Psychosocial characteristics of the general population who habitually use hypnotics: Results from a national survey on drug use among the Japanese.

Aim: The aim of this study was to examine the characteristics of habitual hypnotic users in Japan. Methods: This nationwide, cross-sectional survey used self-administered questionnaires. Data were collected from four national surveys conducted every 2 years between 2015 and 2021. The participants were Japanese individuals who had taken prescription hypnotics in the past year or had never taken them. We divided 13,396 participants into three groups to compare the social background and status of taking medication and controlled drugs, drinking, and smoking among the three groups: people who use hypnotics habitually daily (habitual hypnotic users [HUs]), people who use them only occasionally (occasional hypnotic users [OUs]), and people who do not use them (hypnotic non-users [NUs]). We compared the perception of using hypnotics between the HU and OU groups. Results: HUs were more likely to be older, unemployed, and to habitually use anxiolytics and analgesics than NUs. The main reasons for taking anxiolytics in HUs were alleviating insomnia and reducing anxiety, whereas the main reason for taking analgesics was improving joint pain. Additionally, the HU group had a higher proportion of habitual smokers than the OU group. There was no difference in drinking status or taking of controlled drugs among the three groups. HUs were more likely to use hypnotics and to have concerns about their side-effects than OUs. Conclusion: HUs were more likely to be unemployed, habitually use anxiolytics and analgesics, smoke heavily, and take hypnotic drugs with concerns regarding side-effects. These results may help encourage the appropriate use of hypnotics.

Situational factors affecting abstinence from drugs: Panel data analysis of patients with drug use disorders in residential drug use treatment.

Aim: To identify situational factors that can predict drug abstention in patients with drug use disorders undergoing residential drug use treatment. Methods: Patients with drug use disorders admitted to drug addiction rehabilitation centers (DARCs) in 2016 were involved in this study. Longitudinal panel data were used, with eight follow-up surveys over 6 years, approximately every 6 months. Of the 2752 samples from the eight follow-up surveys, 2293 were analyzed as the complete panel data set. The primary outcome was drug abstention for approximately 6 months. The influences of situational factors during this period on the primary outcome were also assessed using a generalized linear mixed model in which inter-individual differences were controlled as variable effects. Results: The use of residential DARCs positively influenced the primary outcome (adjusted odds ratio [AOR] 3.33, 95% confidence interval [CI] 1.79-6.21) when compared to no DARC usage. The cessation of drinking also positively affected the primary outcome (AOR 3.10, 95% CI 1.79-4.62), while employment status (AOR 2.22, 95% CI 1.12-4.41) and the cessation of drinking (AOR 4.92, 95% CI 2.77-8.72) positively impacted the primary outcomes of patients not using DARCs. Conclusion: The use of residential DARCs and the cessation of drinking positively affected drug abstention rates. Employment and the cessation of drinking for patients who were not using the DARCs also had a positive effect. This information will aid in the development of social recovery strategies for people with drug use disorders.

Mandibular torus thickness associated with age: Postmortem computed tomographic analysis.

Age estimation is an essential step in identifying human corpses. Several mandibular landmarks have been highlighted as skeletal sites for age estimation since aging causes morphological changes. Reports suggest that mandibular torus size may be associated with aging; however, thorough investigation has not been performed owing to the difficulty in measuring it. Therefore, this study aimed to determine the association between age and mandibular torus thickness using postmortem computed tomography data from Japanese corpses. This study included 2,792 corpses with mean (standard deviation) age of 58.0 (22.4) years (range, 0-101 years) and 67.6 % males. Further, 2,662 (95.3 %), 14 (0.5 %), 59 (2.1 %), and 57 (2.0 %) corpses were in the permanent, mixed, primary, and predental dentition periods, respectively. Multivariable analysis was performed to quantify the impact of age on mandibular torus thickness, adjusting for sex, height, weight, and occlusal contact status. The model also included an interaction term between age and occlusal status because of the potential effect modification by occlusion. Results of the multivariable regression analysis showed that mandibular torus thickness increased with age (the regression coefficients (95 % confidence interval) were 0.6 (0.2-1.0), 0.7 (0.3-1.0), 1.0 (0.6-1.4), 1.3 (0.9-1.7), 1.3 (0.8-1.8), and 1.1 (0.4-1.7) for age groups 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years, respectively), especially in males with occlusal contact. A significant association between mandibular torus thickness and age, modified by occlusal status and sex, was identified. Therefore, data regarding the thickness of the mandibular torus and occlusal status may be useful for age estimation in human corpses.

