Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer.

Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.

New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways.

Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of the present study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose-dependent way. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) levels and apoptotic cells with caspase-3 and -9 activation. HL156A inhibited the expression and activation of insulin-like growth factor (IGF)-1 and its downstream proteins, AKT, mammalian target of rapamycin (mTOR), and ERK1/2. In addition, HL156A activated AMP-activated protein kinase/nuclear factor kappa B (AMPK-NF-κB) signaling of FaDu and YD-10B cells. A xenograft mouse model further showed that HL156A suppressed AT84 mouse oral tumor growth, accompanied by down-regulated p-IGF-1, p-mTOR, proliferating cell nuclear antigen (PCNA) and promoted p-AMPK and TUNEL expression. These results suggest the potential value of the new metformin derivative HL156A as a candidate for a therapeutic modality for the treatment of oral cancer.

Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury.

OBJECTIVE: The aim of this study was to assess, in two experiments, the safety and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test the hypothesis that early administration of this oxygen-carrying fluid post-TBI would improve brain tissue oxygenation (Pbt O2 ). METHODS: The first experiment assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured rats using intravital microscopy. The second experiment investigated the effect of Oxycyte on cerebral Pbt O2 using the PQM in TBI model. Animals in the Oxycyte group received a single injection of Oxycyte (6 mL/kg) shortly after TBI, while NON animals received no treatment. RESULTS: Oxycyte did not cause vasoconstriction in small- (<50 µm) or medium- (50-100 µm) sized pial arterioles nor did it cause a significant change in blood pressure. Treatment with Oxycyte while breathing 100% O2 did not improve Pbt O2 . However, in rats ventilated with ~40% O2 , Pbt O2 improved to near pre-TBI values within 105 minutes after Oxycyte injection. CONCLUSIONS: Although Oxycyte did not cause cerebral vasoconstriction, its use at the dose tested while breathing 100% O2 did not improve Pbt O2 following TBI. However, Oxycyte treatment while breathing a lower enriched oxygen concentration may improve Pbt O2 after TBI.

Evaluation of the Accelerate Pheno™ system for rapid identification and antimicrobial susceptibility testing of Gram-negative bacteria in bloodstream infections.

Identification and antimicrobial susceptibility testing (AST) are critical steps in the management of bloodstream infections. Our objective was to evaluate the performance of the Accelerate Pheno™ System, CE v1.2 software, for identification and AST of Gram-negative pathogens from positive blood culture bottles. A total of 104 bottles positive for Gram-negative bacteria collected from inpatients throughout our institution were randomly selected after Gram staining. The time-to-identification and AST results, and the raw AST results obtained by the Accelerate Pheno™ system and routine techniques (MALDI-TOF MS and VITEK®2, EUCAST guidelines) were compared. Any discrepant AST result was tested by microdilution. The Pheno™ significantly improved turn-around times for identification (5.3 versus 23.7 h; p < 0.0001) and AST (10.7 versus 35.1 h; p < 0.0001). Complete agreement between the Accelerate Pheno™ system and the MALDI-TOF MS for identification was observed for 96.2% of samples; it was 99% (98/99) for monomicrobial samples versus 40% (3/5) for polymicrobial ones. The overall categorical agreement for AST was 93.7%; it was notably decreased for beta-lactams (cefepime 84.4%, piperacillin-tazobactam 86.5%, ceftazidime 87.6%) or Pseudomonas aeruginosa (71.9%; with cefepime 33.3%, piperacillin-tazobactam 77.8%, ceftazidime 0%). Analysis of discrepant results found impaired performance of the Accelerate Pheno™ system for beta-lactams (except cefepime) in Enterobacteriales (six very major errors) and poor performance in P. aeruginosa. The Accelerate Pheno™ system significantly improved the turn-around times for bloodstream infection diagnosis. Nonetheless, improvements in the analysis of polymicrobial samples and in AST algorithms, notably beta-lactam testing in both P. aeruginosa and Enterobacteriales, are required for implementation in routine workflow.

