[Association between working in small-scale cultivated land as a daily-life task and the physical and cognitive functions among elderly people in hilly and mountainous areas].

AIM: This study aimed to verify whether working in cultivated land as a daily-life task contributes to the maintenance and improvement of physical and cognitive functions. METHODS: The participants were 91 elderly people of ≥65 years of age who owned cultivated land in the mountainous Koyadaira district in Tokushima Prefecture. Sex, age, body mass index (BMI), walking speed as a physical function, and the mini-mental status examination (MMSE) score as a cognitive function were measured and analyzed in addition to the total working hours per week (WH) in cultivated land. RESULTS: The participants were 31 males and 60 females (mean age 78.5±6.6 years). The average values of the evaluated variables were as follows: WH, 18.0±13.2; BMI, 23.4±3.0 kg/m2; walking speed, 0.95±0.28 m/s; and MMSE score, 26.6±3.1 points. In addition, the Mann-Whitney U test and the Chi-square test showed no significant differences between sexes for each item. A logistic regression analysis showed that WH was significantly associated with MMSE (1, ≥28 points; 0, <28 points), and the odds ratio was 1.054 (p=0.010) in the model adjusted for age and BMI, while it was not significantly associated with walking speed (1, ≥1 m/s; 0, <1 m/s). CONCLUSIONS: Working on small-scale cultivated land was significantly associated with the cognitive function but not the physical function. Routine work on small-scale cultivated land as a daily-life task would contribute to the suppression of cognitive decline in older people living in hilly and mountainous areas.

Social frailty as a predictor of all-cause mortality and functional disability: a systematic review and meta-analysis.

The association between social frailty and adverse health outcomes, especially mortality and functional disability, which are essential health outcomes, has not been systematically summarized or meta-analyzed. In this study, we conducted a systematic review and meta-analysis of the impact of social frailty on all-cause mortality and functional disability, while addressing the components of social frailty. In this study, social frailty was operationally defined in alignment with the previous literature, as follows: "a state of increased vulnerability to the interactive back-and-forth of the community, including general resources, social resources, social behaviors, and needs." Hazard ratios or odds ratios described in each selected literature were used as the meta-analytic results. Considering the impact of social frailty on all-cause mortality, the hazard ratio was 1.96 (95% CI 1.20-3.19), indicating a significant association between the two but high heterogeneity. The hazard and odds ratios for the impact of social frailty on functional disability were 1.43 (95% CI 1.20-1.69) and 2.06 (95% CI 1.55-2.74), respectively. A significant association was found between social frailty and functional disability; both hazard and odds ratios were found, and low heterogeneity between these articles was observed. These results highlight the importance of assessing social frailty using more standardized methods and examining its effects on various health outcomes.

Clinical characteristics of anti-GBM disease with thrombotic microangiopathy: a case report and literature review.

The coexistence of anti-glomerular basement membrane (anti-GBM) disease with thrombotic microangiopathy (TMA) is rarely encountered, and the clinical characteristics of this phenomenon are not well known.A 76-year-old Japanese woman with a history of idiopathic pulmonary disease was diagnosed with anti-GBM disease due to rapidly progressive glomerulonephritis and a positive anti-GBM antibody test result. We treated the patient with hemodialysis, glucocorticoids, and plasmapheresis. During treatment, the patient suddenly became comatose. TMA was then diagnosed because of thrombocytopenia and microangiopathic hemolytic anemia. The activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) was retained at 48%. Although we continued the treatment, the patient died of respiratory failure. An autopsy revealed the cause of respiratory failure to be an acute exacerbation of interstitial pneumonia. The clinical findings of the renal specimen indicated anti-GBM disease; however, there were no lesions suggestive of TMA. A genetic test did not reveal an apparent genetic mutation of the atypical hemolytic uremic syndrome.We conducted a literature review of past case reports of anti-GBM disease with TMA. The following clinical characteristics were obtained. First, 75% of the cases were reported in Asia. Second, TMA tended to appear during the treatment course for anti-GBM disease and usually resolved within 12 weeks. Third, ADAMTS-13 activity was retained above 10% in 90% of the cases. Fourth, central nervous system manifestations occurred in more than half of the patients. Fifth, the renal outcome was very poor. Further studies are required to understand the pathophysiology of this phenomenon.

