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The involvement of intrinsic proteinases in the excystment of Paragonimus ohirai metacercariae was studied in in vitro excystment induced by sodium (Na) cholate, a bile salt and A23187, a Ca2+ ionophore. The effects of various proteinase inhibitors on the in vitro excystment were examined and similar inhibitory profiles were obtained. Benzyloxycarbonyl-L-leucyl-L-leucinal (Z-Leu-Leu-H), a cysteine proteinase inhibitor and 4-(2-aminoethyl)-benzenesulfonyl fluoride (Pefabloc SC), a serine proteinase inhibitor completely inhibited excystment, while L-3-carboxy-2,3-trans-epoxypropionyl-leucylamido (4-guanidino)-butane (E-64), a cysteine proteinase inhibitor and leupeptin, a cysteine/serine proteinase inhibitor permitted partial excystment at a lower rate, but inhibited it from proceeding from the partial excystment stage. In secretions released from metacercariae during excystment, proteinase activities detected towards various fluorogenic peptidyl substrates were almost completely inhibited by Z-Leu-Leu-H and E-64, but not by Pefabloc SC. Sodium cholate induced a higher secretion of cysteine proteinases and a higher rate of excystment than A23187. Profiles of cysteine proteinase activities towards five peptidyl substrates detected were markedly different among the two secretions and the lysate of newly excysted juveniles. Newly excysted juveniles released cysteine proteinases with similar activity profiles and levels to metacercariae induced by Na cholate-incubation, whereas the release of cysteine proteinases was reduced compared with metacercariae induced by A23187-incubation. These results provide valuable information about the involvement of intrinsic proteinases in metacercarial excystment.
Enzyme-linked immunosorbent assays (ELISAs) which detect specific antibodies to fluke cysteine proteinases have provided good sensitivity and specificity for the immunodiagnosis of trematode diseases. To detect specific antibodies without the need for purified proteinase antigens, an immunocapture assay using Protein A was applied for the immunodiagnosis of paragonimiasis and fascioliasis. ELISA plate wells were coated with Protein A, incubated with diluted patient sera, then incubated with a preparation containing fluke cysteine proteinases, excretory–secretory (ES) products of adult Paragonimuswestermani or Fasciola sp. The activity of fluke cysteine proteinases bound on the wells was measured by adding fluorogenic peptidyl substrate, Z-Phe-Arg-MCA or Boc-Val-Leu-Lys-MCA. This assay detected specific immunoglobulin G to cysteine proteinases of P. westermani and Fasciola sp. by measuring proteinase activity on the plate wells. Patient sera showed significant high values of proteinase activity when the wells were treated with the respective homologous ES products, whereas the sera had low values after treatment with the heterologous ES products. The sera of patients with other parasitoses and uninfected healthy individuals also showed low values after treatment with the above fluke ES products. Thus, Protein A immunocapture assay, which detected IgG specific for fluke cysteine proteinases, provided a high sensitivity and specificity for immunodiagnosis of paragonimiasis and fascioliasis.
The corpus callosum (CC) is the largest interhemispheric white matter commissure connecting the cerebral hemispheres and plays a crucial role in interhemispheric communication and cognitive processes. The subdivisions of the CC were attempted to define corresponding areas of the cortex from which the fibers originate. Previous neuroanatomic studies of the CC provide impetus for investigating its role in obsessive-compulsive disorder (OCD).
Methods:
In this study diffusion tensor imaging (DTI) was employed to microstructural abnormalities of white matter of the CC in OCD patients. Nine patients with OCD and matched control subjects underwent DTI. Fractional anisotropy (FA), an index of the integrity of white matter tracts, was determined in the seven subdivisions of the CC.
Results:
Significant reduction in FA was found in the rostrum of the CC of patients with OCD compared with one of controls. FA of the other subdivisions except the rostrum in OCD patients did not differ compared with control subjects. Higher FA in the rostrum correlated with lower Y-BOCS scores (r = -0.852, p = 0.004).
