Structural and functional characterization of the IgSF21-neurexin2α complex and its related signaling pathways in the regulation of inhibitory synapse organization.

The prevailing model behind synapse development and specificity is that a multitude of adhesion molecules engage in transsynaptic interactions to induce pre- and postsynaptic assembly. How these extracellular interactions translate into intracellular signal transduction for synaptic assembly remains unclear. Here, we focus on a synapse organizing complex formed by immunoglobulin superfamily member 21 (IgSF21) and neurexin2α (Nrxn2α) that regulates GABAergic synapse development in the mouse brain. We reveal that the interaction between presynaptic Nrxn2α and postsynaptic IgSF21 is a high-affinity receptor-ligand interaction and identify a binding interface in the IgSF21-Nrxn2α complex. Despite being expressed in both dendritic and somatic regions, IgSF21 preferentially regulates dendritic GABAergic presynaptic differentiation whereas another canonical Nrxn ligand, neuroligin2 (Nlgn2), primarily regulates perisomatic presynaptic differentiation. To explore mechanisms that could underlie this compartment specificity, we targeted multiple signaling pathways pharmacologically while monitoring the synaptogenic activity of IgSF21 and Nlgn2. Interestingly, both IgSF21 and Nlgn2 require c-jun N-terminal kinase (JNK)-mediated signaling, whereas Nlgn2, but not IgSF21, additionally requires CaMKII and Src kinase activity. JNK inhibition diminished de novo presynaptic differentiation without affecting the maintenance of formed synapses. We further found that Nrxn2α knockout brains exhibit altered synaptic JNK activity in a sex-specific fashion, suggesting functional linkage between Nrxns and JNK. Thus, our study elucidates the structural and functional relationship of IgSF21 with Nrxn2α and distinct signaling pathways for IgSF21-Nrxn2α and Nlgn2-Nrxn synaptic organizing complexes in vitro. We therefore propose a revised hypothesis that Nrxns act as molecular hubs to specify synaptic properties not only through their multiple extracellular ligands but also through distinct intracellular signaling pathways of these ligands.

An Alternative Approach to Determining Metabolic Syndrome Component Cutoffs in Children and Adolescents Using Segmental Regression Analysis.

Background: The prevalence of metabolic syndrome is increasing in children and adolescents. Although some diagnostic criteria for metabolic syndrome exist, further research is needed to determine appropriate age-, sex-, and race-specific cutoffs for each component. Methods and Results: Health examinations were conducted in 1,679 children aged 6-15 years in 9 regions of Japan. Participants were divided into 3 age groups for each sex: 6-8, 9-11, and 12-15 years. For metabolic syndrome components in each group, inverse cumulative percentile graphs were drawn and approximated by 3 regression lines using segmented regression analysis. The intersection of each regression line was defined as the breakpoint, and the measured value corresponding to the breakpoint percentile as the breakpoint value. Breakpoint values for waist circumference were age dependent at approximately 60, 70, and 80 cm for ages 6-8, 9-11, and 12-15 years, respectively. Breakpoint values for blood pressure were age- and/or sex dependent, while those for triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose were neither age nor sex dependent. Based on these results, we proposed new cutoffs for diagnosing metabolic syndrome in Japanese children and adolescents. Conclusions: Breakpoint values obtained by segmented regression analysis on inverse cumulative percentile graphs can be useful for determining metabolic syndrome component cutoffs in children and adolescents.

A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.

Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

Recent dental visits and family caregiving among individuals with dental symptoms: A nationwide cross-sectional study in Japan.

