Association between dynapenia and cognitive decline in community-dwelling older Japanese adults: The IRIDE Cohort Study.

AIM: Muscle mass and strength correlate with cognitive function; however, it remains unclear whether dynapenia (i.e., muscle weakness with preserved muscle mass) is relevant. This study aimed to explore whether dynapenia is associated with global cognitive function in community-dwelling older Japanese adults. METHODS: This cross-sectional study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study, which pooled data from five community-based geriatric cohorts. Dynapenia was defined as muscle weakness without muscle mass loss according to the Asian Working Group for Sarcopenia criteria. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). An ordered logistic regression analysis was conducted with dynapenia as the exposure and with cognitive decline stages, defined as an MMSE score of 27-30 for normal cognition, 24-26 for possible cognitive decline, and <24 for cognitive decline, as the outcome, stratified by sex and adjusted for age, muscle mass, education, alcohol consumption, smoking habits, living alone, and non-communicable diseases. RESULTS: We analyzed data for 3338 participants (2162 female) with preserved muscle mass. Of these, 449 (13.5%) had dynapenia, and 79 (2.4%) exhibited cognitive decline. Multivariate odds ratios (95% confidence interval) for cognitive decline among those with dynapenia, compared with those without dynapenia, were 1.51 (1.02-2.24) for males and 2.08 (1.51-2.86) for females. CONCLUSIONS: Muscle weakness is associated with cognitive decline, even in individuals with preserved muscle mass. Further studies are needed to better understand the association between muscle weakness and cognitive decline over time in order to develop dementia prevention strategies for those with dynapenia. Geriatr Gerontol Int 2024; 24: 123-129.

The relationship between working status in old age and cause-specific disability in Japanese community-dwelling older adults with or without frailty: A 3.6-year prospective study.

AIM: To examine the effects of employment engagement, classified by frailty and working status, on the incidence of disability in urban community-dwelling older adults. METHODS: We used data from 6386 initially nondisabled residents aged 65-84 years from Ota City, Tokyo, Japan, in 2016. The observation duration was 3.6 years. Self-administered questionnaires applied the Cox proportional hazard model by assessing the existence of frailty through Check-List 15 (with a score ≥4 indicating the state of frailty), controlling for age, sex, living situation, education level, equivalent income, chronic conditions, body mass index, instrumental activities of daily living, self-rated health, drinking and smoking status, and social activities. We evaluated the predictive value of working status (full-time, part-time, temporary, or nonworker) at baseline for cause-specific disability (dementia-type vs. non-dementia-type) incidence, identified using the long-term care insurance system's nationally unified database. RESULTS: Of the 6386 participants, 806 (63/1134 full-time workers; 58/1001 part-time workers; 61/547 temporary workers; 624/3704 nonworkers) presented with disabilities during the 3.6-year-long duration. Adjustments for conventional covariates showed that nonfrail full-time and part-time workers, as well as frail full-time workers, had significantly lower risks of all-cause disability incidence. Furthermore, nonfrail and frail full-time workers had significantly lower risks of dementia-type and nondementia-type disabilities, respectively. CONCLUSIONS: The incidence of disability in older adults was influenced by working and frailty status. Engaging in full-time work thus prevents disabilities in older adults, regardless of their frailty status. Meanwhile, nonfrail older adults are able to avoid disabilities even when engaging in part-time work. Geriatr Gerontol Int 2023; 23: 855-863.

Age- and sex-specific associations between sarcopenia severity and poor cognitive function among community-dwelling older adults in Japan: The IRIDE Cohort Study.

