Prevalence of early and late oral implant loss among smokers: a nationwide survey in Japan.

A cross-sectional, nationwide survey was conducted in Japan to examine the relationship between tobacco smoking and oral diseases including implant failure. A questionnaire survey was sent to designated facilities by post, and 158 answered questions regarding implant loss. Smoking status, number of implant failures, and other related variables were collected from the participating dentists as secondary data. A total of 1966 patients who were treated with dental implants by participating dentists during the survey period were analysed. Among the total sample, 90 (5%) had early implant loss (≤12 months) and 153 (8%) had late implant loss (>12 months and ≤120 months). The number of pack-years was significantly higher in the total (early and late) implant loss group (31.2±15.9) than in the group with no implant loss (26.1±18.1) (P=0.026). In the multivariate analysis, the number of implants installed, smoking, and pack-years were significant factors for total implant loss. The adjusted odds ratio for implant failure for current smokers compared with never smokers was 2.07 (95% CI 1.19-3.62) for early implant loss and 1.48 (95% CI 0.92-2.37) for late implant loss. This study reaffirms that current smoking is associated with an increased risk of early implant loss, irrespective of the duration of smoking exposure.

Colonoscopic features and malignant potential of sessile serrated adenomas: comparison with other serrated lesions and conventional adenomas.

AIM: Sessile serrated adenomas/polyps (SSA/Ps) have been proposed as precursors of colorectal cancer. The aims of this investigation were to compare the endoscopic findings of SSA/Ps with those of other serrated lesions and to compare the histological findings of SSA/Ps with those of conventional adenomas. METHOD: We retrospectively reviewed colonoscopy records at our institution from 1984 to 2013 and identified cases of endoscopically or surgically resected conventional adenomas and serrated lesions, including SSA/Ps, hyperplastic polyps (HPs) and traditional serrated adenomas (TSAs). The colonoscopic findings of SSA/Ps were compared with those of the other two serrated lesions and histological findings were compared among all groups of lesions. RESULTS: There were 79 HPs in 68 patients, 77 SSA/Ps in 63 patients, 167 TSAs in 145 patients and 6324 conventional adenomas in 4129 patients. The inverted type and flat-elevated type were more frequent among SSA/Ps than among the other two types of serrated lesions. Magnifying colonoscopy revealed that a round and open pit pattern, expanded crypt openings and varicose microvascular vessels were more frequently observed among SSA/Ps than among the other types. The incidence of high-grade dysplasia or carcinoma among SSA/Ps (13.0%) was significantly higher than that among HPs (0%, P < 0.001) and equivalent to that among conventional adenomas (12.3%). CONCLUSION: SSA/Ps have colonoscopic features distinct from those of HPs and TSAs. The malignant potential of SSA/Ps seems to be equal to that of conventional adenomas.

Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder.

Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia.

Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.

A serotonergic discrimination favoring synaptic inputs that accompany robust spike firing in lateral amygdala neurons.

The amygdala and serotonergic innervations thereunto are considered to cooperatively modulate affective behaviors. By whole-cell recording, the present study examined effects of serotonin (5-HT) on synaptic transmission in the rat basolateral amygdala (BLA) complex, which is the amygdalar entrance for sensory information. Application of 5-HT-attenuated excitatory postsynaptic currents at synapses from the lateral amygdala (LA) to the BLA proper, and also at synapses from putative thalamic afferents to LA principal neurons, both depending on 5-HT(2) receptors. This reduction of synaptic responses was confirmed in the BLA under current clamp. In the LA, by contrast, synaptic potentials were not reduced, but enhanced by 5-HT. With 5-HT bath-applied, a prolonged depolarization was induced in LA neurons by strong synaptic stimulation, which appears similar to a slow after-depolarization (sADP) induced by injecting depolarizing currents. Occurrence of such current-induced sADP was confirmed in LA neurons. Both the synaptically-activated prolonged depolarization and the current-induced sADPs depended on 5-HT(2) receptor activation and postsynaptic calcium increase, suggesting that the same postsynaptic intrinsic mechanisms are involved. Reduction of potassium currents was identified as a major ionic mechanism for this sADPs. We thus revealed that 5-HT usually reduces overall synaptic transmission in the whole BLA complex, but enables sADPs to occur, thereby increasing synaptic responsiveness of LA neurons in a positive feedback manner. With this duality of 5-HT actions in operation, a weak input to the BLA complex would be usually eliminated, but could be selected were it associated with sufficiently large depolarization.

