Cardiac autonomic modulation and exercise capacity in older adults with intellectual disability: A 6-month randomised control trial.

BACKGROUND: Despite reported physical and functional improvements with aerobic and sprint interval training (SIT) protocols in individuals with intellectual disability (ID), it is not known if these interventions' effectivity would promote improvements in cardiac autonomic modulation. This study aimed to investigate if a 6-month SIT or a continuous aerobic programme could enhance physical performance and cardiac autonomic modulation at rest, during physical activity (PA) and after it in older adults with an ID. METHODS: This is a randomised control trial. Participants with ID (age: 50.58 ± 7.25) were allocated to one of three groups [multicomponent aerobic training group (MATG), multicomponent interval sprint training group (MISTG) and control group (CG)]. The programmes lasted 24 weeks, with three sessions/week, 75-90 min per session. The HRV was analysed at rest and recovery, the delta of heart rate (HR) was analysed during 6MWT, and the HR t-off kinetics was analysed in recovery after 6MWT. RESULTS: There were not found differences between groups, moments, or interaction for cardiac autonomic modulation at rest and recovery. During exercise, only MSITG showed a significant increase of HR between rest and the first 30 s of exercise (P < 0.05). Physical performance increased only in MSITG (P < 0.05), while CG showed a significant reduction (P < 0.01). CONCLUSIONS: The MSITG improved the physical performance and the vagal withdrawal at the beginning of the submaximal exercise. These findings suggest that high-intensity exercise may positively impact baroreflex function, mitigating the decline in autonomic reflex response capacity associated with aging in individuals with ID.

Association between evacuation and becoming overweight after the Great East Japan Earthquake: a 7-year follow-up of the Fukushima Health Management Survey.

OBJECTIVES: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake. STUDY DESIGN: This was a prospective cohort study. METHODS: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model. RESULTS: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women. CONCLUSION: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.

Development of a patient decision aid for discharge planning of hospitalized patients with stroke.

BACKGROUND: Patient involvement in discharge planning of patients with stroke can be accomplished by providing personalized outcome information and promoting shared decision-making. The aim of this study was to develop a patient decision aid (PtDA) for discharge planning of hospitalized patients with stroke. METHODS: A convergent mixed methods design was used, starting with needs assessments among patients with stroke and health care professionals (HCPs). Results of these assessments were used to develop the PtDA with integrated outcome information in several co-creation sessions. Subsequently, acceptability and usability were tested to optimize the PtDA. Development was guided by the International Patient Decision Aids Standards (IPDAS) criteria. RESULTS: In total, 74 patients and 111 HCPs participated in this study. A three-component PtDA was developed, consisting of: 1) a printed consultation sheet to introduce the options for discharge destinations, containing information that can be specified for each individual patient; 2) an online information and deliberation tool to support patient education and clarification of patient values, containing an integrated "patients-like-me" model with outcome information about discharge destinations; 3) a summary sheet to support actual decision-making during consultation, containing the patient's values and preferences concerning discharge planning. In the acceptability test, all qualifying and certifying IPDAS criteria were fulfilled. The usability test showed that patients and HCPs highly appreciated the PtDA with integrated outcome information. CONCLUSIONS: The developed PtDA was found acceptable and usable by patients and HCPs and is currently under investigation in a clinical trial to determine its effectiveness.

Risk prediction model for early outcomes of revascularization for chronic limb-threatening ischaemia.

BACKGROUND: Quantifying the risks and benefits of revascularization for chronic limb-threatening ischaemia (CLTI) is important. The aim of this study was to create a risk prediction model for treatment outcomes 30 days after revascularization in patients with CLTI. METHODS: Consecutive patients with CLTI who had undergone revascularization between 2013 and 2016 were collected from the JAPAN Critical Limb Ischemia Database (JCLIMB). The cohort was divided into a development and a validation cohort. In the development cohort, multivariable risk models were constructed to predict major amputation and/or death and major adverse limb events using least absolute shrinkage and selection operator logistic regression. This developed model was applied to the validation cohort and its performance was evaluated using c-statistic and calibration plots. RESULTS: Some 2906 patients were included in the analysis. The major amputation and/or mortality rate within 30 days of arterial reconstruction was 5.0 per cent (144 of 2906), and strong predictors were abnormal white blood cell count, emergency procedure, congestive heart failure, body temperature of 38°C or above, and hemodialysis. Conversely, moderate, low or no risk in the Geriatric Nutritional Risk Index (GNRI) and ambulatory status were associated with improved results. The c-statistic value was 0.82 with high prediction accuracy. The rate of major adverse limb events was 6.4 per cent (185 of 2906), and strong predictors were abnormal white blood cell count and body temperature of 38°C or above. Moderate, low or no risk in the GNRI, and age greater than 84 years were associated with improved results. The c-statistic value was 0.79, with high prediction accuracy. CONCLUSION: This risk prediction model can help in deciding on the treatment strategy in patients with CLTI and serve as an index for evaluating the quality of each medical facility.

