Evaluation of Pleasure-Displeasure Induced by Use of Lipsticks with Near-Infrared Spectroscopy (NIRS): Usefulness of 2-Channel NIRS in Neuromarketing.

In order to examine whether near-infrared spectroscopy (NIRS) would be a useful neuromarketing tool, we employed NIRS to evaluate the difference of pleasure-displeasure in women, induced by the use of different types of lipsticks. The subjects used lipsticks A and B; A is softer than B. Concentration changes of oxy-Hb were measured in the bilateral prefrontal cortex (PFC) during use of lipsticks A and B. We evaluated the right and left dominancy of PFC activity by calculating the Laterality Index (LI) (LI = leftΔoxy-Hb - rightΔoxy-Hb); positive LI indicates left-dominant activity while negative LI indicate right-dominant activity. We found a significant interaction between the use of lipsticks A and B, using a two-way factorial analysis of variance [F(1,13) = 9.63, p < 0.01]; Δoxy-Hb in the left PFC was larger than that in the right PFC during the use of lipstick A, while Δoxy-Hb in the right PFC tended to be larger than that in the left PFC during the use of lipstick B (p < 0.1). The LI of lipstick A was larger than that of lipstick B (paired T-test, p = 0.0083). We suggest that lipstick A caused a more positive emotional response than lipstick B, since greater left than right frontal cortical activity is associated with positive affect. These results suggest that 2-channel NIRS may be a useful neuromarketing tool, since it allows objective assessment of pleasure-unpleasure.

A randomized clinical study on postoperative pain comparing between the supraglottic airway device and endotracheal tubing in transabdominal preperitoneal repair (TAPP).

BACKGROUND: Transabdominal preperitoneal (TAPP) repair is the most widely used laparoscopic technique for the treatment of inguinal hernia in Japan. Many studies have shown that in comparison with open hernia repair, laparoscopic repair results in less pain and a shorter convalescence. However, postoperative pain remains a concern. One possible cause of postoperative pain in the early postoperative phase is strain or cough on removal of the endotracheal tube. Use of a supraglottic airway (SGA) device helps to avoid such complaints. We evaluated postoperative pain after TAPP repair using the SGA for general anesthesia. METHODS: We evaluated the postoperative pain in 146 patients with inguinal hernia repaired by TAPP in our hospital between May 2013 and May 2016. A total of 144 adult patients of American Society of Anesthesiologists physical status I and II who underwent needlescopic TAPP surgery were randomly allocated to one of two groups of 72 patients: group A (SGA), in which the patient's airway was secured with an appropriately sized I-gel, and group B (endotracheal tube), in which the airway was secured under laryngoscopy. RESULTS: There was no significant difference between the groups regarding patient background, postoperative hospital stay, and operation time, and TAPP was performed safely in all cases. In the analysis of postoperative pain, the mean Numerical Rating Scale score of peak pain in group A was significantly less than that of group B (2.10 ± 2.05 vs 2.90 ± 2.65; p = 0.043). In group A, the percentage of patients who had an NRS score of 0 was 51.4% 30 min after surgery, 62.5% after 6 h and 68.1% at POD1, and compared to group B, the NRS scores were significantly higher at POD1 (p = 0.003), and the level of postoperative pain in group A tended to decrease earlier than that in group B. CONCLUSIONS: The results of this study are the first to show that an SGA device can reduce postoperative pain after laparoscopic surgery.

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G).

BACKGROUND: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. PATIENTS AND METHODS: WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396. RESULTS: Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months. CONCLUSION: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. CLINICAL TRIALS NUMBER: UMIN000001396.

Deficiency in WT1-targeting microRNA-125a leads to myeloid malignancies and urogenital abnormalities.

The Wilms' tumor gene WT1 is overexpressed in leukemia and solid tumors and has an oncogenic role in leukemogenesis and tumorigenesis. However, precise regulatory mechanisms of WT1 overexpression remain undetermined. In the present study, microRNA-125a (miR-125a) was identified as a miRNA that suppressed WT1 expression via binding to the WT1-3'UTR. MiR-125a knockout mice overexpressed WT1, developed myeloproliferative disorder (MPD) characterized by expansion of myeloid cells in bone marrow (BM), spleen and peripheral blood, and displayed urogenital abnormalities. Silencing of WT1 expression in hematopoietic stem/progenitor cells of miR-125a knockout MPD mice by short-hairpin RNA inhibited myeloid colony formation in vitro. Furthermore, the incidence and severity of MPD were lower in miR-125a (-/-) mice than in miR-125a (+/-) mice, indicating the operation of compensatory mechanisms for the complete loss of miR-125a. To elucidate the compensatory mechanisms, miRNA array was performed. MiR-486 was occasionally induced in compete loss of miR-125a and inhibited WT1 expression instead of miR-125a, resulting in the cancellation of MPD occurrence. These results showed for the first time the post-transcriptional regulatory mechanisms of WT1 by both miR-125a and miR-486 and should contribute to the elucidation of mechanisms of normal hematopoiesis and kidney development.

