Current-induced switching of proximity-induced ferromagnetic surface states in a topological insulator.

Electrical manipulation of magnetization could be an essential function for energy-efficient spintronics technology. A magnetic topological insulator, possessing a magnetically gapped surface state with spin-polarized electrons, not only exhibits exotic topological phases relevant to the quantum anomalous Hall state but also enables the electrical control of its magnetic state at the surface. Here, we demonstrate efficient current-induced switching of the surface ferromagnetism in hetero-bilayers consisting of the topological insulator (Bi1-xSbx)2Te3 and the ferromagnetic insulator Cr2Ge2Te6, where the proximity-induced ferromagnetic surface states play two roles: efficient charge-to-spin current conversion and emergence of large anomalous Hall effect. The sign reversal of the surface ferromagnetic states with current injection is clearly observed, accompanying the nearly full magnetization reversal in the adjacent insulating Cr2Ge2Te6 layer of an optimal thickness range. The present results may facilitate an electrical control of dissipationless topological-current circuits.

Large non-reciprocal charge transport mediated by quantum anomalous Hall edge states.

The topological nature of the quantum anomalous Hall effect (QAHE) causes a dissipationless chiral edge current at the sample boundary1,2. Of fundamental interest is whether the chirality of the band structure manifests itself in charge transport properties. Here we report the observation of large non-reciprocal charge transport3 in a magnetic topological insulator, Cr-doped (Bi,Sb)2Te3. When the surface massive Dirac band is slightly carrier doped by a gate voltage, the edge state starts to dissipate and exhibits a current-direction-dependent resistance with a directional difference as large as 26%. The polarity of this diode effect depends on the magnetization direction as well as on the carrier type, electrons or holes. The correlation between the non-reciprocal resistance and the Hall resistance indicates that the non-reciprocity originates from the interplay between the chiral edge state and the Dirac surface state.

Large Anomalous Hall Effect in Topological Insulators with Proximitized Ferromagnetic Insulators.

We report a proximity-driven large anomalous Hall effect in all-telluride heterostructures consisting of the ferromagnetic insulator Cr_{2}Ge_{2}Te_{6} and topological insulator (Bi,Sb)_{2}Te_{3}. Despite small magnetization in the (Bi,Sb)_{2}Te_{3} layer, the anomalous Hall conductivity reaches a large value of 0.2e^{2}/h in accord with a ferromagnetic response of the Cr_{2}Ge_{2}Te_{6}. The results show that the exchange coupling between the surface state of the topological insulator and the proximitized Cr_{2}Ge_{2}Te_{6} layer is effective and strong enough to open the sizable exchange gap in the surface state.

Visualization of an axion insulating state at the transition between 2 chiral quantum anomalous Hall states.

Quantum-relativistic materials often host electronic phenomena with exotic spatial distributions. In particular, quantum anomalous Hall (QAH) insulators feature topological boundary currents whose chirality is determined by the magnetization orientation. However, understanding the microscopic nature of edge vs. bulk currents has remained a challenge due to the emergence of multidomain states at the phase transitions. Here we use microwave impedance microscopy (MIM) to directly image chiral edge currents and phase transitions in a magnetic topological insulator. Our images reveal a dramatic change in the edge state structure and an unexpected microwave response at the topological phase transition between the Chern number [Formula: see text] and [Formula: see text] states, consistent with the emergence of an insulating [Formula: see text] state. The magnetic transition width is independent of film thickness, but the transition pattern is distinct in differently initiated field sweeps. This behavior suggests that the [Formula: see text] state has 2 surface states with Hall conductivities of [Formula: see text] but with opposite signs.

Tailoring tricolor structure of magnetic topological insulator for robust axion insulator.

