High-resolution magnetic resonance imaging of teeth and periodontal tissues using a microscopy coil.

Purpose: This study aimed to assess the performance of 2-dimensional (2D) imaging with microscopy coils in delineating teeth and periodontal tissues compared with conventional 3-dimensional (3D) imaging on a 3 T magnetic resonance imaging (MRI) unit. Materials and Methods: Twelve healthy participants (4 men and 8 women; mean age: 25.6 years; range: 20-52 years) with no dental symptoms were included. The left mandibular first molars and surrounding periodontal tissues were examined using the following 2 sequences: 2D proton density-weighted (PDw) images and 3D enhanced T1 high-resolution isotropic volume excitation (eTHRIVE) images. Two-dimensional MRI images were taken using a 3 T MRI unit and a 47 mm microscopy coil, while 3D MRI imaging used a 3 T MRI unit and head-neck coil. Oral radiologists assessed dental and periodontal structures using a 4-point Likert scale. Inter- and intra-observer agreement was determined using the weighted kappa coefficient. The Wilcoxon signed-rank test was used to compare 2D-PDw and 3D-eTHRIVE images. Results: Qualitative analysis showed significantly better visualization scores for 2D-PDw imaging than for 3D-eTHRIVE imaging (Wilcoxon signed-rank test). 2D-PDw images provided improved visibility of the tooth, root dental pulp, periodontal ligament, lamina dura, coronal dental pulp, gingiva, and nutrient tract. Inter-observer reliability ranged from moderate agreement to almost perfect agreement, and intra-observer agreement was in a similar range. Conclusion: Two-dimensional-PDw images acquired using a 3 T MRI unit and microscopy coil effectively visualized nearly all aspects of teeth and periodontal tissues.

Omega 3 Fatty Acids Attenuate the Acute Kidney Injury to CKD Transition and Renal Fibrosis: Identification of Antifibrotic Metabolites.

BACKGROUND: AKI is an established risk factor for developing CKD. Recently, the renoprotective effect of omega-3 polyunsaturated fatty acids (ω3PUFAs) has attracted attention. This study aimed to evaluate the effect of ω3PUFAs on the transition of AKI to CKD, and to identify fatty acid active metabolites in renal tissue. METHODS: Two mice models of AKI to CKD (7-week, male) and unilateral ureteral obstruction (UUO)-induced renal fibrosis (11-week, male) were fed linseed oil, rich in ω3PUFAs (Lin group), or with soybean oil, low in ω3PUFAs (Soy group). Renal fatty acids and metabolites composition in mice were measured by liquid chromatography-mass spectrometry. Rat renal fibroblast cells (NRK-49F cells) were used for in vitro study. RESULTS: At day 14 after 35 min bilateral renal ischemia reperfusion (IR), significant increase in survival was observed in the Lin group compared to the Soy group. Using the 30 min bilateral renal IR model (AKI to CKD model), the Lin group showed attenuated renal tissue damage and fibrosis. In addition, the antifibrotic effect of Lin group was also observed in UUO renal fibrosis model. In the two mice models, levels of eicosapentaenoic acid (EPA) and its metabolites were significantly elevated in renal tissue of mice fed with Lin. Cultured NRK-49F incubated with EPA and its metabolites 18-hydroxyeicosapentaenoic acid (18-HEPE), 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 17,18-dihydroxyeicosatetraenoic acid (17,18-diHETE) displayed suppressed TGF-ß1-stimulated α-smooth muscle actin protein expression. These effects were suppressed in the presence of an inhibitor of a cytochrome P450 involved in EPA metabolism. This observation suggests that the EPA metabolites have antifibrotic effects. CONCLUSIONS: ω3PUFAs prevents AKI to CKD and renal fibrosis. Moreover, the EPA metabolites 18-HEPE, 17,18-EpETE and 17,18-diHETE were found to have antifibrotic effects.

Impact and management of integrated dysphagia rehabilitation within cardiac care programs for older patients with cardiovascular disease.

