Indoline hemiaminals: a platform for accessing anthranilic acid derivatives through oxidative deformylation.

2-Aminobenzoyl chlorides possess both a nucleophilic nitrogen atom and an electrophilic carbonyl group, and thus selective acylation of nucleophiles is challenging; self-dimerization and sluggish reactions occur. Herein, we introduce a new synthetic protocol using 2-aminobenzoyl surrogates, allowing concise entry to decorated 2-aminobenzoyl derivatives in the absence of transition metals, acid chlorides, and specific reagents.

Association of the combination of social isolation and living alone with cognitive impairment in community-dwelling older adults: The IRIDE Cohort Study.

BACKGROUND: Living alone has been associated with cognitive impairment; however, findings have been inconsistent. Social isolation among older adults who live alone may contribute to cognitive impairment. This study was carried out to examine the association of social isolation and living alone with cognitive impairment in community-dwelling older adults. METHODS: In this cross-sectional study, data from the Integrated Research Initiative for Living Well with Dementia Cohort Study, which comprises pooled data from five community-based geriatric cohorts, was used. Social isolation was defined as infrequent interactions with others. Participants were categorized into four groups based on their social isolation and living alone statuses. Cognitive function was assessed using the Mini-Mental State Examination, with a score <24 indicating cognitive impairment. The association between social isolation combined with living alone and cognitive impairment was analyzed using logistic regression. RESULTS: Of the 4362 participants included in the analysis (mean age 75.6 years, 44.3 % male), 11 % had cognitive impairment. Regardless of living alone, social isolation was associated with cognitive impairment (no social isolation x not living alone: reference, social isolation x not living alone; odds ratio (OR): 1.74, 95 % confidence interval (CI): 1.29-2.33, social isolation x living alone; OR: 2.10, 95 % CI: 1.46-3.01). CONCLUSIONS: Social isolation is associated with cognitive impairment; however, living alone is not intrinsically associated with cognitive impairment in older adults. Healthcare providers must focus on social interactions to prevent cognitive impairment in older adults rather than simply focusing on living arrangements.

Formal One Carbon Deletion of Indoline Hemiaminals under Tautomeric Control to Access 2-Aminobenzyl Compounds.

Unprecedented tert-BuOK-mediated one carbon deletion of indoline hemiaminals has been achieved. This novel protocol provides an efficient synthetic tool for the construction of 2-aminobenzyl compounds with high chemoselectivity. In addition, functionalized 2-aminobenzyl compounds are difficult to make, for which few limited means of access currently exist. The key to success is the use of in situ generated Heyns rearrangement products (α-amino carbonyl compounds) as precursors for formal one carbon deletion.

Switchable synthesis of 3-aminoindolines and 2'-aminoarylacetic acids using Grignard reagents and 3-azido-2-hydroxyindolines.

The switchable synthesis of 3-aminoindolines and 2'-aminoaryl acetic acids from the same substrates, 3-azido-2-hydroxyindolines, was developed through denitrogenative electrophilic amination of Grignard reagents. The key to success is the serendipitous discovery that the reaction conditions, including solvents and reaction temperature, can affect the chemoselectivity. It is noteworthy that isotope-labeling experiments revealed the occurrence of the aziridine intermediate in the production of 2'-aminoaryl acetic acids.

Associations between information and communication technology use and frailty in community-dwelling old-old adults: results from the ILSA-J.

OBJECTIVES: Frailty is a significant cause of adverse health events including long-term care and hospitalization. Although information and communication technology (ICT) has become an integral part of modern life, it remains unclear whether ICT use is associated with frailty. DESIGN: A cross-sectional study (Integrated Longitudinal Studies on Aging in Japan, ILSA-J). SETTING AND PARTICIPANTS: Aged 75 and older data from the ILSA-J in 2017 (n = 2893). METHODS: ICT use was measured using the technology usage sub-items of the Japan Science and Technology Agency Index of Competence. Specifically, the use of mobile phones, ATMs, DVD players, and sending e-mails were rated as "yes" (able to do) or "no" (unable to do), with the first quintile (≤1 point) defined as ICT non-users. Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria based on the phenotype model (e.g., weight loss, slowness, weakness, exhaustion, and low activity). Further, multivariate logistic regression analysis analyzed its association with ICT use. Subgroup analyses were stratified according to gender, years of education, and living arrangements. RESULTS: Higher ICT use was not associated with frailty after adjusting for covariates (odds ratio [OR]: 0.53; 95%CI 0.39-0.73). Similar associations were found in the sub-groups of women (OR 0.45, 95%CI 0.30-0.66), <13 years of education (OR 0.48, 95%CI 0.34-0.67), living alone (OR 0.46, 95%CI 0.27-0.79), and living together (OR 0.57, 95%CI 0.38-0.85). No association existed between using ICT and frailty in the sub-groups of men and ≥13 years of education. CONCLUSIONS AND IMPLICATIONS: Higher ICT use is associated with the absence of frailty in individuals 75 years and older. Such benefits may be particularly pronounced in women, those with lower levels of education, and older adults living alone or with others.