Exploration of novel electromagnetic phenomena is a subject of great interest in topological quantum materials. One of the unprecedented effects to be experimentally verified is the topological magnetoelectric (TME) effect originating from an unusual coupling of electric and magnetic fields in materials. A magnetic heterostructure of topological insulator (TI) hosts such exotic magnetoelectric coupling and can be expected to realize the TME effect as an axion insulator. We designed a magnetic TI with a tricolor structure where a nonmagnetic layer of (Bi, Sb)2Te3 is sandwiched by a soft ferromagnetic Cr-doped (Bi, Sb)2Te3 and a hard ferromagnetic V-doped (Bi, Sb)2Te3. Accompanied by the quantum anomalous Hall (QAH) effect, we observe zero Hall conductivity plateaus, which are a hallmark of the axion insulator state, in a wide range of magnetic fields between the coercive fields of Cr- and V-doped layers. The resistance of the axion insulator state reaches as high as 109 ohms, leading to a gigantic magnetoresistance ratio exceeding 10,000,000% upon the transition from the QAH state. The tricolor structure of the TI may not only be an ideal arena for the topologically distinct phenomena but can also provide magnetoresistive applications for advancing dissipation-less topological electronics.

Current-Driven Instability of the Quantum Anomalous Hall Effect in Ferromagnetic Topological Insulators.

The instability of the quantum anomalous Hall (QAH) effect has been studied as a function of the electric current and temperature in ferromagnetic topological insulator thin films. We find that a characteristic current for the breakdown of the QAH effect is roughly proportional to the Hall-bar width, indicating that the Hall electric field is relevant to the breakdown. We also find that electron transport is dominated by variable range hopping (VRH) at low temperatures. Combining the current and temperature dependences of the conductivity in the VRH regime, the localization length of the QAH state is evaluated to be about 5 µm. The long localization length suggests a marginally insulating nature of the QAH state due to a large number of in-gap states.

Seasonal Variation in the Daily Urinary Sodium Excretion in Outpatients from the Morioka Region of Northern Japan.

Objective Although the daily urinary sodium excretion (UNaV) is considered to provide the most reliable estimate of the daily sodium intake, it may be affected by salt loss due to sweating in summer. However, the seasonal variation in the daily UNaV associated with a normal lifestyle is unknown. Methods This study was performed in 348 outpatients from the Morioka region during three seasons: summer (summer 1), winter, and the following summer (summer 2). The daily UNaV (g salt/day) was estimated by the second morning urine method three times during each season. Seasonal variation was defined as a significant trend across the three seasons together with a significant difference between winter and both summers. Results In women, the daily UNaV was higher in winter (11.8±3.0 g salt/day) than in summer 1 (11.2±2.9 g salt/day) or summer 2 (11.0±2.9 g salt/day). In contrast, there was no marked seasonal variation in men. An analysis stratified by age (4 quartiles) identified seasonal variation in the older 2 quartiles of women (aged ≥68 years). In these women, the mean seasonal difference in the daily UNaV was 0.9 g of salt/day for both winter vs. summer 1 and winter vs. summer 2, while it was 0.1-0.8 g of salt/day in the other groups. Conclusion Seasonal variation in the daily UNaV only occurred in older female patients and was relatively small. This is evidence for restricting salt intake throughout the year and should reassure patients who are anxious about salt loss due to sweating in summer.

Neurotropin® inhibits calpain activity upregulated by specific alternation of rhythm in temperature in the mesencephalon of rats.

