[The Near Future of Pharmaceutical Education as Higher Education: Concepts at the Heart of the Curriculum].

Under the current Model Core Curriculum for Pharmaceutical Education, competencies and program-level learning outcomes are not differentiated; furthermore, how competencies are developed by specific behavioral objectives, which are subdivided by specialty, needs to be clarified. A clear vision for ensuring academic as well as clinical competencies in Japanese pharmaceutical education, which emphasizes research and education in basic fields, is needed. Standardization is necessary to ensure improvement in quality over time. Thus, it is necessary to establish a model core curriculum as a standard. First, we assigned students a task designed for them to pursue outcome-based education from the perspective of developing competencies. Second, students learned about the importance of "conceptual understanding", which enables them to form generalizations and principles that enable them to deal with new situations. Finally, we discussed the specifics of how to transfer understanding in the cognitive domain and proposed a "concept-based curriculum" that considers a hierarchy of competencies that includes the non-cognitive domain. In addition, we created a draft of a form that had check items for incorporating it into a real curriculum with an eye to practical use. The method used in the present study of organizing a curriculum corresponding to qualitatively different cognitive, metacognitive, and action systems may be applicable to other professions in the medical field.

Higher Serum Soluble TREM2 as a Potential Indicative Biomarker for Cognitive Impairment in Inadequately Controlled Type 2 Diabetes Without Obesity: The DOR-KyotoJ-1.

Objective: Type 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity. Methods: A total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations. Results: During the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023). Conclusions: Glycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

Surface Magnetization Reversal of Wiegand Wire Measured by the Magneto-Optical Kerr Effect.

The Wiegand wire is known to exhibit a unique feature of fast magnetization reversal in the magnetically soft region accompanied by a large Barkhausen jump. We clarified a significant difference between the magnetization reversals at the surface and at the entire cross section of a Wiegand wire. We conducted magnetization measurements based on the magneto-optical Kerr effect and applied conventional methods to determine the magnetization curves. The switching field of the magnetization reversal at the surface was greater than that at the initiation of a large Barkhausen jump. Our analysis suggests that the outer surface layer exhibits low coercivity.

Magnetization Characteristics of Oriented Single-Crystalline NiFe-Cu Nanocubes Precipitated in a Cu-Rich Matrix.

In this study, we evaluated the magnetization properties of a magnetic alloy with single-crystalline cubic nanostructures, in order to clarify its magnetocrystalline anisotropy. Upon applying a specific annealing treatment to the CuNiFe base material, the precipitated magnetic particles grew into cubic granules, resulting in the formation of nanometric cubic single crystals of magnetic CuNiFe in a nonmagnetic Cu-rich matrix. The cubic nanostructures of CuNiFe were oriented along their crystallographic axis, in the <100> direction of the face-centered-cubic structure. We evaluated the static magnetization properties of the sample, which originated primarily from the CuNiFe nanocubes precipitated in the Cu-rich matrix, under an applied DC magnetic field. The magnetocrystalline anisotropy was readily observed in the magnetization curves. The <111> axis of the CuNiFe was observed to be the easy axis of magnetization. We also investigated the dynamic magnetization properties of the sample under an AC magnetic field. By subtracting the magnetic signal induced by the eddy current from the magnetization curves of the sample, we could obtain the intrinsic AC magnetization properties of the CuNiFe nanocubes.

Improvement of Pulse Voltage Generated by Wiegand Sensor Through Magnetic-Flux Guidance.

Magnetization reversal in a Wiegand wire induces a pulse voltage in the pickup coil around the wire, called the Wiegand pulse. The Wiegand sensor features the Wiegand wire and the pickup coil. The amplitude and width of the Wiegand pulse are independent of the frequency of the magnetic-field change. The pulse is generated by the Wiegand sensor, which facilitates the use of the Wiegand sensor as a power supply for equipment without batteries. In order to meet the power consumption requirements, it is necessary to maximize the energy of the pulse signal from the Wiegand sensor, without changing the external field conditions. The distributions of the magnetic field generated from the applied magnet in air and in the Wiegand wire were simulated before the experiments. Simulation predicted an increase in the magnetic flux density through the center of the Wiegand wire. This study determined that the magnetic flux density through the center of the Wiegand wire, the position of the pickup coil, and the angle between the Wiegand sensor and the magnetic induction line were the main factors that affected the energy of a Wiegand pulse. The relationship between these factors and the energy of the Wiegand pulse were obtained.

Output Characteristics and Circuit Modeling of Wiegand Sensor.