Dose-response associations between physical activity and sedentary time with functional disability in older adults with or without frailty: a prospective cohort study.

Purpose: Evidence regarding the dose-response curve shapes of physical activity (PA) and sedentary time (ST) in older adults with functional disability (FD) is extremely limited. Moreover, these associations may differ depending on with/without frailty. We examined the dose-response associations between moderate-to-vigorous PA (MVPA) and ST with FD among older adults with/without frailty. Methods: We included 7,480 initially nondisabled adults (3,795 men and 3,685 women) aged 65-84 years in Ota City, Tokyo, Japan. MVPA and ST were evaluated using the International Physical Activity Questionnaire-Short Form. FD was prospectively identified using a nationally unified database of the long-term care insurance system. Frailty was determined using Check-List 15, validated against Fried's frailty criteria. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and ST for FD were calculated, and dose-response curves were examined using restricted cubic splines. Results: During 3.6 years of follow-up, 1,001 (13.4%) participants had FD. Among all participants, compared with no MVPA, the HRs for FD reduced linearly up to approximately 2000 metabolic equivalents (METs)■min/week of MVPA, and the lowest HR (HR: 0.61, 95% CI: 0.51-0.74) was reached at around 3,000-4,000 METs■min/week. Although the shape of this association was consistent regardless of with/without frailty, the magnitude of the association tended to be stronger in frail older adults than in non-frail older adults. Compared with those for the median (300 min/day) of ST, the HRs for FD increased linearly as ST reached approximately 600 min/day or more, independent of MVPA, with a maximum HR of 1.31 (95% CI: 1.01-1.71) for 1,080 min/day among all participants. This association was more pronounced among non-frail older adults but not statistically significant among frail older adults. Conclusion: Higher MVPA levels consistently reduced the incidence of FD regardless of frailty in a significant inverse nonlinear dose-response manner. A significant positive nonlinear dose-response association between ST and FD risk was identified among non-frail older adults but not among frail older adults. Increasing MVPA and reducing prolonged ST are important for preventing FD among non-frail older adults. However, reducing ST alone may be insufficient; increasing MVPA, even if by only small increments, is highly recommended for frail older adults.

Dependence on visual information in patients with ACL injury for multi-joint coordination during single-leg squats: a case control study.

BACKGROUND: The influence of vision on multi-joint control during dynamic tasks in anterior cruciate ligament (ACL) deficient patients is unknown. Thus, the purpose of this study was to establish a new method for quantifying neuromuscular control by focusing on the variability of multi-joint movement under conditions with different visual information and to determine the cutoff for potential biomarkers of injury risk in ACL deficient individuals. METHODS: Twenty-three ACL deficient patients and 23 healthy subjects participated in this study. They performed single-leg squats under two different conditions: open eyes (OE) and closed eyes (CE). Multi-joint coordination was calculated with the coupling angle of hip flexion, hip abduction and knee flexion. Non-linear analyses were performed on the coupling angle. Dependence on vision was compared between groups by calculating the CE/OE index for each variable. Cutoff values were calculated using ROC curves with ACL injury as the dependent variable and significant variables as independent variables. RESULTS: The sample entropy of the coupling angle was increased in all groups under the CE condition (P < 0.001). The CE/OE index of coupling angle variability during the descending phase was higher in ACL deficient limbs than in the limbs of healthy participants (P = 0.036). The CE/OE index of sample entropy was higher in the uninjured limbs of ACL deficient patients than in the limbs of healthy participants (P = 0.027). The cutoff value of the CE/OE index of sample entropy was calculated to be 1.477 (Sensitivity 0.957, specificity 0.478). CONCLUSION: ACL deficient patients depended on vision to control multiple joint movements not only on the ACL deficient side but also on the uninjured side during single leg squat task. These findings underscore the importance of considering visual dependence in the assessment and rehabilitation of neuromuscular control in ACL deficient individuals.

Higher-level competence: Results from the Integrated Longitudinal Studies on Aging in Japan (ILSA-J) on the shape of associations with impaired physical and cognitive functions.