AIMS: Neurotropin® (NTP), an analgesic for chronic pain, has antihyperalgesic effects in specific alternation of rhythm in temperature (SART)-stressed rats. Previous studies have shown that SART stress induces hyperalgesia, as well as post-translational modification of proteins (including substrates for calpain, a calcium-dependent cysteine protease) in the mesencephalon of rats. To better understand the mechanism of action of NTP, we investigated whether SART stress activates calpain in the mesencephalon of rats and whether NTP inhibits this activation. MAIN METHODS: Wistar rats were exposed to SART stress for 5days. NTP (200NU/kg/day) was administered intraperitoneally every day from the onset of SART stress. The mechanical pain threshold was measured using the Randall-Selitto test on the 6th day. Thereafter, the rat mesencephalon was immediately collected and calpain activity was examined using western blot analysis with a calpain cleavage site-specific antibody. KEY FINDINGS: SART stress induced hyperalgesia and increased the calpain activity in the mesencephalon of rats. In contrast, NTP treatment attenuated the hyperalgesia and prevented the increase in calpain activity in the mesencephalon of SART-stressed rats. Interestingly, a negative correlation was identified between calpain activity and mechanical pain threshold in SART-stressed rats treated with or without NTP. Furthermore, NTP inhibited calpain activity on mammalian uncoordinated-18 in rat mesencephalon homogenate and Ac-LLY-AFC as substrates in an in vitro cell-free system. SIGNIFICANCE: Our data demonstrate that NTP treatment prevents SART stress-induced calpain activation in the mesencephalon of rats and suggests that NTP-mediated antihyperalgesia is associated with an inhibition of calpain activity in the mesencephalon.

Electronic Magnetization of a Quantum Point Contact Measured by Nuclear Magnetic Resonance.

We report an electronic magnetization measurement of a quantum point contact (QPC) based on nuclear magnetic resonance (NMR) spectroscopy. We find that NMR signals can be detected by measuring the QPC conductance under in-plane magnetic fields. This makes it possible to measure, from Knight shifts of the NMR spectra, the electronic magnetization of a QPC containing only a few electron spins. The magnetization changes smoothly with the QPC potential barrier height and peaks at the conductance plateau of 0.5×2e^{2}/h. The observed features are well captured by a model calculation assuming a smooth potential barrier, supporting a no bound state origin of the 0.7 structure.

Excitatory effect of Neurotropin(®) on noradrenergic neurons in rat locus coeruleus.

AIMS: Although the clinical use of Neurotropin® as an analgesic for chronic pain has been firmly established, its analgesic mechanism is still unclear. In this study, we investigate the direct effects of Neurotropin using an electrophysiological method. MAIN METHODS: Blind patch-clamp recordings were made from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem slices of normal rats. The effects of intracerebroventricular (icv) injection of Neurotropin on nociceptive transmission were recorded from spinal substantia gelatinosa (SG) neurons in fifth lumbar spinal nerve-ligated (L5-SNL) rats using an in vivo patch-clamp method. KEY FINDINGS: Neurotropin (0.2­1.0 NU/mL) dose-dependently increased the firing rate in noradrenergic LC neurons of normal rats. Under the voltage-clamp condition, Neurotropin induced an inward current in 90% of LC neurons thatwas not affected by tetrodotoxin or an injection of GDP-ß-S (G protein inhibitor) through recording pipettes. In contrast, Neurotropin had no effects on all PAG neurons tested. Using in vivo patch-clamp recordings, the icv injection of Neurotropin inhibited both frequency and amplitude of pinch-evoked excitatory postsynaptic currents of SG neurons in L5-SNL rats. These results suggest that Neurotropin directly excites the descending noradrenergic LC neurons and inhibits nociceptive transmission in the spinal dorsal horn. SIGNIFICANCE: This study is the first direct demonstration that Neurotropin activates the noradrenergic descending pain inhibitory systems, and this would reinforce the usefulness of Neurotropin in the treatment of human neuropathic pain.

Clinical application of the second morning urine method for estimating salt intake in patients with hypertension.

Estimation of salt intake by cumbersome 24-h urine collection is not suitable for individual patients because of substantial daily variation in intake. We developed the second morning urine (SMU) method for monitoring daily salt intake in healthy subjects by calculating the daily creatinine excretion and measuring the ratio of sodium to creatinine in the SMU specimen. To determine whether the SMU method was applicable to hypertensive patients, we tested it in hospitalized patients under an equilibrated sodium balance as a model population. This review focuses on application of the SMU method in hypertensive patients with mild target organ damage.