Conclusions:
The rostrum contains fibers from inferior premotor as well as medial and caudate/orbital prefrontal regions. These results supported the theory of dysfunction of prefrontal cortex and striatal circuits in OCD and suggested the implication of the orbitofrontal circuit for symptom severity in the OCD patients.
The subdivisions of the corpus callosum (CC) were attempted to define corresponding areas of the cortex from which the fibers originate. Previous neuroanatomic studies of the CC provide impetus for investigating its role in obsessive-compulsive disorder (OCD).
Methods:
In this study diffusion tensor imaging (DTI) was employed to microstructural abnormalities of white matter of the CC in OCD patients. Nine patients with OCD and matched control subjects underwent DTI. Fractional anisotropy (FA), an index of the integrity of white matter tracts, was determined in the seven subdivisions of the CC. We placed each reagions of interest (ROI) over the sagittal plane and all subdivisions were measured.
Results:
Significant reduction in FA was found in the rostrum of the CC of patients with OCD compared with one of controls. FA of the other subdivisions except the rostrum in OCD patients did not differ significantly compared with control subjects. Higher FA in the rostrum correlated significantly with lower Y-BOCS scores (r = -0.803, p = 0.009).
Conclusions:
The rostrum contains fibers from inferior premotor as well as medial and caudate/orbital prefrontal regions. These results supported the theory of dysfunction of prefrontal cortex and striatal circuits in OCD and suggested the implication of the orbitofrontal circuit for symptom severity in the OCD patients.
Patients with psychiatric disorders, including schizophrenia and bipolar disorder, are reported to suffer from sleep disorders.
Objective
To investigate the effects of lurasidone on sleep architecture in rats using sleep electroencephalography.
Methods
Seven adult male rats were used in this study. A pair of electrode wires was implanted in the dura of each rat and electromyograms were recorded from their dorsal neck muscles. Drugs were administered at the start of the lights-on period, and electroencephalograms (EEG)were recorded for 6 hours in individual soundproof boxes. The course of sleep in rats has been classified into 3 stages: WAKE, non-REM (NREM) sleep and rapid eye movement (REM) sleep. Total NREM duration, REM duration, and latencies to the initial REM and NREM were calculated. In addition, the number and mean duration of bouts in every 2-hour period were calculated in each stage. EEG power in each of the following frequency bands during NREM sleep was quantified: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-80 Hz).
Results
Lurasidone shortened REM sleep duration and prolonged the mean duration of one bout in WAKE and NREM sleep. Quantitative frequency analyses during NREM sleep revealed that lurasidone increases slow waves and decreases fast waves. The serotonin 5-HT1A receptor partial agonist, tandospirone, and selective serotonin 5-HT7 receptor antagonist, SB-258741, also exhibited REM-inhibitory effects similar to those of lurasidone.
Conclusion
These results suggest that lurasidone ameliorates sleep disorders associated with psychosis through, at least partly, serotonin 5-HT1A and serotonin 5-HT7 receptors.
There are a number of clinical scores to measure cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) for dementia patients.
Objective
Previous BPSD scores are well established, but they usually take long time. Furthermore they were made almost 20 years ago, and therefore may not even fit a current BPSD because affective expressions may change depending on modern society change.
Aim
To make a new and simple score which fits modern change of BPSD.
Method
Based on BPSD inquiry from 129 caregivers in local area (patients 81.6 ± 9.9 years old and female 70.5%), a new and simple BPSD score was created, and compared to standard BPSD score NPI (neuropsychiatry inventory). Time was measured to complete this new BPSD score (ABS, Abe's BPSD score) and NPI. This ABS was examined before and after a choline esterase inhibitor treatment.
