Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

BACKGROUND: There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. OBJECTIVE: To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. RESULTS: Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. CONCLUSION: Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime.

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.

Relationships between transepidermal water loss, cutaneous microcirculatory function and autonomic nervous activity.

OBJECTIVE: Several studies have shown that a deterioration of skin properties, an impaired cutaneous microcirculatory function and an imbalance of autonomic nervous activity are observed in smokers and in patients with diabetes mellitus or Raynaud's phenomenon. These observations suggest that skin properties are associated with cutaneous microcirculatory function and autonomic nervous activity in pathological conditions. However, there is no published evidence to support the concept that these two functions have any relationship with skin properties even in healthy subjects. To investigate the hypothesis that these properties are related, we conducted a survey of healthy adult subjects to investigate the relationships between cutaneous microcirculatory function and autonomic nervous activity and skin properties. METHODS: The hydration of the stratum corneum and transepidermal water loss (TEWL) were investigated as skin properties, and the responsiveness of skin blood flow (SkBF) to local warming was examined as an index of cutaneous microcirculatory function in 19 healthy adult male subjects. Electrocardiograms were monitored for 24 h and heart rate variability was analysed considering low-frequency power (LF: 0.04-0.15 Hz), high-frequency power (HF: 0.15-0.40 Hz) and a ratio of low- to high-frequency power (LF/HF) as indices of autonomic nervous activity; HF is an index of parasympathetic activity, whereas LF/HF is an index of sympathovagal balance. The relationships between those indices were then analysed. RESULTS: A moderate negative correlation was found between TEWL and the relative maximum rate of increases in the responsiveness of SkBF on local warming. A moderate positive and a moderate negative correlation were observed between TEWL and LF/HF or HF, respectively. Moreover, a moderate negative and a moderate positive correlation were shown between the responsiveness of SkBF and LF/HF or HF, respectively. The hydration of the stratum corneum showed no correlations with any indices of microcirculation or autonomic nervous activity. CONCLUSION: These results indicate that skin barrier function, cutaneous microcirculatory function and autonomic nervous activity are mutually associated in healthy adults.

Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth.

BACKGROUND AND PURPOSE: This investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-α-glycyrrhetinic acid (18α-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine-induced gingival overgrowth. EXPERIMENTAL APPROACH: Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 µM 18α-GA for 24 or 48 h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. KEY RESULTS: 18α-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18α-GA. In addition, 18α-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. CONCLUSIONS AND IMPLICATIONS: 18α-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18α-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.

Anti-platelet effects of chalcones from Angelica keiskei Koidzumi (Ashitaba) in vivo.

Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine that is also regarded in Japan as a health food with potential antithrombotic properties. The ability of the major chalcones, xanthoangelol (XA) and 4-hydroxyderricin (4-HD) extracted from Ashitaba roots to inhibit platelet aggregation activity in vitro was recently determined. However, the anti-platelet activities of Ashitaba chalcones in vivo have remained unclear. The present study examines the anti-platelet effects of Ashitaba exudate and its constituent chalcones using mouse tail-bleeding models that reflect platelet aggregation in vivo. Ashitaba exudate and the major chalcone subtype XA, suppressed the lipopolysaccharide (LPS)-induced shortening of mouse tail bleeding. However, trace amounts of other Ashitaba chalcone subtypes including xanthoangelols B (XB), D (XD), E (XE) and F (XF) did not affect tail bleeding. These results suggest that the major chalcone subtype in Ashitaba, XA, has anti-platelet-activities in vivo.

Effect of young sibling visitation on respiratory syncytial virus activity in a NICU.

OBJECTIVE: To determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (NICU) during the respiratory syncytial virus (RSV) season was associated with a reduction in the rate of RSV infection among NICU patients. STUDY DESIGN: A retrospective chart review of all RSV positive infants from the 2001-2010 RSV seasons. The 2001-2006 RSV seasons (group 1) contained 639 admissions and the 2007-2010 (group 2, with sibling restriction) contained 461 admissions. Groups were compared by using the Fisher's Exact Test. RESULTS: There was a reduction of RSV positive infants from 6.7% in Group 1 to 1.7% in Group 2 (P<0.0001). There was a reduction of symptomatic infants from the number of infants with symptomatic RSV infection from 23/639 infants with young sibling visitation to 2/461 (P<0.001). CONCLUSION: Exclusion of young sibling visitors <13 years of age during RSV season was associated with a significant reduction in the number of RSV positive infants in the NICU.

Diagnostic ionizing radiation exposure in premature patients.

OBJECTIVE: Concern regarding the magnitude and consequences of diagnostic radiation exposure in premature infants in neonatal intensive care units (NICUs) has increased as survival of premature infants has improved. Radiation exposure is not often rigorously monitored in NICU patients. The purpose of this observational study was to quantify the amount of ionizing radiation exposure in infants <33 weeks gestational age and to identify the indications for diagnostic imaging. STUDY DESIGN: We conducted a retrospective review of 215 premature infants who were <33 weeks gestation and who received central venous line (CVL) placement during their NICU stay during the period from 2006 to 2011. Absorbed ionizing radiation was estimated using the method of Puch-Kapst and colleagues (2009) and compared with recommended radiation exposure limits. All infants were 29.2±2.3 weeks (mean±s.d.) and 1262±433 g birth weight. RESULT: Subjects received 15±15 radiographs (4.4±2.9 for CVL placement, 5.7±9.8 for gastrointestinal (GI) evaluations and 5.2±9.3 for respiratory indications). Eleven infants (5.1%) received more than the maximum recommended radiation from radiographs (>1000 µSv). Inclusion of fluoroscopic procedures increased to 26 the number of infants (12.1%) who received more than the maximum recommended 1000 µSv. CONCLUSION: Ionizing radiation exposure that exceeded the recommended maximum in premature infants at high risk for long-term sequelae occurred in 12.1% of infants who were <33 weeks gestation and who were cared for in our NICU over the past 5 years. CVL placement accounted for 22% of this radiation exposure. GI evaluations accounted for the greatest amount of ionizing radiation exposure. We suggest that the increased use of other imaging strategies may reduce total ionizing radiation exposure in this vulnerable population.

Galectin-3 enhances epithelial cell adhesion and wound healing in rat cornea.

BACKGROUND/AIMS: To investigate if galectin-3: (1) enhances adhesion of rat corneal epithelial cells onto a collagen IV substrate and (2) promotes wound healing in rat corneal explants. METHODS: Primary cultures of rat corneal epithelial cells were fixed and immunostained with galectin-3 antibody. To test cellular adherence onto plates coated with collagen type IV, isolated corneal epithelial cells from rats were cultured for 24 h with or without recombinant galectin-3. The attached cells were counted after fixing and staining with 0.1% crystal violet. Direct binding of galectin-3 to collagen IV was tested using a biotin label transfer method. To evaluate wound healing, explants with a 3.5-mm diameter wound in the central corneal epithelium from rats were incubated for 16 h with or without recombinant galectin-3. Changes in the size of the wound were measured with a digital microscope after staining with 5% fluorescein sodium. RESULTS: In rat corneal epithelial cells, galectin-3 was stained throughout the cytoplasm, with increasing density adjacent to the plasma membrane. Exogenous galectin-3, but not epidermal growth factor (EGF), significantly promoted adhesion of corneal epithelial cells onto the collagen IV substrate. Galectin-3 directly bound to collagen IV in vitro. Exogenous galectin-3 significantly enhances wound healing in the corneal explants, which was partially inhibited by ß-lactose. CONCLUSION: Galectin-3 promotes adhesion of corneal epithelial cells onto collagen IV and enhances wound healing in corneal explants. Since galectin-3 functions in promoting wound healing by a different mechanism than that used by EGF, exogenous galectin-3 may be a candidate drug for enhancing epithelial cell wound healing in disorders of the cornea.

A wavelength modulation system for highly sensitive absorption spectroscopy.

We developed a newly designed wavelength modulation (WM) system for highly sensitive absorption spectroscopy. In our system, the WM is realized by yawing an output mirror in a monochromator. In order to control an amplitude Δλ of the WM in a wide range, we employed a forced vibration of a permanent magnet driven by a magnetic field of a solenoid. Our system has an advantage of that the WM amplitude Δλ can be adjusted in extensively wide range from 0.08 nm to 11 nm only by tuning a driving frequency of the applying current to the solenoid, because we utilize a resonance phenomenon of the forced vibration for adjustment of the WM amplitude. By using our system, we measured WM absorption spectra of a Cu(2)O thin film and found clearly spectral structures for weak 2-4P excitonic resonances in the WM absorption spectra.

Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome.

OBJECTIVE: Comparison of the differences between availability of animal-derived surfactant preparations used to treat premature infants is incomplete. The objective of this study was to assess the short-term treatment efficacy of the two most commonly used surfactant preparations in the United States, beractant (100 mg kg(-1) initial and subsequent doses) and poractant alfa (200 mg kg(-1) initial and 100 mg kg(-1) subsequent doses), in very premature, mechanically ventilated infants <30 weeks gestation with respiratory distress syndrome (RDS). STUDY DESIGN: Inborn infants at two institutions, open label, 1:1, randomized controlled trial. Level of respiratory support for first 72 h of life. Morbidities of prematurity observed during the neonatal intensive care unit hospitalization. RESULT: We studied 52 infants 24 0/7 to 29 6/7 weeks gestation; 25 received poractant alfa (27.1±1.6 weeks, birth weight of 930±231 g) and 27 received beractant (26.7±1.7 weeks, P=0.343 and birth weight 900±271 g, P=0.668). Respiratory support for the first 72 h of life was lower in the poractant alfa than beractant group for mean airway pressure (MAP, P=0.003) and respiratory index (MAP × FiO(2), P=0.032). Infants in the poractant alfa group had a greater number of infants extubated at 48 (13/25 vs 6/27, P=0.027) and 72 h (15/25 vs 8/27, P=0.029) than the beractant group. Although the study was not powered to detect morbidities of prematurity, the prevalence of PDA and air leaks was less in the infants treated with poractant alfa than in those treated with beractant. Rates of bronchopulmonary dysplasia (8/23 vs 11/22, P=0.303) or death (2/25 [corrected] vs 5/27, P=0.272) were similar in the infants treated with poractant alfa and beractant, respectively. CONCLUSION: This study suggests significant short-term benefits to the use of the larger initial dose of poractant alfa than beractant in very premature infants with RDS. Further studies involving a larger number of preterm infants are needed to assess long-term effects.

Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome.

OBJECTIVE: Respiratory distress syndrome (RDS), requiring mechanical ventilation and exogenous surfactant treatment, and patent ductus arteriosus (PDA), are common co-morbidities in very premature infants. The effects of intra-tracheal surfactant administration on the cardiovascular and pulmonary systems in very premature infants with RDS and PDAs are not well characterized. We evaluated the effects of poractant alfa and beractant, surfactants with different rapidity of onset and duration of action, in very premature infants with RDS. To assess whether there were differences in PDA hemodynamics in very premature infants with RDS treated with poractant alfa and beractant during the first week of life and to assess whether poractant alfa or beractant had a direct effect on PDAs and PDA hemodynamics following the second dose of surfactant. STUDY DESIGN: We studied 50 in-born, very premature infants with RDS, 24 0 of 7 to 29 6 of 7 weeks gestation, treated with poractant alfa or beractant, in an open label, 1:1, randomized clinical trial. A subgroup of 16 patients with severe RDS, treated with a second dose of surfactant, had echocardiographical assessments before and 20 to 30 min after the second dose of surfactant. RESULT: There were 25 infants treated with poractant alfa (27.1±1.6 weeks, birth weight 930±231 g) and 25 treated with beractant (26.7±1.7 weeks, P=0.407 and birth weight 898±282 g, P=0.666). Clinically significant PDAs were diagnosed and treated in 8 of 25 (32%) of the poractant alfa and 19 of 25 (76%) of the beractant group (P=0.002). Indomethacin treatment was slightly earlier (3.4±2.5 days) in the poractant alfa than in the beractant group (5.1±4.9 days, P=0.038). Right ventricle pressure (RVP)/systolic arterial pressure (SAP) ratio in the first week was slightly lower in the poractant alfa (64±20%) than in the beractant (78±26%, P=0.048) group. Following a second dose of surfactant, neither poractant alfa nor beractant changed PDA flow. These hemodynamic observations were associated with less respiratory support in the poractant alfa group, allowing earlier extubation (13 of 25 at 48 h and 15 of 25 at 72 h), than in the beractant group (6 of 25 at 48 h, P=0.044, and 8 of 25 at 72 h, P=0.049). CONCLUSION: The more rapid improvement in pulmonary function in the poractant alfa-treated infants was associated with a lower RVP/SAP ratio and a corresponding earlier treatment with indomethacin. Neither surfactant had a significant direct effect on PDA hemodynamics. The lower frequency of clinically significant PDAs in the poractant alfa compared with the beractant group may represent an indirect effect of the differences in the pulmonary improvement induced by the two surfactants.

