Association of excess visceral fat and severe illness in hospitalized COVID-19 patients in Japan: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Obesity, defined by body mass index (BMI), is a well-known risk factor for the severity of coronavirus disease 2019 (COVID-19). Adipose tissue distribution has also been implicated as an important factor in the body's response to infection, and excess visceral fat (VF), which is prevalent in Japanese, may contribute significantly to the severity. Therefore, this study aimed to evaluate the association of obesity and VF with COVID-19 severe illness in Japan. SUBJECTS/METHODS: This retrospective cohort study involved 550 COVID-19 patients admitted to a tertiary care hospital with BMI and body composition data, including VF. The primary endpoint was severe illness, including death, due to COVID-19 during hospitalization. Logistic regression analysis was applied to examine the quartiles of BMI and VF on severe illness after adjusting for covariates such as age, sex, subcutaneous fat, paraspinal muscle radiodensity, and comorbidities affecting VF (COPD, cancer within 5 years, immunosuppressive agent use). RESULTS: The median age was 56.0 years; 71.8% were males. During hospitalization, 82 (14.9%) experienced COVID-19 severe illness. In the multivariate logistic regression analysis, Q4 of BMI was not significantly associated with severe illness compared to Q1 of BMI (OR 1.03; 95% CI 0.37-2.86; p = 0.95). Conversely, Q3 and Q4 of VF showed a higher risk for severe illness compared to Q1 of VF (OR 2.68; 95% CI 1.01-7.11; p = 0.04, OR 3.66; 95% CI 1.30-10.26; p = 0.01, respectively). Stratified analysis by BMI and adjusted for covariates showed the positive association of VF with severe illness only in the BMI < 25 kg/m2 group. CONCLUSIONS: High BMI was not an independent risk factor for COVID-19 severe illness in hospitalized patients in Japan, whereas excess VF significantly influenced severe illness, especially in patients with a BMI < 25 kg/m2.

Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity.

OBJECTIVE: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS: For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS: After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

Association Between Heat Exposure and Kawasaki Disease: A Time-Stratified Case-Crossover Study.

Nationwide studies investigating the association between daily mean temperature and Kawasaki disease are lacking. This study aimed to examine the association between ambient temperature and Kawasaki disease by utilizing daily data from nationwide administrative claims databases. The daily number of Kawasaki disease patients younger than 15 years old, who were hospitalized from 2011 to 2022, was extracted from the nationwide administrative claims database of hospitalizations in Japan. Daily mean temperature data and relative humidity data were obtained from the Japan Meteorological Agency. Since the exposure of interest includes heat, hospitalizations during the five warmest months (May through September) were used for analysis. A time-stratified case-crossover study with conditional quasi-Poisson regression analysis was used to estimate the relative risk (RR) of weather exposure for Kawasaki disease hospitalization with a lag of 0-5 days by prefecture. Relative humidity was included in the model simultaneously to control for its potential confounding effect. Random-effects meta-analysis was used to estimate pooled RRs. There was a total of 48,784 cases of Kawasaki disease hospitalization during the study period, of which 87.9% were under 5 years of age. Exposure to high daily mean temperatures was associated with an increased risk of hospitalization for Kawasaki disease. Specifically, exposure to extreme high daily mean temperatures (99th percentile high temperature) was associated with higher risk of hospitalization by 33% (RR 1.33, 95% confidence interval (CI):1.08, 1.65). Similar results were obtained from sensitivity analysis. Future research should elucidate the mechanisms by which high temperature is associated with hospitalization for Kawasaki disease.

Impact of the coronavirus disease 2019 pandemic on the number of colorectal cancer surgeries performed: analysis of a nationwide inpatient database in Japan.

PURPOSE: This study examined the impact of the COVID-19 pandemic on the number of colorectal cancer surgeries performed in Japan. METHODS: We selected patients who underwent colorectal cancer surgeries between January, 2017 and December, 2020 from the Diagnosis Procedure Combination database. The COVID-19 pandemic was divided into three waves. We evaluated the changes in the number of surgeries performed for colorectal cancer during each wave, stratified by cancer stage using Poisson regression. RESULTS: During the first wave, the rate ratio (RR) for stage III colon cancer decreased significantly (RR, 0.94), whereas those for stages 0 to II (RR, 1.01) and stage IV (RR, 1.04) were not different. During the second and third waves, the RR for stage 0 to II colon cancer decreased significantly (RR, 0.96), that for stage IV increased (RR, 1.09), and that for stage III was not different (RR, 0.97). During the first wave, the RR for stage 0 to II rectal cancer increased significantly (RR, 1.09), that for stage IV decreased (RR, 0.84), and that for stage III was not different (RR, 0.97). CONCLUSIONS: The number of colorectal cancer surgeries changed during the pandemic and varied according to the stage of disease.

