Development of Electrodeposited Wire Mesh Grinding Wheel for Cutoff and Grooving Carbon Fiber Reinforced Plastic.

Carbon fiber reinforced plastic (CFRP) is used in various industries because of its high specific strength, but it is well known as a difficult material to cut. In this study, we developed a disc-shaped electrodeposited diamond wire mesh grinding wheel as a new method for cutoff and grooving with a large aspect ratio for CFRP. We confirmed that this tool could be used for machining at a feed rate of 1000 mm/min, equivalent to that of an abrasive waterjet. This tool discharges generated chips through the spaces in the wire mesh, preventing clogging and thereby enabling the suppression of machining temperature. No burrs or delamination were observed on the surface machined with the wire mesh grinding wheel, and the surface roughness was Ra = 2.76 µm. However, the groove width was larger than the wheel thickness due to the runout of the wheel. Additionally, the moderate elasticity and durability of the tool suggest that it might extend tool life by avoiding the crushing of abrasive grains.

Effect of a brief training program based on cognitive behavioral therapy in improving work performance: A randomized controlled trial.

OBJECTIVES: Efforts to improve performance in the workplace with respect to positive mental health have increased, and cognitive behavioral therapy (CBT) has recently attracted attention as an intervention measure to this end. Here, we conducted a randomized controlled trial to evaluate the effectiveness of a brief training program on CBT for improving work performance of employees. METHODS: The participants were employees of an electric company in Japan. The intervention consisted of 1 group session of CBT (120 min) and web-based CBT homework for 1 month. We evaluated employees in both the intervention and control groups at baseline and follow-up after three months. The main outcome was work performance, which was evaluated by a subjective score from 1 to 10. The secondary outcome was self-evaluation of cognitive flexibility. Analyses were conducted based on ITT. RESULTS: In the intervention group, 84 participants attended the group session, with 79 subsequently completing at least 1 instance of online homework. ITT analysis showed that the subjective performance of the intervention group was significantly improved compared with that of the control group (1.47 vs. 0.69, mean difference 0.78 [95% confidence interval {CI}, 0.05 to 1.51], Cohen's d=0.31). The ability to recognize dysfunctional thinking patterns and change them to positive ones significantly improved in the intervention group compared to the control group (0.71 vs. 0.26, mean difference 0.45 [95% CI 0.06 to 0.83], d=0.33). However, after adjustment for baseline scores, no significant difference was observed. The ability to view a situation from multiple perspectives and expand one's repertoire of thought patterns in the intervention group also significantly improved (0.83 vs. 0.35, mean difference 0.48 [95% CI 0.35 to 0.95], d=0.29), but here again, significance was lost after adjusting for baseline scores. DISCUSSION: Our results suggest that a brief training program that combines a group CBT session with web-based CBT homework improved subjective work performance. In addition, this program might help improve employees' cognitive flexibility.

A web-based training program using cognitive behavioral therapy to alleviate psychological distress among employees: randomized controlled pilot trial.

BACKGROUND: A number of psychoeducational programs based on cognitive behavioral therapy (CBT) to alleviate psychological distress have been developed for implementation in clinical settings. However, while these programs are considered critical components of stress management education in a workplace setting, they are required to be brief and simple to implement, which can hinder development. OBJECTIVE: The intent of the study was to examine the effects of a brief training program based on CBT in alleviating psychological distress among employees and facilitating self-evaluation of stress management skills, including improving the ability to recognize dysfunctional thinking patterns, transform dysfunctional thoughts to functional ones, cope with stress, and solve problems. METHODS: Of the 187 employees at an information technology company in Tokyo, Japan, 168 consented to participate in our non-blinded randomized controlled study. The training group received CBT group education by a qualified CBT expert and 1 month of follow-up Web-based CBT homework. The effects of this educational program on the psychological distress and stress management skills of employees were examined immediately after completion of training and then again after 6 months. RESULTS: Although the training group did exhibit lower mean scores on the Kessler-6 (K6) scale for psychological distress after 6 months, the difference from the control group was not significant. However, the ability of training group participants to recognize dysfunctional thinking was significantly improved both immediately after training completion and after 6 months. While the ability of participants to cope with stress was not significantly improved immediately after training, improvement was noted after 6 months in the training group. No notable improvements were observed in the ability of participants to transform thoughts from dysfunctional to functional or in problem-solving skills. A sub-analysis of participants who initially exhibited clinically significant psychological distress (K6 score ≥5) showed that the mean K6 score was significantly improved immediately after training completion for the training group compared to the control group (-2.50 vs -0.07; mean difference 2.43, 95% CI 0.55-4.31; d=0.61), with this effect remaining even after 6 months (-3.49 vs -0.50; mean difference 2.99, 95% CI 0.70-5.29; d=0.60). CONCLUSIONS: Our results suggest that a brief stress management program that combines group CBT education with Web-based CBT homework moderately alleviates the distress of employees with clinically significant psychological distress. In addition, the program might help improve employees' ability to evaluate their own stress management skills.

Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation.

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.

Improvement by minocycline of methamphetamine-induced impairment of recognition memory in mice.

INTRODUCTION: Cognitive deficits are a core feature of patients with schizophrenia and methamphetamine (METH) psychosis. We have recently found that repeated METH treatment (1 mg/kg, s.c.) in mice, which induces behavioral sensitization, impairs long-term recognition memory in a novel object recognition test (NORT) and that the impairment is ameliorated by clozapine, but not haloperidol. Recent studies indicate that minocycline, a second-generation tetracycline, has potent neuroprotective effects in various animal models of neurological diseases. OBJECTIVES: In the present study, we investigated the effect of minocycline on learning and memory in the NORT and behavioral sensitization in mice that had been administered METH for 7 days. RESULTS: When minocycline (20-40 mg/kg) was administered intraperitoneally once a day for seven consecutive days to mice that had previously been treated with METH for 7 days, it ameliorated the METH-induced impairment of recognition memory in a dose-dependent manner, although the same treatment with minocycline had no effect on behavioral sensitization to METH. The administration of minocycline, together with METH, inhibited the development of METH-induced behavioral sensitization. The improvement in memory caused by minocycline was associated with an amelioration of the novelty-induced activation of extracellular signal-regulated kinase 1/2 in the prefrontal cortex of METH-treated mice. CONCLUSIONS: These results suggest that minocycline is useful for the treatment of cognitive deficits in patients with METH psychosis or schizophrenia.

Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages.

Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by various cells, such as monocytes/macrophages (Mphis) in response to lipopolysaccharide (LPS) and proinflammatory signals. We performed immunoblotting, immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) of PTX3 in human monocyte-derived Mphis and neutrophils. PTX3 expression was observed in the cytoplasm of both GM-CSF induced monocyte-derived Mphi (GM-Mphi) and M-CSF induced monocyte-derived Mphi (M-Mphi). PTX3 level in both Mphis was up-regulated at 24 h after LPS stimulation. Moreover, we confirmed PTX3 expression in freshly isolated neutrophils, and PTX3 level was distinctly up-regulated at 6 and 24 h after LPS stimulation. These findings suggested that PTX3 expression, not only in Mphis, but also in neutrophils, may reflect the role of PTX3 in inflammation. We believe that PTX3 can contribute as a diagnostic tool to evaluate inflammation at peripheral sites.

Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex.

Several lines of evidence suggest that extracellular signal-regulated kinase1/2 (ERK1/2) and dopaminergic system is involved in learning and memory. However, it remains to be determined if the dopaminergic system and ERK1/2 pathway contribute to cognitive function in the prefrontal cortex (PFC). The amount of phosphorylated ERK1/2 was increased in the PFC immediately after exposure to novel objects in the training session of the novel object recognition test. An inhibitor of ERK kinase impaired long-term recognition memory 24 h after the training although short-term memory tested 1 h after the training was not affected by the treatment. The dopamine D1 receptor agonist increased ERK1/2 phosphorylation in the PFC in vivo as well as in cortical neurons in vitro. Microinjection of the dopamine D1 receptor antagonist into the PFC impaired long-term recognition memory whereas the D2 receptor antagonist had no effect. Immunohistochemistry revealed that exposure to novel objects resulted in an increase in c-Fos expression in the PFC. Microinjection of the protein synthesis inhibitor anisomycin into the PFC impaired the long-term recognition memory. These results suggest that the activation of ERK1/2 following the stimulation of dopamine D1 receptors is necessary for the protein synthesis-dependent long-term retention of recognition memory in the PFC.

Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.

OBJECTIVE: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed. METHODS AND RESULTS: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group. CONCLUSIONS: The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.

A novel azaindolizinone derivative ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2.

The effect of ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) on cognitive impairment in mice, previously treated with methamphetamine (METH) at a dose of 1 mg/kg for 7 days, was investigated. ZSET1446 showed a significant ameliorating effect on METH-induced impairment of recognition memory, although it had no effect on exploratory behavior. ZSET1446 (1 microg/kg) recovered the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the prefrontal cortex (PFC) of METH-treated mice. The compound increased phosphorylated ERK1/2 levels in the hippocampus but not PFC of naive mice without affecting the total ERK1/2 levels. The ameliorating effect of ZSET1446 on recognition memory in METH-treated mice was negated by pretreatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, SL327 (alpha-[amino-(4-aminophenylthio)methylene]-2-(trifluoromethyl)phenylacetonitrile). Furthermore, the dopamine D1 receptor antagonist, SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)], blocked the ameliorating effect of ZSET1446 on METH-induced memory impairment, whereas the D2 receptor antagonist, raclopride, had no effect. These results suggest that the ameliorative effect of ZSET1446 on METH-induced memory impairment is associated with indirect activation of ERK1/2 following stimulation with dopamine D1 and NMDA receptors of the PFC. ZSET1446 would be a potential candidate for further preclinical study aimed at the treatment of cognitive deficits in Alzheimer's disease and schizophrenia, as well as METH psychosis.

