Posture Estimation Using Surface Electromyography during Wheelchair Hand-Rim Operations.

This study examined competitive wheelchairs that facilitate sports participation. They can be moved straight ahead using only one arm. Our designed and developed competitive wheel-chairs have a dual hand-rim system. Their two hand-rims, attached to a drive wheel on one side, can be operated simultaneously for straight-ahead movement. Specifically, based on integrated electromyography (iEMG) data calculated from surface electromyography (sEMG), we examined the wheelchair loading characteristics, posture estimation, and effects on body posture during one-arm propulsion movement. The first experiment yielded insights into arm and shoulder-joint muscle activation from iEMG results obtained for two-hand propulsion and dual hand-rim system propulsion. Results suggest that muscle activation of one arm can produce equal propulsive force to that produced by two arms. The second experiment estimated the movement posture from iEMG during one-arm wheelchair propulsion. The external oblique abdominis is particularly important for one-arm wheelchair propulsion. The iEMG posture estimation validity was verified based on changes in the user body axis and seat pressure distribution. In conclusion, as confirmed by iEMG, which is useful to estimate posture during movement, one-arm wheelchair use requires different muscle activation sites and posture than when using two arms.

Use of a Healthcare Claims Database for Post-Marketing Safety Assessments of Eribulin in Japan: A Comparative Assessment with a Prospective Post-Marketing Surveillance Study.

BACKGROUND: To understand the extent to which a large-scale healthcare claims database (DB) captures the safety profile of eribulin mesylate (Halaven®, Eisai Co., Ltd., Japan), we compared patient characteristics, drug use, and adverse events (AEs) between data for patients treated with eribulin retrieved from a DB and data for metastatic breast cancer patients from a conventional prospective post-marketing surveillance (PMS). METHODS: We descriptively summarized patient characteristics and AEs of 551 and 951 patients retrieved from DB and PMS, respectively, during 2011‒2013. Using 2814 patient data from the DB during 2011‒2016, the drug use and AE incidence over time were assessed. RESULTS: In both datasets, 99.8% were females, and the mean age was 57.8 ± 10.7 years. The mean number of eribulin administration was 11.1 ± 10.9 and 10.1 ± 7.8 in DB and PMS, respectively. Although, overall, the difference in AE incidence between the two datasets was moderate, gaps were larger for nausea (DB: 73.32% vs. PMS: 15.77%), neutropenia (20.87% vs. 66.67%), stomatitis (37.39% vs. 10.94%), and alopecia (0.36% vs. 12.09%). During 2011‒2016, the observed incidence of anemia or pyrexia significantly decreased (trend test, p = 0.0009 for both). CONCLUSION: Generally, patient characteristics, drug use, and AE incidence between the DB and PMS were comparable; however, AEs such as neutropenia may require defining based on the laboratory data to achieve more comparable results in DBs. Besides the usefulness of healthcare claims DBs for long-term assessments, they may also serve as a good complementary to PMS in the pharmacovigilance of eribulin.

A warped disk around an infant protostar.

Recent exoplanet studies have revealed that the orbital planes of planets are not always aligned with one another or with the equatorial plane of the central star. The misalignment has been ascribed to gravitational scattering by giant planets and/or companion stars1-3 or to fly-bys in stellar cluster environments4. Alternatively, the misalignment could be natal: that is, such planets were born in a warped protostellar disk5,6. Warped disk structures have been reported in some transition disks and protoplanetary disks7,8, but not in the earlier stages of protostar evolution, although such a possibility is suggested by outflow morphology9,10. Here we report millimetre-wavelength dust continuum observations of the young embedded protostar IRAS 04368+2557 in the protostellar core L1527 at a distance11 of 137 parsecs; the protostar's disk is almost edge-on12-16. The inner and outer parts of the disk have slightly different orbital planes, connected at 40 to 60 astronomical units from the star, but the disk has point symmetry with respect to the position of the protostar. We interpret it as a warped disk that is rotationally supported. Because there is no evidence for a companion source17,18, the warped structure must be due to either anisotropic accretion of gas with different rotational axes, or misalignment of the rotation axis of the disk with the magnetic field direction.

Effects of indigo carmine intravenous injection on noninvasive and continuous total hemoglobin measurement with using the Revision L sensor.