Seasonal variation of severe hypoglycemia in hospitalized patients 60 years of age or older presenting to an emergency center hospital between 2004 and 2010.

OBJECTIVE: To investigate the seasonal variation of severe hypoglycemia in hospitalized elderly patients. METHODS: Among the patients hospitalized in our department between 2004 and 2010, we analyzed the records of 67 patients who required emergency admission for severe hypoglycemia and were aged 60 years or older. Comparisons were made between those admitted during the warm season (April-September) and those in the cold season (October-March). PATIENTS: The mean age of the 67 patients was 76±8 years, including 45 men and 22 women. Twenty-four patients were admitted in the warm season and 43 patients were admitted in the cold season, with the average annual number being 3.4±1.9 and 6.1±2.8, respectively (p<0.05). RESULTS: Admissions for patients taking insulin showed no significant difference between the warm and cold season. In contrast, significantly fewer patients taking oral hypoglycemic agents were admitted in the warm season than in the cold season (5 vs. 22, p<0.05). Among them, 26 patients (96%) were taking sulfonylurea, and anorexia associated with acute infections was the main cause of severe hypoglycemia. In the warm season, all of the patients were discharged without complications, while 8 patients had complications in the cold season. CONCLUSION: A seasonal variation regarding hospitalization was observed for severe hypoglycemia among the patients 60 years of age or older, with a higher incidence in the cold season than the warm season, and anorexia related to infections in patients taking sulfonylureas was responsible for this variation. Accordingly, careful management of acute illness is needed for patients using sulfonylureas, especially during the cold season.

[Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension(2) Goal and strategies of dietary salt reduction in the management of hypertension.

In this section of the Report of the Salt Reduction Committee of the Japanese Society of Hypertension, the target level of dietary salt reduction and its scientific evidence, present status of salt consumption in Japan, salt-reducing measures/guidance methods in individuals and population strategies to reduce salt intake are introduced. In the Dietary Reference Intake for the general population in Japan (2010 version), the target levels of salt restriction in men and women were established as less than 9.0 per day and 7.5 g per day, respectively. The Japanese Society of Hypertension Guidelines for the Management of Hypertension 2009 recommended the target level of dietary salt restriction in patients with hypertension as less than 6 g per day. However, the National Health and Nutrition Survey of Japan in 2010 reported that the mean salt intake in adults was 10.6 g per day (men: 11.4 g per day and women: 9.8 g per day). To effectively decrease salt intake in Japan, it is necessary to reduce the consumption of high-salt foods (especially traditional foods) and replace high-salt seasonings (soy sauce and so on) with low-salt alternatives. Health-care professionals must effectively perform salt-reduction guidance for hypertensive patients in hospitals/administrative organizations. To promote population strategies for salt reduction in the whole society of Japan, social strategies, such as administrative policies, companies' cooperation and educational staff's cooperation, are necessary.

[Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension(1) Role of salt in hypertension and cardiovascular diseases.

Dietary salt consumption is closely associated with the level of blood pressure (BP); stricter salt reduction more markedly decreased BP. Obesity/metabolic syndrome, Dietary Approach to Stop Hypertension (DASH) diet, exercise and mental stress influence the BP-elevating effect of high-salt diet. Observational and intervention studies suggested that salt restriction improved the risk of cardiovascular diseases. However, the effects may differ among the types of the hypertensive complications; salt reduction may decrease the risk of stroke more than that of ischemic heart disease. Small-scale studies demonstrated that excess salt increased the risk of the left ventricular hypertrophy, heart failure, the urinary protein/albumin levels and end-stage renal failure. These diverse beneficial effects of salt reduction are probably because low-salt diet is an effective strategy to decrease BP and body fluid volume but is less effective to ameliorate the other cardiovascular risk factors. A mean salt intake in Japan is markedly high. Considering the present condition, salt reduction is essential for the prevention and treatment of hypertension and for the prevention of cardiovascular diseases.

[Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension (3) Assessment and application of salt intake in the management of hypertension.

