NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Effect of clinical experience and training with visual feedback on standardized palpation outcomes-Potential implications for assessment of jaw muscle sensitivity.

BACKGROUND: The evaluation of muscle pain and sensitivity by manual palpation is an important part of the clinical examination in patients with myalgia. However, the effects of clinical experience and visual feedback on palpation of the masticatory muscles with or without a palpometer are not known. OBJECTIVE: To estimate the effects of clinical experience and visual feedback on the accuracy of palpation in standardized settings. METHODS: Thirty-two dentists (age 35 ± 11 years) classified as either specialists (n = 16) or generalists (n = 16) participated in this experiment. All dentists were instructed to target force levels of 500- or 1000-gf, as determined on an electronic scale using either standardized palpometers or manual palpation (MP). All dentists participated in four different tests: MP, MP with visual feedback (MPVF), palpometer (PAL) and PAL with visual feedback (PALVF). Actual force values for each type of palpation from 0 to 2, 2 to 5 and 0 to 5 s were analysed by calculating target force level. RESULTS: The relative differences during 2-5 and 0-5 s with 1000 gf were significantly lower for generalists than for specialists (p < .05). In generalists and specialists, the coefficients of variation and the relative differences during 2-5 s were significantly lower for PAL and PALVF than for MP (p < .05). CONCLUSIONS: These findings suggest that the use of a palpometer, but not clinical experience with palpation of masticatory muscles, increases the accuracy of palpation, and ≥2 s of palpation with a palpometer is optimal for masticatory muscles.

Neural Correlates of Temporal Presentness in the Precuneus: A Cross-linguistic fMRI Study based on Speech Stimuli.

The position of any event in time could be in the present, past, or future. This temporal discrimination is vitally important in our daily conversations, but it remains elusive how the human brain distinguishes among the past, present, and future. To address this issue, we searched for neural correlates of presentness, pastness, and futurity, each of which is automatically evoked when we hear sentences such as "it is raining now," "it rained yesterday," or "it will rain tomorrow." Here, we show that sentences that evoked "presentness" activated the bilateral precuneus more strongly than those that evoked "pastness" or "futurity." Interestingly, this contrast was shared across native speakers of Japanese, English, and Chinese languages, which vary considerably in their verb tense systems. The results suggest that the precuneus serves as a key region that provides the origin (that is, the Now) of our time perception irrespective of differences in tense systems across languages.

Study protocol and baseline characteristics of newly induced dialysis patients: a prospective multi-center cohort study with a biological sample bank, the Ibaraki Dialysis Initiation Cohort (iDIC) study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients' baseline characteristics, and their outcomes. METHODS: The Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities' patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study's primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization. RESULTS: We analyzed 636 patients' cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients' baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality. CONCLUSIONS: Regarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study's findings.

Standardized palpation of the temporalis muscle evoke referred pain and sensations in individuals without TMD.

OBJECTIVES: This study aimed to determine if standardized palpations of the temporalis muscle evoke referred pain and/or sensations in individuals without TMD. MATERIALS AND METHODS: This was a randomized, single-blinded study. The mechanical sensitivity of the right temporalis muscle was assessed in 32 participants without TMD with nine different stimulations to 15 test sites using palpometers (different stimulus intensities (0.5, 1.0, and 2.0 kg) and durations (2, 5, and 10 s). After each stimulus, participants were asked to score perceived pain intensity and intensity of unpleasantness on a 0-100 numeric rating scale as an indicator of mechanical sensitivity in the temporalis muscle and to indicate any areas of referred pain/sensations on a body chart. RESULTS: Pain intensity significantly differed between palpation durations, intensities, and test sites (P < 0.001). In contrast, unpleasantness significantly differed between palparation duration and intensities (P < 0.001), but not test sites. Participants more frequently reported referred pain/sensations evoked by the 10-s (34.4%) as opposed to the 2-s (6.3%) and 5-s (15.6%) palpation duration at the 2.0-kg stimulus intensity (P < 0.05). CONCLUSIONS: Our present results indicate that referred pain/sensations in the orofacial region can be evoked by standardized palpation of the temporalis muscle and influenced by the palpation duration in individuals without TMD. CLINICAL RELEVANCE: Referred pain/sensations from the temporalis muscle were duration- and intensity-dependent processes originating from local stimuli.