PURPOSE: This study assessed the characteristics, management, and outcomes of dysphagia rehabilitation in older patients with CVD in a super-aged society, highlighting the need for comprehensive management strategies in community hospital settings. It aimed to uncover valuable insights into the benefits of integrating dysphagia rehabilitation with cardiac care in patient management. METHODS: We conducted a retrospective review of patients with CVD aged ≥ 65 years who were admitted to Niigata Minami Hospital between January 2019 and December 2021. We focused on patients requiring dysphagia rehabilitation and assessing the effects of these interventions on recovery. RESULTS: The study included 732 participants with an average age of 86.0 ± 7.8 years, of whom 41.9% were male. Approximately 55.1% required dysphagia rehabilitation. Dysphagia rehabilitation significantly improved oral caloric intake and BMI in patients who underwent rehabilitation, and these improvements were comparable to those in patients who did not require dysphagia rehabilitation. Significant enhancement in the ADL of patients was observed at discharge. Patients who required dysphagia rehabilitation also had longer hospital stays and were more likely to be discharged to nursing facilities. CONCLUSION: Dysphagia is common in older patients with CVD, and dysphagia rehabilitation positively affects the maintenance of nutritional status and helps patients achieve ADL independence at discharge. This study highlights the importance of integrating dysphagia rehabilitation into ordinary cardiac rehabilitation programs for older patients with CVD to improve their QOL.

Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH.

Neuronal and non-neuronal functions of the synaptic cell adhesion molecule neurexin in Nematostella vectensis.

The evolutionary transition from diffusion-mediated cell-cell communication to faster, targeted synaptic signaling in animal nervous systems is still unclear. Genome sequencing analyses have revealed a widespread distribution of synapse-related genes among early-diverging metazoans, but how synaptic machinery evolved remains largely unknown. Here, we examine the function of neurexins (Nrxns), a family of presynaptic cell adhesion molecules with critical roles in bilaterian chemical synapses, using the cnidarian model, Nematostella vectensis. Delta-Nrxns are expressed mainly in neuronal cell clusters that exhibit both peptidergic and classical neurotransmitter signaling. Knockdown of δ-Nrxn reduces spontaneous peristalsis of N. vectensis polyps. Interestingly, gene knockdown and pharmacological studies suggest that δ-Nrxn is involved in glutamate- and glycine-mediated signaling rather than peptidergic signaling. Knockdown of the epithelial α-Nrxn reveals a major role in cell adhesion between ectodermal and endodermal epithelia. Overall, this study provides molecular, functional, and cellular insights into the pre-neural function of Nrxns, as well as key information for understanding how and why they were recruited to the synaptic machinery.

Nonionizing diagnostic imaging modalities for visualizing health and pathology of periodontal and peri-implant tissues.

Radiographic examination has been an essential part of the diagnostic workflow in periodontology and implant dentistry. However, radiographic examination unavoidably involves ionizing radiation and its associated risks. Clinicians and researchers have invested considerable efforts in assessing the feasibility and capability of utilizing nonionizing imaging modalities to replace traditional radiographic imaging. Two such modalities have been extensively evaluated in clinical settings, namely, ultrasonography (USG) and magnetic resonance imaging (MRI). Another modality, optical coherence tomography (OCT), has been under investigation more recently. This review aims to provide an overview of the literature and summarize the usage of USG, MRI, and OCT in evaluating health and pathology of periodontal and peri-implant tissues. Clinical studies have shown that USG could accurately measure gingival height and crestal bone level, and classify furcation involvement. Due to physical constraints, USG may be more applicable to the buccal surfaces of the dentition even with an intra-oral probe. Clinical studies have also shown that MRI could visualize the degree of soft-tissue inflammation and osseous edema, the extent of bone loss at furcation involvement sites, and periodontal bone level. However, there was a lack of clinical studies on the evaluation of peri-implant tissues by MRI. Moreover, an MRI machine is very expensive, occupies much space, and requires more time than cone-beam computed tomography (CBCT) or intraoral radiographs to complete a scan. The feasibility of OCT to evaluate periodontal and peri-implant tissues remains to be elucidated, as there are only preclinical studies at the moment. A major shortcoming of OCT is that it may not reach the bottom of the periodontal pocket, particularly for inflammatory conditions, due to the absorption of near-infrared light by hemoglobin. Until future technological breakthroughs finally overcome the limitations of USG, MRI and OCT, the practical imaging modalities for routine diagnostics of periodontal and peri-implant tissues remain to be plain radiographs and CBCTs.