Outcomes and Prognostic Factors of Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Essential Tremor at 2-year Follow-up.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for essential tremor (ET). However, its long-term outcomes and prognostic factors remain unclear. This study aimed to retrospectively investigate 38 patients with ET who underwent MRgFUS thalamotomy and were followed up for >2 years. The improvement in tremor was evaluated using the Clinical Rating Scale for Tremor (CRST). Adverse events were documented, and correlations with factors, such as skull density ratio (SDR), maximum mean temperature (T-max), and lesion size, were examined. Furthermore, the outcomes were compared between two groups, one that met the cutoff values, which was previously reported (preoperative CRST-B ≤ 25, T-max ≥ 52.5°C, anterior-posterior size of lesion ≥ 3.9 mm, superior-inferior [SI] size of lesion > 5.5 mm), and the other that did not. The improvement rate was 59.4% on average at the 2-year follow-up. Adverse events, such as numbness (15.8%), dysarthria (10.5%), and lower extremity weakness (2.6%), were observed even after 2 years, although these were mild. The factors correlated with tremor improvement were the T-max and SI size of the lesion (p < 0.05), whereas the SDR showed no significance. Patients who met the aforementioned cutoff values demonstrated a 69.8% improvement at the 2-year follow-up, whereas others showed a 43.6% improvement (p < 0.05). In conclusion, MRgFUS is effective even after 2 years. The higher the T-max and the larger the lesion size, the better the tremor control. Previously reported cutoff values clearly predict the 2-year prognosis, indicating the usefulness of MRgFUS.

Age estimation by palatal suture using modified Kamijo's method.

The present study aimed to investigate the correlation between palatal suture obliteration and age in modern Japanese and to develop an age estimation equation by modifying Kamijo's (1949) method. The subjects were 195 Japanese skeletal remains (155 males and 40 females) whose age and sex were known. First, obliteration score (OS) was obtained by measuring palatal suture obliteration from photographic images taken at the time of forensic autopsy, and the correlation with age was examined; no significant correlation was found in females. Second, the palatal sutures were divided into 14 sections, and each section was scored from 0 to 4 points according to the degree of the suture obliteration. Suture scores (SS) were then calculated for each of the four sutures, and the sum of the 14 scores (TSS: total suture score) was used to perform regression analysis for age. For male and all subjects (male and female), age significantly increased (p < 0.001) according to increment of SSs for all sutures. TSS has the highest regression coefficient (r = 0.540), and the lowest standard error of estimation (13.54 years) for all of the patients. The intra- and inter-observer agreement scoring showed high reliability. Validation study using the formulae showed a high percentage of correct responses (80 %). In conclusion, age estimation regression formula by palatal suture using modified Kamijo's method was established for Japanese population, and the study showed the formula might be valid for age estimation.

Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

Validity of dental findings for identification by postmortem computed tomography.