[Severe neuropsychiatric disorder developing during busulfan-containing regimen for stem cell transplantation].

Here we describe two patients that required interruption of a busulfan (BU) containing conditioning regimen due to severe mental disorder before stem cell transplantation. The first patient was a 66-year-old man scheduled for unrelated peripheral blood stem cell transplantation with fludarabine/BU conditioning for myelodysplastic syndrome. He received 9.6 mg/kg BU and developed hallucinations that worsened the next day. BU was stopped on the final day, but the patient became comatose (grade 4). He recovered the next day. The second patient was a 69-year-old man scheduled for autologous peripheral blood stem cell transplantation with thiotepa (TT)/BU conditioning for cerebral nervous system relapse of mantle cell lymphoma. He received 12.8 mg/kg BU and developed hallucinations. His mental symptoms worsened on the next day, and thus administration was stopped on the second day of TT. His symptoms improved the next day. Both patients were over 65 years old, and their psychiatric symptoms worsened 1-2 days after the final dose of BU. Our findings suggest that BU may cause psychiatric disorders in elderly patients. When performing BU conditioning, it may be necessary to avoid azole antifungal medication and acetaminophen and to reduce the dose or perform therapeutic dose monitoring for elderly patients.

End-of-Life Care of Acute Myeloid Leukemia Compared with Aggressive lymphoma in Patients Who Are Eligible for Intensive Chemotherapy: An Observational Study in a Japanese Community Hospital.

Background: Patients with hematological malignancies (HMs) are reported to receive more aggressive care at the end of life (EOL) than patients with solid tumors. However, the reasons behind this occurrence are not fully understood. Objectives: To examine whether the care at EOL for HMs is mainly because of the disease characteristics or hematologists' attitudes and systems of care, we compared the EOL care of patients with acute myeloid leukemia (AML) and diffuse large B cell lymphoma (DLBCL). Design: We retrospectively analyzed the EOL care of patients with AML and DLBCL younger than 80 years who were receiving combination chemotherapy at a city hospital in Japan. Results: Fifty-nine patients with AML and 65 with DLBCL were included. Those with AML received chemotherapy more often within their last 30 days (48% vs. 19%, p < 0.001) and 14 days (37% vs. 1.5%, p < 0.001) of life, and consulted the palliative team less frequently (5.3% vs. 29%, p < 0.001). In the last 3 years, the mortality rate in hematological wards decreased from 74% to 29% in the DLBCL group, but only from 95% to 90% in the AML group. In multivariate analysis, AML (odds ratio [OR] 0.065) and death before 2018 (OR, 0.077) were significant factors associated with reduced referrals to specialized palliative teams. Conclusion: Patients with AML tend to have lesser access to specialized palliative care and fewer options for their place of death than those with DLBCL. Detailed EOL care plans are needed for these patients, considering the characteristics of the disease.

A Retrospective Analysis of R-MPV Plus Response-adapted Whole-brain Radiotherapy for Elderly Patients with Primary Central Nervous System Lymphoma.

Objective Few reports have described the real-world outcomes of rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) plus response-adapted whole-brain radiotherapy (WBRT) for elderly patients with primary central nervous system lymphoma (PCNSL). We evaluated the outcome of this regimen. Methods We evaluated >60-year-old patients with newly diagnosed PCNSL who received R-MPV plus WBRT from January 2010 to December 2019 at Toyohashi Municipal Hospital. The patients' characteristics, regimen enforcement, response rate, survival, and toxicity were analyzed. Patients Ten patients were consecutively enrolled. Their median age was 69 years old, and 60% had a performance status of 3 or 4 before induction therapy. Results Seven patients achieved a complete response after induction, and all 10 patients achieved a complete response after consolidation. Seven received reduced-dose WBRT at 23.4 Gy, and 2 received WBRT at 45 Gy. The median follow-up was 44.4 months; the 3-year progression-free survival and overall survival rates were 60% and 80%, respectively; and the cumulative incidence of relapse was 40%. The incidence of symptomatic delayed neurotoxicity was 70%. Of the 7 patients who received reduced-dose WBRT, 4 (57%) developed delayed neurotoxicity, including 1 severely affected patient. Only one patient survived without relapse and delayed neurotoxicity. The ratio of patients who developed relapse or delayed neurotoxicity that impaired daily life was 33% and 100% in the MTX high- and low-intensity groups, respectively. Conclusion This regimen in elderly patients is unsatisfactory because of delayed neurotoxicity. We should consider maintaining an adequate MTX intensity, postponing or minimizing WBRT, and choosing high-dose consolidation therapy for select patients.