Multimodal cross-talk of olfactory and gustatory information in the endopiriform nucleus in rats.

The endopiriform nucleus (EPN) is a large group of multipolar cells located in the depth of the piriform cortex (PC). Although many studies have suggested that the EPN plays a role in temporal lobe epilepsy, the normal function of the EPN remains to be elucidated. By using optical imaging of coronal brain slice preparations with voltage-sensitive dye, we found signal propagation from the PC or gustatory cortex (GC) to the EPN in normal medium. In our previous research, we failed to elicit a reliable signal reproducibly in the EPN by single stimulation either to the PC or GC. In our current research, we found that a double-pulse stimulation to either the PC or GC (interpulse interval: 20-100 ms) induced robust signal propagation to the EPN through excitation in the agranular division of the insular cortex (AI), with further extension to the claustrum. Finally, double site paired-pulse stimulation to the PC and GC also evoked excitation in the AI, claustrum, and EPN. These results suggest that the EPN has dual roles: 1) further processing of modality-specific olfactory and gustatory information from the PC and GC, respectively and 2) synergistic integration of PC-derived olfactory information and GC-derived gustatory information.

Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine.

Several studies have shown increased rates of hyperglycemia and diabetes in schizophrenic patients treated with olanzapine. However, the underlying mechanism is poorly understood. Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic ß cells. Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). We assessed the influence of this GIPR gene polymorphism on glucose metabolism in 60 schizophrenic patients treated with olanzapine and 103 healthy controls. The GIPR gene polymorphism was determined using TaqMan methods. We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. Our findings suggest that schizophrenic patients with the A allele of GIPR rs10423928 are at risk of developing hyperinsulinemia when treated with antipsychotics.

Improvement of tardive dyskinesia and dystonia associated with aripiprazole following a switch to quetiapine: case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. CASE SUMMARY: We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. WHAT IS NEW AND CONCLUSION: There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Hypoxia-induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells.

Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.

Template for preparation of papers for IEEE sponsored conferences & Symposia.

Rotary blood pumps which have contact-less suspension are small, durable and widely used for left ventricular assist devices (LVADs). In order to design a total artificial heart (TAH) with rotary blood pumps, two pumps one for each ventricle, are controlled independently. Some of the challenges for the development of a TAH includes the requirement of a small size and the anatomical fitting of inlets and outlets which should be arranged closely on the circumference in the same direction. And they should be combined into a unit. In this paper, a helical flow total artificial heart (HFTAH) combing two centrifugal pumps with helical inlet in face is proposed in order to achieve a smaller TAH. To examine the pump performance, a preliminary test model for left ventricle was built, the size of the pump was 69.0mm in diameter and 45.0mm height. The size of the impeller was 44.0mm in diameter and 23.0mm height including a 15.0mm-height hydrodynamic bearing. The pump was externally driven by a direct current motor. 5.0L/min flow rate against 100mmHg pressure difference was obtained, where the total power consumption was 5.0W, the system efficiency was 23% with a rotational speed of 2070rpm. In this system, maximum pressure head, flow rate and efficiency were 420mmHg, 15.0L/min and 26%, respectively. In acute animal experiments with three healthy adult goats, the total biventricular bypass assist system using the pumps was able to maintain the maximum aortic flow at approximately 5.0L/min, and the pulmonary arterial flow at approximately 4.6L/min, the mean aorta pressure was 105mmHg, and the mean pulmonary artery pressure was 51mmHg. The development of the control method is undergoing, and a driving system and the pump aiming at the chronic animal experiments will be developed.