Mixed-methods study of medical students' attitudes toward peer physical examinations in Japan.

BACKGROUND: Most Japanese medical schools likely continue to rely on peer physical examination (PPE) as a tool to for teaching physical examination skills to students. However, the attitudes of medical students in Japan toward PPEs have not be identified. Therefore, we evaluated students' attitudes toward PPE in a Japanese medical school as a preparation for developing a PPE policy tailored to the context of Japanese culture. METHODS: We conducted a mixed-methods study with an explanatory sequential approach, in which qualitative data were used to interpret the quantitative findings. Surveys and interviews were conducted with medical students and junior residents at a Japanese university. A total of 63 medical students and 50 junior residents responded to the questionnaire. We interviewed 16 participants to reach theoretical saturation and investigated the attitudes of medical students toward PPE and the themes emerging from the interview data, providing detailed descriptions of the quantitative findings. RESULTS: Female participants were significantly more likely than male participants to report varying degrees of resistance to being a model patient during PPE (male: 59.7%, female: 87%, p < 0.001). Most of the participants who took on the role of patients that involved undressing were males. The participants expected improvements in issues related to the guarantee of freedom to refuse to be a model patient and measures to protect confidentiality. Approximately 22% of the participants reported that they witnessed incidental findings (including variations within the normal range) in front of other students during PPE. CONCLUSIONS: The findings imply that medical students expect high levels of autonomy and confidentiality when volunteering as model patients during PPE. Thus, developing a PPE policy suitable for Japanese culture may be effective in establishing a student-centered PPE environment.

Effectiveness of remdesivir with corticosteroids for COVID-19 patients in intensive care unit: A hospital-based observational study.

The effectiveness of remdesivir on survival in coronavirus disease 2019 (COVID-19), especially in cases treated in the intensive care unit (ICU), is controversial. We investigated the effectiveness of remdesivir with corticosteroids on the survival of COVID-19 patients in a real ICU clinical practice. For laboratory-confirmed COVID-19 patients admitted to the ICU of a tertiary hospital in Tokyo (April 2020-November 2021) and who received corticosteroids, the effectiveness of remdesivir for survival, stratified by interval length (within 9 or 10+ days), was retrospectively analyzed using Cox regression model. A total of 168 patients were included: 35 with no remdesivir use (control), 96 with remdesivir use within 9 days, and 37 with remdesivir use with an interval of 10+ days. In-hospital mortality was 45.7%, 10.4%, and 16.2%, respectively. After adjusting for possible covariates including comorbidities, laboratory data, oxygen demand, or level of pneumonia, remdesivir use within 9 days from symptom onset reduced mortality risk (hazard ratio [HR]: 0.10; 95% confidence interval (CI): 0.025-0.428) compared to the control group. However, remdesivir use with an interval of 10+ days showed no significant association with mortality (HR: 0.42; 95% CI: 0.117-1.524). Among COVID-19 patients who received corticosteroids in ICU, remdesivir use within 9 days from symptom onset was associated with reduced in-hospital mortality risk.

Impact of exposure to secondhand smoke on the risk of obesity in early adolescence.

BACKGROUND: Exposure to secondhand smoke (SHS) might be associated with obesity in children. This study aimed to evaluate whether continuous, quit, or start exposure to SHS was associated with obesity risk in early adolescents. METHODS: We used population-based longitudinal data of primary school students in Adachi City, Tokyo, Japan, in 2018 (4th grade) and 2020 (6th grade) and studied 3605 students. The association between continuous, quit, start, or never exposed to SHS from 4th to 6th grade and BMI categories (underweight or normal weight, overweight, obesity) in 6th grade was investigated using ordinal logistic regression models. RESULTS: Continuous SHS group showed a higher risk of being in the high BMI category than no SHS group (OR = 1.51, 95% CI 1.16-1.96). The stratified analyses by sex showed a similar association in boys (OR = 1.74, 95% CI 1.25-2.44) but not in girls (OR = 1.14, 95% CI 0.74-1.76). Quitting SHS group did not show a higher risk of being in the high BMI category than no SHS group (OR = 1.11, 95% CI 0.75-1.66) and the same was true for boys (OR 1.46, 95% CI 0.88-2.41). CONCLUSIONS: Continuous SHS was a risk factor for obesity in boys in early adolescence; however, quitting SHS may help prevent it. IMPACT: Continuous secondhand smoke (SHS) was not associated with a higher risk of obesity in early adolescence in girls. Continuous SHS can be a risk factor for obesity in early adolescence in boys. Quitting SHS may help to prevent obesity in early adolescence in boys.