Impact of oral motor task training on corticomotor pathways and diadochokinetic rates in young healthy participants.

BACKGROUND: Studies addressing the training-induced neuroplasticity and interrelationships of the lip, masseter, and tongue motor representations in the human motor cortex using single syllable repetition are lacking. OBJECTIVE: This study investigated the impact of a repeated training in a novel PaTaKa diadochokinetic (DDK) orofacial motor task (OMT) on corticomotor control of the lips, masseter, and tongue muscles in young healthy participants. METHODS: A total of 22 young healthy volunteers performed 3 consecutive days of training in an OMT. Transcranial magnetic stimulation was applied to elicit motor evoked potentials (MEPs) from the lip, masseter, tongue, and first dorsal interosseous (FDI, internal control) muscles. MEPs were assessed by stimulus-response curves and corticomotor mapping at baseline and after OMT. The DDK rate from PaTaKa single syllable repetition and numeric rating scale (NRS) scores were also obtained at baseline and immediately after each OMT. Repeated-measures analysis of variance was used to detect differences at a significance level of 5%. RESULTS: There was a significant effect of OMT and stimulus intensity on the lips, masseter, and tongue MEPs compared to baseline (p < .001), but not FDI MEPs (p > .05). OMT increased corticomotor topographic maps area (p < .001), and DDK rates (p < .01). CONCLUSION: Our findings suggest that 3 consecutive days of a repeated PaTaKa training in an OMT can induce neuroplastic changes in the corticomotor pathways of orofacial muscles, and it may be related to mechanisms underlying the improvement of orofacial fine motor skills due to short-term training. The clinical utility should now be investigated.

Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment.

BACKGROUND: We encountered 7 Japanese patients with bile acid synthesis disorders (BASD) including 3ß-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase (3ß-HSD) deficiency (n = 3), Δ4-3-oxosteroid 5ß-reductase (5ß-reductase) deficiency (n = 3), and oxysterol 7α-hydroxylase deficiency (n = 1) over 21 years between 1996 and 2017. AIM: We aimed to clarify long-term outcome in the 7 patients with BASD as well as long-term efficacy of chenodeoxycholic acid (CDCA) treatment in the 5 patients with 3ß-HSD deficiency or 5ß-reductase deficiency. METHODS: Diagnoses were made from bile acid and genetic analyses. Bile acid analysis in serum and urine was performed using gas chromatography-mass spectrometry. Clinical and laboratory findings and bile acid profiles at diagnosis and most recent visit were retrospectively obtained from medical records. Long-term outcome included follow-up duration, treatments, growth, education/employment, complications of treatment, and other problems. RESULTS: Medians with ranges of current patient ages and duration of CDCA treatment are 10 years (8 to 43) and 10 years (8 to 21), respectively. All 7 patients, who had homozygous or compound heterozygous mutations in the HSD3B7, SRD5B1, or CYP7B1 gene, are currently in good health without liver dysfunction. In the 5 patients with CDCA treatment, hepatic function gradually improved following initiation. No adverse effects were noted. CONCLUSIONS: We concluded that CDCA treatment is effective in 3ß-HSD deficiency and 5ß-reductase deficiency, as cholic acid has been in other countries. BASD carry a good prognosis following early diagnosis and initiation of long-term CDCA treatment.

Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration. Because of the diversity of clinical symptoms and onset age, the diagnosis of this disease is difficult. Therefore, biomarker tests have attracted significant attention for earlier diagnostics. In this study, we developed a simultaneous analysis method for five urinary conjugated cholesterol metabolites, which are potential diagnostic biomarkers for a rapid, convenient, and noninvasive chemical diagnosis, using LC/MS/MS. By the method, their urinary concentrations were quantified and the NPC diagnostic performances were evaluated. The developed LC/MS/MS method showed high accuracy and satisfied all analytical method validation criteria. When the urine of healthy controls and patients with NPC was analyzed, three of five urinary conjugated cholesterol metabolite concentrations corrected by urinary creatinine were significantly higher in the patients with NPC. As a result of receiver operating characteristics analysis, these urinary metabolites might have excellent diagnostic marker performance. 3ß-Sulfooxy-7ß-hydroxy-5-cholenoic acid showed particularly excellent diagnostic performance with both 100% clinical sensitivity and specificity, suggesting that it is a useful NPC diagnostic marker. The urinary conjugated cholesterol metabolites exhibited high NPC diagnostic marker performance and could be used for NPC diagnosis.