The effects of intravenous injection of indigo carmine on noninvasive and continuous total hemoglobin (SpHb) measurement were retrospectively evaluated with the Revision L sensor. The subjects were 18 patients who underwent elective gynecologic surgery under general anesthesia. During surgery, 5 mL of 0.4 % indigo carmine was injected intravenously, and changes in SpHb concentrations between before and after the injection were evaluated. The mean age was 52.4 ± 12.8 years. Before injection, the median SpHb level was 10.1 (range, 6.8-13.4) g/dL. The results demonstrated no change in SpHb concentration between before and after indigo carmine injection as detected by the Revision L sensor. SpHb measurements as determined with the Revision L sensor were not affected, even after the intravenous injection of indigo carmine.

Possible involvement of iron-induced oxidative insults in neurodegeneration.

Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research.

Validation of continuous and noninvasive hemoglobin monitoring by pulse CO-oximetry in Japanese surgical patients.

We evaluated the accuracy of noninvasive and continuous total hemoglobin (SpHb) monitoring with the Radical-7(®) Pulse CO-Oximeter in Japanese surgical patients before and after an in vivo adjustment of the first SpHb value to match the first reference value from a satellite laboratory CO-Oximeter. Twenty patients undergoing surgical procedures with general anesthesia were monitored with Pulse CO-Oximetry for SpHb. Laboratory CO-Oximeter values (tHb) were compared to SpHb at the time of the blood draws. Bias, precision, limits of agreement and correlation coefficient of SpHb compared to tHb were calculated before and after SpHb values were adjusted by subtracting the difference between the first SpHb and tHb value from all subsequent SpHb values. Trending of SpHb to tHb and the effect of perfusion index (PI) on the agreement of SpHb to tHb were also analyzed. Ninety-two tHb values were compared to the SpHb. Bias ± 1SD was 0.2 ± 1.5 g/dL before in vivo adjustment and -0.7 ± 1.0 g/dL after in vivo adjustment. Bland-Altman analysis showed limits of agreement of -2.8 to 3.1 g/dL before in vivo adjustment and -2.8 to 1.4 g/dL after in vivo adjustment. The correlation coefficient was 0.76 prior to in vivo adjustment and 0.87 after in vivo adjustment. In patients with adequate perfusion (PI ≥1.4) the correlation coefficient was 0.89. In vivo adjustment of SpHb significantly improved the accuracy in our cohort of Japanese surgical patients. The strongest correlation between SpHb and tHb values was observed in patients with adequate peripheral perfusion suggesting that low perfusion may affect the accuracy of SpHb monitoring.

[Intracranial malignant glioma presenting as subarachnoid hemorrhage].

Cerebral aneurysms are the predominant cause of spontaneous subarachnoid hemorrhage (SAH). However, if an aneurismal cause has been excluded, there remains but a short list of meningiomas or metastatic lesions as possible causes. This article details a case of neoplasm that presented exclusively with SAH. A 31-year-old male presented with a SAH with normal cerebral angiography. The initial magnetic resonance image (MRI) revealed a lesion in the left uncus thought to be recovering hemorrhage. Subsequent MRI, however revealed the mass to be expanding. A neuroendoscopical biopsy of the lesion established a diagnosis of glioblastoma. An affirmation is made that patients experiencing "angiographically-negative" SAH should undergo MRI, occasionally on a serial basis, to exclude other etiologies for hemorrhage, including neoplasma.

Lactococcus lactis subsp. cremoris FC triggers IFN-γ production from NK and T cells via IL-12 and IL-18.

Lactic acid bacteria (LAB) benefit health as probiotics in a strain-dependent way. In this study, we investigated the immunomodulatory effects of Lactococcus lactis subsp. cremoris FC (LcFC) on dendritic cells (DCs), natural killer (NK) cells and T cells. LcFC induced the production of cytokines such as IL-10, IL-12, IL-6 and TNF-α from murine bone marrow DCs (BMDCs) via MyD88-dependent pathway. In comparison with the type strain L. lactis subsp. cremoris ATCC 19257, LcFC induced particularly high production of IL-12 while induction of IL-6 was moderate. Consequently, LcFC triggered IFN-γ production in splenic NK, CD8(+), and CD4(+) cells. Most prominent effect of LcFC on IFN-γ production was observed in NK cells, followed by CD8(+) cells, which was completely inhibited by combination of neutralizing anti-IL-12 and anti-IL-18 mAbs. Moreover, oral administration of LcFC enhanced the production of IFN-γ and IL-10 from splenocytes of treated mice. These findings suggest that this LAB strain is an efficient activator of protective cellular immunity via stimulation of myeloid cells including DCs.