Nationwide study of surgery for primary infected abdominal aortic and common iliac artery aneurysms.

BACKGROUND: Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. METHODS: A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). RESULTS: Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P < 0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P = 0.093 and P =0.472 respectively). CONCLUSION: In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes.

We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a ß-blocker-based strategy (ß-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 × 10-8). rs11124945 G allele carriers had lower odds for NOD when exposed to the ß-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24-0.60), P=4.0 × 10-5), whereas A/A homozygotes exposed to the ß-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39-2.92), P=2.0 × 10-4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression.

Vascular endothelial growth factors C and D and lymphangiogenesis at the early stage of esophageal squamous cell carcinoma progression.

We conducted a detailed study of lymphangiogenesis and subsequent lymph node metastasis in early-stage esophageal squamous cell carcinoma (ESCC) using immunostaining for D2-40 and vascular endothelial growth factor (VEGF)-C and D. The study materials included 13 samples of normal squamous epithelium, 6 samples of low-grade intraepithelial neoplasia (LGIN), and 60 samples of superficial ESCC (M1 and M2 cancer 24; M3 or deeper cancer 36). We assessed lymphatic vessel density (LVD) using D2-40 and immunoreactivity for VEGF-C and D in relation to histological type, lymphatic invasion, and lymph node metastasis. LVD in M1 and M2 lesions and M3 or deeper lesions was significantly higher than in normal squamous epithelium (P < 0.001). High expression of VEGF-C and D was observed in M1 and M2 cancer and in M3 or deeper cancer, but not in normal squamous epithelium or LGIN. LVD in VEGF-C- and D-positive cases was significantly higher than in negative cases (P < 0.001). In M3 or deeper cancer, the correlation between VEGF-C or D status and lymphatic invasion or lymph node metastasis was not significant. LVD in cases with positive lymphatic invasion and those with lymph node metastasis was significantly higher than in cases lacking either (P = 0.02 and 0.03, respectively). ESCC cells produce VEGF-C and D from the very early stage of progression. VEGF-C and D activate lymphangiogenesis, and this increase of lymphatic vessels leads to lymphatic invasion and subsequent lymph node metastasis.

The fate of Osterix-expressing mesenchymal cells in dental root formation and maintenance.

OBJECTIVES: Osterix (Osx)-expressing mesenchymal cells are progenitors for tooth root forming cells. The aim of this study was to reveal the fates of Osx-expressing cells during and after root formation using a lineage tracing experiment. MATERIAL AND METHODS: To reveal the fates of Osx-expressing dental mesenchymal progenitors, we took advantage of tamoxifen-inducible Cre reporter system. Osx-creER; R26R-tdTomato mice received tamoxifen (0.1 mg/body) at postnatal day 3 (P3). In this system, Osx-expressing at P3 (Osx-P3) cells undergo recombination, and they and their descendants continue to express Tomato red fluorescence protein permanently. Mandibles were dissected at serial time points ranging from P4 to P116 to investigate how Osx-P3 cells participated in root formation. Tomato+ cells on frozen sections were imaged under fluorescence microscopy. RESULTS: Osx-P3 cells and their descendants differentiated into all kinds of cells that contributed to the root and periodontal tissues, such as odontoblasts, cementoblasts, alveolar bone osteoblasts and periodontal ligament (PDL) cells during root formation. Even after root formation was completed, they persisted in dental pulp and PDL to provide progenitor cells for odontoblasts and cementoblasts. CONCLUSION: Osx-expressing cells play important roles in the entire processes of tooth root formation; their progeny continue to contribute to maintenance of tooth root even after root formation is complete.

Sequence and localization of an ultraviolet (sws1) opsin in the retina of the Japanese sardine Sardinops melanostictus (Teleostei: Clupeiformes).