OBJECTIVES: With the increasing number of family caregivers due to the ageing population, physical and mental health problems among caregivers are of concern. However, few studies have evaluated their oral health. This study aimed to evaluate the association between being a family caregiver and recent dental visits for dental symptoms in Japan, with consideration of gender. METHODS: A cross-sectional study was conducted using the 2016 Comprehensive Survey of Living Conditions (CSLC) in Japan. Participants with dental symptoms were included in this study. The primary outcome was recent dental visits. The exposure variable of interest was being a primary caregiver for a family member requiring long-term care. A logistic regression analysis was conducted adjusting for contributing factors such as age, gender, marital status, working hours per week, education, household expenditure per month, self-rated health and the interaction between gender and caregiving. A stratified analysis by gender was also performed. RESULTS: Of the 5100 eligible participants, 233 (4.6%) were family caregivers. Of all participants, 2746 (53.8%) reported dental visits. The adjusted odds ratio (aOR) of family caregivers having recent dental visits was 0.83 (95% confidence interval [CI], 0.64-1.09). In a gender stratified analysis, family caregivers were less likely to visit dental clinics than were non-family caregivers in the male subsample (aOR: 0.56, 95% CI: 0.34-0.92) but not in the female subsample (aOR: 0.99, 95% CI: 0.72-1.38). CONCLUSIONS: The findings indicate that family caregivers, especially male caregivers, had fewer dental visits than non-family caregivers. These findings suggest the need to improve the accessibility of dental clinics to family caregivers with dental symptoms.

Workplace factors associated with willingness to undergo human immunodeficiency virus testing during workplace health checkups.

BACKGROUND: To examine workplace factors associated with willingness to undergo human immunodeficiency virus (HIV) testing during workplace health checkups. METHODS: This cross-sectional study used an Internet-based self-administered questionnaire to obtain data from a pool of 24,287 Japanese workers. Binary and multiple logistic regression analyses evaluated the association between workplace factors and HIV testing. Data were adjusted for sex, age, marital status, education, and history of HIV testing. RESULTS: We gathered information from 4,143 (17.1%) respondents, of whom 1,129 (27.3%) were willing to be tested for HIV as part of a workplace health checkup. The participants were 20-59 years old. Approximately half of the participants were male (49.9%), half were married (48.9%), and half had completed higher education (47.6%). Workplace hepatitis testing was offered to 15.6% of the respondents, and most participants underwent health checkups without their colleagues (52.1%) at a medical facility (60.2%). Willingness to undergo HIV testing was positively correlated with having an increased risk of occupational blood exposure (vs. not at risk, adjusted odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.41-2.15) or working in medical and welfare roles (vs. manufacturing, OR: 1.40, 95% CI: 1.07-1.84). The presence of occupational health staff at the workplace (vs. their absence, adjusted OR: 1.35, 95% CI: 1.16-1.59) and hepatitis testing (vs. not testing, adjusted OR: 2.02, 95% CI: 1.66-2.44) increased willingness to undergo HIV testing. CONCLUSIONS: A pilot HIV-testing program involving individuals at an increased risk of occupational blood exposure and undergoing hepatitis tests in workplaces providing occupational health staff support is recommended.

Dental Utilization Stratified by the Purpose of Visit: A Population-Based Study in Japan.

BACKGROUND: This study aimed to provide a stratified description of dental visit utilisation by Japanese residents based on patient age, sex, prefecture, and the purpose of the visits. METHODS: This cross-sectional study used the National Database of Health Insurance Claims of Japan to identify participants visiting dental clinics in Japan (April 2018-March 2019). Dental care utilisation by populations stratified by age, sex, and prefecture was assessed. We estimated the slope index of inequality (SII) and relative index of inequality (RII) to evaluate regional differences based on regional income and education. RESULTS: Amongst the Japanese population, 18.6% utilised preventive dental care visits; 59,709,084 participants visited dental clinics, with children aged 5 to 9 years having the highest proportion. SII and RII were higher for preventive dental visits than those for treatments in all settings. The largest regional differences for preventive care were observed in SII of children aged 5 to 9 years and in RII of men in their 30s and women aged 80 years and older. CONCLUSIONS: This nationwide population-based study revealed that the proportion of people utilising preventive dental care in Japan was low, with regional differences. Preventive care needs to be more easily accessible and available to improve the oral health of residents. The above findings may provide an important basis for improving policies related to dental care for residents.

α-Synuclein Preformed Fibrils Bind to ß-Neurexins and Impair ß-Neurexin-Mediated Presynaptic Organization.