Did "Kayoinoba" Prevent the Decline of Mental and Physical Functions and Frailty for the Home-Based Elderly during the COVID-19 Pandemic?

The purpose of this study is to grasp the management situation of "Kayoinoba" under the conditions of self-quarantine due to the COVID-19 pandemic. It is also to clarify the efficacy of "Kayoinoba" using the Kihon Checklist (KCL) for the assessment of mental and physical functions in the elderly. The respondents were 136 elderly people aged 65 years and over who lived in A City, a standard rural area in Japan. The age, gender, living style, affluence for living, and the frequency of participation in "Kayoinoba" were examined by using the KCL as a self-completed questionnaire. Finally, 101 respondents were included in the final analysis. There was no difference in the participation status before and after the spread of COVID-19. The frailty ratio tended to decrease from 23.8% to 19.8% between the two periods, but there was no difference in the frailty ratio. It is suggested that the participants in "Kayoinoba" may have suppressed the deterioration of mental and physical conditions, excluding physical activity. This would prevent the frailty of the elderly, even during self-quarantine due to the spread of COVID-19.

Isolation of recombinant human antithrombin isoforms by Cellufine Sulfate affinity chromatography.

Human antithrombin (hAT) is a major serine protease inhibitor that regulates blood coagulation in human plasma, and it has been applied for the treatment of antithrombin (AT) deficiency and disseminated intravascular coagulation (DIC). In the past, hAT for therapeutic use has been obtained from human plasma; however, hAT can now be sourced from transgenic animals and Chinese hamster ovary (CHO) cells by recombinant technology. The dominant form of hAT in plasma is the α form, which is glycosylated with four oligosaccharides and sialylated at its terminals. However, it would be preferable to remove the poorly sialylated α form of hAT, the minor ß form with unoccupied glycosylation sites, and the inactive forms. Cellufine Sulfate, a heparin-mimic affinity resin made of cellulose and modified with sulfate groups, has an affinity for heparin-binding proteins and can be used in cation exchange chromatography. Based on these properties, the α and ß forms of hAT could be separated and purified depending on the rate of sialylation. Consequently, Cellufine Sulfate was used to enrich the highly sialylated α form with a considerably higher step yield than that obtained using conventional heparin-immobilized resins. Furthermore, subsequent hydrophobic interaction chromatography could eliminate the inactive forms. These results suggested that Cellufine Sulfate was more effective than heparin-immobilized resins in purifying the highly sialylated α form of hAT for therapeutic applications.

Influence of salty food preference on daily salt intake in primary care.

PURPOSE: A salt preference questionnaire may be a convenient and cost-effective method for predicting salt intake; however, the influence of salt preference on daily salt intake is unclear. This study aimed at revealing the effectiveness of the salt preference question in determining the daily salt intake in primary care outpatients. PATIENTS AND METHODS: This cross-sectional study included 1,075 outpatients (men, n=436, 40.6%) at six primary care institutions in Japan. Primary outcomes included a salty food preference assessed by using one question and a daily salt intake, assessed using early morning second urine samples. Multivariate analyses determined the relationships between the salt intake and the two salt preference levels. RESULTS: The mean age was 67.6±14.6 years, and 594 (55.3%) preferred salty foods. The daily salt intake was 12.3±4.0 g per day and 11.4±3.7 g per day in the salt preference and nonsalt preference groups, respectively (P<0.001). A salt intake <10 g per day was consumed by 169 (28.5%) and 181 (37.6%) patients (P=0.001), respectively, and <6 g salt per day was consumed by 28 (4.7%) and 26 (5.4%) patients (P=0.606), respectively. The patients who preferred salty foods consumed a significantly larger amount of salt per day than those who did not prefer salty foods (ß coefficient, 0.621; 95% confidence interval [CI], 0.146-1.095). There was no difference in the number of patients who consumed <10 g salt per day (adjusted odds ratio [ad-OR], 1.29; 95% CI, 0.99-1.69) or <6 g salt per day (ad-OR, 1.39; 0.90-1.69) between the groups. CONCLUSION: Preference for salty foods was positively associated with daily salt intake. However, daily salt intake was not always appropriate, even in the patients who did not prefer salty foods. Behavioral interventions for salt restriction after an assessment of daily salt intake are necessary for primary care patients, regardless of their preference for salty foods.