Contribution of Phe112, Ser114, and Tyr115 to Drug-Binding Selectivity in the A Variant of α1-Acid Glycoprotein.

The plasma protein α1-acid glycoprotein (AGP) primarily affects the pharmacokinetics of basic drugs. There are two AGP variants in humans, A and F1*S, exhibiting distinct drug-binding selectivity. Elucidation of the drug-binding selectivity of human AGP variants is essential for drug development and personalized drug therapy. Herein, we aimed to establish the contribution of amino acids 112 and 114 of human AGP to drug-binding selectively. Both amino acids are located in the drug-binding region and differ between the variants. Phe112/Ser114 of the A variant and its equivalent residues in the F1*S variant (Leu112/Phe114) were swapped with each other. Binding experiments were then conducted using the antiarrhythmic drug disopyramide, which selectively binds to the A variant. A significant decrease in the bound fraction was observed in each singly mutated A protein (Phe112Leu or Ser114Phe). Moreover, the bound fraction of the double A mutant (Phe112Leu/Ser114Phe) was decreased to that of wild-type F1*S. Intriguingly, the double F1*S mutant (Leu112Phe/Phe114Ser), in which residues were swapped with those of the A variant, showed only partial restoration in binding. The triple F1*S mutant (Leu112Phe/Phe114Ser/Asp115Tyr), where position 115 is thought to contribute to the difference in pocket size between variants, showed a further recovery in binding to 70% of that of wild-type A. These results were supported by thermodynamic analysis and acridine orange binding, which selectively binds the A variant. Together, these data indicate that, in addition to direct interaction with Phe112 and Ser114, the binding pocket size contributed by Tyr115 is important for the drug-binding selectivity of the A variant.

Evolution of glial cells: a non-bilaterian perspective.

Nervous systems of bilaterian animals generally consist of two cell types: neurons and glial cells. Despite accumulating data about the many important functions glial cells serve in bilaterian nervous systems, the evolutionary origin of this abundant cell type remains unclear. Current hypotheses regarding glial evolution are mostly based on data from model bilaterians. Non-bilaterian animals have been largely overlooked in glial studies and have been subjected only to morphological analysis. Here, we provide a comprehensive overview of conservation of the bilateral gliogenic genetic repertoire of non-bilaterian phyla (Cnidaria, Placozoa, Ctenophora, and Porifera). We overview molecular and functional features of bilaterian glial cell types and discuss their possible evolutionary history. We then examine which glial features are present in non-bilaterians. Of these, cnidarians show the highest degree of gliogenic program conservation and may therefore be crucial to answer questions about glial evolution.

Contribution of the α1-Acid Glycoprotein in Drug Pharmacokinetics: The Usefulness of α1-Acid Glycoprotein-Knockout Mice.