Introduction: This study examined whether the association between sarcopenia severity and cognitive function differed according to sex and age in community-dwelling older adults in Japan. Methods: This is a cross-sectional study of older adults (age ≥ 65 years) consisting of five regional cohorts integrated as the Integrated Research Initiative for Living Well with Dementia (IRIDE) Cohort Study. Sarcopenia severity was determined based on the Asian Working Group for Sarcopenia 2019, which assessed grip strength, walking speed, and skeletal muscle mass index. Poor cognitive function was defined as a Mini-Mental State Examination score of ≤ 23. Odds ratios (ORs) and 95% confidence intervals (CIs) for poor cognitive function were calculated by sex and age group (65-74 and ≥75 years) using binomial logistic regression models, which were adjusted for age, educational attainment, history of non-communicable diseases, smoking and drinking habits, living alone, frequency of going outdoors, exercise habits, and depressive symptom. Results: Of the 8,180 participants, 6,426 (1,157 men aged 65-74 and 1,063 men aged 75 or older; 2,281 women aged 65-74 and 1,925 women aged 75 or older) were analyzed. The prevalence ratio of sarcopenia and severe sarcopenia were 309 (13.9%) and 92 (4.1%) among men and 559 (13.3%) and 166 (3.7%) among women, respectively. A total of 127 (5.8%) men and 161 (3.9%) women had a poor cognitive function. Setting non-sarcopenia as a reference, the adjusted ORs (95% CI) of poor cognitive function were 2.20 (1.54, 3.15) for sarcopenia and 3.56 (2.20, 5.71) for severe sarcopenia. A similar trend was observed in analyses stratified by sex and age, with linear associations (P for trend <0.05) in both categories. Furthermore, there was a significant interaction (P < 0.05) between sex and sarcopenia severity, indicating a stronger linear association of sarcopenia severity with poor cognitive function in women compared with men. Discussion and conclusion: Sarcopenia severity was linearly associated with poor cognitive function in adults aged ≥ 65 years, with a stronger association in women compared with men.

Revisiting Cryptocyanine Dye, NK-4, as an Old and New Drug: Review and Future Perspectives.

NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4's antioxidative and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases.

Modifiable healthy behaviours and incident disability in older adults: Analysis of combined data from two cohort studies in Japan.

Healthy behaviours reduce the risk of incident disability; however, their components require further consideration. Specifically, little evidence exists on healthy behaviours that comprise modifiable factors, including social aspects, and their effects on those who do not engage in them. This study aimed to examine the association between engaging in healthy behaviours with modifiable factors and incident disability among community-dwelling older adults; as well as identify factors associated with nonengagement in healthy behaviours. We analysed data obtained from 1357 older adults aged 65 years and more without disabilities at baseline. The outcome was incident disability, which was defined based on the long-term care insurance certification in Japan. This study included regular exercise (≥1 day/week), favourable eating habits (≥4 dietary variety score), and social participation (engaging in two or more social activities) as components of healthy behaviours. We used the Cox proportional hazards model to calculate hazard ratios (HR) for incident disabilities. The proportion of those who satisfied all healthy behaviours was 21 %. During the follow-up period (median: 6.3 years), 282 incident disabilities were confirmed. Compared to those who engaged in one healthy behaviour, those who satisfied all healthy behaviours showed a 31 % (95 % confidence interval: 0.48, 0.98) lower HR of incident disability after adjusting for covariates. Current smoking and depressive mood were associated with non-engagement in healthy behaviours. This study found that having physically and socially active lifestyles and favourable eating habits are effective in reducing the risk of incident disability. Meanwhile, several older adults lack the components of a healthy lifestyle. Approaches that focus on multiple healthy behaviours are necessary to enhance the benefits of healthy lifestyles.

Combined Impacts of Physical Activity, Dietary Variety, and Social Interaction on Incident Functional Disability in Older Japanese Adults.