Association between the initiation of insurance coverage for fetal echocardiography and mortality from congenital heart disease in infants: An interrupted time series analysis.

BACKGROUND: The effectiveness of fetal echocardiography in reducing the mortality from congenital heart disease (CHD) is largely unknown. OBJECTIVES: This study aimed to evaluate whether the widespread use of fetal echocardiography owing to the initiation of insurance coverage in Japan was associated with a decreasing trend in the annual number of CHD-related deaths. METHODS: Data regarding the number of deaths from CHD in infants aged <12 months were extracted from Japanese demographic statistics (2000-2018). Segmented regression analysis was performed on the interrupted time series data by stratifying the sample into CHD subgroups based on ICD-10 classification and sex. RESULTS: After the initiation of insurance coverage for fetal echocardiography in 2010, a decrease was observed in the trends of annual deaths in patients with congenital malformations of aortic and mitral valves (ratio of trends before and after the initiation of insurance coverage for fetal echocardiography 0.96, 95% confidence interval 0.93, 0.99). In this group, the decrease persisted after adjusting for annual total infant deaths and cardiac surgery mortality and in the analysis of trends in the proportion of deaths in this group per total CHD deaths. However, a decrease in trends was not observed in other patient groups with CHD. In the sex-stratified analysis, a decrease was noted only in male patients with congenital malformations of aortic and mitral valves. CONCLUSIONS: The nationwide trend in annual CHD deaths decreased after the initiation of insurance coverage for fetal echocardiography only among patients with congenital malformation of aortic and mitral valves. These findings suggest that prenatal diagnosis with fetal echocardiography has led to improved mortality outcomes among these patients in Japan.

Association between socioeconomic status and net survival after primary lung cancer surgery: a tertiary university hospital retrospective observational study in Japan.

BACKGROUND: Inequalities in opportunities for primary lung cancer surgery due to socioeconomic status exist. We investigated whether socioeconomic inequalities exist in net survival after curative intent surgery at a tertiary university hospital, in Japan. METHODS: Data from the hospital-based cancer registry on primary lung cancer patients who received lung resection between 2010 and 2018 were linked to the surgical dataset. An area deprivation index, calculated from small area statistics and ranked into tertiles based on Japan-wide distribution, was linked with the patient's address as a proxy measure for individual socioeconomic status. We estimated net survival of up to 5 years by deprivation tertiles. Socioeconomic inequalities in cancer survival were analyzed using an excess hazard model. RESULTS: Of the 1039 patient-sample, advanced stage (Stage IIIA+) was more prevalent in the most deprived group (28.1%) than the least deprived group (18.0%). The 5-year net survival rates (95% confidence interval) from the least to the most deprived tertiles were 82.1% (76.2-86.6), 77.6% (70.8-83.0) and 71.4% (62.7-78.4), respectively. The sex- and age-adjusted excess hazard ratio of 5-year death was significantly higher in the most deprived group than the least deprived (excess hazard ratio = 1.64, 95% confidence interval: 1.09-2.47). The hazard ratio reduced toward null after additionally accounting for disease stage, suggesting that the advanced stage may explain the poor prognosis among the deprived group. CONCLUSION: There was socioeconomic inequality in the net survival of patients who received curative intent surgery for primary lung cancer. The lower socioeconomic status group might be less likely to receive early curative surgery.

Comparison of Disease Patterns and Outcomes Between Non-Japanese and Japanese Patients at a Single Tertiary Emergency Care Center in Japan.