Child and Maternal Factors That Influence Child Blood Pressure in Preschool Children: An Exploratory Study.

PURPOSE: Hypertension is a risk factor for cardiovascular disease (CVD) in adults and children and has its origins in childhood. While the prevalence of hypertension in children is estimated to be 2 to 5%, instance elevations in blood pressure readings (BPRs) in school-age children and adolescents are more common, track to adulthood, and are an independent risk factor for CVD. Less information is available about BPR in the preschool period and what child factors could influence those BPR. The primary aims of this exploratory study were to determine child blood pressure (BP) levels and determine effect sizes of the relationships between child and maternal factors that can influence child BP. METHODS: A convenience sample of 15 rural and 15 urban children enrolled in Head Start programs (13 males; 14 females; all black) with ability to understand and speak English and with mothers who gave consent and could understand, read and speak English were enrolled. Mothers completed demographic information about their child including, gender, birth history and age. Height, weight, waist circumference and BP were measured in the mothers and the children. Children gave saliva specimens for cortisol and C-reactive protein. RESULTS: Over 37% of the children had elevated BPR with over 20% at or above the 95th percentile. Effect sizes of relationships ranged from very small to large. CONCLUSION: Elevations in BPR may be seen as early as preschool. It is important to examine factors, both child and maternal that influence BP.

Association between chlorinated pesticides in the serum of prepubertal Russian boys and longitudinal biomarkers of metabolic function.

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, ß-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)(2))) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p'-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p'-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12-13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin.

Environmental drivers impact the accumulation and diversity of antibiotic resistance in green stormwater infrastructure.

Antibiotic resistance poses an urgent public health concern, with the environment playing a crucial role in the development and dissemination of resistant bacteria. There is a growing body of research indicating that stormwater is a significant source and transport vector of resistance elements. This research sought to characterize the role of green stormwater infrastructure (GSI), designed for stormwater infiltration, in accumulating and propagating antibiotic resistance in the urban water cycle. Sampling included 24 full-scale GSI systems representing three distinct types of GSI - bioswales, bioretention cells, and constructed wetlands. The results indicated that GSI soils accumulate antibiotic resistance genes (ARGs) at elevated concentrations compared to nonengineered soils. Bioretention cells specifically harbored higher abundances of ARGs, suggesting that the type of GSI influences ARG accumulation. Interestingly, ARG diversity in GSI soils was not impacted by the type of GSI design or the diversity of the microbial community and mobile genetic elements. Instead, environmental factors (catchment imperviousness, metals, nutrients, and salts) were identified as significant drivers of ARG diversity. These findings highlight how environmental selective pressures in GSI promote ARG persistence and proliferation independently of the microbial community. Therefore, GSI systems have the potential to be a substantial contributor of abundant and diverse ARGs to the urban water cycle.

The fuzzy Kullback-Leibler divergence for estimating parameters of the probability distribution in fuzzy data: an application to classifying Vietnamese Herb Leaves.

In this paper, we address the challenge of estimating probability distributions which are typically represented by parameter-based values. However, this estimation is prone to errors and does not comprehensively capture the nature of real-world data. Additionally, real-world data often follows a mixed form of probability distributions, where sub-datasets may contain incomplete information. To enhance flexibility, especially in classification problems, we propose a new method for describing parameters estimated through Bayesian statistics. Our method introduces fuzzy parameters and assesses the similarity between probability distributions using the fuzzy extended Kullback-Leibler divergence. We demonstrate the practical application of our approach in Vietnamese Herb Leaves classification. By incorporating fuzzy parameters and leveraging Bayesian statistics, our method provides more robust estimations of probability distributions and enables improved flexibility in classification tasks.

Detection of Abnormality in Coronary Artery Magnetic Resonance Imaging using Bit Plane Slicing and Deep Learning.