BACKGROUND: This 3.6-year prospective study examined combined impacts of physical activity, dietary variety, and social interaction on incident disability and estimated population-attributable fraction for disability reduction in older adults. METHODS: Participants were 7,822 initially non-disabled residents (3,966 men and 3,856 women) aged 65-84 years of Ota City, Tokyo, Japan. Sufficiency of moderate-to-vigorous-intensity physical activity (MVPA) ≥150 min/week, dietary variety score (DVS) ≥3 (median), and social interaction (face-to-face and/or non-face-to-face) ≥1 time/week was assessed using self-administered questionnaires. Disability incidence was prospectively identified using the long-term care insurance system's nationally unified database. RESULTS: During a follow-up of 3.6 years, 1,046 (13.4%) individuals had disabilities. Independent multivariate-hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA, DVS, and social interaction sufficiency for incident disability were 0.68 (95% CI, 0.59-0.78), 0.87 (95% CI, 0.77-0.99), and 0.90 (95% CI, 0.79-1.03), respectively. Incident disability HRs gradually reduced with increased frequency of satisfying these behaviors (any one: HR 0.82; 95% CI, 0.65-1.03; any two: HR 0.65; 95% CI, 0.52-0.82; and all three behaviors: HR 0.54; 95% CI, 0.43-0.69), in an inverse dose-response manner (P < 0.001 for trend). Population-attributable fraction for disability reduction in satisfying any one, any two, and all three behaviors were 4.0% (95% CI, -0.2 to 7.9%), 9.6% (95% CI, 4.8-14.1%), and 16.0% (95% CI, 8.7-22.8%), respectively. CONCLUSION: Combining physical activity, dietary variety, and social interaction substantially enhances the impacts on preventing disability among older adults, with evidence of an inverse dose-response manner. Improving insufficient behavior elements through individual habits and preexisting social group activities may be effective in preventing disability in the community.

Association between sarcopenia and oral functions in community-dwelling older adults: A cross-sectional study.

BACKGROUND: Few studies have examined the state of oral function in older adults with sarcopenia. We assessed the oral functions of community-dwelling older adults with sarcopenia from multiple perspectives to clarify their potentially low oral function. METHODS: A total of 1517 (86.2%; 990 women, 527 men; mean age 76.1 ± 7.6 years) participants were included in this study. Grip strength, gait speed and skeletal muscle mass index were assessed, and sarcopenia was evaluated according to the criteria of the Asian Working Group for Sarcopenia 2019. The degree of tongue coating, oral moisture, occlusal force, tongue-lip motor function, tongue pressure, masticatory function and swallowing function were assessed. The criteria for oral hypofunction (a disease that is a combination of multiple low oral functions) were used to assess oral function. Statistical analyses were performed using Kolmogorov-Smirnov test, unpaired t-test, Mann-Whitney U test, χ2 test, and univariate and multivariable logistic regression analyses, with each oral function as the dependent variable and sarcopenia as one of the independent variables. The significance level was set at P < 0.05. RESULTS: The prevalence rates of sarcopenia and severe sarcopenia were 14.2% and 3.8%, respectively. The prevalence of oral hypofunction was 39.9%. Compared with the robust group, the sarcopenia and severe sarcopenia groups tended to have a higher frequency of the following components (all P < 0.01): low occlusal force, low tongue-lip motor function, low tongue pressure, low masticatory function, low swallowing function and oral hypofunction. Univariate logistic regression analysis showed that sarcopenia was associated with low occlusal force, low tongue-lip motor function, low tongue pressure, low masticatory function, low swallowing function and oral hypofunction. The odds ratios and 95% confidence intervals of sarcopenia for each oral function were 2.62 [2.00, 3.43], 2.21 [1.69, 2.89], 3.66 [2.79, 4.81], 3.23 [2.46, 4.25], 1.66 [1.26, 2.20] and 3.59 [2.72, 4.72], respectively. Multivariable logistic regression analysis showed that sarcopenia was associated with low occlusal force (1.63 [1.10, 2.40]), low tongue pressure (2.28 [1.65, 3.15]), low masticatory function, (1.94 [1.27, 2.97]), low swallowing function (1.64 [1.17, 2.28]) and oral hypofunction (2.17 [1.52, 3.09]). CONCLUSIONS: This study demonstrated that multiple aspects of oral function were low among community-dwelling older adults with sarcopenia. The potential decline in oral functions in older adults with sarcopenia may have been overlooked until now. This study indicates the need for dental perspectives in intervening with older adults with sarcopenia and the need to encourage them to see dental professionals.