Result
We gave final scores to each BPSD items with such temporal frequencies taken into account ranging 0-9, and finalized a new BPSD score of score 0-44 between no BPSD to full BPSD. Average time to complete both NPI and ABS was 308.9 ± 86.3 sec and 46.5 ± 16.2 sec (**p< 0.01), respectively. Galantamine showed an improvement of average ABS with - 2.3 ± 1.0 (*p< 0.05) from original score of 6.1 ± 6.6 after 3 month of the treatment.
Conclusion
These data suggest that this new and simple BPSD score (ABS) may be beneficial to quickly evaluate BPSD before and after a treatment of dementia patients.
A variety of hereditary spinocerebellar ataxia (SCA) develops a broad spectrum of both ataxia and non-ataxia symptoms. Cognitive and affective changes are one such non-ataxia symptoms, but have been described only in hereditary SCAs with exonic CAG gene expansion.
Methods:
We newly found intronic hexanucleotide GGCCTG gene expansion in NOP56 gene as the causative mutation (=SCA36) in nine unrelated Japanese familial SCA originating from Asida river area in the western part of Japan, thus nicknamed Asidan for this mutation. These patients show unique clinical balance of cerebellar ataxia and motor neuron disease (MND), locating on the crossroad of these two diseases. We examined cognitive and affective analyses on 12 Asidan patients who agreed to join the examination.
Results:
The 12 Asidan patients demonstrated a significant decrease in their frontal executive functions measured by frontal assessment battery (FAB) and Montreal cognitive assessment (MoCA) compared with age- and gender-matched controls, whilst mini-mental state examination (MMSE) and Hasegawa dementia score-revised (HDS-R) were within normal range. the decline of frontal executive function was related to their disease duration and scale for the assessment and rating of ataxias (SARA). They also demonstrated mild depression and apathy. Single-photon emission tomography (SPECT) analysis showed that these Asidan patients showed decline of regional cerebral blood flow (rCBF) in a particular areas of cerebral cortices such as Brodmann areas 24 and 44-46.
Conclusions:
These data suggest the patients with Asidan mutation show unique cognitive and affective characteristics different from other hereditary SCAs with exonal CAG expansion or MND.
The acquisition and extinction of conditioned fear underlies the pathophysiology of anxiety disorders, including PTSD. Women have higher lifetime prevalence and greater risk of PTSD than men. Such sex differences may be attributed to a combination of genetic and hormonal factors. The catechol-O-methyltransferase (COMT) gene encodes an enzyme that metabolizes catechol compounds, including dopamine. The COMT Val158Met polymorphism affects the enzymatic activity of dopamine and has been associated with altered fear memory performance. Besides, when estrogen secretion is elevated, women show a greater extinction of conditioned fear than men. Here, we investigated the relationship between the COMT genotype and sex in the acquisition and extinction of conditioned fear. In a 3-day cued fear conditioning experiment, acquisition and extinction performance of 75 healthy men (21.8 years) and 45 healthy women in follicular phase (21.2 years) were examined. Visual cues and electric shocks were used as the conditioned stimulus and unconditioned stimulus, respectively. Subjects with Met/Met homozygotes showed less fear acquisition (p < .0001). Female Val carriers showed more extinction (p = .009) and less reconsolidation (p < .0001) than male Val carriers. Women with Val/Val homozygotes were less affected by a reinforcing stimulus than men with Val/Val homozygotes (p = .0001). These findings suggest a clear interaction between the COMT gene and sex in fear memory function, and that women have a greater tolerance for aversive experiences than men. Higher estrogen levels mediate increased dopaminagic activity, potentially optimizing the prefrontal function known to contribute to the fear-related symptomatology of PTSD.
We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March–April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.