BACKGROUND: Japan's historically low immigration rate and monolingual culture makes it a particularly interesting setting for clarifying non-national medical care. Our study objective was to examine disease patterns and outcome differences between Japanese and non-Japanese patients in a rapidly globalizing nation. METHODS: A secondary data analysis of 325 non-Japanese and 13,370 Japanese patients requiring tertiary care or intensive-care unit or high-care unit admission to the emergency department at the Tokyo Medical and Dental University medical hospital from 2010 through 2019 was conducted. Multivariable linear and logistic regressions models were applied to examine differences in percentage of diagnosis, mortality rates, and length of stay, stratified by Glasgow Coma Scale (GCS) scores to consider the impact of language barriers. Sex and age were adjusted. RESULTS: Non-Japanese patients had more anaphylaxis, burns, and infectious disease, but less cardiovascular diagnoses prior to adjustment. After adjustment, there were significantly more anaphylaxis (adjusted odds ratio [aOR] 2.7; 95% confidence interval [CI], 1.7-4.4) and infectious disease diagnoses (aOR 2.2; 95% CI, 1.3-3.7), and marginally more burn diagnoses (aOR 2.3; 95% CI, 0.96-5.3) than Japanese patients. Regardless of GCS scores, there were no significant differences between non-Japanese and Japanese patient length of stay for anaphylaxis, burn, and infectious disease after covariate adjustment. CONCLUSION: There were more non-Japanese patients diagnosed with anaphylaxis, burns, and infectious disease, but no notable patient care differences for length of stay. Further prevention efforts are needed against anaphylaxis, burns, and infectious disease for non-Japanese tourists or residents.

Joint Roles of Oxytocin- and Dopamine-Related Genes and Childhood Parenting Experience in Maternal Supportive Social Network.

How genes and parenting determine maternal social support availability, an important preventive factor of postpartum depression, has been little studied. Our study aimed to examine the interaction effects of maternal sociality-related gene and parenting on maternal social support. We analyzed data of 115 triads of Japanese grandmothers, mothers, and their infants. An interaction between parenting and cumulative genetic risk, calculated on the sociality-related genes (OXTR rs53576, rs2254298, rs1042778; COMT rs4680), was found. Mothers with high genetic risk received less social support if received poorer parenting (B = - 0.02, 95%CI = - 0.04 to - 0.01), while no association among low-risk mothers. Poorer social support was associated with severer depression in high-risk mothers (B = - 0.88, 95%CI = - 1.45 to -0.30). Our results suggest that mothers carrying risk alleles of sociality-related genes are particularly sensitive to childhood parenting, underscoring the importance of childhood parenting and genetic risk to understand maternal help-seeking behavior.

Concerns and needs of people with intellectual disabilities and their caregivers during the COVID-19 pandemic in Japan.

BACKGROUND: People with intellectual disabilities (IDs) and their caregivers face difficulties during the COVID-19 pandemic. However, limited studies have comprehensively investigated their challenges, especially in Japan. We aimed to clarify the concerns and needs of people with IDs and their caregivers during the COVID-19 pandemic in Japan. METHOD: From March to August 2021, 27 in-depth interviews were conducted with principal caregivers of people with moderate to profound IDs in Japan. We then transcribed the interviews and conducted deductive coding using predetermined codes focused on their daily life difficulties. Inductive coding was used to ensure that no important themes were overlooked. RESULTS: We found four concerns and four needs among people with IDs and their caregivers as significant themes. CONCLUSIONS: Our results provide useful information for supporting people with IDs and their caregivers, especially among those who need medical or social care in accordance with the infection control and social-distancing policies.

Interplay between social isolation and loneliness and chronic systemic inflammation during the COVID-19 pandemic in Japan: Results from U-CORONA study.

In the face of the global coronavirus disease 2019 (COVID-19) pandemic, billions of people were forced to stay at home due to the implementation of social distancing and lockdown policies. As a result, individuals lost their social relationships, leading to social isolation and loneliness. Both social isolation and loneliness are major risk factors for poor physical and mental health status through enhanced chronic inflammation; however, there might be an interplay between social isolation and loneliness on the association with chronic inflammation. We aimed to clarify the link between social relationships and inflammation in the context of the COVID-19 pandemic by distinguishing whether social isolation only, loneliness only, or both were associated with chronic inflammation markers among community-dwelling adults. The data of 624 people (aged 18-92 years, mean 51.4) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, which targeted randomly sampled households in Utsunomiya city, Japan, were analyzed. Social isolation was assessed as a structural social network by asking the number of social roles they have on a daily basis. Loneliness was measured with the UCLA loneliness scale. As chronic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR) and the concentration of high-sensitivity C-reactive protein (CRP) were measured. Generalized estimating equations method was employed to take into account the correlations within households. Isolated-Lonely condition (i.e., being both socially isolated and feeling lonely) was associated with higher NLR among men (B = 0.141, 95%CI = -0.01 to 0.29). Interestingly, Nonisolated-Lonely condition (i.e., not socially isolated but feeling lonely) was associated with lower CRP among women (B = -0.462, 95%CI = -0.82 to -0.10) and among the working-age population (B = -0.495, 95%CI = -0.76 to -0.23). In conclusion, being both socially isolated and feeling lonely was associated with chronic inflammation. Assessing both social isolation and loneliness is critical for proper interventions to mitigate the impact of poor social relationships on health, especially in the context of the COVID-19 pandemic.

