Impacts of probiotics on the efficacies of immune checkpoint inhibitors with or without chemotherapy for patients with advanced non-small-cell lung cancer.

The relationships between the therapeutic effects of immune checkpoint inhibitors (ICIs) and the intestinal flora have attracted increasing attention. However, the effects of oral probiotics on the efficacies of ICIs used to treat non-small-cell lung cancer (NSCLC) remain unclear. We investigated the effects of probiotics on the efficacies of ICIs in patients treated with and without chemotherapy. We investigated patients with advanced NSCLC on ICI monotherapy or combination ICI and chemotherapy using the Okayama Lung Cancer Study Group Immunotherapy Database (OLCSG-ID) and the Okayama Lung Cancer Study Group Immunochemotherapy Database (OLCSG-ICD). In total, 927 patients (482 on ICI monotherapy, 445 on an ICI + chemotherapy) were enrolled. Most were male, of good performance status, smokers, and without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations. Probiotics were administered to 19% of patients on ICI monotherapies and 17% of those on ICIs + chemotherapy. Of the former patients, progression-free survival (PFS) and overall survival (OS) were significantly better in the probiotics group (PFS 7.9 vs. 2.9 months, hazard ratio [HR] 0.54, p < .001; OS not attained vs. 13.1 months, HR 0.45, p < .001). Among patients receiving ICI and chemotherapy, there were no significant differences in PFS between those on probiotics and not but OS was significantly better in the probiotics group (PFS 8.8 vs. 8.6 months, HR 0.89, p = .43; OS not attained vs. 22.6 months, HR 0.61, p = .03). Patients on probiotics experienced better outcomes following ICI treatment.

Association between trajectory of socioeconomic position and regional brain volumes related to dementia: Results from the NEIGE study.

BACKGROUND: Low socioeconomic position (SEP) has been linked to an increased risk of dementia. However, little is known about the association between SEP trajectory and regional brain volumes related to dementia. METHODS: A random sample of community-dwelling older adults (n = 428, age = 73.1 ± 5.5) living in Tokamachi City (Niigata Prefecture, Japan) without medical histories of dementia, Parkinson's disease, and depression who underwent automated assessment of brain volumes on magnetic resonance imaging and responded to a self-administered questionnaire survey in 2017. We measured SEP in childhood (household SEP at age 15), young adulthood (education), mid-adulthood (the longest occupation), and late adulthood (current wealth), and further performed group-based trajectory analysis to identify lifetime trajectory patterns on SEP. Multivariate regression models were employed to investigate the association between SEP trajectories and four regional brain volumes related to the development of Alzheimer's Disease (AD) (i.e., entorhinal cortex, hippocampus, amygdala, and the parahippocampus), the most common type of dementia. RESULTS: We found three distinct SEP trajectories [stable middle-class (68%), downward (23%), and upward (9%)]. Compared to those who experienced stable middle-class, older adults who experienced the upward SEP mobility had significantly larger hippocampus (ß: 213.2, 95%CI: 14.7, 411.8). On the other hand, older adults who experienced downward SEP mobility showed no significant differences in any of the four brain structural volumes. CONCLUSION: Our findings indicate that upward life-course SEP mobility is associated with larger volumes of hippocampus in old age. SEP trajectory may offer us a useful lens to enhance our understanding of the etiology of dementia.

CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer.

Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer.

Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.

Association of revision of Money Lending Business Act and suicide rate in Japan: An interrupted time series analysis.

OBJECTIVE: Debt problems are associated with suicide. In Japan, the Money Lending Business (MLB) Act was revised in December 2006 and fully enforced in June 2010 to reduce multiple debt problems. This study aimed to examine the association between the full enforcement of the revised act and suicide rates. METHODS: An interrupted time series analysis was used to the national registry data of death records between January 2000 and December 2016. Stratified analysis was conducted to assess the differences between gender and age groups. RESULTS: The effects of the full enforcement on the suicide rate were the greatest among men aged 40-64 years; after the enforcement, there was a significant decrease of -0.3085 per 100,000 persons in the level of the suicide rate (95% confidence interval [CI] -0.529 to -0.0881) and -0.0165 per 100,000 persons (95% CI -0.0215 to -0.0115) in the trend. Among women aged 40-64 and ≥65 years, an increase in the level of the suicide rate was observed after the enforcement. CONCLUSIONS: The full enforcement of the revised MLB Act was associated with decreased suicide rates, particularly among middle-aged men. Policy interventions for addressing debt problems may have the potential to prevent suicide.