In vitro maturation and development of porcine oocytes cultured in a straw or dish using a portable incubator with a CO2 chamber.

We investigated the effects of a portable incubator with a CO(2) chamber on the viability and development of porcine oocytes/embryos for their transportation and examined the operational suitability of a straw or dish as a container for culturing the oocytes or embryos in the portable incubator. In the first experiment, the cumulus-oocyte complexes (COCs) were placed either in a dish or straw; and they were then cultured for 44 h in a standard CO(2) incubator, in the CO(2) chamber in an incubator, or in the CO(2) chamber in a portable incubator. The matured oocytes were fertilized with frozen-thawed spermatozoa and then cultured in a dish in the standard CO(2) incubator for 8 days. There were no differences in the proportions of oocytes reaching metaphase II stage among the groups. However, the proportions of cleavage and development to blastocysts derived from oocytes matured in a straw were lower than those from oocytes matured in a dish, irrespective of the type of incubator used. In the second experiment, the COCs were matured in a dish in the standard CO(2) incubator, and the matured oocytes were fertilized and then placed either in a dish or straw. These were then cultured for 8 days in the standard CO(2) incubator or portable incubator. Some zygotes cultured in the portable incubator developed to the blastocyst stage. The proportions of cleavage and development to blastocysts were significantly lower for putative zygotes cultured in straw than for those cultured in dish, irrespective of the type of incubator used. Our results indicate that a portable incubator with a CO(2) chamber can maintain the viability and development of oocytes/embryos, but the straw is not a suitable system for in vitro culture of the oocytes/embryos during transportation.

Time process study with UML.

OBJECTIVES: We propose a new business-process analysis approach, Time Process Study (TPS), which comprises process analysis and time and motion studies (TMS). TPS offsets weaknesses of TMS; the cost of field studies and the difficulties in applying them to tasks whose time span differs from those of usual tasks. METHODS: In TPS, the job procedures are first displayed using a unified modeling language (UML). Next, time and manpower for each procedure are studied through interviews and TMS, and the information is appended to the UML diagram. We applied TPS in the case of a hospital-based cancer registry (HCR) of a university hospital to clarify the work procedure and the time required, and investigated TPS's availability. RESULTS: Meetings for the study were held once a month from July to September in 2008, and one inquirer committed a total of eight hours to the hospital survey. TPS revealed that HCR consisted of three tasks and 14 functions. The registration required 123 hours/month/person, the quality control required 6.5 hours/ 6 months/person and filing data into the population-based cancer registry required 0.5 hours/6 months/person. Of the total tasks involved in registration, 116.5 hours/month/person were undertaken by a registration worker, which shows the necessity of employing one full-time staff. CONCLUSION: With TPS, it is straightforward to share the concept among the study-team because the job procedure is first displayed using UML. Therefore, it requires a few workload to conduct TMS and interview. The obtained results were adopted for the review of staff assignment of HCR by Japanese government.

Hashimoto encephalopathy presenting with progressive cerebellar ataxia.

Hashimoto encephalopathy has a wide clinical spectrum with various neuropsychiatric features. The detection of anti-thyroid antibodies in patient sera is helpful, but alone not sufficient for the diagnosis of Hashimoto encephalopathy because of the high prevalence of antibodies in the normal population. Here, a patient with Hashimoto encephalopathy, who presented with progressive cerebellar ataxia with mild abnormality on electroencephalography (EEG) and who showed marked improvement after steroid administration, is described. This emphasises that Hashimoto encephalopathy can present with isolated cerebellar ataxia and is responsive to immunosupression.

Pathological gambling associated with cabergoline in a case of recurrent depression.