Association Between Maternal Working Status and Unintentional Injuries Among 3 to 4-Month-Old Infants in Japan.

OBJECTIVES: Globally, unintentional injuries are one of the leading causes of infant death. Established risk factors for injuries during infancy include single parent households, socioeconomic disadvantage and maternal postpartum depression. We sought to examine whether maternal working status is associated with unintentional injury among infants in Japan. METHODS: We used data from an original questionnaire targeting mothers who participated in a 3 or 4-month health check-up program in Aichi prefecture, Japan. Experience of any type of unintentional injury was used as the primary outcome, and we also examined the experience of "falls" and "near-drowning" as secondary outcomes. We conducted multivariable logistic regression analysis, adjusting for covariates. We also performed propensity score matching in order to balance covariates between paid employment and unpaid employment groups. RESULTS: Among 6,465 valid responses (response rate, 67%), 9.8% of infants experienced unintentional injuries. After matching on propensity for maternal employment (based on 26 covariates), we found that infants of mothers in paid employment were 1.35 times (95% CI: 1.04-1.74) more likely to experience injures, including 1.60 times higher likelihood of falls (95% CI: 1.14-2.24). Near-drowning was not significantly associated with maternal employment. We also found that father's employment status was positively associated with risk of falls. CONCLUSION: Both multivariable logistic analysis and propensity score matching analysis revealed that maternal paid employment status was associated with unintentional injuries among Japanese infants. To prevent infant injuries, comprehensive support for working families should be considered.

Can social support during pregnancy affect maternal DNA methylation? Findings from a cohort of African-Americans.

BACKGROUND: While stress and the absence of social support during pregnancy have been linked to poor health outcomes, the underlying biological mechanisms are unclear. METHODS: We examined whether adverse experiences during pregnancy alter DNA methylation (DNAm) in maternal epigenomes. Analyses included 250 African-American mothers from the Boston Birth Cohort. Genome-wide DNAm profiling was performed in maternal blood collected after delivery, using the Infinium HumanMethylation450 Beadchip. Linear regression models, with adjustment of pertinent covariates, were applied. RESULTS: While self-reported maternal psychosocial lifetime stress and stress during pregnancy was not associated with DNAm alterations, we found that absence of support from the baby's father was significantly associated with maternal DNAm changes in TOR3A, IQCB1, C7orf36, and MYH7B and that lack of support from family and friends was associated with maternal DNA hypermethylation on multiple genes, including PRDM16 and BANKL. CONCLUSIONS: This study provides intriguing results suggesting biological embedding of social support during pregnancy on maternal DNAm, warranting additional investigation, and replication.

Maternal persistent marijuana use and cigarette smoking are independently associated with shorter gestational age.

BACKGROUND: Research assessing the effects of marijuana use on preterm birth has found mixed results, in part, due to lack of attention to the role of maternal tobacco smoking during pregnancy. OBJECTIVES: The study objective was to investigate whether maternal marijuana use was independently associated with gestational age, preterm birth, and two preterm birth subtypes (spontaneous vs clinician-initiated). METHODS: Participants included 8261 mother-newborn pairs from the Boston Birth Cohort. Information on gestational age was collected from electronic medical records. Marijuana use and tobacco smoking during pregnancy were assessed through a standard questionnaire after birth. Linear and log-linear regression models were used to assess associations between marijuana use with and without tobacco smoking during pregnancy and the outcomes of interest. RESULTS: Of the 8261 mothers, 27.5% had preterm births. About 3.5% of mothers with term deliveries and 5.2% of mothers with preterm births used marijuana during pregnancy. Marijuana use and cigarette smoking were independently associated with a decrease in gestational age by 0.50 weeks (95% confidence interval [CI] -0.87, -0.13) and 0.52 weeks (95% CI -0.76, -0.28), respectively. Marijuana use during early or late pregnancy was associated with a similar decrease in gestational age by 0.50 weeks. When we examined the effects on the preterm birth subtypes, simultaneous marijuana use and tobacco smoking were associated with higher risk of spontaneous preterm birth (RR 1.64, 95% CI 1.23, 2.18). The elevated risk was not observed with clinician-initiated preterm birth. CONCLUSIONS: In this high-risk US population, maternal marijuana use and cigarette smoking during pregnancy were independently associated with shorter gestational age. When we examined the effects on preterm birth subtypes, the elevated risk was only observed with spontaneous preterm birth.