Association between the social network of medical students and their academic performance on the anatomy written examination.

Although medical students learn human anatomy within a social network of friends/classmates, limited research has examined how social network structure is related to student's performance in human anatomy examinations. This study aimed to examine the association between centrality (i.e., the degree to which a student is connected to other students in class) before the start of the anatomy laboratory and changes in centrality owing to the start of the laboratory and failing the written examination taken on the last day of the course. Data included all 211 medical students at Tokyo Medical and Dental University who took anatomy classes in 2018 and 2019. The in-class social network before the laboratory was defined as "connected" if the student had more than one connection to the same individual in terms of the type of club activity, high school, and affiliation with an extracurricular program. The laboratory group adds the connection to the prelaboratory network, resulting in a postlaboratory network. Logistic regression models were used to estimate the association of degree and eigenvector centrality and changes in centrality after the laboratory with failing the written examination. Of the 211 students, 38 failed the examination. A one standard deviation increase in eigenvector centrality before the laboratory was significantly associated with a 44% decrease in odds of failing the examination (OR: 0.56, 95% CI: 0.34, 0.92). Changes in centrality measures were not associated with the performance of students in the examination. Higher in-class network centrality was associated with lower odds of failing the written examination.

Oxytocin Reactivity during a Wilderness Program without Parents in Adolescents.

While wilderness programs are recognized as a feasible intervention to promote psychological independence in adolescence, little is known about physiological changes. The present study focused on oxytocin, a key hormone for social cognition and behavior, and investigated changes in OT concentrations during a wilderness program among adolescents. Twenty-one 4th-7th graders were separated from parents and immersed with adventures and challenges in the woodlands of Motegi, Tochigi Prefecture, Japan for 31 days, and dataset of 20 boys aged 9-13 years-old were used for analysis. OT concentrations in early morning saliva samples on days 2, 5, 8, 13, 18, 20, 21, 22 and 30 were determined using ELIZA. We performed multi-level regression analyses to compare the OT concentrations before and after solo and team-based survival challenges, and across the nine observational points, adjusting for potential covariates. We found that adolescents increased OT level in a situation where they needed others' cooperation and support for survival (coefficient: 2.86, SE: 1.34, p = 0.033). Further, we found that adolescents gradually decreased their basal OT level during a long separation from parents (coefficient: -0.083, SE: 0.034, p = 0.016). A combination of these findings suggest the OT level may be a marker for psychological independence.

Depressive symptoms homophily among community-dwelling older adults in japan: A social networks analysis.

Late-life depression is one of the most common mental illnesses that cause serious consequences, but the majority do not reach out for mental health services and relapses are common. The present study investigated profiled similarity of older adults' social networks in terms of depressive symptoms. In 2017, we distributed questionnaires inquiring about confidants in the community, depressive symptoms based on the 15-item Geriatric Depression Scale (GDS-15), and demographic and functional characteristics to all the community-dwelling older adults under the national insurance system in Wakuya City (Miyagi prefecture, Japan). Applying the Exponential Random Graph Model, we estimated the likelihood of a confidant relational tie by the similarity of overall and specific depressive symptoms within 217,470 potential ties among 660 respondents eligible for analysis. The overall depressive symptom homophily was marginally significant (p < 0.10), indicating that the likelihood of a confidant relational tie between two community-dwelling older adults was decreased by 5%, with one point increase in their difference in the total number of depressive symptoms (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.90-1). Focusing on specific domains of depressive symptoms, we found significant apathy homophily (p < 0.05) but no significant suicidal ideation of homophily. The results indicated that there is a 19% decrease in the likelihood of a confidant relational tie between two community-dwelling older adults by one point increase in their difference in the total number of apathy symptoms (OR, 0.81; 95%CI, 0.67-0.98) but no change by increasing the difference in their total number of suicidal ideation symptoms (OR, 1; 95%CI, 0.87-1.14). These findings suggest depressive symptom homophily, particularly with respect to apathy domains, in confidant social networks of community-dwelling older adults, and the importance of network intervention in preventing late-life depression.