A fast magnetization reversal in a twisted FeCoV wire induces a pulse voltage in a pick-up coil wound around a wire. The Wiegand sensor is composed of this magnetic wire and the pick-up coil. As the output pulse voltage does not depend on a changing ratio of the applied magnetic field to switch the magnetization of the wire, the Wiegand sensor is used for to perform rotation and other detections. Recently, the Wiegand sensor has attracted significant attention as a power supply for battery-less operation of electric devices and for energy harvesting. In this study, we propose a concept of obtaining an intrinsic pulse voltage from the Wiegand sensor as its power source, and demonstrate its effectiveness in circuit simulation. The equivalent circuit for the Wiegand sensor is expressed by the intrinsic pulse voltage, internal resistance, and inductance of the pick-up coil. This voltage as a power source and circuit parameters are determined by MATLAB/Simulink simulation. The output voltage calculated using the equivalent circuit of the Wiegand sensor agrees with the experimentally measured results.

Circuit Parameters of a Receiver Coil Using a Wiegand Sensor for Wireless Power Transmission.

We previously demonstrated an efficient method of wireless power transmission using a Wiegand sensor for the application in implantable medical devices. The Wiegand sensor has an advantage in inducing sharp pulse voltage independent of the drive frequency. A down-sized receiver coil for wireless power transmission within blood vessels has been prepared, which enables medical treatment on any part of a human body. In order to develop practical applications of the Wiegand sensor as implantable medical devices, the circuit design is important. The circuit parameters in the circuit model of the Wiegand sensor must be clearly identified. However, a fast reversal of magnetization of the magnetic wire used in the Wiegand sensor, known as a large Barkhausen jump, and the induced nonlinear pulse signal make the inductance of the receiver coil time-dependent and inconsistent as conventionally considered in circuit analysis. In this study, the voltage and current responses of a wire-core coil are analyzed, and the time-dependent inductance is determined. The results showed that the inductance depends on the magnetization state of the wire, which can be negative during the fast reversal of magnetization.

Development of an Analytical Method for Estimating Three-Dimensional Distribution of Sediment-Associated Radiocesium at a Reservoir Bottom.

After the Fukushima Daiichi Nuclear Power Station accident, the distributions of sediment-associated radiocesium were investigated to evaluate the dispersion and accumulation of radiocesium in the reservoir field. To develop an analytical method for measuring the horizontal and vertical distributions of radiocesium on a wide scale, we obtained 253 gamma-ray spectra at the bottoms of 64 ponds in Fukushima during 2014-2016 by using a NaI(Tl) scintillation detector. For visualizing horizontal distribution, the correlation between detector counting rate and radiocesium concentration of the bottom sediment was confirmed. In estimating vertical distribution, the depth profile of sediment-associated radiocesium was found to be correlated to the intensities of scattered and photo peaks. Good agreement was observed between the results of in situ spectrometry and core sampling. These results indicate that the developed method is suitable for understanding the behavior of radiocesium and determining whether decontamination of reservoirs is required.

Conservative Treatment for Idiopathic Adrenal Hemorrhage Tracked by a Long-term Series of CT Images.

A 55-year-old man was transported to our hospital after a sudden onset of left lower abdominal pain while driving. Computed tomography (CT) of the abdominal region revealed an extensive iso-intense signal region that had a maximum area of 14×15 cm, which we treated conservatively. A series of follow-up CT images showed the gradual decrease of the left peritoneal mass, while continuity with the left adrenal gland became apparent. He was diagnosed with idiopathic adrenal hemorrhage. Adrenal hemorrhage presenting with huge retroperitoneal tumors is rare, and most cases are treated surgically. Therefore, CT images with conservative treatment are rare, holding both clinical interest and significance.

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.

Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.

Osmotic demyelination syndrome complicating diabetes with anti-glutamic acid decarboxylase antibodies and Graves' disease: A case report.

ODS associated with hyperglycemia is rare, with few reports.Immune responses have been recently reported as a mechanism of ODS onset. In the present case, an autoimmune predisposition may have contributed to ODS pathogenesis.

Rotation of Magnetization Derived from Brownian Relaxation in Magnetic Fluids of Different Viscosity Evaluated by Dynamic Hysteresis Measurements over a Wide Frequency Range.

The dependence of magnetic relaxation on particle parameters, such as the size and anisotropy, has been conventionally discussed. In addition, the influences of external conditions, such as the intensity and frequency of the applied field, the surrounding viscosity, and the temperature on the magnetic relaxation have been researched. According to one of the basic theories regarding magnetic relaxation, the faster type of relaxation dominates the process. However, in this study, we reveal that Brownian and Néel relaxations coexist and that Brownian relaxation can occur after Néel relaxation despite having a longer relaxation time. To understand the mechanisms of Brownian rotation, alternating current (AC) hysteresis loops were measured in magnetic fluids of different viscosities. These loops conveyed the amplitude and phase delay of the magnetization. In addition, the intrinsic loss power (ILP) was calculated using the area of the AC hysteresis loops. The ILP also showed the magnetization response regarding the magnetic relaxation over a wide frequency range. To develop biomedical applications of magnetic nanoparticles, such as hyperthermia and magnetic particle imaging, it is necessary to understand the mechanisms of magnetic relaxation.

Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

Reduction of Dimethylnitrosamine-Induced Liver Fibrosis by the Novel Gene Regulator PI Polyamide Targeting Transforming Growth Factor ß1 Gene.

Pyrrole-imidazole (PI) polyamide is a novel gene regulating agent that competitively inhibits transcription factor binding to the promoter of the specific target gene. Liver fibrosis is an integral stage in the development of chronic liver disease, and transforming growth factor ß (TGFß) is known to play a central role in the progression of this entity. The aim of this study was to evaluate the effect of PI polyamide targeting TGFß1 on rat liver fibrosis. PI polyamide was designed to inhibit activator protein 1 (AP-1) transcription factor binding to the TGFß1 gene promoter. The effect of PI polyamide on hepatic stellate cells was evaluated by real time polymerase chain reaction (PCR) in RI-T cells. To determine the effect of PI polyamide in vivo, PI polyamide was intravenously administered at a dose of 3 mg/kg/week in dimethylnitrosamine (DMN)-induced rat model of liver fibrosis. Treatment of RI-T cells with 1.0 µM PI polyamide targeting TGFß1 significantly inhibited TGFß1 mRNA expression. Azan staining showed that DMN treatment significantly increased areas of fibrous materials compared with controls. PI polyamide targeting TGFß1 significantly decreased the fibrous area compared with DMN group. mRNA expression levels of α-smooth muscle actin and matrix metalloproteinase-2 were significantly increased in DMN-treated group compared with control. Treatment with TGFß1 PI polyamide significantly decreased mRNA expression of these genes compared with DMN group. The novel gene regulator PI polyamide targeting TGFß1 may be a feasible therapeutic agent for the treatment of chronic liver disease.

Aftereffects of Subduction-Zone Earthquakes: Potential Tsunami Hazards along the Japan Sea Coast.

The 2011 Tohoku-Oki Earthquake is a typical subduction-zone earthquake and is the 4th largest earthquake after the beginning of instrumental observation of earthquakes in the 19th century. In fact, the 2011 Tohoku-Oki Earthquake displaced the northeast Japan island arc horizontally and vertically. The displacement largely changed the tectonic situation of the arc from compressive to tensile. The 9th century in Japan was a period of natural hazards caused by frequent large-scale earthquakes. The aseismic tsunamis that inflicted damage on the Japan Sea coast in the 11th century were related to the occurrence of massive earthquakes that represented the final stage of a period of high seismic activity. Anti-compressive tectonics triggered by the subduction-zone earthquakes induced gravitational instability, which resulted in the generation of tsunamis caused by slope failing at the arc-back-arc boundary. The crustal displacement after the 2011 earthquake infers an increased risk of unexpected local tsunami flooding in the Japan Sea coastal areas.

Cardio-ankle vascular index predicts for the incidence of cardiovascular events in obese patients: a multicenter prospective cohort study (Japan Obesity and Metabolic Syndrome Study: JOMS).

OBJECTIVE: The cardio-ankle vascular index (CAVI) is an index of arterial stiffness less dependent on blood pressure and an indicator suitable for assessing the arterial dysfunction. However, it remains unclear whether CAVI can predict the outcome of cardiovascular diseases (CVD) in obese patients. METHODS: A total of 425 obese Japanese outpatients (189 men and 236 women, mean age: 51.5 years) were enrolled in a multicenter prospective cohort Japan, the Japan Obesity and Metabolic Syndrome Study (JOMS). Primary analysis regarding measurements of cardiovascular risk factors including CAVI and the occurrence of macrovascular complications was based on following the participants over a 5-year period. RESULTS: Of the eligible patients, 300 (78%) were followed into the fifth year. During the study period, 15 coronary heart disease, 7 stroke, and 6 arteriosclerosis obliterans events occurred. All events occurred in 28 patients, and CVD incidence rate was 15.8 per 1000 person-years. In the analysis of adjusted models for traditional risk factors, CAVI was a significant factor for the incidence of events. In addition, high CAVI and low HDL-cholesterol were significant factors for the incidence of events in Cox stepwise multivariate analysis when age- and sex-adjusted (CAVI [per 1]: HR = 1.44 [1.02-2.02], p = 0.037; HDL-cholesterol [per 1 mmol/L]: HR = 0.20 [0.06-0.69], p = 0.011). In addition, CAVI added value to atherosclerotic cardiovascular disease risk score in predicting the development of CVD. CONCLUSION: This study demonstrates for the first time that CAVI is an effective predictor of CVD events in obese patients.

Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases.

Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub(+) ) and that the number of Ub(+) pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub(+) pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub(+) pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub(+) inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub(+) immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub(+) inclusions, while OP and AEF had fewer Ub(+) inclusions. These results suggest that the extent of Ub(+) inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub(+) inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs.