Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal.

BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

[Uterine cervical cancer screening in kitakyushu city: present and future].

Uterine cervical cancer is the most common primary gynecologic malignant tumor in Japan. Conventional cervical screening Papanicolaou (Pap) test has been shown to be extremely effective in reducing cervical cancer incidence and mortality, but the consultation rate for cancer screening in Japan is markedly low, at 20% of prescribed subjects, in comparison with other developed countries. In 2001, 15,501 women (6.8%) received a Pap test in Kitakyushu City, and that was less than half of national average. From 2009, free coupons for uterine cervical cancer screening were distributed to Japanese woman who were 20, 25, 30, 35 or 40 years of age as part of the project for women-specific cancer screening. The rate of participation in Pap testing was 22.3% in 2012, with 31,970 women receiving cervical tests. It was almost as high as the national level. It's obvious that high risk human papillomavirus (HPV) is responsible for cervical cancer incidence and HPV mainly infects through sexual practice. The rate of early cervical neoplasms and invasive cancers is currently increasing in young women. Abnormal Pap tests were detected in 2.3% of the women in 2008. To increase the population's participation in this screening process, a cost-effective and efficient system should be established. National and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation, and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer.

Enhanced superconductivity close to a non-magnetic quantum critical point in electron-doped strontium titanate.

Studies on quantum critical points (QCP) have focused on magnetic QCPs to date. Remarkable phenomena such as superconductivity due to avoided criticality have been discovered, but we focus here on the non-magnetic counterpart, i.e., the superconductivity of SrTiO3 regarded as being close to a ferroelectric QCP. Here we prepare high-quality Sr1-xLaxTi(16O1-z18Oz)3 single crystals without localisation at low temperatures, which allow us to systematically investigate the La substitution of Sr as an alternative to introducing oxygen vacancies. Analysis of our data based on a theoretical model predicts an appearance of the ferroelectric QCP around 3 × 1018 cm-3. Because of the QCP, the superconducting dome of Sr1-xLaxTiO3 can be raised upwards. Furthermore, remarkable enhancement of Tc (~0.6 K) is achieved by 18O exchange on the Sr1-xLaxTiO3 crystals. These findings provide a new knob for observing intriguing physics around the ferroelectric QCP.

Management patterns and healthcare costs for hospitalized patients with cerebral infarction.

OBJECTIVES: Although evidence shows the importance of specialized intensive care of patients with cerebral infarction, it is not well known whether resources are generously applied in the initial period and how patterns of medical resource utilization are associated with characteristics of providers and patient outcomes. In this study, we analyzed changing patterns of daily medical cost using administrative healthcare claim data and identified a management pattern in each case. METHODS: We used Japan's administrative data to identify medical costs on a day-to-day basis. Data of 3136 patients with acute cerebral infarction from 14 medical institutions were included in the analyses. Using the data, we calculated the costs from the perspective of the third-party payer. Institutions were divided into three groups according to the distribution of medical costs in the first 2 days, and patient background, treatment process, and outcomes were compared across the groups. RESULTS: Medical cost was not necessarily intensively allocated during the early hospitalization period. Wide variations were observed in medical cost utilization patterns across institutions. The differences in medical cost for the initial hospitalization period appears to be more influenced by ICU utilization and management policies of institutions than the clinical condition of patients. CONCLUSIONS: We proposed a methodology that uses administrative claim data to examine management patterns of ischemic stroke. We believe that the use of our method, in conjunction with accurate and detailed clinical data, can help elucidate the relationship among acute-period medical resource utilization, process of care, and patient outcomes.

Anomalous enhancement of the sheet carrier density beyond the classic limit on a SrTiO3 surface.

Electrostatic carrier accumulation on an insulating (100) surface of SrTiO3 by fabricating a field effect transistor with Parylene-C (6 nm)/HfO2 (20 nm) bilayer gate insulator has revealed a mystifying phenomenon: sheet carrier density is about 10 times as large as ( is the sheet capacitance of the gate insulator, VG is the gate voltage, and e is the elementary charge). The channel is so clean to exhibit small subthreshod swing of 170 mV/decade and large mobility of 11 cm(2)/Vs for of 1 × 10(14) cm(-2) at room temperature. Since does not depend on either VG nor time duration, beyond is solely ascribed to negative charge compressibility of the carriers, which was in general considered as due to exchange interactions among electrons in the small limit. However, the observed is too large to be naively understood by the framework. Alternative ideas are proposed in this work.

Distribution of the extrinsic proteins as a potential marker for the evolution of photosynthetic oxygen-evolving photosystem II.

Distribution of photosystem II (PSII) extrinsic proteins was examined using antibodies raised against various extrinsic proteins from different sources. The results showed that a glaucophyte (Cyanophora paradoxa) having the most primitive plastids contained the cyanobacterial-type extrinsic proteins (PsbO, PsbV, PsbU), and the primitive red algae (Cyanidium caldarium) contained the red algal-type extrinsic proteins (PsO, PsbQ', PsbV, PsbU), whereas a prasinophyte (Pyraminonas parkeae), which is one of the most primitive green algae, contained the green algal-type ones (PsbO, PsbP, PsbQ). These suggest that the extrinsic proteins had been diverged into cyanobacterial-, red algal- and green algal-types during early phases of evolution after a primary endosymbiosis. This study also showed that a haptophyte, diatoms and brown algae, which resulted from red algal secondary endosymbiosis, contained the red algal-type, whereas Euglena gracilis resulted from green algal secondary endosymbiosis contained the green algal-type extrinsic proteins, suggesting that the red algal- and green algal-type extrinsic proteins have been retained unchanged in the different lines of organisms following the secondary endosymbiosis. Based on these immunological analyses, together with the current genome data, the evolution of photosynthetic oxygen-evolving PSII was discussed from a view of distribution of the extrinsic proteins, and a new model for the evolution of the PSII extrinsic proteins was proposed.

Effects of electroacupuncture at GB points on markers of osteoporosis and bodyweight in ovariectomised rats.

BACKGROUND: Based on a description of acupuncture to treat a bone disease resembling osteoporosis in the ancient text of Huangdi Neijing, we aimed to assess the effects of electroacupuncture (EA) at GB points in ovariectomised (OVX) rats. METHODS: 40 female Wistar rats were randomly divided into four groups (n=10 each): ovariectomised model group (OVX); ovariectomised group treated with EA at GB points (OVX+GB); ovariectomised group treated with EA at non-GB points (OVX+N) in the hindlimb; and a sham surgery group (Sham). Three months after ovariectomy, rats in the OVX+GB and OVX+N groups received EA treatment for 3 months. Urine, blood and femur samples were collected from each animal for analysis. RESULTS: Bodyweight (BW) in the OVX+GB group decreased after EA treatment, reaching a minimum of ∼12% below the OVX and OVX+N groups at 1 month. Concentrations of urine deoxypyridinoline, a bone resorption marker, were significantly elevated in the OVX and OVX+N groups but not the OVX+GB group. Concentrations of serum bone specific alkaline phosphatase, a bone formation marker, were significantly higher in the OVX+GB group versus the Sham and OVX groups. Bone mineral density (BMD) did not differ between the OVX, OVX+GB and OVX+N groups, but was ∼10% lower than the Sham group. However, BMD/BW in the OVX+GB group was significantly higher than in the OVX and OVX+N groups and similar to the Sham group. Histological assessment of the femur showed that EA at GB points improved the bone architecture. CONCLUSIONS: EA treatment at GB points had anti-osteoporotic effects in a rat model of osteoporosis.

Reproduction of scalp acupuncture therapy on strokes in the model rats, spontaneous hypertensive rats-stroke prone (SHR-SP).

Scalp acupuncture (SA) therapy on strokes has been empirically established and widely used in clinics in China. SA is particularly effective at ameliorating paralyses and speech disturbances, and the recovery rate is twice that for those treated with medication alone. To investigate the effects of SA on a scientific basis, we have developed a new experimental system that provides reliable controls and excludes psychological effects by using a genetic strain of rats, spontaneous hypertensive rats-stroke prone. Here we report that SA indeed has rapid and powerful effects to remove limb paralyses caused either by cerebral infarct or by cerebral haemorrhage. This model is well suited to study the mechanism of the effects of SA in parallel with clinical studies, and to describe the whole recovery process after the stroke onset.

A patient with delayed posthypoxic demyelination: a case report of hyperbaric oxygen treatment.

A 62-year-old man who developed akinetic mutism with delayed white matter demyelination after hypoxia was treated with hyperbaric oxygen (HBO). HBO in the subacute period markedly improved the patient's activity in daily life, cognitive function and organization on EEG. 1H-MRS showed a recovery of aerobic metabolism of the neurons. However, dementia and cerebral atrophy slowly progressed despite HBO treatment. Thus, HBO had a beneficial effect on the activity of depressed neurons but did not improve the prognosis.

Rhynchophylline-induced vasodilation in human mesenteric artery is mainly due to blockage of L-type calcium channels in vascular smooth muscle cells.

Rhynchophylline (Rhy) is a pharmacologically active substance isolated from Uncaria rhynchophylla which has been used to treat cardiovascular diseases and has drawn considerable attention in recent years for its antihypertensive activities. We investigated the actions of Rhy on endothelium-denuded human mesenteric artery by tension measurement and its actions on high conductance Ca(2+)-activated K(+) channels (BKCa) currents and calcium currents (ICa) in freshly isolated smooth muscle cells using perforated patch clamp technique. Intracellular Ca(2+) level was measured in Fura-2-loaded cells. Rhy inhibited both the KCl and BayK-evoked mesenteric artery constrictions in a dose-dependent manner. K(+) channel blockers (TEA, glibenclamide, IbTX, and 4-AP) did not affect the vasorelaxing effect of Rhy. Rhy inhibited L-type voltage-gated Ca(2+) current (ICa,L) but had no significant effect on macroscopic BKCa current. Rhy preincubation markedly reduced the elevation of [Ca(2+)]i level induced by KCl depolarization. Caffeine-stimulated [Ca(2+)]i elevation was also decreased to some extent by pretreatment with Rhy for 20 min. Our results show that Rhy relaxes smooth muscles of human mesenteric resistance arteries, mainly due to inhibition of Ca(2+) influx by blockage of L-type Ca(2+) channels and thereby the decrease in [Ca(2+)]i.

Electrolyte-gated SmCoO3 thin-film transistors exhibiting thickness-dependent large switching ratio at room temperature.

A Mott transistor that exhibits a large switching ratio of more than two orders at room temperature is demonstrated by using the electric double layer of an ionic liquid for gating on a strongly correlated electron system SmCoO3. From the thickness dependence of the on-state channel current, we estimate the screening length of the SmCoO3 to be ∼5 nm. The good carrier confinement within the Thomas-Fermi screening length demonstrates that the SmCoO3-channel electric double layer transistor is the first candidate for a two-dimensional Mott transistor.

Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats.

BACKGROUND: Oseltamivir phosphate (OP, Tamiflu(®)) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. OBJECTIVE: The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. METHODS: Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 10(5) plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. RESULTS: We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. CONCLUSION: Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

[Construction and identification of the expression plasmid of SK2 (KCNN2) gene from human atrial myocytes with overlapping PCR].

OBJECTIVE: Small conductance calcium activated potassium channels type 2 (SK2) play a crucial role in atrial repolarization. It is difficult to acquire the full-length of its coded gene KCNN2 by RT-PCR with one step. We aim to get the full-length of KCNN2 gene and construct the plasmid by Overlapping PCR, and further more discuss the application of Overlapping PCR. METHODS: Total RNA was extracted from human right atrial tissue and cDNA was acquired with reverse transcription. Overlapping PCR was conducted with three pairs of primers which were designed according to the sequence of KCNN2 (AY258141) gene. The expression plasmid of pIRES-hrGFP-SK2 was constructed by directed cloning with restriction enzyme site and identified by enzyme cutting and sequencing. RESULTS: Three parts of PCR amplification were consistent with predicted size. The sequence of the plasmid was consistent with the gene-bank data except two sites, however, which were the same as gene in different tissues. CONCLUSION: The expression plasmid pIRES-hrGFP-SK2 was constructed successfully. Overlapping PCR is a good choice for amplifying these genes with long size or low expression.

Unique action of sodium tanshinone II-A sulfonate (DS-201) on the Ca(2+) dependent BK(Ca) activation in mouse cerebral arterial smooth muscle cells.

Sodium tanshinone II-A sulfonate (DS-201) is a water-soluble derivative of tanshinone IIA, a main active constituent of Salvia miltiorrhiza which has been used for treatments of cardio- and cerebro-vascular diseases. DS-201 activates large conductance Ca(2+)-sensitive K(+) channels (BK(Ca)) in arterial smooth muscle cells, and reduces the vascular tone. Here we investigated the effect of DS-201 on the BK(Ca) channel kinetics by analyzing single channel currents. Smooth muscle cells were freshly isolated from mouse cerebral arteries. Single channel currents of BK(Ca) were recorded by patch clamp. DS-201 increased the total open probability (NPo) of BK(Ca) in a concentration-dependent manner. But this action required intracellular Ca(2+), and the effect depended on the Ca(2+) concentration ([Ca(2+)](free)). DS-201 activated BK(Ca) with the half maximal effective concentration (EC(50)) of 111.5µM at 0.01µM [Ca(2+)](free), and 68.5µM at 0.1µM [Ca(2+)](free.) The effect of DS-201 on NPo was particularly strong in the range of [Ca(2+)](free) between 0.1 and 1µM. Analysis of the channel kinetics revealed that DS-201 had only the effect on the channel closing without affecting the channel opening, which was a striking contrast to the effect of [Ca(2+)](free), that is characterized by changing the channel opening without changing the channel closing. DS-201 may be bound to the open state of BK(Ca), and have an inhibitory effect on the transition from the open to closed state. By this way DS-201 may enhance the activity of BK(Ca), and exhibit a strong vasodilating effect against vasoconstriction in the range of [Ca(2+)](free) between 0.1 and 1µM.

Strain-mediated phase control and electrolyte-gating of electron-doped manganites.

A prototype Mott transistor, the electric double layer transistor with a strained CaMnO(3) thin film, is fabricated. As predicted by the strain phase diagram of electron-doped manganite films, the device with the compressively strained CaMnO(3) exhibits an immense conductivity modulation upon applying a tiny gate voltage of 2 V.

Scalp acupuncture effects of stroke studied with magnetic resonance imaging: different actions in the two stroke model rats.

BACKGROUND: Scalp acupuncture (SA) therapy on strokes has been empirically established and widely used in clinics in China. The evidence from clinical studies suggests that SA produces significant benefits for some patients with stroke. METHODS: The effect of scalp acupuncture was studied using MRI for two different stroke models: spontaneously hypertensive stroke-prone (SHR-SP) rats and rats with transiently induced focal cerebral ischaemia by middle cerebral artery occlusion for 2 h (MCAO rats). RESULTS: Stroke onset in SHR-SP rats was characterised by a development of vasogenic oedema without any appearance of cytotoxic oedema. Scalp acupuncture reduced rapidly neurological dysfunction in SHR-SP rats and reduced the volume of the vasogenic oedema during the same period. In contrast, in MCAO rats, focal cerebral ischaemia caused an immediate development of cytotoxic oedema without any appearance of vasogenic oedema. Vasogenic oedema developed after reperfusion. Scalp acupuncture had no significant effects on the cytotoxic oedema, vasogenic oedema or neurological dysfunction of the MCAO rats within the time span examined. CONCLUSION: Scalp acupuncture had a rapid and strong effect on neurological dysfunction only in the hypertensive stroke-model by reducing the vasogenic oedema. Our results suggest that, if there are similar underlying mechanisms in human strokes, scalp acupuncture may be more beneficial for patients with strokes of hypertension-caused vasogenic origin than ischaemic origin.

Long-lasting potassium channel inactivation in myoepithelial fibres is related to characteristics of swimming in diphyid siphonophores.

Diphyid siphonophores swim using bursts of propulsive jets, which are produced by contractions of a monolayer of subumbrellar myoepithelial fibres lining the nectophore. This swimming behaviour is characterised by successive increases in the force generating the jets during the initial jets of the burst. Action potentials that generate the contractions propagate throughout the myoepithelial layer: both their amplitude and duration successively increase during the first part of the burst. To investigate the ionic mechanism of this action potential augmentation, single myoepithelial cells were enzymatically dissociated and whole-cell voltage clamped. Na+, Ca2+ and K+ currents were recorded under different internal and external salt compositions. The Na+ current was blocked by a relatively high concentration (4 micromol l-1 or higher) of tetrodotoxin (TTX), indicating that the Na+ channel belongs to a group of TTX-resistant Na+ channels. The Ca2+ current was blocked by nifedipine (10 micromol l-1) and Co2+ (5 mmol l-1), indicating that the Ca2+ channel is L-type. The K+ current possessed a unique property of long-lasting inactivation. The K+ current fully inactivated during a depolarisation to +30 mV with a time-constant of approximately 9 ms, and the time constant of recovery from inactivation at -70 mV was 13.2 s. This long-lasting inactivation of the K+ channel was the major factor in the augmentation of both action potentials and contractions of the myoepithelial sheet during the initial part of the burst.

Excitation-contraction coupling in skeletal and caudal heart muscle of the hagfish Eptatretus burgeri Girard.

Hagfishes are regarded as the most primitive living craniates. Excitation-contraction (E-C) coupling mechanisms were studied in skeletal and caudal heart muscle fibres of the hagfish Eptatretus burgeri. In white (fast) skeletal muscle fibres from the musculus tubulatus, force generation in response to electrical stimulation was maintained in nominally Ca(2+) free artificial seawater (ASW) (0Ca(2+)-ASW) containing 10 mmol l(-1) Co(2+) (a blocker of Ca(2+) currents). Similarly, in red (slow) fibres from parietal muscle bathed in 0Ca(2+)-ASW containing 10 mmol l(-1) Co(2+), force generation occurred in association with K(+) depolarisation when the external K(+) concentration was increased to 100 mmol l(-1). Therefore, external Ca(2+) is not required for muscle contraction. Hence, both white and red fibres possess the function of depolarisation-induced Ca(2+)-release from intracellular Ca(2+) stores. This function is the same as in the skeletal muscle of all other vertebrates. In caudal heart muscle fibres, twitches in response to electrical stimuli were maintained in 0Ca(2+)-ASW containing 30 mmol l(-1) Co(2+). In fibres loaded with fluo-3 bathed in 0Ca(2+)-ASW containing 30 mmol l(-1) Co(2+), an increase in the intracellular free Ca(2+) level associated with K(+) depolarisation was observed after the external K(+) concentration was increased to 100 mmol l(-1). Thus E-C coupling in the caudal heart muscle is also of the vertebrate skeletal muscle type.

Ionic currents in isolated and in situ squid Schwann cells.

Ionic currents from Schwann cells isolated enzymatically from the giant axons of the squids Loligo forbesi, Loligo vulgaris and Loligo bleekeri were compared with those obtained in situ. Macroscopic and single channel ionic currents were recorded using whole-cell voltage and patch clamp. In the whole-cell configuration, depolarisation from negative holding potentials evoked two voltage-dependent currents, an inward current and a delayed outward current. The outward current resembled an outwardly rectifying K+ current and was activated at -40 mV after a latent period of 5-20 ms following a step depolarisation. The current was reduced by externally applied nifedipine, Co2+ or quinine, was not blocked by addition of apamin or charibdotoxin and was insensitive to externally applied L-glutamate or acetylcholine. The voltage-gated inward current was activated at -40 mV and was identified as an L-type calcium current sensitive to externally applied nifedipine. Schwann cells were impaled in situ in split-open axons and voltage clamped using discontinuous single electrode voltage clamp. Voltage dependent outward currents were recorded that were kinetically identical to those seen in isolated cells and that had similar current-voltage relations. Single channel currents were recorded from excised inside-out patches. A single channel type was observed with a reversal potential close to the equilibrium potential for K+ (E(K)) and was therefore identified as a K+ channel. The channel conductance was 43.6 pS when both internal and external solutions contained 150 mM K+. Activity was weakly dependent on membrane voltage but sensitive to the internal Ca2+ concentration. Activity was insensitive to externally or internally applied L-glutamate or acetylcholine. The results suggest that calcium channels and calcium-activated K+ channels play an important role in the generation of the squid Schwann cell membrane potential, which may be controlled by the resting intracellular Ca2+ level.