A full-length complementary (c)DNA encoding ultraviolet (UV)-sensitive opsin (sws1) was isolated from the retina of the Japanese sardine Sardinops melanostictus. The sws1 phylogenetic tree showed a sister group relationship with the Cypriniformes, following the ray-finned fish phylogeny. By expressing reconstituted opsin in vitro, it was determined that the maximum absorbance spectrum (λmax ) of sws1 is around 382 nm, being intermediate in position between two subtypes of sws1 pigment that are UV sensitive (λmax = 355-380 nm) and violet sensitive (λmax = 388-455 nm), which have been reported to date. The ocular media transmitted >20% transmittance of light in the range of 360-600 nm. In situ hybridization analyses revealed that sws1 messenger (m)RNA is localized in a central single cone surrounded by four double cones in a square mosaic. The square mosaic occupies the ventro-temporal quadrant of the retina and the in situ hybridization signals were dominant in this area suggesting that the fish may use UV vision when looking upward. Based on these results, considerable significances of potential UV sensitivity, in relation to characteristic habits of S. melanostictus, are discussed.

Demethylation of an NF-κB enhancer element orchestrates iNOS induction in osteoarthritis and is associated with altered chondrocyte cell cycle.

OBJECTIVE: To examine the methylation profile of the nuclear factor (NF)-κB enhancer region at -5.8 kb of inducible nitric oxide synthase (iNOS) and the subsequent role in the induction of osteoarthritis (OA) via cell cycle regulation. METHODS: Percentage methylation was determined by pyrosequencing, gene expression by qRT-PCR and cell proliferation was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Transient transfections were induced to determine the effect of the NF-κB enhancer region on cell proliferation and the influence of DNA methylation. RESULTS: In vitro de-methylation with 5-aza-dC showed decreased levels of DNA methylation at CpG sites localised at -5.8 kb, which correlated with higher levels of iNOS expression. In vitro methylation of the NF-κB enhancer region at -5.8 kb increased the percentage of cells at G0/G1 cell cycle phase. Loss of methylation within this region correlated with, enhanced proliferation and increased number of cells at G2/M phase. OA chondrocytes demonstrated up-regulation of the G0/G1 cell cycle progression markers Cyclin D1 and CDK6 in contrast to control cells. We demonstrate the loss of methylation that occurs at specific CpG sites localised at the -5.8 kb NF-κB enhancer region of the iNOS gene in OA chondrocytes permits the binding of this transcription factor activating the expression of iNOS. This results in subsequent altered cell cycle regulation, altered proliferative phenotype and transmission of the pathogenic phenotype to daughter cells. CONCLUSIONS: This study indicates that inhibition of cell cycle progression by iNOS enhancer hypermethylation is capable of reducing pro-inflammatory responses via down-regulation of NF-κB with important therapeutic implications in OA.

Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis.

OBJECTIVE: To determine whether altered IL8 methylation status is associated with increased expression of IL8 in human osteoarthritic (OA) chondrocytes. METHODS: IL8 expression levels and the percentage CpG methylation in human chondrocytes were quantified by qRT-PCR and pyrosequencing in OA patients and in non-OA osteoporotic controls. The effect of CpG methylation on IL8 promoter activity was determined using a CpG-free vector; co-transfections with expression vectors encoding nuclear factor-kappa B (NF-κB), AP-1 and C/EBP were subsequently undertaken to analyse for IL8 promoter activity in response to changes in methylation status. RESULTS: IL8 expression in OA patients was 37-fold higher than in osteoporotic controls. Three CpG sites in the IL8 promoter were significantly demethylated in OA patients. Multiple regression analysis revealed that the degree of methylation of the CpG site located at -116-bp was the strongest predictor of IL8 expression. In vitro DNA methylation was noted to decrease IL8 promoter basal activity. Furthermore, NF-κB, AP-1 and C/EBP strongly enhanced IL8 promoter activity whilst DNA methylation inhibited the effects of these three transcription factors. CONCLUSIONS: The present study demonstrates the key role of DNA methylation status on the expression of IL8 in human chondrocytes. We demonstrate a quantitative relationship between percentage methylation and gene expression within clinical samples. These studies provide direct evidence linking the activation of IL8, DNA demethylation and the induction of the OA process with important therapeutic implications therein for patients with this debilitating disease.

The influence of preceding dive cycles on the foraging decisions of Antarctic fur seals.

The foraging strategy of many animals is thought to be determined by their past experiences. However, few empirical studies have investigated whether this is true in diving animals. We recorded three-dimensional movements and mouth-opening events from three Antarctic fur seals during their foraging trips to examine how they adapt their behaviour based on past experience--continuing to search for prey in the same area or moving to search in a different place. Each dive cycle was divided into a transit phase and a feeding phase. The linear horizontal distance travelled after feeding phases in each dive was affected by the mouth-opening rate during the previous 244 s, which typically covered two to three dive cycles. The linear distance travelled tended to be shorter when the mouth-opening rate in the previous 244 s was higher, i.e. seals tended to stay in the same areas with high prey-encounter rates. These results indicate that Antarctic fur seals follow decision-making strategies based on the past foraging experience over time periods longer than the immediately preceding dive.