α1-Acid glycoprotein (AGP) is a primary binding protein for many basic drugs in plasma. The number of drugs that bind to AGP, such as molecular target anticancer drugs, has been continuously increasing. Since the plasma level of AGP fluctuates under various pathological conditions such as inflammation, it is important to evaluate the contribution of AGP to drug pharmacokinetics. Here, we generated conventional AGP-knockout (AGP-KO) mice and used them to evaluate the contribution of AGP. The pharmacokinetics of drugs that bind to two AGP variants (F1*S or A variants) or albumin were evaluated. Imatinib (a F1*S-binding drug) and disopyramide (an A-binding drug) or ibuprofen (an albumin-binding drug) were administered to wild-type (WT) and AGP-KO. The plasma level of imatinib and disopyramide decreased rapidly in AGP-KO as compared to WT. In AGP-KO, AUC and t1/2 were decreased, then CLtot was increased. Compared with disopyramide, imatinib pharmacokinetics showed more marked changes in AGP-KO as compared to WT. The results seemed to be due to the difference in plasma level of each AGP variant (F1*S:A = 2-3:1). No differences were observed in ibuprofen pharmacokinetics between the WT and AGP-KO mice. In vitro experiments using plasma from WT and AGP-KO showed that unbound fractions of imatinib and disopyramide were higher in AGP-KO. These results suggest that the rapid elimination of imatinib and disopyramide in AGP-KO could be due to decreased protein binding to AGP. Taken together, the AGP-KO mouse could be a potential animal model for evaluating the contribution of AGP to the pharmacokinetics of various drugs.

Concomitant Administration of Vancomycin with a High Dose of Meropenem May Cause Acute Kidney Injury.

Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a case of acute kidney injury (AKI) caused by coadministration of vancomycin with high-dose meropenem that manifested as a rapid increase in serum creatinine levels and an associated increase in vancomycin trough concentrations. The patient was diagnosed with meningioma at 50 years and was followed up regularly. The patient underwent surgery and antibiotic treatment between 63 and 66 years for suspected meningitis and pneumonia. Coadministration of vancomycin with high-dose meropenem (6.0 g/day) caused AKI; however, no AKI occurred when vancomycin was administered alone or with a low dose of meropenem (1.5 or 3.0 g/day). To our knowledge, this report is the first to show that administering different dosages of meropenem in combination with vancomycin may contribute to the risk of developing AKI. We suggest that coadministered vancomycin and high-dose meropenem (6.0 g/day) may increase the risk of AKI. Our report adds to the limited literature documenting the coadministration of vancomycin with varying doses of meropenem and its impact on the risk of AKI and highlights the importance of investigating AKI risk in response to varying dosages of meropenem when it is coadministered with vancomycin.

Accuracy of a portable lower-limb muscle strength measuring device with a training function.

[Purpose] Quadriceps muscle strength is essential for daily living activities. Therefore, we developed a compact and simple lower limb muscle strength measuring device (LocomoScan [LCS]). This study aimed to compare LCS with other instruments to analyze its simplicity, reproducibility, and accuracy. [Participants and Methods] One hundred and four healthy university students (56 males and 48 females) were included in the study. The knee extension force was measured using LCS, and the knee extension torque was measured using other devices (Cybex). In addition, lower leg muscle mass was measured using a body composition meter. The reproducibility of LCS and the correlation between the knee extension torque and lower leg muscle mass were evaluated. [Results] The measurement reproducibility of LCS was significantly higher. The knee extension force confirmed the proportional relative reliability of Cybex with knee extension torque. A relationship between knee extension force and lower limb muscle mass was also observed, indicating that muscle mass cannot be estimated as muscle strength. [Conclusion] The high reproducibility of the knee extension force measurement using LCS demonstrates its potential as a portable alternative instrument for muscle strength measurement in clinical practice. Therefore, LCS device is a simple and effective tool for assessing muscle strength.

Mirror-Image Human Serum Albumin Domain III as a Tool for Analyzing Site II-Dependent Molecular Recognition.

Human serum albumin (HSA) as a drug carrier can significantly improve the pharmacokinetic profiles of short-lived therapeutics. Conjugation of albumin-binding moieties (ABMs) to therapeutic agents may prolong their serum half-life by promoting their association with endogenous HSA. To discover a new molecular class of ABMs from mirror-image chemical space, a preparation protocol for bioactive HSA domain III and its d-enantiomer (d-HSA domain III) was established. Structural and functional analyses suggested that the synthetic protein enantiomers exhibited mirror-image structures and stereoselective neonatal fragement crystallizable receptor (FcRn) recognition. Additionally, the ligand-binding properties of synthetic l-HSA domain III were comparable with those of site II in native HSA, as confirmed using site II-selective fluorescent probes and an esterase substrate. Synthetic d-HSA domain III is an attractive tool for analyzing the site II-dependent molecular recognition properties of HSA.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Carbon monoxide-loaded cell therapy as an exercise mimetic for sarcopenia treatment.