Recovery of functional peptide transporter PepT1 in budded baculovirus fraction.

Transporters play a critical role in many physiological and pathological states and expression of the functional transporter protein is essential in exploring its kinetics and developing effective drugs. We describe here the recovery of functional transporter protein in the baculovirus fraction. We introduced a gene encoding human peptide transporter PepT1, important for the absorption of protein hydrolytic products or peptide-mimetic drugs, into a baculovirus vector. After infection, a large amount of PepT1 appeared in the budded virus fraction compared with Sf9 cells. Uptake of [14C]glycylsarcosine was markedly increased in an acidic condition and showed a clear overshoot in PepT1-expressing virus fraction. The apparent Michaelis constant for [14C]glycylsarcosine was 0.55 +/- 0.06 mM. [14C]Glycylsarcosine uptake was inhibited by di- and tripeptides and orally active beta-lactam antibiotics. These results suggest that functional PepT1 recovers efficiently in a budded virus fraction, and, thus, this expression system will be a useful tool for characterization and screening of peptide-mimetic drugs in drug discovery.

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma.

For detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis, serum alpha-fetoprotein has been widely used, but its sensitivity has not been satisfactory, especially in small, well-differentiated HCC, and complementary serum marker has been clinically required. Glypican-3 (GPC3), a heparan sulfate proteoglycan anchored to the plasma membrane, is a good candidate marker of HCC because it is an oncofetal protein overexpressed in HCC at both the mRNA and protein levels. In this study, we demonstrated that its NH(2)-terminal portion [soluble GPC3 (sGPC3)] is cleaved between Arg(358) and Ser(359) of GPC3 and that sGPC3 can be specifically detected in the sera of patients with HCC. Serum levels of sGPC3 were 4.84 +/- 8.91 ng/ml in HCC, significantly higher than the levels seen in liver cirrhosis (1.09 +/- 0.74 ng/ml; P < 0.01) and healthy controls (0.65 +/- 0.32 ng/ml; P < 0.001). In well- or moderately-differentiated HCC, sGPC3 was superior to alpha-fetoprotein in sensitivity, and a combination measurement of both markers improved overall sensitivity from 50% to 72%. These results indicate that sGPC3 is a novel serological marker essential for the early detection of HCC.

Outcome of breast-conserving therapy in the Tokyo Women's Medical University Breast Cancer Society experience.

BACKGROUND: The results of BCT in Japanese women have not been fully evaluated. The Tokyo Women's Medical University Breast Cancer Society initiated BCT protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and identify prognostic factors. METHODS: The study population comprised 348 patients (353 breasts) with UICC clinical stage 0,I or II breast cancer, for whom wide excision (n= 294), quadrantectomy (n= 56) and tumorectomy (n= 3) were performed. The final pathological margin states were positive in 102 breasts (cancer cells remained within 5 mm of the surgical margin). The whole breast was irradiated to a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with negative surgical margins. The patients with positive or close margins received 48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All but 2 patients received a radiation boost to the tumor bed and all tumor beds were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240 cases. The median follow-up time was 4.3 years. RESULTS: The 5-year overall, cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%, respectively. Recurrence was observed in 29 patients including 11 patients with loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom were premenopausal. The 5-year local control and loco-regional control rates were 98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant prognostic factor for disease-free survival. No severe morbidity has been observed. Cosmetic results were excellent or good in 73% of patients. CONCLUSION: Our BCT protocols provide a high rate of local control and good cosmetic outcome. Pathologic margin status was not a major prognostic factor for local recurrence. Long term follow-up is required to reach a definite conclusion on optimal BCT protocols.

Monoclonal antibodies against blood group A secretors and nonsecretors saliva.

To obtain monoclonal antibodies (MAbs) that distinguish secretor and nonsecretor from their saliva in forensic casework, two (K7405 and K7422) and one (K7516) MAbs reacting to blood group A antigen were produced by immunization of mice with salivary mucin obtained from blood group A secretors and nonsecretors, respectively. K7405, produced by immunization with salivary mucin obtained from A secretor, reacted with the A substances bound to the carrier protein but not with the A substance separated from the carrier protein. On the other hand, the K7422 and K7516 were reactive to the A substance separated from carrier protein. From these results, we conclude that K7405 recognizes the A substances clustered on the carrier protein and K7422 and K7516 recognize the isolated A substance. In the forensic blood typing of body fluids, A secretors and A nonsecretors can be clearly discriminated by the combined application of two MAbs (K7405 and K7516), which react differently against saliva samples.