Combination of jaw and tongue movement training influences neuroplasticity of corticomotor pathways in humans.

Since humans in daily life perform multiple motor behaviors that often involve the simultaneous activation of both jaw and tongue muscles, it is essential to understand the effects of combined orofacial sensorimotor tasks on plasticity in corticomotor pathways. Moreover, to establish novel rehabilitation programs for patients, it is important to clarify the possible interrelationships in corticomotor excitability between jaw and tongue motor control. The aim of this study was to examine the effect of a combination of a repetitive tooth bite task (TBT) and a repetitive tongue lift task (TLT) on corticomotor excitability of the tongue and jaw muscles as assessed by transcranial magnetic stimulation (TMS). Sixteen healthy individuals participated in three kinds of training tasks consisting of 41-min TBT, 41-min TLT, and 82-min TBT + TLT. Motor-evoked potentials (MEPs) from the tongue muscle, masseter muscle, and first dorsal interosseous muscle were measured before and after the training tasks. The amplitude of tongue MEPs after training with TLT and TLT + TBT, and masseter MEPs after training with TBT and TLT + TBT, were significantly higher than before training (P < 0.05). Tongue MEPs and masseter MEPs were significantly higher after TLT + TBT than after TBT or TLT (P < 0.05). The present results suggest that a task combining both jaw and tongue movement training is associated with a greater degree of neuroplasticity in the corticomotor control of jaw and tongue muscles than either task alone.

Mechanical sensitivity and psychological factors in patients with burning mouth syndrome.

OBJECTIVES: The aim of this study was to compare mechanical sensitivity on the tongue using quantitative sensory testing (QST) and psychological factors using the General Health Questionnaire (GHQ) between burning mouth syndrome (BMS) patients and healthy participants. MATERIALS AND METHODS: Participants comprised 20 female BMS patients (68.1 ± 7.4 years) and 20 healthy females (65.4 ± 4.6 years). Psychological factors were evaluated with GHQ. Tactile detection thresholds (TDT) and filament-prick pain detection thresholds (FPT) were used to evaluate mechanical sensitivity on the tongue in all participants. TDT and FPT were measured on the tongue within both the painful area and the non-painful area in BMS patients, and on the tongue on both sides in healthy participants. As controls, TDT and FPT were measured with Semmes-Weinstein monofilaments on the skin of the mentum and palm in all participants. RESULTS: GHQ scores were significantly higher in BMS patients than in healthy participants (P = 0.024). No significant differences in TDT or FPT on the tongue, mentum, or palm were seen between BMS patients and healthy participants (P > 0.05). BMS patients showed no significant differences in TDT or FPT between the painful and non-painful areas on the tongue (P > 0.05). There were no significant correlations among TDT/FPT and GHQ score in BMS patients (P > 0.05). CONCLUSIONS: These findings could indicate a more important role for psychological factors than mechanical sensitivity in BMS pathophysiology. CLINICAL RELEVANCE: Pain on the tongue in elderly female patients with BMS may be more related to psychological factors.

Quantitative and qualitative assessment of sensory changes induced by local anesthetics block of two different trigeminal nerve branches.

OBJECTIVES: The aims were to use different techniques to assess the degree of sensory changes and magnitude of perceived size changes in the facial region induced by nerve blocks of two different trigeminal nerve branches in healthy participants. MATERIALS AND METHODS: This placebo-controlled study included 30 healthy volunteers. The participants underwent quantitative and qualitative sensory testing (QST and QualST) thrice: before, 10 min, and 2 h after mental (n = 15) and infraorbital (n = 15) nerve blocks and during control (saline) sessions. Perceived numbness, temperature changes, and perceptual distortion were also measured at all time points during the nerve block and control sessions. Differences in outcome parameters between the sessions and time points were analyzed using analyses of variance and McNemar's tests. RESULTS: There was a significant degree of sensory loss to most QST and all QualST parameters, with significant numbness and increased perceived size at the injection site 10 min and 2 h after the nerve blocks compared with saline (P < 0.030) and the baseline (P < 0.042). Two hours after the nerve blocks, the sensitivity was significantly closer to baseline than after 10 min to most of the QST parameters (P < 0.011). CONCLUSIONS: QST and QualST revealed that the nerve blocks in the orofacial region resulted in complete or partial blockade of afferent nerve fibers mediating thermal and mechanical function for more than 2 h with significant numbness and perceptual distortion. CLINICAL RELEVANCE: Both QST and QualST can provide information on the degree of blockade of afferent nerve fibers after nerve blocks in the orofacial region.