Navigation surgery for intraoperative sentinel lymph node detection using Indocyanine green (ICG) fluorescence real-time imaging in breast cancer.

A new sensitive fluorescence imaging system was developed for the real-time identification of sentinel lymph nodes (SLNs) in patients with early breast cancer. The purpose of this study was to evaluate the utility of a color charge-coupled device camera system for the intraoperative detection of SLNs and to determine its clinical efficacy and sensitivity in patients with operable breast cancer. We assessed a total of 168 patients diagnosed with or suspected of having early-stage breast cancer without metastasis in SLNs. The intraoperative detection of SLNs was performed using the conventional Indigo Carmine dye (indigotindisulfonate sodium) technique combined with a new Indocyanine green (ICG) imaging system (HyperEye Medical System: HEMS, MIZUHO IKAKOGYO, Japan) to map SLNs, in which the lymphatic vessels and SLNs were visualized transcutaneously with illuminating ICG fluorescence. Between January 2012 and May 2013, SLNs were successfully identified in all 168 patients (detection rate: 100%). By histopathology, the sensitivity was 93.8% for the detection of the metastatic involvement of SLNs (15 of 16 nodal-positive patients). After a median follow-up of 30.5 months, none of the patients presented with axillary recurrence. These results suggest that the HEMS imaging system is a feasible and effective method for the detection of SLNs in breast cancer. Furthermore, the HEMS device permitted the transcutaneous visualization of lymphatic vessels under light conditions, thus facilitating the identification and detection of SLNs without affecting the surgical procedure, together with a high sensitivity and specificity.

Establishment and analysis of SLC22A12 (URAT1) knockout mouse.

In order to elucidate the mechanisms of post-exercise acute renal failure, one of the complications of hereditary renal hypouricemia, we have targeted the mouse Slc22a12 gene by the exchange of exons 1-4 with pMC1neo-polyA. The knockout mice revealed no gross anomalies. The concentration ratio of urinary urate/creatinine of the knockout mice was significantly higher than that of wildtype mice, indicating an attenuated renal reabsorption of urate. The plasma levels of urate were around 11 muM and were similar among the genotypes. Although the fractional excretion of urate of knockout mice was tend to higher than that of wildtype mice, the urate reabsorption ability remained in the kidney of knockout mice, indicating a urate reabsorptive transporter other than Urat1.

Proliferation and apoptosis of tumour cells before and after neoadjuvant therapy for high-grade extremity sarcomas: divergent associations with tumour response and prognosis.

AIMS: To evaluate proliferation and apoptosis in high-grade sarcomas of the extremities before and after preoperative radio-hyperthermo-chemotherapy (RHC) and to determine the relationship between these parameters and treatment outcomes. METHODS AND RESULTS: Pre- and post-RHC specimens of 41 soft tissue and bone tumours were immunohistochemically stained for minichromosome maintenance protein (MCM) 2 and caspase 3 as proliferation and apoptosis markers, respectively, based on a preliminary study comparing them with conventional markers. Indices were calculated as a percentage of positive cells by counting tumour cells in the most frequently labelled areas. MCM2, caspase 3 and MCM2/caspase 3 (growth) indices were 45.3 +/- 21.9%, 4.1 +/- 7.1% and 82.9 +/- 104.5, respectively, in pre-RHC specimens and 35.4 +/- 30.8%, 39.2 +/- 34.6% and 5.3 +/- 11.7, respectively, in post-RHC specimens. Response scores showed positive correlation with pre-RHC MCM2 and post-RHC caspase 3 indices, inverse correlation with post-RHC MCM2 and post-RHC growth indices and no correlation with prognosis. Multivariate analysis revealed high pre-RHC MCM2 and high post-RHC growth indices as significant unfavourable prognostic factors. CONCLUSIONS: High proliferative activity in untreated sarcoma may predict good response to neoadjuvant therapy, but poor prognosis, whereas a high growth index, i.e. high proliferation:apoptosis ratio in a post-neoadjuvant therapy tumour specimen may indicate poor response and poor prognosis.