Synucleinopathies form a group of neurodegenerative diseases defined by the misfolding and aggregation of α-synuclein (α-syn). Abnormal accumulation and spreading of α-syn aggregates lead to synapse dysfunction and neuronal cell death. Yet, little is known about the synaptic mechanisms underlying the α-syn pathology. Here we identified ß-isoforms of neurexins (ß-NRXs) as presynaptic organizing proteins that interact with α-syn preformed fibrils (α-syn PFFs), toxic α-syn aggregates, but not α-syn monomers. Our cell surface protein binding assays and surface plasmon resonance assays reveal that α-syn PFFs bind directly to ß-NRXs through their N-terminal histidine-rich domain (HRD) at the nanomolar range (KD: ~500 nM monomer equivalent). Furthermore, our artificial synapse formation assays show that α-syn PFFs diminish excitatory and inhibitory presynaptic organization induced by a specific isoform of neuroligin 1 that binds only ß-NRXs, but not α-isoforms of neurexins. Thus, our data suggest that α-syn PFFs interact with ß-NRXs to inhibit ß-NRX-mediated presynaptic organization, providing novel molecular insight into how α-syn PFFs induce synaptic pathology in synucleinopathies such as Parkinson's disease and dementia with Lewy bodies.

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that WT MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1ß, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1-NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.

Symptom severity trajectories and distresses in patients undergoing video-assisted thoracoscopic lung resection from surgery to the first post-discharge clinic visit.

This study aimed to characterize patients' symptom severity trajectories and distresses from video-assisted thoracoscopic lung resection to the first post-discharge clinic visit. Seventy-five patients undergoing thoracoscopic lung resection for diagnosed or suspected pulmonary malignancy prospectively recorded daily symptom severity on a 0-10 numeric scale using the MD Anderson Symptom Inventory until the first post-discharge clinic visit. The causes of postoperative distresses were surveyed, and symptom severity trajectories were analyzed using joinpoint regression. A rebound was defined as a statistically significant positive slope after a statistically significant negative slope. Symptom recovery was defined as symptom severity of ≤3 in two contiguous measurements. The accuracy of pain severity on days 1-5 for predicting pain recovery was determined using area under the receiver operating characteristic curves. We applied Cox proportional hazards models for multivariate analyses of the potential predictors of early pain recovery. The median age was 70 years, and females accounted for 48%. The median interval from surgery to the first post-discharge clinic visit was 20 days. Trajectories of several core symptoms including pain showed a rebound from day 3 or 4. Specifically, pain severity in patients with unrecovered pain had been higher than those with recovered pain since day 4. Pain severity on day 4 showed the highest area under the curve of 0.723 for predicting pain recovery (P = 0.001). Multivariate analysis identified pain severity of ≤1 on day 4 as an independent predictor of early pain recovery (hazard ratio, 2.86; P = 0.0027). Duration of symptom was the leading cause of postoperative distress. Several core symptoms after thoracoscopic lung resection showed a rebound in the trajectory. Specifically, a rebound in pain trajectory may be associated with unrecovered pain; pain severity on day 4 may predict early pain recovery. Further clarification of symptom severity trajectories is essential for patient-centered care.

Delayed Diagnosis and Prognostic Impact of Breast Cancer During the COVID-19 Pandemic.

BACKGROUND: Breast screening services were suspended for several months owing to the coronavirus disease 2019 (COVID-19) pandemic. We estimated the potential impact on breast cancer mortality using long-term global observations. However, the magnitude of the impact may vary across countries; therefore, we conducted an analysis and modeling study of this impact in Japan. PATIENTS AND METHODS: We compared the clinicopathological features of breast cancers between the nonpandemicgroup (April 1, 2019 to October 31, 2019) and the pandemic group (April 1, 2020 to October 31, 2020). We also compared the estimated 10-year survival rates between the two groups based on the weighted average of the 10-year survival rate by clinical stage and site (2004-2007). RESULTS: Results...Pandemic-related disruption decreased the number of breast cancer cases from296 to 249 during both 7-month periods. The percentage of patients with stage IIB or higher disease was significantly higher in the pandemic group than in the non-pandemic group (22.0% vs. 31.3%, P = 0.0133). The percentage of cases with a Ki-67 labeling index higher than 20% tended to be higher in the pandemic group than in the non-pandemic group (62.2% vs. 54.4%). The estimated 10-year survival rate was lower in the pandemic group than in the non-pandemic group (83.9% vs. 87.9%, 95% confidence interval of the difference: 0.87-8.8, P > 0.05). CONCLUSION: We found more aggressive and advanced disease afterthe suspension of breast cancer screening services owing to the COVID-19 pandemic. This may have affected the long-term clinical outcomes of patients with breast cancer.