Community-level social capital, parental psychological distress, and child physical abuse: a multilevel mediation analysis.

PURPOSE: The purpose of this study was to investigate the association between community-level social capital and physical abuse towards children, and the mediating effect of parental psychological distress by multilevel mediation analyses. METHODS: We analyzed data from a population-based study of first-grade elementary school children (6-7 years old) in Adachi City, Tokyo, Japan. The caregivers of first-grade students from all elementary schools in Adachi City (N = 5355) were asked to respond to a questionnaire assessing parents' self-reported physical abuse (beating and hitting) and neighborhood social capital. Among them, 4291 parents returned valid responses (response rate 80.1%). We performed multilevel analyses to determine the relationships between community-level parental social capital and physical abuse, and further multilevel mediation analyses were performed to determine whether parental psychological distress mediated the association. RESULTS: Low community-level social capital was positively associated with physical abuse (both beating and hitting) after adjustment for other individual covariates (beating: middle, OR = 1.54, 95% CI 1.11-2.13; low, OR = 1.33, 95% CI 0.94-1.88; and hitting: middle, OR = 1.35, 95% CI 1.02-1.80; low, OR = 1.16, 95% CI 0.86-1.57). Multilevel mediation analyses revealed that community-level parental psychological distress did not mediate the association (indirect effect ß = 0.10, 95% CI - 0.10 to 0.29, p = 0.34 for beating; ß = 0.03, 95% CI - 0.16 to 0.23, p = 0.74 for hitting). CONCLUSIONS: Fostering community-level social capital might be important for developing a strategy to prevent child maltreatment, which may have a direct impact on abusive behavior towards children.

Acromesomelic dysplasia, type maroteaux caused by novel loss-of-function mutations of the NPR2 gene: Three case reports.

The C-type natriuretic peptide (CNP)-natriuretic peptide receptor 2 (NPR2) signaling pathway plays an important role in chondrocyte development. Homozygous loss-of-function mutations of the NPR2 gene cause acromesomelic dysplasia, type Maroteaux (AMDM). The aim of this study was to identify and characterize NPR2 loss-of-function mutations in patients with AMDM. The NPR2 gene was sequenced in three Korean patients with AMDM and functional analysis of the mutated proteins was performed in vitro. Five novel NPR2 mutations were found in the three patients: two compound heterozygous mutations [c.1231T>C (Tyr411His) and c.2761C>T (Arg921X) in Patient 1 and c.1663A>T (Lys555X) and c.1711-1G>C (M571VfsX12) in Patient 3] and a homozygous mutation [c.2762G>A (Arg921Gln) in Patient 2]. Serum NT-proCNP concentration was significantly increased in each patient compared to control subjects. Cells transfected with the expression vector of each mutant except those found in Patient 3 showed a negligible or a markedly low cGMP response after treatment with CNP. HA-tagged wild-type (wt) and HA-mutant NPR2 were expressed at comparable levels: there were two bands of ∼130 and ∼120 kDa in wt and Arg921Gln, a single ∼120 kDa band in Tyr411His, and a single ∼110 kDa in the nonsense mutant. With respect to subcellular localization, Arg921Gln as well as wt-NPR2 reached the cell surface, whereas Tyr411His and Arg921X mutants did not. The Tyr411His and Arg921X NPR2 proteins were co-localized with an endoplasmic reticulum (ER) marker and failed to traffic from the ER to the Golgi apparatus. These results are consistent with deglycosylation experiments. Tyr411His and Arg921X NPR2 are complete loss-of-function mutations, whereas Arg921Gln behaves as a receptor for CNP with limited function.