/kg), the T1 group received ketoprofen (2.2 mg/kg) 5 minutes before thiopental, and the T2 group received dexamethasone (0.2 mg/kg) 5 minutes before thiopental. After anesthesia, clinical parameters of anesthesia, heart rate, respiration rate and electrocardiography were measured. Serum sample was also used to assay thiopental concentration using HPLC method, and then thiopental pharmacokinetic parameters were calculated. Changes in rate of heart and respiration were significant intra-group differences 5 and 10 minutes after anesthesia.In addition, in the ketoprofen group, premature atrial contractions (PACs) were seen after induction of anesthesia with thiopental. Recovery time parameters showed a significant difference between T1 and control groups (P<0.05). Elimination and half-life of thiopental in the T1 group compared to the control and T2 groups showed a significant decrease and increase, respectively. In addition, the distribution volume of thiopental in T1 showed a significant increase compared to other groups. However, thiopental clearance in T1 and T2 groups did not show a significant decrease compared to control (P> 0.05). It can be concluded that dexamethasone can be used as an anti-inflammatory drug combination with thiopental in comparison with ketoprofen.

The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.