Simple Resistance Exercise helps Patients with Non-alcoholic Fatty Liver Disease.

To date, only limited evidence has supported the notion that resistance exercise positively impacts non-alcoholic fatty liver disease. We evaluated the effects of resistance exercise on the metabolic parameters of non-alcoholic fatty liver disease (NAFLD) in 53 patients who were assigned to either a group that performed push-ups and squats 3 times weekly for 12 weeks (exercise group; n=31) or a group that did not (control; n=22). Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of the exercise were compared between the 2 groups after 12 weeks. Fat-free mass and muscle mass significantly increased, whereas hepatic steatosis grade, mean insulin and ferritin levels, and the homeostasis model assessment-estimated insulin resistance index were significantly decreased in the exercise group. Compliance with the resistance exercise program did not significantly correlate with patient background characteristics such as age, sex, BMI and metabolic complications. These findings show that resistance exercise comprising squats and push-ups helps to improve the characteristics of metabolic syndrome in patients with non-alcoholic fatty liver disease.

Electrical Stimulation-Based Twitch Exercise Suppresses Progression of Immobilization-Induced Muscle Fibrosis via Downregulation of PGC-1?/VEGF Pathway.

This study aimed to determine whether electrical stimulation-based twitch exercise is effective in inhibiting the progression of immobilization-induced muscle fibrosis. 19 Wistar rats were randomly divided into a control group (n=6), an immobilization group (n=6; with immobilization only), and a Belt group (n=7; with immobilization and twitch exercise through the belt electrode device, beginning 2 weeks after immobilization). The bilateral soleus muscles were harvested after the experimental period. The right soleus muscles were used for histological analysis, and the left soleus muscles were used for biochemical and molecular biological analysis. As a result, in the picrosirius red images, the perimysium and endomysium were thicker in both the immobilization and Belt groups compared to the control group. However, the perimysium and endomysium thickening were suppressed in the Belt group. The hydroxyproline content and alpha-SMA, TGF-beta1, and HIF-1alpha mRNA expressions were significantly higher in the immobilization and belt groups than in the control group. These expressions were significantly lower in the Belt group than in the immobilization group. The capillary-to-myofiber ratio and the mRNA expressions of VEGF and PGC-1alpha were significantly lower in the immobilization and belt groups than in the control group, these were significantly higher in the Belt group than in the immobilization group. From these results, Electrical stimulation-based twitch exercise using the belt electrode device may prevent the progression of immobilization-induced muscle fibrosis caused by downregulating PGC-1alpha/VEGF pathway, we surmised that this intervention strategy might be effective against the progression of muscle contracture. Keywords: Immobilization, Skeletal muscle, Fibrosis, Electrical stimulation-based twitch exercise, PGC-1alpha/VEGF pathway.

Skeletal Muscle Electrical Stimulation Prevents Progression of Disuse Muscle Atrophy via Forkhead Box O Dynamics Mediated by Phosphorylated Protein Kinase B and Peroxisome Proliferator-Activated Receptor gamma Coactivator-1alpha.

Although electrical muscle stimulation (EMS) of skeletal muscle effectively prevents muscle atrophy, its effect on the breakdown of muscle component proteins is unknown. In this study, we investigated the biological mechanisms by which EMS-induced muscle contraction inhibits disuse muscle atrophy progression. Experimental animals were divided into a control group and three experimental groups: immobilized (Im; immobilization treatment), low-frequency (LF; immobilization treatment and low-frequency muscle contraction exercise), and high-frequency (HF; immobilization treatment and high-frequency muscle contraction exercise). Following the experimental period, bilateral soleus muscles were collected and analyzed. Atrogin-1 and Muscle RING finger 1 (MuRF-1) mRNA expression levels were significantly higher for the experimental groups than for the control group but were significantly lower for the HF group than for the Im group. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNA and protein expression levels in the HF group were significantly higher than those in the Im group, with no significant differences compared to the Con group. Both the Forkhead box O (FoxO)/phosphorylated FoxO and protein kinase B (AKT)/phosphorylated AKT ratios were significantly lower for the Im group than for the control group and significantly higher for the HF group than for the Im group. These results, the suppression of atrogin-1 and MuRF-1 expression for the HF group may be due to decreased nuclear expression of FoxO by AKT phosphorylation and suppression of FoxO transcriptional activity by PGC-1alpha. Furthermore, the number of muscle contractions might be important for effective EMS.