Salt-reduction guidance to hypertensive patients should be performed by evaluating salt intake of the individuals. However, each method to assess salt intake has both merits and limitations. Therefore, evaluation methods must be selected in accordance with the subject and facility's environment. In special facilities for hypertension treatment, measurement of sodium (Na) excretion with 24-h pooled urine or a survey on dietary contents by dietitians is recommended. In medical facilities in general, measurement of the levels of Na and creatinine (Cr) using second urine samples after waking-up or spot urine samples is recommended. The reliability of this method improves by using formulae including a formula to estimate 24-h Cr excretion. A method to estimate salt intake based on the Na excretion per gram Cr using the Na/Cr ratio in spot urine is simple, but not reliable. The method to estimate the daily excretion of salt from nighttime urine using an electronic salt sensor installed with a formula is recommended to hypertensive patients. Although its reliability is not high, patients themselves can measure this parameter simply at home and thus useful for monitoring salt intake and may intensify consciousness regarding salt reduction. Using these methods, salt intake (excretion) should be evaluated, and salt-reduction guidance targeting <6 g (Na: 100 mmol) per day should be conducted in the management of hypertension.

Combined antiallodynic effect of Neurotropin® and pregabalin in rats with L5-spinal nerve ligation.

AIMS: In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice. MAIN METHODS: The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments. Thiopental sodium was intravenously administered in mice and sleeping time was measured. In L5-SNL rats, an isobolographic analysis was performed to clarify the combined antiallodynic effect of Neurotropin and pregabalin 14 days after ligation in rats. In isobolographic analysis and thiopental-induced sleep test, Neurotropin and pregabalin were orally administered to coincide with the timing of the peak effect of each drug. KEY FINDINGS: Neurotropin (50-200 NU/kg) and pregabalin (2.5-10mg/kg) showed a dose-dependent antiallodynic action in L5-SNL rats. The antiallodynic effect of pregabalin was reversed by intrathecal injection of yohimbine or ondansetron. Isobolographic analysis suggested that the combined antiallodynic effect of Neurotropin and pregabalin in L5-SNL rats may have been more than a mere additive effect. Neurotropin (50-400 NU/kg) had no effect on thiopental-induced sleeping time whereas pregabalin (30-100mg/kg) significantly prolonged it. When the dose of pregabalin was 30 mg/kg, Neurotropin (50-400 NU/kg) did not further exacerbate the prolongation effect of pregabalin on thiopental-induced sleep. SIGNIFICANCE: It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin.

[Thymic carcinoid associated with multiple endocrine neoplasia type 1].

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.

Second morning urine method is superior to the casual urine method for estimating daily salt intake in patients with hypertension.

The accuracy of the casual urine (CU) method for estimating daily salt intake was compared with the second morning urine (SMU) method and with 24-h urine collection (24 UC) method as the gold standard. Data were obtained from three previously reported studies, in which we evaluated the daily salt intake by the SMU method. Using SMU samples from 1315 outpatients, the estimated salt intake was lower with the CU method than the SMU method. In inpatients with a daily salt intake of 7, 8 or 18 g, the CU method was applied to SMU specimens. It underestimated salt intake compared with the 24-h collection method whereas the SMU method and 24 UC method gave similar results. In the present study, 24 UC was done and then urine was collected at 0800, 1100, 1400, 1700 and 1900 hours, with a daily salt intake of 6 g in 8 inpatients, 10 g in 11 inpatients or 15 g in 5 inpatients. In comparison with the 24 UC method, the CU method underestimated a high salt intake (15 g) when morning specimens were used and overestimated a low salt intake (6 g) when afternoon specimens were used. The correlation between the CU method and 24 UC method was weaker (R = 0.57) than that between the SMU method and 24 UC method (R = 0.85). In conclusion, the CU method is heavily influenced by the timing of urine collection and by the actual daily salt intake, so the SMU method provides a better estimate of individual salt intake.