Sarcopenia is characterized by loss of muscle strength and muscle mass with aging. The growing number of sarcopenia patients as a result of the aging population has no viable treatment. Exercise maintains muscle strength and mass by increasing peroxisome growth factor activating receptor γ-conjugating factor-1α (PGC-1α) and Akt signaling in skeletal muscle. The present study focused on the carbon monoxide (CO), endogenous activator of PGC-1α and Akt, and investigated the therapeutic potential of CO-loaded red blood cells (CO-RBCs), which is bioinspired from in vivo CO delivery system, as an exercise mimetic for the treatment of sarcopenia. Treatment of C2C12 myoblasts with the CO-donor increased the protein levels of PGC-1α which enhanced mitochondrial biogenesis and energy production. The CO-donor treatment also activated Akt, indicating that CO promotes muscle synthesis. CO levels were significantly elevated in the skeletal muscle of normal mice after intravenous administration of CO-RBCs. Furthermore, CO-RBCs restored the mRNA expression levels of PGC-1α in the skeletal muscle of two experimental sarcopenia mouse models, denervated (Den) and hindlimb unloading (HU) models. CO-RBCs also restored muscle mass in Den mice by activating Akt signaling and suppressing the muscle atrophy factors myostatin and atrogin-1, and oxidative stress. Treadmill tests further showed that the reduced running distance in HU mice was significantly restored by CO-RBC administration. These findings suggest that CO-RBCs have potential as an exercise mimetic for sarcopenia treatment.

Differentiation of radicular cysts and radicular granulomas via texture analysis of multi-slice computed tomography images.

OBJECTIVES: This study aimed to establish a method for differentiating radicular cysts from granulomas via texture analysis (TA) of multi-slice computed tomography (CT) images. METHODS: A total of 222 lesions with multi-slice computed tomography images acquired at our hospital between 2013 and 2022 that were pathologically diagnosed were included in this study. Cases of contrast-enhanced images, severe metallic artefacts, and lesions that were not sufficiently large to be analysed were excluded. The images were chronologically divided into a training group and a validation group. The radiological characteristics were determined. Subsequently, a TA was performed. Pyradiomics software was used for the TA of three-dimensionally segmented volumes extracted from 2 mm slice thickness images with a soft-tissue algorithm. Features that differed significantly between the two lesions in the training group were extracted and used to create machine-learning models. The discriminative ability of these models was evaluated in the validation group using receiver operating characteristic curve analysis. RESULTS: A total of 131 lesions, comprising 28 radicular cysts and 103 granulomas, were analysed. Forty-three texture features that exhibited significant variations were extracted. A support vector machine and decision tree model, with areas under the curves of 0.829 and 0.803, respectively, were created. These models showed high discriminative abilities, even for the validation group, with areas under the curve of 0.727 and 0.701, respectively. Both models showed superior performance compared with that of the models based on radiographic findings. CONCLUSION: Discriminatory models were established for the TA of radicular cysts and granulomas using CT images.

Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable Stage III non-small cell lung cancer.

BACKGROUND: Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown. METHODS: In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid. RESULTS: Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31-11.38) compared with no irAEs and 11.58 (95% CI, 2.11-63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8+ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration. CONCLUSIONS: The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid-treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.

Atezolizumab-related sclerosing cholangitis with multiple liver abscesses in a patient with lung squamous cell carcinoma: A case report.