Heart rate variability in 2014 predicted delayed onset of internalizing problems in 2015 among children affected by the 2011 Great East Japan Earthquake.

Experience of natural disaster was related to an increased risk of long-term child internalizing problems. Initial traumatic experiences are hypothesized to work as disaster-related stresses and sensitize neural circuitry, leading to heightened reactivity to subsequent stressful experiences, which in turn results in delayed onset of internalizing problems. However, empirical evidence is lacking. Thus, we aimed to examine the association between heart rate variability (HRV) and internalizing problems among children exposed to the disaster. The Great East Japan Earthquake Follow-up for Children (GEJE-FC) study followed children aged 4-6 years old and their siblings and parents from three affected prefectures (Miyagi, Fukushima, and Iwate) and one unaffected prefecture (Mie) in Japan over four periods: from August 2012 to June 2013 (= T1), August 2013 to April 2014 (= T2), July 2014 to December 2014 (= T3), and August 2015 to December 2015 (= T4) (n = 155). HRV was assessed at T2 and T3 as a biomarker of autonomic nervous system activity. Child internalizing problems were assessed by caregivers at T3 and T4, using the Child Behavior Checklist. HRV measurements at T2 were not associated with child internalizing problems at T3. However, HRV in low frequency domains at T3 showed an inverse association with child internalizing problems at T4 (B = -1.72, 95% CI = -3.12 to -0.31). The findings indicated that later exacerbation of internalizing problems could be predicted by dysfunction of autonomic nervous system measured by HRV.

The frequency of job participation and well-being of older people in Japan: Results from JAGES study.

We investigated the association between the frequency of job participation and well-being among older people in Japan, using data from a prospective nation-wide survey, the Japan Gerontological Evaluation Study (JAGES). The frequency of work was classified into "not working," "sometimes or less" (≤3 times/week), and "often or more" (≥4 times/week), and we conducted binary and continuous outcome analyses using logistic or Poisson regression and linear regression. After adjusting for covariates, we have found that participants who worked "often or more" and "sometimes or less" were less likely to display poor subjective health (often or more = odds ratio (OR): 0.55, 95% confidence interval (CI): 0.48 to 0.62; sometimes or less = OR: 0.57, 95% CI: 0.49 to 0.67) and depression (often or more = OR: 0.62, 95% CI: 0.53 to 0.73; sometimes or less = OR: 0.58, 95% CI: 0.47 to 0.71), and more likely to be happy (often or more = prevalence ratio (PR): 1.05, 95% CI: 1.03 to 1.07; sometimes or less = PR: 1.03, 95% CI: 1.00 to 1.05). Linear regression analysis of ordinal discrete outcomes showed similar trends, and furthermore suggested that more work conferred more benefits. The participants who worked "often or more" were less likely to have poor subjective health and were happier than those who worked "sometimes or less" (linear coefficients of -0.04 and 0.15 respectively). Further research is required to investigate possible explanations for the association between frequent job participation and health and well-being at older ages.

Investigation of Age-Associated Cognitive Functional Homophily in Community-Dwelling Older Adults' Confidant Social Networks Using Exponential Random Graph Model.

One of the prominent interventions to tackle loneliness and social isolation in older adults is social facilitation. The present study investigated whether similarities in cognitive functions that are sensitive to age play a role in confidant social networks among older adults. We analyzed the data of 252 community-dwelling older adults in Wakuya City, Miyagi Prefecture, Japan, who responded to a self-administered questionnaire and cognitive health checkups provided by the city in 2017. We performed Exponential Random Graph Model and investigated educational attainment, orientation, word registration, clock drawing, delayed recall, verbal fluency and logical memory homophily while adjusting for density, reciprocity, age, sex living arrangement, presence of disability in instrumental activities of daily living, educational attainment and cognitive impairment status. The probability of a confidant tie with an older adult was significantly reduced by 6% (odds ratio (OR): 0.94, 95% confidence interval (CI): 0.90-0.99) for one score difference in logical memory, and marginally increased by 5% (OR: 1.05; 95% CI: 1.00-1.11) for one score difference in delayed recall. There was no significant association between educational attainment and other age-associated cognitive functional scores. Our findings suggest that similar logical memory functions play a role in strong social network building among community-dwelling older adults in Japan.

Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration.

Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.

Association Between Procrastination in Childhood and the Number of Remaining Teeth in Japanese Older Adults.

BACKGROUND: Procrastination is associated with stress and unhealthy behaviors. The oral condition reflects the long-term history of an individual's stress exposure and oral health behaviors; however, empirical studies on the association of procrastination in childhood with remaining teeth in older age are limited. We investigated the association of procrastination in childhood with the number of remaining teeth among community-dwelling older Japanese adults. METHODS: In total, 1,616 community-dwelling senior residents of Wakuya City (Miyagi Prefecture, Japan) who were enrolled in the National Health Plan & the Medical Care System for the Elderly completed a self-administered questionnaire on the number of teeth. Procrastination was measured using a single binary question about timing of holiday homework completion in childhood. The number of remaining teeth was assessed via a questionnaire with response options of ≥20, 10-19, 1-9, and 0 teeth. Ordered logistic regression models with potential confounders (sex, age, maternal education, childhood socioeconomic status [SES], childhood maltreatment, conscientiousness trait) and mediators (adulthood SES, smoking history, alcohol use history) were estimated. RESULTS: Forty-six percent of participants reported a higher tendency to procrastinate in childhood. The proportions of participants with ≥20, 10-19, 1-9, and 0 teeth were 39.6%, 22.7%, 24.0%, and 13.7%, respectively. After adjusting for all covariates, a higher tendency to procrastinate in childhood was significantly associated with having fewer remaining teeth (odds ratio 1.28; 95% confidence interval, 1.05-1.57). CONCLUSION: A higher tendency to procrastinate in childhood was associated with having fewer remaining teeth in later life.

Association between childhood parental involvement and late-life cognitive function: A population-based cross-sectional study among cognitively intact community-dwelling older adults in Japan.

AIM: Although poor childhood rearing environment is known to negatively impact late-life cognitive function, there is a scarcity of evidence on the contribution of positive parenting behaviors. The present study investigates the association between parental involvement in childhood and late-life cognitive function. METHODS: A total of 266 older adults aged between 65 and 88 years living in Wakuya City, Miyagi Prefecture, Japan, without indication of mild cognitive impairment or dementia, participated in a survey. Parental involvement in childhood was assessed by a questionnaire, and late-life cognitive function was measured by the Japanese version of the Quick Mild Cognitive Impairment (QMCI) screening test (range: 0-100). Multiple regression analysis was performed to investigate the association, adjusting for potential confounders and mediators. RESULTS: After adjusting for age, sex, other child-rearing environment, and academic performance in grade 6, older adults with a high level of positive parental involvement in childhood scored 6.00 (95% CI: 2.39, 9.61) points higher for the QMCI total score than those without. Parental involvement in childhood showed significant dose-response positive associations with the QMCI total score (P < 0.001), clock-drawing test score (P < 0.05), and verbal fluency score (P < 0.001). Among the six types of positive parental involvement, book reading showed a significant independent positive association with QMCI total score (P < 0.01) and logical memory score (P < 0.01). CONCLUSIONS: Greater parental involvement in childhood, particularly book reading, was associated with better late-life cognitive function. Geriatr Gerontol Int 2021; 21: 794-801.

Dacomitinib as a retreatment for advanced non-small cell lung cancer patient with an uncommon EGFR mutation.

In non-small cell lung cancer (NSCLC), uncommon epidermal growth factor receptor (EGFR) mutations are mutations other than Ex19 deletion and Ex21 L858R, which are common mutations highly sensitive to EGFR-tyrosine kinase inhibitors. Afatinib, a second-generation EGFR-tyrosine kinase inhibitor, has been shown to be effective in patients with uncommon mutations. Dacomitinib, another second-generation EGFR-tyrosine kinase inhibitor, has not previously been shown to be effective in patients with uncommon mutations. Here, we report the efficacy of dacomitinib for uncommon EGFR mutations in a 71-year-old woman diagnosed with metastatic lung adenocarcinoma with uncommon EGFR mutation (Ex18 G719A). Afatinib was administered as the first-line treatment, and a remarkable antitumor effect was observed. However, the tumor grew after 14 months. Pemetrexed plus carboplatin followed by pemetrexed, docetaxel, atezolizumab and S-1 were performed in sequence. Although approximately four years had passed since the start of treatment, her physical condition was good. The patient started dacomitinib as the sixth-line treatment. Lesions were markedly reduced and treatment with dacomitinib was continued for 7.8 months. Dacomitinib is a possible treatment option for NSCLC with uncommon mutations.

Association between positive grandparental involvement during childhood and generativity in late life among community-dwelling, cognitively intact, older adults in Japan.

AIM: Generativity is increasingly being recognized as a key element of healthy aging. The present study investigated whether children who received more positive grandparental involvement would show higher generativity in late life. METHODS: In 2017, 173 older adults living in Wakuya City (Miyagi Prefecture, Japan), and who showed normal cognition based on the Quick Mild Cognitive Impairment Screen, participated in a self-report life course survey (age range: 65-88 years). The association between positive grandparental involvement in childhood and generativity (measured by the Loyola Generativity Scale) was investigated using multiple linear regression adjusted for potential confounders. RESULTS: Compared with older adults without or had low positive grandparental involvement in childhood, a higher level of generativity was observed among those with medium (ß = 1.93, 95% confidence interval [CI]: 0.24-3.62) and high positive grandparental involvement (ß = 2.09, 95% CI: 0.32-3.87), adjusting for age, gender, memory performance, depressive symptoms, childhood socio-economic status and parental involvement. The significant dose-response association remained even after further adjusting for education and current grandparental experiences. CONCLUSION: Greater positive grandparental involvement in childhood was associated with a higher level of generativity among community-dwelling, cognitively intact, Japanese older adults. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

Association between Childhood Suicidal Ideation and Geriatric Depression in Japan: A Population-Based Cross-Sectional Study.

Adverse childhood experiences (ACEs) are assumed to increase the risk of depression in late life via development of poor mental health conditions; however, the association between mental distress in childhood and geriatric depression has not been directly examined. This study examined the association between childhood suicidal ideation and geriatric depression, using population-based, cross-sectional survey data from 1140 community-dwelling, functionally independent older adults in Wakuya City, Japan. We assessed childhood suicidal ideation by asking the participants whether they had seriously considered attempting suicide before the age of 18, together with geriatric depression, using the Japanese version of the 15-item Geriatric Depression Scale. Poisson regression was applied to adjust for potential confounders and mediators. In total, 6.1% of the participants reported childhood suicidal ideation. After adjustment for sex, age, personality attributes and ACEs, childhood suicidal ideation was positively associated with geriatric depression prevalence ratio [PR]: 1.40, 95% Confidence Interval (95%CI): 1.04-1.88). The increased PR of geriatric depression remained significant, even after further adjustment for adulthood socio-economic status, recent life stressors and current health status (PR: 1.38, 95%CI: 1.02-1.88). Further prospective studies are warranted, but efforts to deliver mental health services to children with suicidal ideation potentially diminish the highly prevalent geriatric depression.

Patients help other patients: Qualitative study on a longstanding community cooperative to tackle leprosy in India.