Effect of sleep restriction on somatosensory sensitivity in the oro-facial area: An experimental controlled study.

BACKGROUND: No studies have addressed the effect of SR on somatosensory function in the oro-facial area. OBJECTIVES: The aim of this study was to investigate the effect of sleep restriction (SR) on the somatosensory perception of the tip of the tongue. MATERIALS AND METHODS: Using a crossover study design, 13 healthy participants took part in a random order, to a two arms experiments: the SR and control/no SR-arms. For all participants, the Epworth Sleepiness Scale (ESS) was used to assess sleepiness and mechanical sensitivity, and pain detection threshold was estimated at the tongue tip and right thumb (as a body area control site). In the SR-arm of the study, on day one, we estimated sensory baseline perception and repeated tests on day two, after a night of voluntary SR, and on day 3, after a recovery night. In the second arm, same sensory tests were done but no SR was requested. RESULTS: Significantly more sleepiness was observed after SR in comparison with baseline and recovery testing days (P < 0.05). After SR, mechanical pain threshold on the tip of the tongue was significantly lower on day after SR (day 2) and a rebound, higher values, were observed on the third day (P < 0.05); no difference on thumb site. In the control arm, no SR and no significant differences between days were observed for all the variables of interest. CONCLUSIONS: The present results suggest that SR may affect somatosensory perception in the oro-facial area.

Human-specific dual regulations of FXR-activation for reduction of fatty liver using in vitro cell culture model.

Nuclear receptor farnesoid X receptor activation inhibits fatty acid synthesis through the liver X receptor-α-sterol regulatory element binding protein-1c pathway universally in animals, but also has human-specific crosstalk with the peroxisome proliferator-activated receptor-α. The effects of farnesoid X receptor-ligands on both the synthesis and degradation of fatty liver through nuclear receptor-related regulation were investigated in both human and murine hepatocytes. A fatty liver culture cell model was established using a synthetic liver X receptor-α-ligand (To901317) for both human and mouse non-neoplastic hepatocytes. The hepatocytes were exposed to natural or synthetic farnesoid X receptor-ligands (bile acids, GW4064, obeticholic acid) together with or after To901317. Cellular triglyceride accumulation was significantly inhibited by the farnesoid X receptor-ligands along with inhibition of lipogenic genes and up-regulation of farnesoid X receptor-target small heterodimer partner in both human and mouse cells. The accumulated triglyceride was significantly degraded by the farnesoid X receptor-ligands only in the human cells accompanied with the up-regulations of peroxisome proliferator-activated receptor-α and fatty acid ß-oxidation. Farnesoid X receptor-ligands can be therapeutic agents for treating human fatty liver through dual effects on inhibition of lipogenesis and on enhancement of lipolysis.

Origin of myofibroblasts in the fibrotic liver in mice.

Hepatic myofibroblasts are activated in response to chronic liver injury of any etiology to produce a fibrous scar. Despite extensive studies, the origin of myofibroblasts in different types of fibrotic liver diseases is unresolved. To identify distinct populations of myofibroblasts and quantify their contribution to hepatic fibrosis of two different etiologies, collagen-α1(I)-GFP mice were subjected to hepatotoxic (carbon tetrachloride; CCl4) or cholestatic (bile duct ligation; BDL) liver injury. All myofibroblasts were purified by flow cytometry of GFP(+) cells and then different subsets identified by phenotyping. Liver resident activated hepatic stellate cells (aHSCs) and activated portal fibroblasts (aPFs) are the major source (>95%) of fibrogenic myofibroblasts in these models of liver fibrosis in mice. As previously reported using other methodologies, hepatic stellate cells (HSCs) are the major source of myofibroblasts (>87%) in CCl4 liver injury. However, aPFs are a major source of myofibroblasts in cholestatic liver injury, contributing >70% of myofibroblasts at the onset of injury (5 d BDL). The relative contribution of aPFs decreases with progressive injury, as HSCs become activated and contribute to the myofibroblast population (14 and 20 d BDL). Unlike aHSCs, aPFs respond to stimulation with taurocholic acid and IL-25 by induction of collagen-α1(I) and IL-13, respectively. Furthermore, BDL-activated PFs express high levels of collagen type I and provide stimulatory signals to HSCs. Gene expression analysis identified several novel markers of aPFs, including a mesothelial-specific marker mesothelin. PFs may play a critical role in the pathogenesis of cholestatic liver fibrosis and, therefore, serve as an attractive target for antifibrotic therapy.