High-density lipoprotein size distribution can differ between subjects with alcoholic and non-alcoholic fatty liver disease.

BACKGROUND: While alcohol consumption is associated with levels of high-density lipoprotein (HDL)-cholesterol (HDL-C), a cardiovascular risk marker, HDL size distribution has yet to be characterized in subjects with alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The present study compared HDL subfractional characteristics between subjects with AFLD (36 men, age 61 +/- 14) and NAFLD (35 men, age 65 +/- 13), recruited during general health check-ups. Serum HDL subfractions were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The subjects with AFLD had a significantly greater proportion of small-sized HDL part (6.6 +/- 5.7%) than those with NAFLD (3.8 +/- 4.9%, p = 0.029). CONCLUSIONS: More percentages of small-sized HDL part were observed in the subjects with AFLD than in those with NAFLD in Japanese general population. Whether the difference of HDL size is associated with cardiovascular manifestations should be studied further.

Equol producers can have low leptin levels among prediabetic and diabetic females.

OBJECTIVES: Soy isoflavones have received great attention for their beneficial effects on health and disease, i.e., in patients with diabetes. Equol is a biologically active isoflavone-related metabolite with interindividual differences in its production. The current study investigated the relationship between an equol-producing state and the levels of adipocytokine markers in a prediabetic and diabetic population. SUBJECTS AND METHODS: A total of 79 subjects (34 males/45 females) in a prediabetic or diabetic state recruited from the general population were examined regarding their ability to produce equol using urine samples. Clinical data, such as age, smoking as well as anthropometric and biochemical variables, including body mass index (BMI), lipids, insulin, glucose, hemoglobin A1c, leptin and adiponectin, were recorded. RESULTS: Equol producers exhibited lower leptin and leptin/BMI than non-producers among females. Simple correlation tests and stepwise multiple regression analyses revealed a significant inverse correlation between the leptin/BMI and equol-production. This relationship was not found in males. CONCLUSIONS: Female equol producers can have favorable metabolic traits in relation to leptin metabolism in this population. Further studies are needed to confirm these results.

Structures and reaction mechanisms of the two related enzymes, PurN and PurU.

The crystal structures of glycinamide ribonucleotide transformylases (PurNs) from Aquifex aeolicus (Aa), Geobacillus kaustophilus (Gk) and Symbiobacterium toebii (St), and of formyltetrahydrofolate hydrolase (PurU) from Thermus thermophilus (Tt) were determined. The monomer structures of the determined PurN and PurU were very similar to the known structure of PurN, but oligomeric states were different; AaPurN and StPurN formed dimers, GkPurN formed monomer and PurU formed tetramer in the crystals. PurU had a regulatory ACT domain in its N-terminal side. So far several structures of PurUs have been determined, yet, the mechanisms of the catalysis and the regulation of PurU have not been elucidated. We, therefore, modelled ligand-bound structures of PurN and PurU, and performed molecular dynamics simulations to elucidate the reaction mechanisms. The evolutionary relationship of the two enzymes is discussed based on the comparisons of the structures and the catalytic mechanisms.

Sleep status and low-density lipoprotein particle size in a general Japanese female population: the MIMA study.

OBJECTIVE: This study investigated the relationship between sleep adequacy and small dense low-density lipoprotein (sdLDL) in a Japanese population. SUBJECTS AND METHODS: Clinical data, including atherosclerotic risk factors, in addition to the mean LDL particle size (LDL-PS) measured by gel electrophoresis, were evaluated in 136 community-dwelling female subjects (40-80 years old). The sleep status was self-reported and the subjects were divided into those who had inadequate sleep (≤ 6 or ≥ 9 h of sleep) and had adequate sleep (7-8 h). RESULTS: The mean LDL-PS was significantly smaller in subjects with inadequate sleep [n = 68, 26.4 ± 0.4 (SD) nm] than in those with adequate sleep (n = 68, 26.6 ± 0.4 nm, p < 0.05). This difference remained significant and independent after adjusting for confounders (ß = 0.15-0.19, p < 0.05). CONCLUSION: Sleep adequacy was associated with the presence of sdLDL, while the influence of the sleep status on LDL-PS was minor in this population. Further research on the associations among sleep, sdLDL and cardiovascular disease prevention is warranted.