Postmortem computed tomography (PMCT) images help identify individuals and extract information from corpses. PMCT may substitute for a standard examination when bodies are severely damaged or when resources are limited in a mass fatality incident. In such situations, the dental information revealed by PMCT has the potential to narrow down candidates for identification further. However, the validity of the dental findings obtained from PMCT images remains unclear. In this study, we investigated the validity of dental findings on PMCT images compared to regular dental examinations as the reference standard. We routinely collected PMCT images of 148 unidentified corpses and compared the dental findings of each tooth obtained from PMCT with those of a regular dental examination. The validity of dental findings of PMCT was measured by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We also evaluated the accuracy of dental findings per corpse using 32 teeth as the denominator. The dental findings with high sensitivity and high specificity were a present tooth (0.96 and 0.97), a missing tooth (0.97 and 0.97), pontic (0.92 and 1.00), a dental implant (1.00 and 1.00), and a root filling (0.94 and 0.99). The mean accuracy of the dental findings per corpse in PMCT was 95.6% (standard deviation: 6.9, minimum ≤ median ≤ maximum: 65.6 ≤ 100 ≤ 100). The number of corpses with 100% accuracy in the dental findings was 81 (54.7%). The information obtained in this study highlights the potential use of PMCT during human identification in several settings with limited resources, such as the number of specialists present and the condition of the corpses.

Dental characteristics associated with methamphetamine use: analysis using forensic autopsy data.

BACKGROUND: Little is known regarding the oral conditions in nonelderly methamphetamine users, such as the presence of dental caries and periodontitis. We aimed the oral conditions between methamphetamine users and non-users stratified by age groups. METHODS: In this cross-sectional study, computed tomography images were obtained from 3,338 decedents at two forensic medicine departments in Japan. Decedents aged > 20 or ≤ 64 years were included in the study and categorised into methamphetamine-detected (MA) and undetected (control) groups based on toxicological examinations. Decedents in the MA and control groups were matched for age and sex in a 1:4 ratio. The matched pairs were further categorised into young adults (20-44 years) and middle-aged adults (45-64 years). Oral characteristics, including the decayed, missing, and filled teeth (DMFT) index; periodontitis; distributional patterns of each tooth condition; and occlusal status, were compared between the MA and control groups for each age category. Among 3,338 decedents, 37 young and 55 middle-aged adults in the MA group were matched with 148 and 220 adults in the control group, respectively. RESULTS: In the young adult group, methamphetamine use was significantly associated with higher DMFT index (mean [standard deviation], 14.2 [7.6] vs 11.0 [6.1]; p = 0.007), smaller number of filled teeth (2.8 [2.9] vs 5.3 [4.0]; p = 0.001), higher proportion of periodontitis (39.0% vs 6.8%; p < 0.001), and lower proportion of occlusal support (54.1% vs 81.1%; p = 0.001). Young adult methamphetamine users tended to have untreated decayed canines and molars and missing molars. These findings were similar to those in middle-aged adults except the tendency to have missing maxillary incisors. CONCLUSIONS: Nonelderly methamphetamine users had distinctive oral characteristics that may help screen for methamphetamine abuse through dental examinations.

Resting State Networks Related to the Maintenance of Good Cognitive Performance During Healthy Aging.

Purpose: Maintenance of cognitive performance is important for healthy aging. This study aims to elucidate the relationship between brain networks and cognitive function in subjects maintaining relatively good cognitive performance. Methods: A total of 120 subjects, with equal number of participants from each age group between 20 and 70 years, were included in this study. Only participants with Addenbrooke's Cognitive Examination - Revised (ACE-R) total score greater than 83 were included. Anatomical T1-weighted MR images and resting-state functional MR images (rsfMRIs) were taken from all participants using a 3-tesla MRI scanner. After preprocessing, several factors associated with age including the ACE-R total score, scores of five domains, sub-scores of ACE-R, and brain volumes were tested. Morphometric changes associated with age were analyzed using voxel based morphometry (VBM) and changes in resting state networks (RSNs) were examined using dual regression analysis. Results: Significant negative correlations with age were seen in the total gray matter volume (GMV, r = -0.58), and in the memory, attention, and visuospatial domains. Among the different sub-scores, the score of the delayed recall (DR) showed the highest negative correlation with age (r = -0.55, p < 0.001). In VBM analysis, widespread regions demonstrated negative correlation with age, but none with any of the cognitive scores. Quadratic approximations of cognitive scores as functions of age showed relatively delayed decline compared to total GMV loss. In dual regression analysis, some cognitive networks, including the dorsal default mode network, the lateral dorsal attention network, the right / left executive control network, the posterior salience network, and the language network, did not demonstrate negative correlation with age. Some regions in the sensorimotor networks showed positive correlation with the DR, memory, and fluency scores. Conclusion: Some domains of the cognitive test did not correlate with age, and even the highly correlated sub-scores such as the DR score, showed delayed decline compared to the loss of total GMV. Some RSNs, especially involving cognitive control regions, were relatively maintained with age. Furthermore, the scores of memory, fluency, and the DR were correlated with the within-network functional connectivity values of the sensorimotor network, which supported the importance of exercise for maintenance of cognition.