A 76-year-old man underwent an operation for lung squamous cell carcinoma in the right lower lobe, followed by initial adjuvant therapy with atezolizumab, an antibody against anti-programmed death-ligand 1 (PD-L1). On day 4 after atezolizumab treatment, the patient developed general malaise and fatigue. He was diagnosed with atezolizumab-induced sclerosing cholangitis. Steroid treatment was started, and patient's condition, including symptoms, laboratory data and imaging findings, improved. Antibiotic treatments were ended on day 40, and the steroid dose was gradually reduced. Multiple liver abscesses were observed on day 106, and another treatment with antibiotics became necessary. The patient eventually recovered from liver abscesses. Sclerosing cholangitis induced by immune checkpoint inhibitor is rare, and the long-term clinical data about this adverse effect is limited. Hence, we think it is important to raise an alarm over sclerosing cholangitis coupled with liver abscesses after immunosuppressive therapy.

Impaired Cholesterol Efflux Capacity rather than Low HDL-C Reflects Oxidative Stress under Acute Myocardial Infarction.

AIMS: Acute myocardial infarction (AMI) causes irreversible damage to cardiomyocytes due to the discontinuation of oxygen supply and leads to systemic oxidative stress. It has been reported that high-density lipoprotein (HDL) particles have antioxidant capacity, and reduced antioxidant capacity is associated with decreased cholesterol efflux capacity (CEC). The purpose of this study was to clarify the usefulness of CEC measurement in patients with AMI. METHODS: We investigated the association between CEC and oxidative stress status in a case-control study. This study included 193 AMI cases and 445 age- and sex-matched controls. We examined the associations of CEC with HDL-cholesterol (HDL-C) and oxidized human serum albumin (HSA), an index of systemic oxidative stress status, and the effect of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which has been reported to affect HDL-C level and risk for MI, on these associations. RESULTS: Both bivariable and multivariable analyses showed that CEC was positively correlated with HDL-C levels in both AMI cases and controls, with a weaker correlation in AMI cases than in controls. In AMI cases, oxidized HSA levels were associated with CEC in both bivariable and multivariable analyses, but not with HDL-C. These associations did not differ among the ALDH2 genotypes. CONCLUSIONS: CEC, but not HDL-C level, reflects systemic oxidative stress status in patients with AMI. CEC measurement for patients with AMI may be useful in that it provides information on systemic oxidative stress status as well as atherosclerosis risk.

Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis.

The pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known to have anti-oxidative, anti-inflammatory, and anti-apoptotic effects. However, Trx is a low molecular weight protein and is rapidly eliminated from the blood. To overcome the low availability of Trx, HSA-Trx fusion protein was produced and evaluated the therapeutic effect on high-fat diet (HFD)-induced NASH model mice. HSA-Trx administered before the formation of NASH pathology showed it to have a preventive effect. Specifically, HSA-Trx was found to prevent the pathological progression to NASH by suppressing lipid accumulation, liver injury markers, and liver fibrosis. When HSA-Trx was administered during the early stage of NASH there was a marked reduction in lipid accumulation, inflammation, and fibrosis in the liver, indicating that HSA-Trx ameliorates NASH pathology. The findings indicate that HSA-Trx influences multiple pathological factors, such as oxidative stress, inflammation, and apoptosis, to elicit a therapeutic benefit. HSA-Trx also inhibited palmitic acid-induced lipotoxicity in HepG2 cells. Taken together, these results indicate that HSA-Trx has potential as a therapeutic agent for NASH pathology.

Visually induced symptoms questionnaire (VISQ): A subjective evaluation method for biomedical effects induced by stereoscopic 3D video.

The purpose of this paper is to establish an easy-to-use questionnaire for subjective evaluations of visually induced motion sickness (VIMS) and visual fatigue caused by stereoscopic 3D (s3D) images. We reviewed previously used questionnaires and extracted 51 important subjective evaluation items from them. We then recruited 251 participants to observe 3D images designed to easily induce sickness or visual fatigue, and we asked them to respond to the 51 items. As a result of exploratory factor analysis, four factors were extracted according to their factor loadings, and the number of items was reduced to 21. Further processing by confirmatory factor analysis led to the selection of 15 items. Comparing mean ratings for each factor before and after item reduction indicated that item reduction did not significantly affect the participant responses. Therefore, the 15-item Visually Induced Symptoms Questionnaire (VISQ), can be used to evaluate VIMS and s3D visual fatigue.