Minohlite, a new copper-zinc sulfate mineral related to schulenbergite, was found in the oxidized zone of the Hirao mine at Minoh (Minoo) City, Osaka Prefecture, Japan. The mineral occurs in cracks in altered shale as rosette aggregates up to 100 m m in diameter, composed of hexagonal platy crystals up to 50 μm m in diameter and 10 μm m in thickness. The associated minerals are chamosite, muscovite, smithsonite, serpierite, ramsbeckite, 'limonite' and chalcopyrite. Minohlite has hexagonal (or trigonal) symmetry with unit-cell parameters of a = 8.2535(11), c = 8.1352(17) Å, V = 479.93(16) Å3 and Z = 1, and possible space groups P6, P, P6/m, P22, P6mm, P2m and P6/mmm (or P3, P3, P321, P3m1, Pm1, P312, P31m and P1m). The six strongest reflections in the powder X-ray diffraction pattern [d in Å (I) hkl] are 8.138 (20) 001; 4.128 (24) 110; 2.702 (100) 120; 2.564 (76) 121; 1.560 (43) 140; and 1.532 (24) 141. Electron microprobe analyses gave the following values (wt.%): CuO 37.18, ZnO 21.08, FeO 0.49, SO3 16.78, SiO2 0.44, and H2O 24.03 (by difference). The empirical formula, calculated on the basis of Cu + Zn + Fe + S + Si = 9 atoms per formula unit, is (Cu4.43Zn2.45Fe0.06)Σ6.94[(SO4)1.99(SiO4)0.07]Σ2.06(OH)9.64·7.81H2O, which leads a simplified formula of (Cu,Zn)7(SO4)2(OH)10·8H2O where Cu > Zn. The mineral is bluish-green and transparent with a pearly to vitreous lustre. The streak is pale green. Cleavage is perfect on {001}. The Mohs hardness number is less than 2. The calculated density is 3.28 g cm−3. The mineral is named after Minoh City, where it was discovered.
The technique of investigating 3-dimensional interconnections and the shapes of crystals in a rock by X-ray computerized tomography (CT) and image analysis was developed using a graphic granite specimen as an example. Fifty 2-dimensional tomographic images (slices) of the graphic granite were obtained ‘non-destructively’ using a medical X-ray CT scanner. Since a CT value of the specimen was decreased with increasing cross-sectional sample area by the effect of beam-hardening, the CT value was corrected using the area of each slice. Binary images of the slices were made comparing one of them with a thin-section of the slice. Using the binary images, connection analysis of quartz rods in the graphic granite specimen was performed on the basis of percolation theory (cluster labelling). This analysis showed that at least 89.9% of the quartz rods were connected in three dimensions. Furthermore, the 3-dimensional shape of the quartz rods was analysed using the 2-point correlation function calculated from the binary images. The average shape of the quartz rods was obtained by fitting an ellipsoid to the high-value region of the 2-point correlation function. The elongation axis of the ellipsoid agreed well with the crystallographic c-axes of the quartz rods.
The order Chiroptera is considered the second largest group of mammals in the world, hosting important zoonotic virus and bacteria. Bartonella and hemotropic mycoplasmas are bacteria that parasite different mammals’ species, including humans, causing different clinical manifestations. The present work aimed investigating the occurrence and assessing the phylogenetic positioning of Bartonella spp. and Mycoplasma spp. in neotropical bats sampled from Brazil. Between December 2015 and April 2016, 325 blood and/or tissues samples were collected from 162 bats comprising 19 different species sampled in five states of Brazil. Out of 322 bat samples collected, while 17 (5·28%) were positive to quantitative PCR for Bartonella spp. based on nuoG gene, 45 samples (13·97%) were positive to cPCR assays for hemoplasmas based on 16S rRNA gene. While seven sequences were obtained for Bartonella (nuoG) (n = 3), gltA (n = 2), rpoB (n = 1), ftsZ (n = 1), five 16S rRNA sequences were obtained for hemoplasmas. In the phylogenetic analysis, the Bartonella sequences clustered with Bartonella genotypes detected in bats sampled in Latin America countries. All five hemoplasmas sequences clustered together as a monophyletic group by Maximum Likelihood and Bayesian Inference analyses. The present work showed the first evidence of circulation of Bartonella spp. and hemoplasmas among bats in Brazil.