FTO gene polymorphisms and platelet counts in a general Japanese population.

The fat mass and obesity-associated (FTO) gene has recently attracted attention as one of the obesity-related genes. Obesity-related gene polymorphisms may be associated with the development of atherothrombosis in relation to platelets. The present study investigated the association between FTO gene polymorphisms (rs1558902, T/A) and hematological parameters, in particular the platelet counts. Anthropometric, hematological, and biochemical parameters, in addition to genotyping by an allele-specific DNA assay, were measured in 209 asymptomatic community-dwelling Japanese subjects (male/female: 80/129; mean age, 65 years; mean [SD] body mass index, 24.0 [3.0] kg/m). The subjects with the A-allele (n = 73) showed significantly higher platelet counts than those without the A-allele (mean [SD], 237 [58] vs 217 [57] × 10/L, P < 0.05). Even when multiple-adjusted analyses were performed, the platelet counts continued to differ significantly and independently of other variables, including obesity-related parameters such as the index of insulin resistance or high-sensitivity C-reactive protein, between the subjects with and without the A-allele. The FTO gene polymorphisms may be associated with the minor but significant modulation of platelet counts in this population.

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study.

This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P < .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P = .016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (ß = 0.133, P = .030), adiponectin levels (ß = -0.242, P < .001), and the SNP276 G allele (ß = -0.142, P = .014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles.

The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and High-density Lipoprotein Cholesterol in A General Japanese Population: A Consideration of the Obesity Status.

BACKGROUND: Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. METHODS: Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2), and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. CONCLUSIONS: The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk.

The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study.

BACKGROUND: The clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL) in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP) of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL. METHODS: In 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years), the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C) (1.7 ± 3.4 vs. 0.8 ± 1.9%; p < 0.05). A multiple regression analysis showed that the area of sdLDL was significantly and negatively correlated with the Clock 3111 T/C SNP (ß = -0.114, p < 0.05), independently of age, sex, body mass index, and exercise habits. CONCLUSION: Our findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL.

Dietary salt reduction in rural patients with albuminurea using family and community support: the Mima study.

BACKGROUND: Residents of rural communities are often more socially connected compared to urban dwellers. Using family and community support to motivate health behavior change may be useful in rural settings. The objective of this study was to pilot a salt reduction (SR) intervention for rural albuminuria patients using support from family and neighborhood residents compared to a usual care condition. The primary outcome was change in urine albumin-creatinine ratio (ACR). METHODS: All consecutive outpatients with an ACR >= 30 mg/gCr were recruited from the Koyadaira Clinic. Patients self-selected their participation in the intervention group (IG) or the control group (CG) because the rural population expressed concern about not being treated at the same time. In the IG, patients and their families were educated in SR for 30 minutes in their home by experienced dieticians. In addition, patients, families and neighborhood residents were also educated in SR for 2 hours at a public town meeting hall, with educational content encouraging reduction in salt intake through interactive activity. The CG received conventional treatment, and ACR and blood pressure (BP) were measured after 3 months. RESULTS: Of the 37 subjects recruited (20 male, 16 female, mean age; 72.8 +/- 9.2 years), 36 completed the 3-month follow up and were analyzed. In the IG, ACR decreased significantly from baseline (706 +/- 1,081 to 440 +/- 656; t = 2.28, p = 0.04) and was reduced compared to the CG (213 +/- 323 to 164 +/- 162; F = 3.50, p = 0.07), a treatment effect approaching significance. Systolic BP in the IG (145 +/- 14 to 131 +/- 13 mmHg; t = 3.83, p = 0.002) also decreased significantly compared to the CG (135 +/- 13 to 131 +/- 14; F = 4.40, p = 0.04). CONCLUSIONS: Simultaneous education of patients, their families and neighborhood residents may be important in rural areas for treatments and interventions requiring health behavior change. TRIAL REGISTRATION: UMIN000001972.