Chemo- and Site-Selective Replacement of N-Terminal Carbamates in Peptides.

In peptide synthesis, it is important to distinguish the terminal amino group and carry out the selective transformation of only the N-terminal protecting group. We describe herein a reaction for the chemo- and site-selective replacement of carbamates with various other carbamates only at the N-terminus of peptides. We demonstrate the scope of carbamates and peptides and the introduction of fluorine into a peptide. This strategy is applicable to the late stage of peptide synthesis.

Simple screening models for cognitive impairment in community settings: The IRIDE Cohort Study.

AIM: Community settings often need simple screening, rather than detailed tests, to identify cognitive impairment. This study aimed to develop models to screen older adults with cognitive impairment. METHODS: This study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study and included 5830 older adults. Individuals were considered cognitively impaired if their Mini-Mental State Examination score was less than 24. Three screening models were developed: the simple model (age, sex, and education), the base model comprising 13 candidate variables available in the questionnaire, and the enhanced model, where grip strength and gait speed were added to the base model. We performed binary logistic regression analysis with stepwise backward elimination (P < 0.1 for retention in the model) to develop each model. Then, we calculated integer scores from coefficients to develop score-based models. The area under the receiver operating characteristic curve (AUC) was used to evaluate discrimination. RESULTS: Participants with cognitive impairment accounted for 4.0% (n = 233) of the total. The score-based simple model comprised three variables (AUC = 0.72, sensitivity: 72%, specificity: 61%). The score-based base model included nine variables (AUC = 0.76, sensitivity: 70%, specificity: 67%). The score-based enhanced model comprised eight variables, including grip strength and gait speed (AUC = 0.79, sensitivity: 73%, specificity: 70%). CONCLUSIONS: This study developed three screening models with acceptable discriminant validity for cognitive impairment. These models comprised simple questionnaire-based items and common physical performance measurements. These models could enable screening of older adults suspected of cognitive impairment without the need to conduct cognitive tests in community settings. Geriatr Gerontol Int 2022; 22: 292-297.

Dose-response relationships of sarcopenia parameters with incident disability and mortality in older Japanese adults.

BACKGROUND: Sarcopenia-related parameters may have differential impacts on health-related outcomes in older adults. We examined dose-response relationships of body composition, muscle strength, and physical performance with incident disability and mortality. METHODS: This prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check-ups. Outcomes were incident disability and all-cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi-frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate-adjusted hazard ratios (HRs) for disability and mortality relative to sex-specific reference values (FMI: medians; SMI: 7.0 kg/m2 for men and 5.7 kg/m2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions. RESULTS: The median follow-up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose-response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07-4.46) and 0.43 (0.20-0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose-response relationship with disability in both sexes [HGS: 1.71 (1.00-2.91) and 0.31 (0.09-0.99), respectively, in men, 2.42 (1.18-4.96) and 0.41 (0.20-0.85), respectively, in women; UGS: 2.14 (1.23-3.74) and 0.23 (0.08-0.67), respectively, in men, 3.26 (2.07-5.14) and 0.11 (0.05-0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84-16.47) and 0.06 (0.02-0.21), respectively; UGS: 2.67 (1.14-6.27) and 0.30 (0.11-0.85), respectively], independent of body composition, but did not impact mortality in men. CONCLUSIONS: Disability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults.

Calpain-1 C2L domain peptide protects mouse hippocampus-derived neuronal HT22 cells against glutamate-induced oxytosis.