The Fukushima Nuclear Energy Workers' Support (NEWS) Project Study previously showed that experiences related to the Fukushima nuclear disaster on 11 March 2011 had a great impact on psychological states, including post-traumatic stress response (PTSR) and general psychological distress (GPD), among the Fukushima nuclear plant workers. To determine the causal relationship between disaster-related experiences and levels of psychological states, we conducted a 3-year longitudinal study from 2011 to 2014.
Method
PTSR and GPD of the nuclear plant workers were assessed by annual questionnaires conducted from 2011 to 2014. The present study included a total of 1417 workers who provided an assessment at baseline (2011). A total of 4160 observations were used in the present analysis. The relationship between disaster-related experiences and psychological states over time was analysed using mixed-effects logistic regression models.
Results
A declining influence of disaster-related experiences on PTSR over time was found. However, the impact on PTSR remained significantly elevated even 3 years after the disaster in several categories of exposure including the experience of life-threatening danger, experiences of discrimination, the witnessing of plant explosion, the death of a colleague and home evacuation. The associations between GPD and disaster-related experiences showed similar effects.
Conclusions
The effects of disaster-related experiences on psychological states among the nuclear plant workers reduced over time, but remained significantly high even 3 years after the event.
For the improvement of oxidation resistance of Nb-based alloys, PdAl-B2 is expected as Al reservoir for Al2O3 surface layer because it is in equilibrium with Nbss (bcc) phase. However, PdAl forms cracks during casting caused by B2 -> β’ transformation. To suppress B2 -> β’ transformation, Rh, Ru and Ir were chosen as additive elements. It is found that bcc / B2 two-phase field in Nb-Pd-Ir-Al system is limited to be small fraction of Ir, while (Pd,Rh)Al-B2 is in equilibrium with bcc solid solution in a wide composition range and addition of Rh prevents occurrence of B2 -> β’ transformation. Composition range of (Pd,Ru)Al-B2 in equilibrium with bcc phase is wider than (Pd,Ir)Al-B2 but narrower than (Pd,Rh)Al-B2. Rh and Ru addition are also beneficial for improving eutectic temperature of Nb-bcc / B2 aluminide two-phase alloys.
Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.
A laser ion source (LIS) is a promising candidate as an ion source for heavy-ion inertial fusion (HIF), where a pulsed ultra-intense and low-charged heavy ion beam is required. It is a key development for a LIS to transport laser-produced plasma with a magnetic field to achieve a high-current beam. The effect of a tapered magnetic field on laser-produced plasma is demonstrated by comparing the results with a straight solenoid magnet. The magnetic field of interest is a wider aperture on a target side and narrower aperture on an extraction side. Based on the experimentally obtained results, the performance of a scaled LIS for HIF was estimated.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from the intestine in response to enteral feeding to stimulate insulin secretion. We investigated the relationship serum GIP and GLP-1 levels with gestational age, and insulin secretion in preterm infants. Serum GIP and GLP-1 levels were measured at birth and at 1, 2 and 4 weeks after birth in 30 infants, including 12 born before 30th week of gestation (early group) and 18 born after 30th week of gestation (late group). Blood glucose and serum insulin levels were measured, and the quantitative insulin sensitivity check index (QUICKI) was also calculated. The levels of GLP-1 at 2 and 4 weeks were significantly higher in the early group than those in the late group. The levels of GIP were not significantly different between two groups. At 4 weeks, serum insulin level was significantly higher and QUICKI was significantly lower in the early group. Furthermore, GLP-1 levels were significantly correlated with QUICKI and the serum insulin levels in all infants at 4 weeks. In preterm infants, enteral feeding to premature intestine may be associated with GLP-1 secretion. GLP-1 is also related to stimulated insulin secretion in early postnatal period.
Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.