Examination of the usefulness of non-invasive stroke volume variation monitoring for adjusting fluid supplementation during laparoscopic adrenalectomy in patients with pheochromocytoma.

PURPOSE OF THE STUDY: The measurement of stroke volume variation (SVV) using the FloTrac™ system (Edwards Lifescience, USA) is useful to estimate cardiac preload. We evaluated the benefits of SVV monitoring for adjusting fluid supplementation during laparoscopic adrenalectomy under anesthesia in patients with pheochromocytoma. SUBJECTS AND METHODS: Among 10 patients who underwent laparoscopic adrenalectomy for pheochromocytoma in our institution from June 2004 to December 2009, SVV was not monitored in 5 patients (group I) and in the other 5 patients (group II), SVV monitoring was performed. Subject age, height and body weight, total volume of fluid supplemented, blood loss, urine output and net fluid in-out balance during the procedure were retrospectively assessed. In those with SVV monitoring, infusion volume was adjusted for SVV less than 13%. RESULTS: There were significant differences in the patient age and body weight between the two groups (group I: 64.2 years old and 55.1 kg; group II: 43.6 years old and 71.7 kg). Both total infusion volume and urine output were significantly higher in group I compared with group II (5,610 vs. 2,400 ml and 1,125 vs. 750 ml, respectively). Total blood loss was similar between the two groups. Values of the net fluid balance divided by the body weight and total anesthesia period (hr) were significantly lower in group II compared with group I (I; +13.2 in group I and +6.2 in group II, ml/kg/hr). CONCLUSIONS: These data suggest that SVV monitoring is helpful to estimate the optimal volume for fluid supplementation and could prevent excessive fluid infusion during surgical procedures.

[Preoperative second-derivative of photoplethysmography measurement predicts the hemodynamic response to general anaesthesia induction].

BACKGROUND: Second-derivative of photoplethysmography (SDPTG) is a non-invasive method for the assessment of structural and functional arterial properties. We studied the hemodynamic responses to induction of anaesthesia and whether SDPTG could be used in predicting these responses. METHODS: SDPTG was performed in 71 subjects (35 males, 36 females) undergoing general anaesthesia for elective operation. Anaesthesia was inducted with propofol 2 mg x kg(-1), fentanyl 2 microg x kg(-1), vecuronium 0.1 mg x kg(-1), and sevoflurane 3% in a mixture of 100% oxygen. RESULTS: The SDPTG indices (b/a and d/a values) significantly correlated with the percentage decrease in systolic blood pressure in both genders. Regression equations (x = SDPTG indices, y = percentage of decrease in systolic blood pressure) were as follows: (1) b/a, r(male) = 0.39, P < 0.05, y = 23.26x + 40.67; r(female) = 0.39, P < 0.05, y = 17.95x + 39.61; (2) d/a, r(male) = -0.37, P < 0.05, y = -31.29x + 16.22 and r(female) = -0.48, P < 0.01, y = -34.46x + 18.55. CONCLUSIONS: These results suggest that preoperative SDPTG is useful in predicting the hemodynamic response to induction of general anaesthesia.

Expression profiling of mouse placental lactogen II and its correlative genes using a cDNA microarray analysis in the developmental mouse placenta.

The placenta is a highly differentiated organ essential for embryonic growth and development. In order to search for key molecules that are associated with mouse placental lactogen II (mPL-II) gene expression, we applied mouse cDNA microarray analysis to RNAs extracted from placentae on days 10, 12, 14, 16 and 18 of pregnancy. Changes in gene expression were categorized between days 10 and 12, 12 and 14, 14 and 16 and 16 and 18 of pregnancy. After microarray analysis, which had a minimum detectable fold change for differential expression of 2, we selected 10 genes, Apoa2, Apoc2, Ceacam14, Creg1, Fmo1, Igf2, Slc2a1, Spink3, Spi1-1 and Tpbpa, exhibiting a expression pattern similar to the mPL-II gene. Furthermore, we performed real-time PCR analysis and in situ hybridization (ISH) to find correlative expression genes for the mPL-II gene. From these results, we identified a resemblance in gene expression between mPL-II and Igf2 and selected these genes for performance of double-fluorescence immunohistochemical staining. We colocalized these proteins in labyrinthine trophoblast cells. These results strongly suggest that the expression of mPL-II and Igf2 is highly related to placental development in mice. This large-scale identification of genes regulated during placentogenesis assists in further elucidation of the molecular basis of extraembryonic development and function.

Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice.

This study investigated the influence of advancing age on dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication from the perspective concerning the relationship between dopaminergic function and behavioral features. Young (10 weeks) and older (14-15 months) C57BL/6 mice were treated with one to four injections of MPTP (20 mg/kg at 2h intervals). Although young mice showed no mortality in either MPTP treatment, older mice exhibited mortality from only two injections of MPTP during the experimental period. An extensive dopaminergic cell loss was found in both the striatum and substantia nigra of older mice given one and two injections of MPTP with marked decrease in striatal dopamine (DA) levels, but not young mice. We also found a behavioral change in the tail suspension test associated with the extent of decrease in striatal DA levels in MPTP-treated older mice, but not in young mice. These results clearly present age-related vulnerability to MPTP neurotoxicity in C57BL/6 mice and strongly support our previous report showing that there is a critical threshold level of the decrement in striatal DA contents causing motor dysfunction in this mouse model of Parkinson's disease.

H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice.

Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy ((1)H MRS) to identify changes in energy metabolism in the striatum of MPTP-treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR-12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP-treated mice. The present study indicates that (1)H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.

Neural mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL/6 mice.

Contradictory data on behavioral changes in MPTP-treated C57BL/6 mice have been reported, even though the toxin-treated mice have been widely used for non-clinical studies as an in vivo model of Parkinson's disease (PD). We found that the duration of immobility in the tail suspension test (TST) was significantly increased in MPTP-treated C57BL/6 mice as compared with control mice without a significant change in the locomotor activity (LA). Dopamine (DA) contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased in the toxin-treated mice. These behavioral and neurobiochemical changes were almost completely inhibited by a pretreatment with deprenyl, a monoamine oxidase-B inhibitor. The stimulation of dopaminergic neurotransmission induced by L-dopa or a dopamine D2 receptor agonist ameliorated the increase in immobility time. Threshold level of striatal DA that produced the increase in immobility time in MPTP-treated mice was estimated to be between 11 and 27% of control level. We concluded that the increase in immobility time in the TST was induced by the nigrostriatal dopaminergic degeneration and was thought to be a consequence of motor dysfunction in this mouse model of PD.

Differential effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the olfactory bulb and the striatum in mice.

The present study was undertaken to examine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage of dopaminergic glomerular cells of the olfactory bulb (OB) in C57BL/6 mice. At 3 days after MPTP treatment, dopamine level in the striatum and the OB decreased to 13% and 84% of the control mice, respectively. While a small reduction of tyrosine hydroxylase protein level was observed in the OB of MPTP-treated mice, dopamine transporter (DAT) was undetectable at the protein level in this region. These results indicate that the DAT protein level could account for resistance of the OB to the Parkinsonism-inducing toxin.

Cathepsin gene expression in mouse placenta during the latter half of pregnancy.

Gene expressions and their interaction are complex and have not been definitely clarified in the placenta. To identify interactions of gene products previously not studied, we applied cDNA subtraction analyses to the placenta between days 12 and 16, days 12 and 14, days 14 and 16 of pregnancy. Among subtracted cDNAs cathepsin M, Q and R in PECs were specifically identified on days 14 and 16 pregnancy. All of these gene expressions exhibited a similar pattern to the mPL-II gene expression determined by northern blot and RT-PCR analyses. By means of in situ hybridization, these mRNAs were localized in the basal and labyrinth zones of the placenta on day 16 of pregnancy. Double staining studies of cathepsin Q or cathepsin R mRNA by in situ hybridization followed by immunohistochemical staining of mPL-II in the same section revealed that signals for cathepsin Q and cathepsin R mRNAs were colocalized in mPL-II immunopositive trophoblast cells in the basal and labyrinth zones of the placenta on day 16 of pregnancy. Possible association of cathepsins with mPL-II may play important roles in placental functions during the latter half of pregnancy in mice.

Serotonergic modulation of psychological stress-induced alteration in synaptic plasticity in the rat hippocampal CA1 field.