Calpains are Ca2+-dependent cysteine proteases; their aberrant activation is associated with several neurodegenerative diseases. The µ-calpain catalytic subunit, calpain-1, is located in the cytoplasm as well as in the mitochondria. Mitochondrial calpain-1 cleaves apoptosis-inducing factor (AIF), leading to apoptotic cell death. We have previously reported that short peptides of calpain-1 C2-like domain conjugated with cell penetrating peptide HIV-Tat (Tat-µCL) selectively inhibit mitochondrial calpain-1 and effectively prevent neurodegenerative diseases of the eye. In this study, we determined whether mitochondrial calpain-1 mediates oxytosis (oxidative glutamate toxicity) in hippocampal HT22 cells using Tat-µCL and newly generated polyhistidine-conjugated µCL peptide and compared their efficacies in preventing oxytosis. TUNEL assay and single strand DNA staining revealed that both µCL peptides inhibited glutamate-induced oxytosis. Additionally, both the peptides suppressed the mitochondrial AIF translocation into the nucleus. All polyhistidine-µCL peptides (containing 4-16 histidine residues) showed higher cell permeability than Tat-µCL. Notably, tetrahistidine (H4)-µCL exerted the highest cytoprotective activity. Thus, H4-µCL may be a potential peptide drug for calpain-1-mediated neurodegenerative diseases such as Alzheimer's disease.

Sarcopenia: prevalence, associated factors, and the risk of mortality and disability in Japanese older adults.

BACKGROUND: There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community-dwelling older adults. METHODS: We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check-ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi-frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all-cause mortality and incident disability. RESULTS: The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia-related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P-values <0.05) among men and cognitive impairment (P = 0.004) and depressed mood (P < 0.001) among women. Individuals with sarcopenia had higher risks of mortality [hazard ratios (95% confidence interval): 2.0 (1.2-3.5) in men and 2.3 (1.1-4.9) in women] and incident disability [1.6 (1.0-2.7) in men and 1.7 (1.1-2.7) in women]. Compared with the individuals without any sarcopenia components, those having low grip strength and/or slow gait speed without low ALMI tended to have an increased risk of disability [1.4 (1.0-2.0), P = 0.087], but not mortality [1.3 (0.8-2.2)]. We did not find increased risks of these outcomes in participants having low ALMI in the absence of low grip strength and slow gait speed [1.2 (0.8-1.9) for mortality and 0.9 (0.6-1.3) for incident disability]. CONCLUSIONS: Japanese older men and women meeting Asian criteria of sarcopenia had increased risks of all-cause mortality and disability. There were no significant increased risks of death or incident disability for both participants with muscle weakness and/or low performance without low muscle mass and those with low muscle mass with neither muscle weakness nor low performance. Further studies are needed to examine the interaction between muscle loss, muscle weakness, and low performance for adverse health-related outcomes.

Healthy lifestyle behaviors and transitions in frailty status among independent community-dwelling older adults: The Yabu cohort study.

Frailty is a dynamic condition that can worsen or improve. Although previous studies have identified demographic and intrinsic factors associated with transitions in frailty status, less evidence is available regarding associations with daily activities. This longitudinal study examined associations of behavioral factors with incident frailty, adverse events (e.g. residence in a nursing home, hospitalization, and death), and frailty improvement among older adults. The analysis included data from 3,769 independent older adults aged 65 years or more (mean age, 76.3 ± 7.2years; proportion of frail participants, 30.1%) from the Yabu cohort study (baseline, 2012; follow-up, 2017). The Kaigo-Yobo Checklist, a standardized questionnaire, was used to assess frailty status (non-frail or frail) and seven behavioral factors: farming, shopping, exercise, eating habit, intellectual activity, social participation, and smoking. At the 5-year follow-up survey, the proportions of participants transitioning from non-frail to frail, from non-frail to incident adverse events, from frail to non-frail, and from frail to incident adverse events were 16.8%, 13.9%, 15.2%, and 50.1%, respectively. In the analysis of non-frail participants, farming, exercise, intellectual activity, and social participation were associated with lower odds of becoming frail and experiencing adverse events. In the analysis for frail participants, farming, intellectual activity, and social participation were significantly associated with improvement in frailty status, and farming, shopping, and social participation were associated with lower odds of incident adverse events. These findings suggest that farming, healthy daily activities, and social participation help improve and prevent frailty/adverse events.