Factors associated with methamphetamine use in Japanese people who died of unnatural causes: Analysis using forensic autopsy reports.

This study aimed to examine factors related to methamphetamine use in Japanese people who died of unnatural causes. This study used a cross-sectional design. A total of 3343 forensic autopsy reports were obtained from two forensic medicine departments in the Kanto region of Japan. We classified the decedents who underwent forensic autopsies into methamphetamine/amphetamine (MA) and undetected (comparison) groups based on toxicological examination. We matched the decedents in the MA group with those in the comparison group at a 1:4 ratio based on sex and age. The variables, including gang members, criminal records, tattoos, body mass index, infections, concurrent psychotropic drug use, and cause of death, were compared between the groups. Of the 3343 decedents, we matched 109 in the MA group with 436 in the comparison group. Methamphetamine use was significantly associated with gang membership (13.8% vs. 3%, p < 0.001), criminal records unrelated to methamphetamine (47.7% vs. 13.8%, p < 0.001), tattoos (29.2% vs. 6.4%, p < 0.001), and hepatitis C virus infection (48.0% vs. 3.6%, p < 0.001). One-third of the patients in the MA group died from poisoning. This is the first study to show the physical and social characteristics associated with methamphetamine use in Japanese people who died of unnatural causes. Our results could be extended to people with methamphetamine use disorder at risk of death and enable the development of policies and practices to provide necessary intervention in a timely manner.

Fatal airway obstruction due to Ludwig's angina from severe odontogenic infection during antipsychotic medication: A case report and a literature review.

Ludwig's angina is characterized by inflammation of the sublingual and submandibular spaces and is mainly caused by odontogenic infection, which leads to cellulitis of the soft tissues of the floor of the mouth and the neck. This causes asphyxia due to elevation and posterior deviation of the tissues of the floor of the mouth. We report a fatal case of airway obstruction due to Ludwig's angina. A woman in her forties who had no physical complications, but had a mental illness, was undergoing outpatient dental treatment for caries in the first premolar of the left mandible. She was admitted to a psychiatric hospital because of insomnia caused by pain, where she developed cardiopulmonary arrest while sleeping and died 14 days after onset of the dental infection. Postmortem computed tomography (PMCT) prior to autopsy showed swelling of the soft tissues-from the floor of the mouth to the oropharyngeal cavity, the supraglottic larynx, and the prevertebral tissue. Autopsy revealed a markedly swollen face and neck, an elevated tongue, and a highly edematous epiglottis and laryngopharyngeal mucosa. There was also cellulitis and abscess of the facial, suprahyoid, and neck musculature, which suggested that the cause of death was asphyxiation due to airway obstruction. This was an alarming case, with mental illness leading to risk of severe odontogenic infection, and in which obesity and use of antipsychotic medication might have acted synergistically leading to airway obstruction. This is also a case of Ludwig's angina captured by PMCT, which has rarely been reported.

Structural changes of regulatory domain heterodimer of N-methyl-D-aspartate receptor subunits GluN1 and GluN2B through the binding of spermine and ifenprodil.