INTRODUCTION: This paper presents a novel approach for detecting abnormality in coronary arteries using MRI data in RGB images. The study evaluates the test accuracy of the weak classifiers and the test accuracy and F1 score of the strong classifier. METHODS: The method involves separating the image into information planes, including R, G, and B color space, or bit-planes, and training a VGG-like convolutional neural network model on each plane separately, referred to as a "weak classifier." The classification results of these planes are aggregated using a proposed soft voting method, forming a "strong classifier," with the weights for the aggregation determined by the model's performance on the training set. RESULTS: The results indicate that the strong classifier achieves a test accuracy and F1 score of around 68% to 74% on our private coronary artery dataset. Moreover, by aggregating the top three highest bit-plane levels in a grayscale image, the accuracy is slightly lower than that of the three color spaces but requires a significantly smaller CNN model of nearly 4M parameters. CONCLUSION: The potential of bit-planes in reducing model storage costs is suggested. This approach holds promise for improving the detection of abnormalities in coronary arteries using MRI data.

Microscopic Video-Based Grouped Embryo Segmentation: A Deep Learning Approach.

PURPOSE: The primary aim of this research is to enhance the utilization of advanced deep learning (DL) techniques in the domain of in vitro fertilization (IVF) by presenting a more refined approach to the segmentation and organization of microscopic embryos. This study also seeks to establish a comprehensive embryo database that can be employed for future research and educational purposes. METHODS: This study introduces an advanced methodology for embryo segmentation and organization using DL. The approach comprises three primary steps: Embryo Segmentation Model, Segmented Embryo Image Organization, and Clear and Blur Image Classification. The proposed approach was rigorously evaluated on a sample of 5182 embryos extracted from 362 microscopic embryo videos. RESULTS: The study's results show that the proposed method is highly effective in accurately segmenting and organizing embryo images. This is evidenced by the high mean average precision values of 1.0 at an intersection over union threshold of 0.5 and across the range of 0.5 to 0.95, indicating a robust object detection capability that is vital in the IVF process. Segmentation of images based on various factors such as the day of development, patient, growth medium, and embryo facilitates easy comparison and identification of potential issues. Finally, appropriate threshold values for clear and blur image classification are proposed. CONCLUSION: The suggested technique represents an indispensable stage of data preparation for IVF training and education. Furthermore, this study provides a solid foundation for future research and adoption of DL in IVF, which is expected to have a significant positive impact on IVF outcomes.

Correlation between energy band transition and optical absorption spectrum in bilayer armchair graphene nanoribbons.

In this work, we investigate the intrinsic as well as modulated optical properties of the AB-stacking bilayer armchair graphene ribbons in the absence and presence of external electric fields. Single-layer ribbons are also considered for comparison. By using a tight-binding model in combination with the gradient approximation, we examine the energy bands, the density of states and the absorption spectra of the studied structures. Our results demonstrate that when external fields are not present, the low-frequency optical absorption spectra display numerous peaks and they vanish at the zero point. In addition, the number, the position, and the intensity of the absorption peaks are strongly associated with the ribbon width. With the wider ribbon width, more absorption peaks are present and a lower threshold absorption frequency is observed. Interestingly, in the presence of electric fields, bilayer armchair ribbons exhibit a lower threshold absorption frequency, more absorption peaks, and weaker spectral intensity. When increasing the strength of the electric field, the prominent peaks of the edge-dependent selection rules are lowered, and the sub-peaks satisfying the extra selection rules come to exist. The obtained results certainly provide a more comprehensive understanding of the correlation between the energy band transition and the optical absorption, in both single-layer and bilayer graphene armchair ribbons, and could provide new insights into developments of optoelectronic device applications based on graphene bilayer ribbons.

Influence of thickness and morphology of MoS2 on the performance of counter electrodes in dye-sensitized solar cells.