Perceptual distortion of the tongue by lingual nerve block and topical application of capsaicin in healthy women.

OBJECTIVES: The aim of this study was to examine reports of perceptual distortion evoked by transient deafferentation and burning pain as models of aspects of burning mouth syndrome (BMS). MATERIALS AND METHODS: Sixteen healthy women took part in three experimental sessions that included exposure to lingual nerve block, capsaicin, and control substance. In each session, reported perceptual distortion and mechanical detection threshold (MDT) were assessed at four areas (the tongue, lower front teeth, lower lip, and right thumb) before and at 5, 15, 30 min and 1 and 3 h after the injection or application. A numerical rating scale (NRS) and a template matching procedure were used to quantify the perceptual distortions. RESULTS: There was a significantly higher MDT on the tongue during the lingual nerve block session at 5 min up until 1 h, with the perceived tongue size significantly increased at 5, 15, and 30 min and at 1 h compared to baseline (P < 0.05). Although the perceived size determined by the NRS scores during the capsaicin session was significantly larger for the lower lip at 5 min compared to baseline (P < 0.001), there were no significant effects on the MDT or the perceived sizes for the tongue, lower front teeth, or right thumb at any of the time points. CONCLUSIONS: Perceptual distortions of the tongue may be influenced by non-nociceptive somatosensory changes rather than nociceptive activity. CLINICAL RELEVANCE: The perceptual distortion of the tongue was investigated with models of aspects of BMS and may have implications for future studies in clinical populations.

Effect of a repeated tongue-lift motor task for tongue function.

This study investigated the effect of repeated tongue motor tasks on suprahyoid muscle activity and tongue pressure. Fourteen participants performed three series of a standardized tongue-lift training (TLT) task on each of five consecutive days. Electromyographic (EMG) activity from suprahyoid muscles and tongue pressure were recorded. In the first and third TLT series, participants were instructed only to target different force levels. During the second TLT series, visual feedback of the force level was given. One series consisted of three measurements [at 10%, 20%, and 40% of maximum voluntary contraction (MVC), respectively]. The coefficient of determination of the target force level-EMG curve and the target force level-tongue pressure curve was calculated from all series. There were no statistically significant day-to-day differences in EMG-root mean square (RMS) values and tongue pressure during MVC. The coefficients of determination of tongue pressure in the first series on day 1 were statistically significantly lower than the coefficients of determination in the first series on day 5. These findings suggest that the control of tongue pressure improved, while the maximum force remained constant. These results could have implications for treatment paradigms related to learning for patients with compromised tongue function, such as swallowing disorders or dysphagia.

Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids.

The chemical synthesis of the 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids is reported. For initiating the synthesis of the 9α-hydroxy derivative of chenodeoxycholic acid, cholic acid was used; for the synthesis of the 9α-hydroxy derivative of lithocholic acid, deoxycholic acid was used. The principal reactions involved were (1) decarbonylation of conjugated 12-oxo-Δ(9(11))-derivatives using in situ generated monochloroalane (AlH2Cl) prepared from LiAlH4 and AlCl3, (2) epoxidation of the deoxygenated Δ(9(11))-enes using m-chloroperbenzoic acid catalyzed by 4,4'-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9α-hydroxylation of the Δ(9(11))-enes with AlH2Cl, and (4) selective oxidation of the primary hydroxyl group at C-24 in the resulting 3α,9α,24-triol and 3α,7α,9α,24-tetrol to the corresponding C-24 carboxylic acids using sodium chlorite (NaClO2) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and sodium hypochlorite (NaOCl). The (1)H- and (13)C-NMR spectra are reported. The 3α,7α,9α-trihydroxy-5ß-cholan-24-oic acid has been reported to be present in the bile of the Asian bear, and its 7-deoxy derivative is likely to be a bacterial metabolite. These bile acids are now available as authentic reference standards, permitting their identification in vertebrate bile acids.