Preferential expression of cancer/testis genes in cancer stem-like cells: proposal of a novel sub-category, cancer/testis/stem gene.

Cancer/testis (CT) antigens encoded by CT genes are immunogenic antigens, and the expression of CT gene is strictly restricted to only the testis among mature organs. Therefore, CT antigens are promising candidates for cancer immunotherapy. In a previous study, we identified a novel CT antigen, DNAJB8. DNAJB8 was found to be preferentially expressed in cancer stem-like cells (CSCs)/cancer-initiating cells (CICs), and it is thus a novel CSC antigen. In this study, we hypothesized that CT genes are preferentially expressed in CSCs/CICs rather than in non-CSCs/-CICs and we examined the expression of CT genes in CSCs/CICs. The expression of 74 CT genes was evaluated in side population (SP) cells (=CSC) and main population (MP) cells (=non-CSC) derived from LHK2 lung adenocarcinoma cells, SW480 colon adenocarcinoma cells and MCF7 breast adenocarcinoma cells by RT-PCR and real-time PCR. Eighteen genes (MAGEA2, MAGEA3, MAGEA4, MAGEA6, MAGEA12, MAGEB2, GAGE1, GAGE8, SPANXA1, SPANXB1, SPANXC, XAGE2, SPA17, BORIS, PLU-1, SGY-1, TEX15 and CT45A1) showed higher expression levels in SP cells than in MP cells, whereas 10 genes (BAGE1, BAGE2, BAGE4, BAGE5, XAGE1, LIP1, D40, HCA661, TDRD1 and TPTE) showed similar expression levels in SP cells and MP cells. Thus, considerable numbers of CT genes showed preferential expression in CSCs/CICs. We therefore propose a novel sub-category of CT genes in this report: cancer/testis/stem (CTS) genes.

Evaluation of anatomical references for locating the course of the posterior superior alveolar artery for dental implant surgery.

This retrospective cohort study aimed to identify the best anatomical reference for predicting the posterior superior alveolar artery (PSAA) location. Computed tomographic images of 90 maxillary sinuses were evaluated. We studied five references, including the alveolar crest, maxillary sinus floor, zygomatoalveolar crest, hard palate and soft palate, and measured the distances between them and the PSAA. Variations in the distance were evaluated by the standard deviation and coefficient of variation (CV). The zygomatoalveolar crest was an unstable reference, owing to its high standard deviation and CV. The smallest CV was for the distance between the alveolar crest and PSAA, although the distance was smaller in edentulous jaws than dentulous jaws. The distance between the sinus floor and PSAA was larger in male and edentulous patients. The PSAA was detected in 40.0%, 44.4%, 54.4% and 56.7% of the sinus walls at the first and second premolar and the first and second molar positions, respectively. At these tooth positions, the respective heights above the hard palate were 11.2 ± 4.9, 8.2 ± 4.9, 6.2 ± 2.8 and 8.1 ± 2.9 mm. The hard palate was the most stable reference for predicting the location of the PSAA, irrespective of sex, age and dentition.

Cortactin, an actin binding protein, regulates GLUT4 translocation via actin filament remodeling.

Insulin regulates glucose uptake into fat and skeletal muscle cells by modulating the translocation of GLUT4 between the cell surface and interior. We investigated a role for cortactin, a cortical actin binding protein, in the actin filament organization and translocation of GLUT4 in Chinese hamster ovary (CHO-GLUT4myc) and L6-GLUT4myc myotube cells. Overexpression of wild-type cortactin enhanced insulin-stimulated GLUT4myc translocation but did not alter actin fiber formation. Conversely, cortactin mutants lacking the Src homology 3 (SH3) domain inhibited insulin-stimulated formation of actin stress fibers and GLUT4 translocation similar to the actin depolymerizing agent cytochalasin D. Wortmannin, genistein, and a PP1 analog completely blocked insulin-induced Akt phosphorylation, formation of actin stress fibers, and GLUT4 translocation indicating the involvement of both PI3-K/Akt and the Src family of kinases. The effect of these inhibitors was even more pronounced in the presence of overexpressed cortactin suggesting that the same pathways are involved. Knockdown of cortactin by siRNA did not inhibit insulin-induced Akt phosphorylation but completely inhibited actin stress fiber formation and glucose uptake. These results suggest that the actin binding protein cortactin is required for actin stress fiber formation in muscle cells and that this process is absolutely required for translocation of GLUT4-containing vesicles to the plasma membrane.