Modeling the binding sites for spermine and ifenprodil on the regulatory (R) domains of the N-methyl-D-aspartate receptor GluN1 and GluN2B subunits was carried out after measuring spermine stimulation and ifenprodil inhibition at receptors containing GluN1 and GluN2B R domain mutants. Models were constructed based on the published crystal structure of the GluN1 and GluN2B R domains, which form a heterodimer (Nature 475:249-253, 2011). The experimental results and modeling suggest that a binding site for spermine was formed by the residues near the cleft between the R1 and R2 lobes of the GluN1 R domain (GluN1R) together with residues on the surface of the R2 (C-terminal side) lobe of the GluN2B R domain (GluN2BR). The ifenprodil binding site included residues on the surface of the R1 lobe (N-terminal side) of GluN1R together with residues near the cleft between the R1 and R2 lobes of GluN2BR. It was confirmed using a Western blot analysis that GluN1R and GluN2BR formed a heterodimer. Models of spermine and ifenprodil binding to the heterodimer were constructed. The modeling suggests that an open space between the two R1 lobes of GluN1R and GluN2BR is promoted through spermine binding and that the R1 lobes of GluN1R and GluN2BR approach each other through ifenprodil binding--an effect opposite to that seen with the binding of spermine.

Efficiency of blended e-learning classes using nursing practice example.

We are developing a nursing education system utilizing e-learning. The objective of the study project we conducted and are describing herein is to show how efficient e-learning is when applied for nursing education along with ordinary face-to-face teaching classes held in parallel. We call this instruction mode blended e-learning. This paper reports the efficiency of such an education method based on a survey of the evaluations produced by students who actually attended e-learning classes in 2007.

Binding of spermine and ifenprodil to a purified, soluble regulatory domain of the N-methyl-D-aspartate receptor.

The binding of spermine and ifenprodil to the amino terminal regulatory (R) domain of the N-methyl-D-aspartate receptor was studied using purified regulatory domains of the NR1, NR2A and NR2B subunits, termed NR1-R, NR2A-R and NR2B-R. The R domains were over-expressed in Escherichia coli and purified to near homogeneity. The K(d) values for binding of [(14)C]spermine to NR1-R, NR2A-R and NR2B-R were 19, 140, and 33 microM, respectively. [(3)H]Ifenprodil bound to NR1-R (K(d), 0.18 microM) and NR2B-R (K(d), 0.21 microM), but not to NR2A-R at the concentrations tested (0.1-0.8 microM). These K(d) values were confirmed by circular dichroism measurements. The K(d) values reflected their effective concentrations at intact NR1/NR2A and NR1/NR2B receptors. The results suggest that effects of spermine and ifenprodil on NMDA receptors occur through binding to the regulatory domains of the NR1, NR2A and NR2B subunits. The binding capacity of spermine or ifenprodil to a mixture of NR1-R and NR2A-R or NR1-R and NR2B-R was additive with that of each individual R domain. Binding of spermine to NR1-R and NR2B-R was not inhibited by ifenprodil and vice versa, indicating that the binding sites for spermine and ifenprodil on NR1-R and NR2B-R are distinct.

The pore region of N-methyl-D-aspartate receptors differentially influences stimulation and block by spermine.

The transmembrane and pore-forming regions of N-methyl-D-aspartate receptors containing the NR1 and NR2B subunits were studied by measuring the effects of various NR1 and NR2B mutants on stimulation and block by spermine. Block by spermine was predominantly affected by mutations in the M3 segment of NR1 and especially in the M1 and M3 segments of NR2B. These regions are in the outer vestibule of the channel pore and may contribute to a spermine binding site. Mutations in different regions-predominantly the M3 segment and M2 loop of NR1 and the M3 segment of NR2B-influenced spermine stimulation, a surprising finding because spermine stimulation is thought to involve a spermine binding site in the distal, extracellular regulatory domain. However, some of these mutations also influence sensitivity to ifenprodil and protons, and changes in spermine sensitivity may be secondary to changes in proton sensitivity. The results are consistent with the proposal that the relative positions of the M1 and M3 transmembrane segments and M2 loops are staggered or asymmetric in NR1 and NR2 subunits, and with the idea that stimulation and block by spermine involve separate binding sites and distinct mechanisms, although some residues in the receptor subunits can affect both stimulation and block.