Repeated clenching causes plasticity in corticomotor control of jaw muscles.

This study tested the effect of short-term tooth-clenching on corticomotor excitability of the masseter muscle using transcranial magnetic stimulation (TMS). Fifteen subjects with normal stomatognathic function participated. All subjects performed a tooth-clenching task (TCT) on five consecutive days. The TCT consisted of 10, 20, and 40% of maximum voluntary contraction in a randomized order within 1 h. All subjects underwent TMS in four sessions: pretask day 1 (baseline), post-task day 1, pretask day 5, and post-task day 5. Motor-evoked potentials (MEPs) from the masseter and the first dorsal interosseous (FDI) muscles were obtained using TMS in four sessions. Motor thresholds decreased, after the TCT, for the masseter muscle MEPs. Masseter muscle MEPs were dependent on stimulus intensity and on session, whereas FDI muscle MEPs were only dependent on stimulus intensity. Post-hoc Tukey tests demonstrated significantly higher masseter muscle MEPs post-task on day 5 with 80 and 90% stimulus intensity and above when compared with pre- and post-task day 1 values. Our results suggest that the performance of repeated TCTs can trigger neuroplastic changes in the corticomotor control of the jaw-closing muscles and that such neuroplastic changes may contribute to the mechanism underlying the clinical manifestations of tooth clenching.

Cytotoxic and apoptosis-inducing activities, and anti-tumor-promoting effects of cyanogenated and oxygenated triterpenes.

Two of each semisynthetic lanostane- and cycloartane-type triterpenes with a cyano-enone functionality, i.e., 13 and 18, and 23 and 28, respectively, sixteen of their synthetic intermediates, 9-12, 14-17, 19-22, and 24-27, along with seven semisynthetic oxygenated triterpene acetates, 29-35, and eight natural hydroxy triterpenes, 1-8, were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines. One natural triterpene, 8, and ten semisynthetic triterpenes, 9, 13, 15, 18, 23, 25, 28, 29, 32, and 33, exhibited potent cytotoxicities against one or more cell lines with IC50 values in the range of 1.4-9.9 µM. Two lanostane-type triterpenes with a cyano-enone functionality, 3-oxolanosta-1,8,24-triene-2-carbonitrile (13) and 3-oxolanosta-1,8-diene-2-carbonitrile (18), induced apoptosis in HL60 cells, as observed by membrane phospholipid exposure in flow cytometry. Western blot analysis showed that 13 and 18 significantly reduced procaspases-3, -8, and -9, and increased cleaved caspases-3, -8, and -9. These findings indicated that compounds 13 and 18 induced apoptosis in HL60 cells via both the mitochondrial and the death receptor-mediated pathways. In addition, upon evaluation of the inhibitory effects on EpsteinBarr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, seven natural triterpenes, 1-6 and 8, and ten semisynthetic triterpenes, 9, 10, 14, 15, 19, 20, 24, 25, 29, and 30, exhibited inhibitory effects which were higher than that of ß-carotene, a vitamin A precursor studied widely in cancer-chemoprevention animal models.

Analysis of definite awake bruxism using a portable electromyography device.

PURPOSE: This study aimed to compare awake bruxism events between subjective and objective evaluations using a questionnaire survey and a modified portable electromyography (EMG) device, and to examine correlations between sleep quality and awake bruxism. METHODS: The Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and awareness of awake bruxism as clarified via interviews were conducted on 34 participants as subjective evaluations. The EMG device was used to record left temporal muscle activity for 6.5 h (from 09:00 to 15:30) and the number of awake bruxism episodes per hour. The participants were then classified into "bruxer" and "non-bruxer" groups based on the number of awake bruxism episodes. RESULTS: The mean number of awake bruxism episodes per hour was 33.6 ± 21.4, and 23% of the participants who reported having no awareness of awake bruxism in the interviews were defined as "bruxers" in the objective evaluations. In the bruxer group, positive correlations were found between the number of awake bruxism episodes and both ESS and PSQI scores. CONCLUSION: These findings suggest that objective measurements using a portable EMG device can increase the diagnostic accuracy for awake bruxism, and that sleep quality is a major risk factor for awake bruxism.