Determination of daytime clenching events in subjects with and without self-reported clenching.

To confirm the validity of self-awareness of daytime clenching, specific electromyogram (EMG) characteristics of clenching behaviour were determined using surface EMG recordings. Temporal muscle EMGs were recorded for 5 h in 13 subjects with self-reported clenching (clenching group: 27·5 ± 3·8 years old) and 12 subjects without self-reported clenching (control group: 28·6 ± 7·1 years old). All EMG data were recorded and stored on a portable EMG apparatus. The device was similar in size to a hearing aid, and suitable to record daytime EMG without restriction of daily activities. A clenching event was defined as muscle activity exceeding 10% of the maximum voluntary contraction. Furthermore, simultaneous voice recording was also performed to identify the corresponding EMG event as functional or parafunctional. The mean number of clenching events was 192·8 ± 228·8 and 24·8 ± 26·5 in the clenching and the control groups, respectively (P < 0·05, Mann-Whitney U-test); the number of functional events was not significantly different between the groups. Because there was a significant difference in the number of clenching events between the groups, self-reported daytime clenching is considered to be a reliable screening parameter for awake bruxism.

Feasibility of cytological diagnosis of sarcoidosis with endobronchial US-guided transbronchial aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value in sarcoidosis if the obtained histological specimen is indicative of a non-caseating epithelioid-cell granuloma. However, EBUS-TBNA in sacoidosis sometimes affords solely cytological specimens. OBJECTIVE: To investigate the relevance of EBUS-TBNA cytology specimens in diagnosing sarcoidosis. DESIGN: The study population comprised 72 patients with sarcoidosis and 116 patients who had thoracic malignancies and intrathoracic lymphadenopathy but were eventually proven to be metastasis-free (controls). The EBUS-TBNA samples obtained for these subjects were blindly evaluated for the presence of epithelioid cell clusters by 2 independent cytoscreeners and a pathologist. RESULTS: Interobserver variability in the specimen grading was minimal. The sensitivity and specificity were 65.3% and 94.0%, respectively. The sensitivity was high, at 87.5%, for the combined cytological and histological examinations. Of 7 controls whose cytological specimens showed epithelioid cell clusters, 3 were also deemed positive for sarcoidosis on histological examination, which indicated that they had sarcoid reaction to cancer. CONCLUSIONS: Cytological evaluation of the EBUS-TBNA specimens had higher sensitivity than histological evaluation alone for intrathoracic lymphadenopathy due to sarcoidosis. It should be recognized, however, that up to 6% of patients with thoracic malignancy may have sarcoid reaction in non-metastatic lymph nodes.

Cystatin C is a sensitive marker for detecting a reduced glomerular filtration rate when assessing chronic kidney disease in patients with rheumatoid arthritis and secondary amyloidosis.

OBJECTIVE: Chronic kidney disease is a predictor of end-stage renal disease, and evaluating the glomerular filtration rate (GFR) is necessary to make a definite diagnosis. We assessed the utility of serum cystatin C (cysC) for identifying a reduced GFR in patients who have rheumatoid arthritis (RA) with secondary amyloidosis. METHODS: Fifty patients with RA and secondary amyloidosis (mean age 60.9+/-11.2 years; 45 women) were evaluated. The revised 24-h creatinine clearance (r24-hC(Cr)), which was determined by multiplying the original value by 0.719, was used as a reference for the GFR. The screening potential of the serum cysC and some estimates of the GFR calculated from the serum cysC (cysC-eGFR: eGFR(Hoek) and eGFR(Rule)) for detecting a reduced GFR (r24-hC(Cr)<60 mL/min/1.73 m(2)) were analysed. RESULTS: Both cysC-eGFRs were strongly correlated with the r24-hC(Cr) (eGFR(Hoek), r=0.846, p<0.001; eGFR(Rule), r=0.820, p<0.001). The difference between the average eGFR(Rule) (37.1+/-31.2 mL/min/1.73m(2)) and average r24-hC(Cr) (35.3+/-30.9 mL/min/1.73 m(2)) was small, whereas eGFR(Hoek) and sCr-eGFR were higher than eGFR(Rule) and r24-hC(Cr). In receiver operating characteristic (ROC) curve analyses of a reduced GFR, serum cysC gave a greater area under the curve (AUC=0.958) than the sCr-eGFR (0.939-0.942). The specificity and positive predictive value (PPV) reached 100% when serum cysC >1.365 mg/L was used. CONCLUSIONS: Serum cysC can identify a reduced GFR more accurately than sCr-eGFRs. Serum cysC >1.09 mg/L (i.e. eGFR(Rule)<60 mL/min/1.73 m(2)) could be a marker of a reduced GFR, and serum cysC >1.365 mg/L would strongly suggest a reduced GFR in patients who have RA with secondary amyloidosis.

Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution.

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

Nitric oxide attenuates vascular endothelial cadherin-mediated vascular integrity in human chronic inflammation.

In this study, we examined the role of nitric oxide (NO) in controlling vascular integrity mediated by vascular endothelial (VE)-cadherin in chronic inflammation. Periapical granulomas were analysed for the expression of inducible NO synthase (iNOS) and VE-cadherin, and more iNOS expression than VE-cadherin was shown. Human umbilical vein endothelial cells (HUVECs) were stimulated with proinflammatory cytokines and lipopolysaccharide extracted from Porphyromonas gingivalis and it induced iNOS expression, whereas it reduced VE-cadherin expression, compared with negative controls. On the other hand, pre-incubation with 1400W, an iNOS-specific inhibitor, markedly reduced iNOS expression in stimulated HUVECs and restored VE-cadherin expression to its control level, suggesting that vascular integrity was modulated in conjunction with the reduction of NO. Immunocytochemistry confirmed the functional role of NO in cultured HUVEC monolayers with or without 1400W. These data are consistent with a hypothesis suggesting that NO could attenuate VE-cadherin-mediated vascular integrity in human chronic inflammation.

Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.

Autoantibodies against oxidized low-density lipoprotein (LDL) and carotid atherosclerosis in patients with rheumatoid arthritis.

OBJECTIVES: To examine the relationship between autoantibodies against oxidized low-density lipoprotein (oxLDL-Abs) and the progression of carotid atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients without evidence of risk factors for atherosclerosis (RA group) and 30 healthy volunteers (normal group) were investigated. The mean intima-media thickness of the common carotid artery (mean CCA-IMT) was measured by high-resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT, IgG oxLDL-Ab titer and patient factors such as body mass index, systolic blood pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum lipid levels were examined. RESULTS: Mean CCA-IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA group than in the normal group. Although mean CCA-IMT showed a positive correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA group were positively associated with mean CCA-IMT and independently with age and sex by multiple regression analysis. CONCLUSIONS: IgG oxLDL-Abs appear to be associated with the degree of carotid atherosclerosis in patients with RA, and are independent of traditional risk factors for atherosclerotic diseases. These results suggest a possible link between autoimmune mechanisms and accelerated atherosclerosis in RA.

Advance directives and other medical decisions concerning the end of life in cancer patients in Japan.

The purpose of our survey was to investigate the experience of physicians regarding advance directives and other medical decisions concerning the end of life. A postal questionnaire was sent to 500 Japanese physicians who were most involved in medical care of terminal patients. A total of 339 (68%) physicians responded. In dealing with terminal patients, approximately half gave priority to their patients' wishes for medical care, if known, regardless of the patient's competency. Of the respondents, 149 had been presented with advance directives by their patients and 35% followed all advance directives presented in their practice. Cardiopulmonary resuscitation (CPR) for arrested patients to enable their family to be at the bedside at the time of the death was common. More than 60% of the respondents thought that active euthanasia and assisted suicide were never ethically justified. Our study indicates that the wishes of patients are currently not always given top priority in medical decisions concerning the end of life.

Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy.

The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

Familial aggregation and covariation of diseases in a Japanese rural community: comparison of stomach cancer with other diseases.

PURPOSE: We investigated familial aggregation as well as familial covariation of diseases by means of a questionnaire survey dealing with family histories of stomach cancer, stroke, hypertension, diabetes and tuberculosis as well as life style among 2,769 inhabitants of a rural community (84% of census population). METHODS: The strength of familial aggregation was shown by an odds ratio (OR) that compared the number of families in which siblings suffered from one of the above diseases among families in which at least one parent suffered from it, and among families in which neither did. Probands were divided into two groups for analysis: an under-55 "young group," and a 55-and-older "old group." RESULTS: The OR for stomach cancer was lowest and insignificant in the young group, and significant (2.2, p < 0.05) only in the old group. The OR for stroke, hypertension, and tuberculosis was 4.5-5.1 (p < 0.05) in the young group but decreased to 2.3-3.2 in the old group. Diabetes increased from 3.9 to 5.7 (p < 0.05) with advancing age. Age-related OR trends were not affected by exposure to cigarette smoke in the past. Stomach cancer showed a borderline familial covariation with diabetes and a borderline inverse covariation with hypertension. Hypertension showed a familial covariation with stroke and diabetes. CONCLUSIONS: Among the investigated diseases, familial aggregation was weakest for stomach cancer. The results suggest that stomach cancer may share a common familial etiologic factor with diabetes and hypotension.

Influenza vaccination levels and influenza-like illness in long-term-care facilities for elderly people in Niigata, Japan, during an influenza A (H3N2) epidemic.

Surveys on influenza vaccination and illness in long-term-care facilities in Niigata Prefecture during an influenza A (H3N2) epidemic revealed that >20% of facilities had outbreaks and >10% of residents experienced influenza. Outbreaks and number of cases were significantly reduced by vaccination, which should be strongly recommended for institutionalized elderly people.

Role of positive airway pressure on pulmonary acinar perfusion heterogeneity.

Perfusion of the pulmonary acinus has been shown to be generally homogeneous, but there is a significant component that is heterogeneous. To investigate the contribution of the alveolar septal capillary network to acinar perfusion heterogeneity, the passage of fluorescent dye boluses through the subpleural microcirculation of isolated dog lung lobes was videotaped using fluorescence microscopy. As the videotapes were replayed, dye-dilution curves were recorded from each of the tributary branches of Y-shaped venules that drained single acini. For each Y-shaped venule, the mean appearance time difference between the pair of tributary branches was calculated from the dye curves. When the complex septal capillary networks were derecruited by high positive airway pressure, venular perfusion became proportionally more homogeneous. This result shows that septal capillary resistance and pathlength differences are important contributors to intra-acinar perfusion heterogeneity.

Pulmonary capillary perfusion: intra-alveolar fractal patterns and interalveolar independence.

Pulmonary capillary perfusion was analyzed from videomicroscopic recordings to determine flow switching characteristics among capillary segments in isolated, blood-perfused canine lungs. Within each alveolus, the rapid switching pattern was repetitive and was, therefore, nonrandom (fractal dimensions near 1.0). This self-similarity over time was unexpected in a network widely considered to be passive. Among adjacent alveoli, the relationship among the switching patterns was even more surprising, for there was virtually no relationship between the perfusion patterns (coefficients of determination approaching zero). These findings demonstrated that the perfusion patterns in individual alveolar walls were independent of their next-door neighbors. The lack of dependence among neighboring networks suggests an interesting characteristic: the failure of one alveolar-capillary bed would leave its neighbors relatively unaffected, a feature of a robust design.

Perfusion heterogeneity in the pulmonary acinus.

There is little information on the distribution of acinar perfusion because it is difficult to resolve blood flow within such small regions. We hypothesized that the known heterogeneity of arteriolar blood flow and capillary blood flow would result in heterogeneous acinar perfusion. To test this hypothesis, the passage of fluorescent dye boluses through the subpleural microcirculation of isolated dog lobes was videotaped by using fluorescence microscopy. As the videotapes were replayed, dye-dilution curves were recorded from each of the tributary branches of Y-shaped venules that drained an acinus. From the dye curves, we calculated the mean appearance time of each curve. The difference in mean appearance times between venular tributary branches was small in most cases. In 43% of the observed venular branch pairs, the dye curves were essentially superimposable (the mean appearance-time difference was <5%); and in another 42%, the mean appearance-time difference between curves was 5-10%. From these results, we conclude that acinar perfusion is unexpectedly homogeneous.