BACKGROUND: Although leprosy is portrayed as a disappearing disease, leprosy affected persons in India are still suffering massively. Even further, nearly 60% of the world's newly detected cases are appearing from India alone. The problem has exacerbated due to the drastic decrease of global funding after India's official declaration of 'elimination', which did not foster the actual pain of patients beyond prevalence. Leprosy patients have hardships in their lives due to disabilities, stigma and poverty; thus, they require sustained, continuous care even after release from treatment. Yet, current interventions mostly have a vertical, short-term approach, not showing much progress in lightening the burden of leprosy. In contrast, Little Flower Hospital Community (LFHC) in India has been remarkably providing holistic care for thousands of leprosy patients for 35 years. However, there has not been any research conducted to uncover the underlying factors of this longstanding leprosy control model. Therefore, this research explores the in-depth contextual attributes of this hospital community that has been able to successfully provide sustainable care for a long time even without excessive external funds. METHODS AND FINDINGS: This qualitative research used a grounded theory approach, involving 28 in-depth interviews of 11 patients, 13 workers, and 4 board members from the hospital. The interview data were inductively analyzed to examine the contextual factors of the hospital's sustainability. Open coding, axial coding and selective coding were conducted, and Glaser's Six C's model was used to create a theoretical model of the sustainability of LFHC. The fundamental cause of the sustainability was the leprosy patients' strong craving for life with dignity, despite the isolation from the society. The desire resulted in a bottom-up formation of a 'consumer-provider cooperative', where patients mutually support each other with basic treatment learned from experience. The profits earned from the patients' occupational efforts such as dairy farming, cover the costs needed to manage the hospital community, which contributes to economical sustainability. Social sustainability was established through the holistic care including psychosocial, educational, medical, and residential support. The wholesome care socially rehabilitated the patients to be included in the society with satisfaction, social justice and social cohesion. The main limitation of this study is that this study cannot be generalized due to the nature of Grounded Theory based study. CONCLUSIONS: This study investigated the determinants that made LFHC sustainable, and the findings suggested the importance of forming a cooperative community and implementing social rehabilitation for sustainable leprosy control. More exploration on transferring this model to other leprosy colonies will have great impact in maintaining sustainable care for leprosy patients. Furthermore, this research may highlight the importance of sustainable development in policies targeting neglected tropical diseases beyond leprosy as well.

Association between grandparent co-residence, socioeconomic status and dental caries among early school-aged children in Japan: A population-based prospective study.

Globally many children are living with grandparents, and it has been suggested that grandparent co-residence may be associated with dental caries in infants and toddlers possibly through passive parenting style, accompanied by children's cariogenic behaviors such as feeding sugary sweets. However, little is known about this association in schoolchildren, adjusted for socioeconomic status. Therefore, this study investigates the association between grandparent co-residence, socioeconomic status, and dental caries among schoolchildren. All caregivers of first-grade children (age 6-7 years) in Adachi City, Tokyo, were administered a questionnaire about children's grandparent co-residence status and oral health-related behaviors, and responses were linked with dental examination records conducted by school dentists (N = 3,578). Multilevel Poisson regression analysis was applied to examine the association between grandparent co-residence, socioeconomic status, and dental caries status for each individual tooth, adjusting for potential covariates. The percentage of dental caries experience was higher among children living with grandparents (48.9%) than among children living without grandparents (44.0%). The risk for caries, however, did not differ according to grandparent co-residence status when tooth type, child's age and sex, and parental socio-economic status and structure were adjusted (PR, 1.13; 95%CI, 0.90, 1.42). The association between grandparent co-residence and dental caries among early school-aged children in urban Japan was confounded by socioeconomic status.

Association between childhood socioeconomic status and subjective memory complaints among older adults: results from the Japan Gerontological Evaluation Study 2010.

BACKGROUND: Subjective memory complaints (SMC) have been suggested as an early marker of mild cognitive impairment and dementia. However, there is a paucity of evidence on the effects of early life conditions on the development of SMC in old age. This study is aimed at investigating the association between childhood socioeconomic status (SES) and SMC in community-dwelling older adults. METHODS: We used the data of the Japan Gerontological Evaluation Study, a population-based cohort study of people aged 65 years or older enrolled from 28 municipalities across Japan. Childhood SES and SMC in everyday life were assessed from the self-report questionnaire administered in 2010 (n = 16,184). Poisson regression was performed to determine their association, adjusted for potential confounders and life-course mediators and examined cohort effects. RESULTS: We identified SMC in 47.4% of the participants. After adjusting for sex, age, and number of siblings, low and middle childhood SES were associated with 29% (prevalence ratio [PR]: 1.29, 95% confidence interval [CI]: 1.22, 1.36) and 10% higher prevalence of SMC (PR: 1.10, 95%CI: 1.04, 1.17), respectively, compared with high childhood SES (p for trend <.001). The interaction terms between childhood SES and age groups were not statistically significant. CONCLUSION: Childhood SES is significantly associated with SMC among community-dwelling older adults. Efforts to minimize childhood poverty may diminish or delay the onset of SMC and dementia in later life.