Pathological gambling has been described frequently in patients with Parkinson disease or other movement disorders who were treated with dopamine agonists. Here, we report a patient with recurrent depression who developed pathological gambling after administration of the dopamine agonist cabergoline. A 36-year-old male Japanese patient presented with his third episode of depression. His depressive symptoms responded minimally to fluvoxamine. Cabergoline was then added to augment the antidepressant's efficacy. Although this regimen resulted in dramatic improvement, he started to spend considerable money and time every day in pachinko parlors and go to the horse racing track every weekend. He spent more than twenty thousand US dollars in total. He tried to stop gambling many times but failed to control his urge. His gambling behavior did not stop even though he was experiencing a marital crisis. He had not displayed any manic symptoms during this entire period. This complication fulfilled the criteria for pathological gambling according to the Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition, Text Revision edition. The patient's perplexing behavior did not end until cabergoline was discontinued. Thus far, pathological gambling associated with cabergoline has rarely been reported while gambling associated with pramipexole and ropinirole, dopamine agonists, has frequently been documented. In addition, this is the first case of depression in which the patient developed pathological gambling during treatment with a dopamine agonist. In conclusion, clinicians should be aware of the potential for pathological gambling when prescribing cabergoline to patients with depression.

Development of a novel high power sub-THz second harmonic gyrotron.

Record-breaking high power coherent radiation at a subterahertz frequency region from a gyrotron utilizing second harmonic resonance modes was attained with a simple cavity. In order to aim at high power and high frequency simultaneously, the oscillation mode was selected carefully enough to realize stable radiation free from mode competition. The cavity radius was determined from the viewpoints of the oscillation frequency, the coupling coefficient between the electron beam, and the rf-electric field. The cavity length was also optimized for the highest perpendicular efficiency. In addition, a new electron gun which is capable of generating a thin laminar beam for a large current was introduced. Consequently, single mode second harmonic radiation with powers of 52 and 37 kW at frequencies of about 349 and 390 GHz, respectively, was achieved.

Subterahertz gyrotron developments for collective Thomson scattering in LHD.

Collective Thomson scattering (CTS) is expected to provide the spatially resolved velocity distribution functions of not only thermal and tail ions but also alpha particles resulting from fusion reactions. CTS using gyrotrons with frequency higher than the conventional ones used for plasma heating would have advantages to alleviate refraction, cutoff effects, and background electron cyclotron emission noise. Therefore, a high-power pulse gyrotron operating at approximately 400 GHz is being developed for CTS in Large Helical Device (LHD). A single-mode oscillation with a frequency greater than 400 GHz, applying the second-harmonic resonance, was successfully demonstrated in the first stage. At the same time, concrete feasibility study based on ray tracing, scattering spectra, and electron cyclotron emission calculations has been conducted.

VATS management of an enlarging multicystic pneumatocele.

A multicystic pneumatocele progressively enlarged when the patient required positive pressure ventilation for an intercurrent respiratory syncytial virus infection. Video Assisted Thoracoscopic Surgery was used to visualize the pneumatocele for cannulation. One chamber of the pneumatocele was cannulated with a pigtail catheter and another large chamber ruptured, without cannulation. The multicystic pneumatocele resolved with this therapy.

Prediction of metabolic clearance of diclofenac in adjuvant-induced arthritis rats using a substrate depletion assay.

1. The purpose of this study was to evaluate drug clearance measured by the metabolic intrinsic clearance (CL(int)) in a substrate depletion assay in comparison with the in vivo clearance (CL(tot)) observed in adjuvant-induced arthritis (AA) rats. 2. After intravenous administration of diclofenac as a model drug, CL(tot) was 2.8-fold higher in AA rats than in control rats. In two different substrate depletion assays with liver microsomes for glucuronidation and hydroxylation, the CL(int) values for glucuronidation was significantly decreased in AA rats to 60% of the value in control rats, whereas the CL(int) values for hydroxylation were similar. The unbound fraction of diclofenac in plasma (f(u, plasma)) was significantly higher (2.8-fold) in AA rats than in control rats. 3. Hepatic clearance predicted from the CL(int) values for both biotransformation pathways and f(u, plasma) was higher in AA rats than in control rats, with good consistency between predicted and observed values. The same results were obtained for experiments using hepatocytes. 4. The plasma protein-binding activities, rather than metabolic clearance, in both types of rats would be a determining factor in the pharmacokinetic behaviour differences between control and AA rats. 5. In summary, substrate depletion assays with liver microsomes and hepatocytes in combination with protein binding assessment can help to predict changes in pharmacokinetics under AA conditions.