In order to elucidate possible involvement of the serotonergic neuronal system in the stress-induced alteration in synaptic plasticity, the effects of contextual fear conditioning (CFC) on long-term potentiation (LTP) in the hippocampal CA1 field were examined in 5-HT-depleted rats by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.). LTP induction was suppressed by footshock (FS) stimulation in 5-HT-lesioned rats and vehicle-treated controls. When rats were exposed to CFC, which was received 24 h after FS stimulation, LTP was also blocked in both-treated groups. CFC-induced impairment of LTP, however, significantly attenuated in 5-HT-lesioned rats when compared with that in controls. Fear-related freezing behavior after FS stimulation occurred similarly in both treated groups, whereas the behavior observed during exposure to CFC significantly reduced in 5-HT-lesioned rats. These results suggest that the serotonergic mechanism is involved in the psychological stress-induced alteration in synaptic plasticity, which appears to be associated with fear-related behavior.

Changes in synaptic properties in cortical-limbic communications induced by repeated treatments with fluvoxamine in rats.

There is evidence indicating that dysregulation of coordinated interactions of the cortical-limbic circuitry is associated with anxiety and mood disorders. Our previous study has reported that an enhancement of long-term plasticity in the "limbic-cortical" pathway produced by repeated treatments with fluvoxamine may be involved in the clinical effects of a selective serotonin (5-HT) reuptake inhibitor (SSRI). Here we assessed the effects of single and repeated treatments with fluvoxamine on the synaptic transmission and plasticity in the "cortical-limbic" pathway in vivo. The evoked potentials in the basolateral amygdaloid complex (BLA) by stimulation of the medial prefrontal cortex (mPFC) in halothane-anesthetized rats were recorded. Single administration of fluvoxamine (10 and 30 mg/kg, i.p.) enhanced the efficacy of synaptic transmission at the mPFC-BLA synapses dose-dependently. The enhanced synaptic efficacy induced by 30 mg/kg fluvoxamine was suppressed after long-term administration of fluvoxamine (30 mg/kg per day x 21 days, orally). Repeated treatments with fluvoxamine affected short-term, but not long-term, synaptic plasticity in the mPFC-BLA pathway. These findings indicate that the 5-HTergic system contributes to modulation of synaptic changes in this pathway. Our results also suggest that different changes in synaptic properties in cortical-limbic communications induced by repeated treatments with fluvoxamine may be associated with therapeutic effects of SSRI.

The serotonergic modulation of synaptic plasticity in the rat hippocampo-medial prefrontal cortex pathway.

The ability of the serotonergic (5-HTergic) system to affect the hippocampo-medial prefrontal cortex (mPFC) synaptic properties was examined in rats with lesions of 5-HTergic neurons. Intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) resulted in selective depletion of 5-HT and 5-hydroxyindoleacetic acid in the cerebral cortex, hippocampus and raphe regions. The 5,7-DHT-lesioned rat had no changes in basal synaptic transmission in the hippocampo-mPFC pathway. Conversely, we observed the augmentation of short-term synaptic plasticity, i.e. paired-pulse facilitation, when compared with sham-operated rats in this pathway. The magnitude of long-term potentiation (LTP) was significantly augmented in 5,7-DHT-lesioned rats. This augmentation of hippocampo-mPFC LTP had a significant correlation with the degree of cortical 5-HT levels. These results suggest that the 5-HTergic system may modulate plastic properties at the hippocampal-mPFC synapses in vivo.

Analyses of mitogen-activated protein kinase function in the maturation of porcine oocytes.

The function of mitogen-activated protein kinase (MAPK) during porcine oocyte maturation was examined by injecting oocytes with either mRNA or antisense RNA of porcine c-mos protein, an upstream kinase of MAPK. The RNAs were injected into the cytoplasm of porcine immature oocytes immediately after collection from ovaries, then the oocytes were cultured for maturation up to 48 h. The phosphorylation and activation of MAPK were observed at 6 h after injection of the c-mos mRNA injected-oocytes, whereas in control oocytes, MAPK activation was detected at 24 h of culture. The germinal vesicle breakdown (GVBD) rate at 24 h of culture was significantly higher in c-mos mRNA-injected oocytes than in control oocytes. In contrast, although injection of c-mos antisense RNA completely inhibited phosphorylation and activation of MAPK throughout the maturation period, the GVBD rate and its time course were the same in noninjected oocytes. The degree of maturation-promoting factor (MPF) activation was, however, very low in oocytes in the absence of MAPK activation. Most of those oocytes had both abnormal morphology and decondensed chromosomes at 48 h of culture. These results suggest that MAPK activation is not required for GVBD induction in porcine oocytes and that the major roles of MAPK during porcine oocyte maturation are to promote GVBD by increasing MPF activity and to arrest oocytes at the second metaphase.