SorCS1 inhibits amyloid-ß binding to neurexin and rescues amyloid-ß-induced synaptic pathology.

Amyloid-ß oligomers (AßOs), toxic peptide aggregates found in Alzheimer's disease, cause synapse pathology. AßOs interact with neurexins (NRXs), key synaptic organizers, and this interaction dampens normal trafficking and function of NRXs. Axonal trafficking of NRX is in part regulated by its interaction with SorCS1, a protein sorting receptor, but the impact of SorCS1 regulation of NRXs in Aß pathology was previously unstudied. Here, we show competition between the SorCS1 ectodomain and AßOs for ß-NRX binding and rescue effects of the SorCS1b isoform on AßO-induced synaptic pathology. Like AßOs, the SorCS1 ectodomain binds to NRX1ß through the histidine-rich domain of NRX1ß, and the SorCS1 ectodomain and AßOs compete for NRX1ß binding. In cultured hippocampal neurons, SorCS1b colocalizes with NRX1ß on the axon surface, and axonal expression of SorCS1b rescues AßO-induced impairment of NRX-mediated presynaptic organization and presynaptic vesicle recycling and AßO-induced structural defects in excitatory synapses. Thus, our data suggest a role for SorCS1 in the rescue of AßO-induced NRX dysfunction and synaptic pathology, providing the basis for a novel potential therapeutic strategy for Alzheimer's disease.

Developmental trajectories at a high risk for childhood overweight/obesity.

BACKGROUND: The associations between developmental patterns (trajectories) in children and maternal factors have been widely investigated, but paternal effects on these trajectories are unclear. This study aimed to determine child and parental factors involved in developmental trajectories at high risk for causing adverse cardiovascular (CV) profiles in children. METHODS: We analyzed longitudinal anthropometric data from birth to the present and CV profiles of 1,832 healthy volunteers (51% girls) aged 3-15 years who participated in a nationwide study between July 2012 and January 2014. Six trajectory latent class growth models were developed using body mass index z- scores. Predictors for being in developmental trajectories at high risk for causing adverse CV profiles were determined by multivariate regression analysis. RESULTS: The mean±standard deviation number of anthropometric data points was 12±3 for both boys and girls. Among the six trajectories, the infantile onset and continual increase groups had significantly worse levels of many CV profiles than those in the remaining groups. Paternal overweight/obesity was an independent predictor for boys being in the infantile onset group and for girls being in the continual increase group. Additionally, maternal pre-pregnancy overweight/obesity in boys and maternal excessive gestational weight gain in girls were independent predictors for being in the infantile onset group. Having no sibling in boys and an older maternal age were independent predictors for being in the continual increase group. CONCLUSIONS: Interventions to prevent childhood obesity should include strategies that focus on fathers and mothers as well as those that focus on children with certain types of familial background.

Revisiting the Geographical Distribution of Thyroid Cancer Incidence in Fukushima Prefecture: Analysis of Data From the Second- and Third-round Thyroid Ultrasound Examination.

BACKGROUND: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. METHODS: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. RESULTS: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74). CONCLUSION: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.

Mortality differences in disabled older adults by place of care in Japan: nationwide 10-year results.

This longitudinal study aimed to compare 1-year mortality between users of home- and community-based services (HCBS) and residential facilities (nursing homes, group homes, and geriatric apartments) among non-hospitalized frail older adults in Japan. Using three nationwide data sources, we conducted a nationwide pooled cohort study of 1-year follow-up among certified users of long-term care insurance (LTCI) aged 65 years and older from 2007 through 2016 to compare 1-year mortality using a logistic regression model. Overall, compared to HCBS users, mortality was higher in residents in nursing homes and geriatric apartments but lower in group home residents. While mortality gradually increased over time among those in residential facilities, it remained at a level similar to that of HCBS users. Since 2006, Japan's public health policy has been to increase end-of-life care in residential facilities. Our results indicate that this policy resulted in an increase in mortality in residential facilities, possibly due to accommodation of more severely ill people there, or a shift in their focus from transferring dying residents to hospitals to preserve the dignity of residents.

Association of marital status and access to dental care among the Japanese population: a cross-sectional study.