[Impact of lifestyle-related diseases and frailty on the incidence of loss of independence in Japanese community-dwelling older adults: A Longitudinal Study on Aging and Health in Kusatsu].

Objectives　This study aimed to determine risk factors for frailty and lifestyle-related diseases impacting the incidence of loss of independence among Japanese community-dwelling older adults, and to measure the magnitude of these associations.Methods　We conducted an 8.1-year prospective study involving 1,214 residents of the town of Kusatsu, aged 65 years and over, who were initially free of disability and underwent the comprehensive geriatric assessment between 2002 and 2011. Loss of independence was defined as the incidence of disability or having died before the occurrence of disability was certified by the Long-Term Care Insurance program in Japan. Risk factors for lifestyle-related diseases and health status comprised hypertension, diabetes mellitus, overweight, chronic kidney disease, current smoking, past history of stroke, heart disease and cancer, frailty, underweight, anemia, hypoalbuminemia, and cognitive decline. Frailty was defined as the presence of three or more of the following criteria: Weight loss, weakness, exhaustion, slowness, and low levels of physical activity. Prefrailty was defined as the presence of one or two of these same criteria. Cox proportional-hazard regression model was used to estimate hazard ratios (HR) and the population attributable fraction (PAF) of loss of independence.Results　During the follow-up, 475 cases, including 372 disabilities and 103 deaths, were identified as having experienced loss of independence. The multivariable HRs for the loss of independence were 1.3 to 2.2-fold higher for the presence of frailty, past history of stroke, cognitive decline, prefrailty, and smoking. The PAF of loss of independence was the greatest for prefrailty (19%), followed by frailty (12%). The PAF was relatively large for prefrailty (19%) and smoking (11%) in men, and frailty (18%), prefrailty (18%), and chronic kidney disease (11%) in women. Stratified by age category, participants aged 65-74 years having frailty and several lifestyle-related diseases showed significantly higher HRs for loss of independence and greater PAFs for prefrailty (18%), frailty (13%), and smoking (11%).Conclusions　Loss of independence among Japanese community-dwelling older adults who underwent screening examinations was largely attributed to frailty and prefrailty. Our findings suggest that the screening and the intervention for frailty and lifestyle-related diseases in the early stages of old age might be beneficial in prolonging healthy life expectancy of Japanese community-dwelling older adults.

Concise synthesis of carbazole-1,4-quinones and evaluation of their antiproliferative activity against HCT-116 and HL-60 cells.

We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types.

Is prophylactic decompression of the optic canal necessary in surgical correction of fronto-orbital fibrous dysplasia?: a review of 11 consecutive cases.

Fronto-orbital fibrous dysplasia is a disease characterized by frontal bossing and orbital dystopia. Simultaneous, prophylactic optic canal decompression remains controversial in the surgical correction of this condition. The authors review a series of 11 patients with fronto-orbital fibrous dysplasia. All patients underwent intracranial malformation excision. Concomitant optic canal decompression was carried out in 6 of 11 cases. Simultaneous reconstruction was carried out using autologous bone in all cases except for 1. Esthetic morphological satisfaction was obtained in all 11 cases. In 2 of 6 cases with optic canal decompression, 1 exhibited half-blindness, and the other exhibited quarter-blindness postoperatively. In 5 cases without decompression, there have been no changes in visual acuity through follow-up ranging from 5 to 22 years. Although therapeutic decompression is well accepted, prophylactic decompression is controversial and the efficacy of prophylactic decompression is questionable. Current strategies should focus on esthetic improvement, with careful observation carried out to assess for optic canal encroachment without prophylactic decompression.

Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells.

9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 µM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity.

[7 fractionated cyberknife radiotherapy for giant skull metastasis: a case report].

This is a report on the experience of using stereotactic radiotherapy for a large symptomatic metastatic skull tumor. The stereotactic radiotherapy was delivered in 7 fractions using the Cyberknife and produced excellent therapeutic results. This case concerns a 75-year-old female. Nineteen months after uterine cancer surgery, the patient demonstrated metastasis to the mediastinum lymph node and a tumor at the parietal bone tumor but was still undergoing observation. An increase of the parietal bone tumor became evident and the appearance of right hemiplegia, aphasia, and cognitive dysfunction caused her to consult this hospital. We observed a large 236 cm3 tumor spread over the subcutaneous tissue of the superior sagittal sinus, pressing the brain out of the dura mater and causing bone destruction. As a result of our findings, we began stereotactic Cyberknife radiotherapy delivered in 7 fractions. At the follow up visit one month after the treatment, the image of the tumor had already decreased, and after three months it was confirmed that the image of the tumor had disappeared. The patient's symptoms ameliorated rapidly. As a result, the patient has returned to an independent home-lifestyle, with amelioration of her quality-of-life defects. Six months after irradiation, there is no evidence of tumor regrowth or complications such as dermatopathy, cerebral edema, or necrosis. Cyberknife radiotherapy could shorten the treatment period and result in a reduction of the amount of irradiation to unaffected parts of the brain. In this case, though the tumor had spread widely in the subcutaneous tissue, the exposure doses were delivered at 2Gy/time and could be limited to under 70Gy. It is thought that Cyberknife radiotherapy will become one of the key treatments to help improve quality of life when treating symptomatic metastatic tumors.

Haemangioma of the forehead: radiographic diagnosis and definitive surgical treatment in a Japanese series.

Haemangioma of the skull is usually encountered as a solitary lesion, so few separate cases have been reported, and the protocol for treatment has not been confirmed. Here we describe its treatment in five consecutive Japanese patients. Three men and two women aged from 36 to 40 years were studied. The lesions were noticed in the left frontal bone, one in the supraorbital region and the rest in the forehead; they were 1.5-2.5 cm in diameter. The preoperative diagnosis was made precisely by plain and tangential radiographs and computed tomographic (CT) views. Once the lesion was suspected, radical resection and immediate reconstruction were required to prevent recurrence. All five radical resections were reconstructed immediately by split calvarial bone harvested from the ipsilateral parietal bone in the same operative field. The postoperative course was uneventful in all cases, and the postoperative contour of the reconstructed site and the donor site were nearly perfect. There were no particular complications. Two to 10 years have passed without recurrence.

Lymphocytic infundibulo-neurohypophysitis and infundibulo-panhypophysitis regarded as lymphocytic hypophysitis variant.

Lymphocytic infundibulo-neurohypophysitis (LINH) was first reported by Saito et al. and Imura et al. as a cause of idiopathic central diabetes insipidus. Magnetic resonance (MR) imaging with a contrast medium demonstrates thickening of the pituitary stalk, enlargement of the neurohypophysis, or both with homogeneous enhancement. Histological examination reveals a posterior pituitary that is heavily infiltrated by lymphocytes with occasional plasma cells and other inflammatory cells. In early reports of the disorder, the lesion seemed to be limited to the neurohypophysis, but the present review showed cases with a combination of hypopituitarism and diabetes insipidus. Some of them showed partial hypopituitarism. The so-called lymphocytic infundibulo-panhypophysitis (LIPH) is now regarded as a lymphocytic hypophysitis variant. LINH and LIPH are essentially self-limited. In typical cases, conservative care with steroids and hormone replacement is recommended. Surgical intervention should be avoided because the natural course of the disorder may be self-limited. Pathophysiology of the disorder is still unknown. The unique clinical manifestations of the disorder are discussed and reviewed here.