Pharmacological characterization and gene expression profiling of an L5/L6 spinal nerve ligation model for neuropathic pain in mice.

L5/L6 spinal nerve ligation (SNL) in rodents induces behavioral signs similar to the symptoms of neuropathic pain in humans. L5/L6 SNL in rats has been well characterized so far, but there have been few studies using mice. In this study, we established an L5/L6 SNL model in mice and examined the effects of known antinociceptive drugs in the model. We also analyzed the changes in gene expression in dorsal root ganglions with special reference to those which are known to change in a neuropathic pain state to validate the model. Mechanical allodynia in the ipsilateral side paw was observed beginning on day 1 and lasted for at least 2 months following surgery. Diclofenac showed no significant effect on the mechanical allodynia. Gabapentin and pregabalin completely reversed allodynia, but they also caused a decrease in locomotor activity. Duloxetine caused a partial recovery of the threshold. Mexiletine completely reversed allodynia, but it also caused sedation or motor impairment. Morphine caused a partial recovery of the threshold and hyper-locomotion. This mouse L5/L6 SNL model represents a robust mechanical allodynia, which shows a similar pharmacological response to that reported in rats and human patients with neuropathic pain. The pattern changes in gene expression also resembled those reported in rats. This model will therefore be useful for investigation of the effects of novel antinociceptive compounds and the mechanisms of neuropathic pain.

The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis.

The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.

Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors.

Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/beta-catenin signals. Phosphoinositide-3 kinase (PI3K)/Akt signaling regulates the 'stemness' of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.

Adenovirus serotype 35 vector-mediated transduction into human CD46-transgenic mice.

We previously demonstrated that systemic administration of adenovirus serotype 35 (Ad35) vectors to mice does not mediate efficient transduction in organs, probably because expression of the mouse analog of the subgroup B Ad receptor, human CD46 (membrane cofactor protein), is limited to the testis. Here, we describe the in vitro and in vivo transduction characteristics of Ad35 vectors by using homozygous and hemizygous human CD46-transgenic (CD46TG) mice, which ubiquitously express human CD46. An Ad35 vector more efficiently transduced the primary dendritic cells and macrophages prepared from CD46TG mice than those from wild-type mice. In vivo transduction experiments demonstrated that CD46TG mice are more susceptible to Ad35 vector-mediated in vivo transduction than are wild-type mice. In particular, homozygous CD46TG mice, which express higher levels of CD46 in the organs than hemizygous CD46TG mice, tend to exhibit higher transduction efficiencies after intraperitoneal administration than hemizygous CD46TG mice. Intraperitoneal administration of Ad35 vectors resulted in efficient transduction into the mesothelial cells of the peritoneal organs in homozygous CD46TG mice. These results indicate that an Ad35 vector recognizes human CD46 as a cellular receptor in CD46TG mice. However, the in vivo transduction efficiencies of Ad35 vectors in CD46TG mice are much lower than those of conventional Ad5 vectors in wild-type mice.

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells.

Embryonic stem (ES) cells can self-renew indefinitely without losing their differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt signaling plays a pivotal role in various stem cell systems, including the formation of embryonic germ (EG) cells from primordial germ cells and self-renewal of neural stem cells. Here, we show that myristoylated, active form of Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt were reversible, because LIF dependence and pluripotent differentiation activity were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also maintained the pluripotency of not only mouse but also cynomolgus monkey ES cells. These results clearly demonstrate that Akt signaling sufficiently maintains pluripotency in mouse and primate ES cells, and support the notion that PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell systems.

Using a flat-panel detector in high resolution cone beam CT for dental imaging.

OBJECTIVES: Cone beam CT (CBCT) requires a two-dimensional X-ray detector. In the several CBCT systems developed for dental imaging, detection has been by the combination of an X-ray image intensifier and charge-coupled device (CCD) camera. In this paper, we propose a new CBCT system in which the detector is of the flat-panel type and evaluate its performance in dental imaging. METHODS: We developed a prototype CBCT that has a flat-panel-type detector. The detector consists of a CsI scintillator screen and a photosensor array. First, the flat panel detector and image intensifier detector were compared in terms of the signal-to-noise ratio (SNR) of projected images. We then used these data and a theoretical formula to evaluate noise in reconstructed images. Second, reconstructed images of a bar pattern phantom were obtained as a way of evaluating the spatial resolution. Then, reconstructed images of a skull phantom were obtained. RESULTS: The SNR of the developed system was 1.6 times as high as that of a system with an image intensifier detector of equal detector pitch. The system was capable of resolving a 0.35 mm pattern and its field of view almost completely encompassed that of an image intensifier detector which is used in dentomaxillofacial imaging. The fine spatial resolution of the detector led to images in which the structural details of a skull phantom were clearly visible. CONCLUSIONS: The system's isotropically fine resolution will lead to improved precision in dental diagnosis and surgery. The next stage of our research will be the development of a flat panel detector system with a high frame acquisition rate.