Biosynthesis and secretion of beta-thromboglobulin by a human megakaryoblastic cell line (MEG-01).

The de-novo synthesis and secretion of beta-thromboglobulin (BTG) by a human megakaryoblastic cell line (MEG-01) were studied by measuring and immunoblotting of BTG in culture supernatant and immunoprecipitation of radiolabeled BTG synthesized after incubation with [35S]methionine. It was demonstrated that BTG synthesized by MEG-01 was secreted into culture media in a monomer form having a molecular weight of 8,800. Furthermore, we purified BTG from culture medium of MEG-01 with a heparin affinity column and compared BTG from MEG-01 with that from normal platelets. The molecular weights of BTG purified from both sources were 8,800 using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). These results provide direct evidence for the synthesis and secretion of BTG by megakaryocytes.

Transmitter release at frog end-plate loaded with a Ca2+-chelator, BAPTA: hypertonicity and erythrosin B augment the release independently of internal Ca2+.

A Ca2+-chelator, bis-(aminophenoxy)ethane-tetraacetic acid (BAPTA) was loaded into the presynaptic nerve terminal of frog end-plate. The BAPTA-loaded preparation showed little facilitation. However, the facilitation reappeared upon addition of an ionophore, X-537A, supporting the view that the loss of facilitation was due to the Ca2+-buffering action of BAPTA. Both hypertonic conditions and erythrosin B increased both the size of end-plate potentials and frequency of miniature end-plate potentials without any recovery of facilitation at the BAPTA-loaded end-plate. This suggested that transmitter release was increased by both conditions with little change in internal Ca2+ concentration.

Both augmentation and potentiation occur independently of internal Ca2+ at the frog neuromuscular junction.

Augmentation and potentiation of surface recorded endplate potentials (EPPs) were examined during and after tetanic nerve stimulation in both the normal and BAPTA (a Ca2+-chelator)-loaded frog neuromuscular junction (NMJ). In the BAPTA-loaded NMJ, in contrast to a great reduction of facilitation, the amplitudes and the time constants of augmentation and potentiation were almost the same as those in the normal NMJ. The slowly increasing process of transmitter release during tetanus was a little larger in the BAPTA-loaded NMJ than in the normal NMJ. These observations strongly suggest that both augmentation and potentiation occur independently of internal Ca2+ concentration.

Sr2+ induce a release of divalent cation from internal Ca2+ store by nerve stimulation at frog neuromuscular junction.

The effects of Sr2+ on the transmitter release at the frog neuromuscular junction were examined electrophysiologically. The nerve trunk was stimulated by paired pulses at various time intervals after replacing extracellular Ca2+ by Sr2+, the paired-pulse facilitation at the 10 ms interval was smaller than that at 20-30 ms intervals. Administration of several intracellular Ca2+ mobilizers decreased the paired-pulse facilitation. These results suggest that the transmitter release in Sr2+ solution is caused, at least partly, by the release of divalent cations from the intracellular stores.

Effects of Mg2+ on the stimulation-induced changes in transmitter release at the frog neuromuscular junction.

Four components of stimulation-induced changes in neurotransmitter release are known as the synaptic plasticity at the frog neuromuscular junction. These are: fast and slow facilitation, augmentation and potentiation, classified by their decay time constants after repetitive nerve stimulation. Most experiments support the view that fast facilitation is caused by residual Ca2+. However, the causes of the other three components are not clear. We have studied electrophysiologically the effect of Mg2+ on these three components. Transmitter release was estimated by the amplitudes of endplate potential (EPP) and by the frequencies of miniature endplate potential (MEPP). The increase in the transmitter release by nerve stimulation is described as the product of four components. The magnitude of potentiation of MEPP frequencies after a tetanic nerve stimulation (100 Hz, 5000 times) increased markedly in high Mg2+ concentrations. Conversely, the magnitude of augmentation (MEPP frequencies and EPP amplitude) decreased in the higher Mg2+ Ringer solution.