Non-platinum electrodes for photoelectric devices are challenging and attractive to the scientific community. A thin film of molybdenum disulfide (MoS2) was prepared on substrates coated with fluorine-doped tin oxide (FTO) to substitute the platinum counter electrode (CE) for dye-sensitized solar cells (DSSCs). Herein, we synthesized layered and honeycomb-like MoS2 thin films via the cyclic voltammetry (CV) route. Thickness and morphology of the MoS2 thin films were controlled via the concentration of precursor solution. The obtained results showed that MoS2 thin films formed at a low precursor concentration had a layered morphology while a honeycomb-like MoS2 thin film was formed at a high precursor concentration. Both types of MoS2 thin film were composed of 1T and 2H structures and exhibited excellent electrocatalytic activity for the I3 -/I- redox couple. DSSCs assembled using these MoS2 CEs showed a maximal power conversion efficiency of 7.33%. The short-circuit value reached 16.3 mA·cm-2, which was higher than that of a conventional Pt/FTO CE (15.3 mA·cm-2). This work reports for the first time the possibility to obtain a honeycomb-like MoS2 thin film morphology by the CV method and investigates the effect of film structure on the electrocatalytic activity and photovoltaic performance of CEs for DSSC application.

Correlation of Chest X-Ray Scores in SARS-CoV-2 Patients With the Clinical Severity Classification and the Quick COVID-19 Severity Index.

Objectives This study aimed to assess the role of chest X-ray (CXR) scoring methods and their correlations with the clinical severity categories and the Quick COVID-19 Severity Index (qCSI). Methods We conducted a retrospective study of 159 COVID-19 patients who were diagnosed and treated at the University Medical Center between July and September 2021. Chest X-ray findings were evaluated, and severity scores were calculated using the modified CXR (mCXR), Radiographic Assessment of Lung Edema (RALE), and Brixia scoring systems. The three scores were then compared to the clinical severity categories and the qCSI using Spearman's correlation coefficient. Results Overall, 159 patients (63 males and 96 females) (mean age: 58.3 ± 15.7 years) were included. The correlation coefficients between the mCXR score and the Brixia and RALE scores were 0.9438 and 0.9450, respectively. The correlation coefficient between the RALE and Brixia scores was marginally higher, at 0.9625. The correlation coefficients between the qCSI and the Brixia, RALE, and mCXR scores were 0.7298, 0.7408, and 0.7156, respectively. The significant difference in the mean values of the three CXR scores between asymptomatic, mild, moderate, severe, and critical groups was also noted. Conclusions There were strong correlations between the three CXR scores and the clinical severity classification and the qCSI.

Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.

Multidrug resistance is a significant clinical crisis in cancer treatment and has been linked to the cellular expression of multidrug efflux transporters. The aim of this study was to examine the effects and mechanisms of the metformin derivative HL156A on human multidrug resistance (MDR) cancer cells. Here, HL156A significantly suppressed cell growth and colony formation through G2/M phase cell cycle arrest in MDR cancer cells. HL156A also reduced the wound closure rate and cell migration and induced caspase-3-dependent apoptosis. We found that HL156A inhibited the expression of MDR1 by inhibiting the HOXC6-mediated ERK1/2 signaling pathway and increased the sensitivity to paclitaxel or doxorubicin in MDR cells. Furthermore, HL156A significantly inhibited angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These results suggest the potential of the metformin derivative HL156A as a candidate therapeutic modality for the treatment of human multidrug-resistant cancers.

Preliminary study of clinical outcomes for single implant-retained mandibular overdentures.

This study evaluated marginal bone loss and prosthetic complications associated with single implant-retained mandibular overdentures (1-IODs) with locator attachments. The 1-IOD was placed in the mandibular midline by using a conventional loading protocol in 22 patients with an edentulous mandible. Marginal bone loss at the start of loading and 12 months postoperatively was assessed by radiographic and crestal bone evaluation. The crestal bone was defined as the distance between the customized abutment shoulder and the top of the bone, as indicated by probing. In addition, implant stability quotient and prosthetic complications were recorded. The cumulative implant survival rate was 95.5%. Median implant stability quotient remained greater than 80, and median radiographic bone loss was 0.56 mm. Crestal measurement showed a median crestal bone loss of 0.16, 0.43, 0.39, and 0.52 mm on the buccal, right, lingual, and left sides, respectively. Both radiographic and crestal bone loss values significantly differed between the start of implant loading and 12 months postoperatively (except on the buccal and lingual sides; P < 0.05). The need to replace the nylon insert was the most common complication. Conventional loading of a 1-IOD with a locator attachment resulted in a high survival rate, good implant stability, and acceptable marginal bone loss.

Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428.

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.

Novel pressure-induced topological phase transitions of supercooled liquid and amorphous silicene.

This molecular dynamics (MD) simulation carries a detailed analysis of a pressure-induced structural transition supercooled liquid and amorphous silicene (a-silicene). Low-density models of supercooled liquid and a-silicene containing 10 000 atoms are obtained by rapid cooling processes from the melts. Then, an a-silicene model at T = 1000 K, a supercooled liquid model at T = 1500 K and a liquid silicon model at T = 2000 K have been isothermally compressed step by step up to a high density in order to observe the pressure-induced structural changes. Specifically 'Cairo tiling' pentagonal and square lattices of silicene are discovered in our calculations. Structural properties of those penta-silicene and tetra-silicene models have been carefully analyzed through the radial distribution functions, interatomic distances, bond-angle distributions under high-pressure condition. The dependence of pressure on formation behaviors is calculated via pressure-volume and energy-density relationships. The first order transition from low-density supercooled liquid/amorphous silicene to high-density penta-silicene and continuous transition from low-density liquid to high-density tetra-silicene are discussed. Atomic mechanism and sp3/sp2 hybridization evolution are inspected whereas the role of low-membered ring defects/boundary promises remarkable application and advanced research in future.

Hypobaria during long-range flight resulted in significantly increased histopathological evidence of lung and brain damage in a swine model.

BACKGROUND: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine. METHODS: Anesthetized Yorkshire swine underwent a simulated 4 h "transport" to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis. RESULTS: All parameters were similar prior to and after "transport" with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals. CONCLUSION: Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.

Antioxidant modifications induced by the new metformin derivative HL156A regulate metabolic reprogramming in SAMP1/kl (-/-) mice.

Aging is characterized by a reduced ability to defend against stress, an inability to maintain homeostasis, and an increased risk of disease. In this study, a metabolomics approach was used to identify novel metabolic pathways that are perturbed in a mouse model of accelerated aging (SAMP1/kl-/-) and to gain new insights into the metabolic associations of the metformin derivative HL156A. Extensive inflammation and calcification were observed in the tissues of the SAMP1/kl-/- mice with premature aging. In mouse embryonic fibroblasts (MEFs) obtained from SAMP1/kl-/- mice, we observed that HL156A induced FOXO1 expression through inhibition of the IGF-1/AKT/mTOR signaling pathways. Treatment of HL156A decreased reactive oxygen species production and enhanced mitochondrial transmembrane potential in SAMP1/kl-/- MEFs. A metabolomic profile analysis showed that HL156A increased the GSH/GSSG ratio in the kidneys of SAMP1/kl-/- mice (8-12 weeks old). In addition, treating SAMP1/kl-/- mice with HL156A (30 mg/kg) for 4 weeks improved survival and decreased the significant elevation of oxidized GSH (GSSG) that was observed in SAMP1/kl-/- mice. In histological sections, HL156A administered SAMP1/kl-/- mice exhibited a decrease in excessive calcification. Based on these findings, we conclude that the new metformin derivative HL156A may inhibit oxidative damage by inducing glutathione metabolism and antioxidant pathways.

The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

BACKGROUND: Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. METHODS: This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular denture types. Clinical outcomes, such as implant survival rate, marginal bone loss, and prosthodontic complications, will also be recorded. DISCUSSION: The results of this randomized crossover trial will clarify whether mandibular single implants and overdentures for edentulous individuals provide better patient general satisfaction when compared to conventional complete dentures. TRIAL REGISTRATION: This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000017883).