[The effect and role of the intraaortic balloon pumping in off-pump coronary artery bypass].

Eighty consecutive patients who underwent off-pump coronary artery bypass (OPCAB) were studied. They were divided into group I (n = 10) which received preoperative intraaortic balloon pumping (IABP), and group II (n = 70) which did not receive IABP. The indications for preoperative IABP were severe left main coronary artery disease in 7 patients, severe 3 vessel disease in 3 patients, unstable angina in 5 patients, acute myocardial infarction in 3 patients. There was no operative mortality in both groups. The average number of distal anastomosis 2.7/patients in group I and 3.3/patients in group II. There was no differences in ventilator support time, length of stay in the intensive care unit and morbidity between 2 groups. The average postoperative IABP support time was 5.4 hours. There was no IABP-related complication in group I. IABP was very effective to perform OPCAB surgery safety. Preoperative IABP may be effective modality to support OPCAB surgery not only in emergent case but also in elective case.

[Routine application of trans-sternal off-pump coronary artery bypass grafting using innovative technique].

OBJECTIVE: With specific apparatus and surgical techniques, we have extended the use of off-pump coronary artery bypass grafting (CABG) [OPCAB] through sternotomy approach to all of the patients with multiple coronary vessel lesions necessitating CABG. The objective of this study is to assess the safety and efficacy of our technique. METHODS: All of the consecutive 100 patients with multiple coronary vessel lesions necessitating CABG underwent trans-sternal OPCAB using our innovative technique between September 2000 and December 2002. Our new technique included left pericardial traction with sternal spreader, right pericardial compression with pericardial retractor and routine use of our original coronary shunt tube. RESULTS: The total number of distal anastomoses was 322 and the individual grafts were to left anterior descending coronary artery branch (LAD) 127, circumflex (CX) 101 and right coronary artery (RCA) 94. The mean number of the grafts was 3.22 +/- 0.97. The conduits included left internal thoracic artery (LITA) 103, right internal thoracic artery (RITA) 29, radial artery (RA) 82, gastro-epiploic artery (GEA) 43 and saphena magna vein graft (SVG) 65. Predischarge graft angiogram showed over all patency of 99.1% (arterial graft 100% and vein graft 95.4%). Postoperative course was uneventful in all cases with no other organ failures. There was no operative or hospital death. CONCLUSIONS: OPCAB of our technique is effective and safe. The early clinical outcome and excellent patency rates suggests its more widespread use in CABG cases.

Quantification of minimal residual disease in patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia using a real-time RT-PCR assay.

Using a real-time RT-PCR method, we analyzed the expression of e1a2 BCR-ABL mRNA in bone marrow samples from 13 patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia (ALL) at different time points during chemotherapy and after bone marrow transplantation (BMT). The detection limit of the method, assessed using serial dilutions of ALL/MIK cells, was found to be 1:10(5), similar to what is observed for the conventional RT-nested PCR method. The e1a2 BCR-ABL values were normalized with respect to those of the housekeeping gene GAPDH. The decrease in the e1a2 BCR-ABL/GAPDH ratio after remission induction chemotherapy reflects well the response to chemotherapy and consequently correlates with the prognosis. Although molecular remission was achieved by chemotherapy alone, some patients relapsed, and the e1a2 BCR-ABL/GAPDH ratios in these cases progressively increased to the levels seen prior to hematological relapse. Long-term hematological complete remission (more than 30 months) could be achieved in cases in which a more than 4.0 log decrease in the e1a2 BCR-ABL/GAPDH ratio was obtained by chemotherapy alone, and BMT was then performed. In conclusion, real-time RT-PCR allows for an evaluation of the kinetics of e1a2 BCR-ABL/GAPDH expression during the various phases of chemotherapy or after BMT and may be effective for the indication and control of disease relapse in Ph-positive ALL patients.