BACKGROUND: Health disparities according to marital status have been reported worldwide. Although spouses provide an important social network that influences heath behaviors, limited studies have examined the association between marital status and access to dental care. Therefore, this study aimed to analyze the association between marital status and access to dental care. METHODS: A secondary analysis of the 2013 Comprehensive Survey of Living Conditions in Japan which is a national survey, was performed in this study. Out of 367,766 respondents, 4111 respondents, aged over 40 years who selected oral symptoms as their most concerning subjective symptom were recruited as participants. The independent variable of interest was marital status-married or non-married (single, divorced, widowed); and the dependent variable was access to dental care. We performed Poisson regression analyses stratified by sex with adjustment for age, educational status, employment, equivalent household expenditure, and smoking habits. RESULTS: Among respondents who reported oral symptoms, 3024 were married, and 1087 were non-married. Further, 29.4% and 40.4% of married and non-married men, respectively, did not receive dental treatment for their symptoms. Meanwhile, 27.5% and 25.0% of married and non-married women, respectively, did not receive dental treatment for their symptoms. The prevalence ratio for not receiving dental treatment was significantly higher among non-married men (prevalence ratio: 1.33; 95% confidence interval: 1.14-1.56) than among married men. However, no significant association was observed among women. CONCLUSIONS: Non-married men were highly unlikely to receive dental treatment than married men, while no significant association was observed among women. The results implicate the importance of implementing a public dental health policy for protecting the dental health of non-married individuals.

Characteristics of Hospitals Employing Dentists, and Utilization of Dental Care Services for Hospitalized Patients in Japan: A Nationwide Cross-Sectional Study.

Dental care for hospitalized patients can improve nutritional status and feeding function while reducing complications. However, such care in Japan is not uniformly provided. This investigation examined the presence and characteristics of hospitals where dentists work and the collaboration between medical and dental teams. This cross-sectional study involves 7205 hospitals using the administrative reports on the Hospital Bed Function of 2018. Indicators described were the proportion of hospitals employing dentists, those providing perioperative oral care, and those with a nutrition support team (NST) that included dentists. A two-level logistic regression model was performed using hospital-based and secondary medical area-based factors to identify factors associated with hospitals employing dentists and dental care services. Some hospitals had poor medical and dental collaboration, even those with dentists, and no-dentist hospitals had rare medical and dental collaboration. Factors positively associated with hospitals that employed dentists were diagnosis-procedure-combination-hospital types, the Japanese government-established hospitals compared with hospitals established by public organizations, among others. In conclusion, the present study found poor medical and dental collaboration was observed in some hospitals and that hospital type, region, and hospital founders were associated with the performance of collaborative medical and dental care.

[Validation of using disqualification from long-term care insurance registry as a proxy of death].

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

Association between exposure to secondhand smoking at home and tooth loss in Japan: A cross-sectional analysis of data from the 2016 National Health and Nutrition Survey.

INTRODUCTION: Tooth loss affects oral health and physical and social functions. With widespread population aging, its prevalence is increasing. Secondhand smoking is a risk factor for oral diseases; however, in Japan, there are currently no regulations restricting exposure to secondhand smoke at home. This cross-sectional study examined the association between secondhand smoking at home and tooth loss among Japanese adults. METHODS: The study examined secondary data from the 2016 National Health and Nutrition Survey, Japan. The self-reported responses of 18812 non-smokers aged ≥20 years were analyzed. The association between exposure to secondhand smoke at home and number of teeth was examined through multiple linear regression with multiple imputation. To obtain a more normal distribution, logarithmic transformation was applied to the number of teeth that deviated substantially from a normal distribution. Adjustments were made for sex, age, occupation, household size, dental check-up within the past year, and exposure to secondhand smoke outside the home. RESULTS: Overall, 8.4% of the respondents were exposed to secondhand smoking at home almost every day; this percentage was larger among younger respondents, who also had more teeth than the older respondents. Although the univariate linear regression did not show a positive association between exposure to secondhand smoke and tooth loss, the multivariate-adjusted analysis revealed that respondents who were exposed to secondhand smoke at home almost every day had fewer teeth (ß= -0.04; 95% CI: -0.07 - -0.01). CONCLUSIONS: The present results suggest that exposure to secondhand smoke at home increases the risk of tooth loss.