AIM: This study aimed to examine the relationships between levels of competence and impaired physical and cognitive functions in older adults. METHODS: We used a data set of the Integrated Longitudinal Studies on Aging in Japan for 2017 including 5475 community-dwelling older adults. Levels of competence were assessed using the Japan Science and Technology Agency Index of Competence (JST-IC). Grip strength (low grip strength: <28 kg for men and <18 kg for women) and gait speed (slow gait speed: <1.0 m/s for both sexes) were evaluated as physical function measurements, and the Mini-Mental State Examination (cognitive decline: <24 on the Mini-Mental State Examination) was used to assess cognitive function. RESULTS: The JST-IC had areas under the curve estimated from receiver operating characteristic analysis ranging from 0.65 to 0.73 for detecting low function as assessed by these tests. Restricted cubic spline curves showed that the shape of the association between the JST-IC and impaired function depended on sex and the test used. The comparison between perfect and imperfect JST-IC scores showed significant differences in the prevalence of low grip strength in both sexes, slow gait speed in women, and cognitive decline in men. CONCLUSIONS: It may be insufficient to identify those with impaired physical or cognitive function using the JST-IC. The shape of the association with the JST-IC varies across their measurements. Our findings can help interpret JST-IC scores in the context of low physical and cognitive functions. Geriatr Gerontol Int 2024; 24: 352-358.

Synthetic strategies for the construction of C3-N1' bisindoles.

C3-N1' bisindoles are unique structures, and the construction of these structures has drawn much attention. However, their synthesis still presents significant challenges that limit the functional group compatibility. This minireview summarizes the recent progress in the methodology for constructing C3-N1' bisindoles. There are two approaches for access to C3-N1' bisindoles: (1) direct approaches including reverse polarity techniques. (2) Stepwise approaches using designed and prefunctionalized substrates enable further functionalization by additional reactions to facilitate access to the target products. I believe that this review will allow its readers to develop novel approaches for the synthesis of C3-N1' bisindoles.

On Demand Synthesis of C3-N1' Bisindoles by a Formal Umpolung Strategy: First Total Synthesis of (±)-Rivularin A.

In this work, a straightforward synthesis of C3-N1' bisindolines is achieved by a formal umpolung strategy. The protocols were tolerant of a wide variety of substituents on the indole and indoline ring. In addition, the C3-N1' bisindolines could be converted to C3-N1' indole-indolines and C3-N1'-bisindoles. Also, we have successfully synthesized (±)-rivularin A through a biomimetic late-stage tribromination as a key step.

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.

Sacrificial Mechanical Bond is as Effective as a Sacrificial Covalent Bond in Increasing Cross-Linked Polymer Toughness.

Sacrificial chemical bonds have been used effectively to increase the toughness of elastomers because such bonds dissociate at forces significantly below the fracture limit of the primary load-bearing bonds, thereby dissipating local stress. This approach owes much of its success to the ability to adjust the threshold force at which the sacrificial bonds fail at the desired rate, for example, by selecting either covalent or noncovalent sacrificial bonds. Here, we report experimental and computational evidence that a mechanical bond, responsible for the structural integrity of a rotaxane or a catenane, increases the elastomer's fracture strain, stress, and energy as much as a covalent bond of comparable mechanochemical dissociation kinetics. We synthesized and studied 6 polyacrylates cross-linked by either difluorenylsuccinonitrile (DFSN), which is an established sacrificial mechanochromic moiety; a [2]rotaxane, whose stopper allows its wheel to dethread on the same subsecond time scale as DFSN dissociates when either is under tensile force of 1.5-2 nN; a structurally homologous [2]rotaxane with a much bulkier stopper that is stable at force >5.5 nN; similarly stoppered [3]rotaxanes containing DFSN in their axles; and a control polymer with aliphatic nonsacrificial cross-links. Our data suggest that mechanochemical dethreading of a rotaxane without failure of any covalent bonds may be an important, hitherto unrecognized, contributor to the toughness of some rotaxane-cross-linked polymers and that sacrificial mechanical bonds provide a mechanism to control material fracture behavior independently of the mechanochemical response of the covalent networks, due to their distinct relationships between structure and mechanochemical reactivity.

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.

Fluctuations in Cognitive Test Scores and Loss to Follow-Up in Community-Dwelling Older Adults: The IRIDE Cohort Study.

INTRODUCTION: We examined the relationship between previous fluctuations in Mini-Mental State Examination (MMSE) scores, future changes in MMSE scores, and attrition from follow-up surveys, which helps in a more comprehensive interpretation of repeatedly collected MMSE scores. METHODS: This 4-year longitudinal study included 2,073 community-dwelling older adults aged ≥65 years in Japan. The MMSE was administered at baseline (T0), 2 years (T1), and 4 years (T2) follow-up. We performed multinomial logistic regression analysis with the dependent variable, indicating the change in MMSE score from T1 to T2 (categorized as increase, no change [reference category], and decrease) and attrition at T2. The independent variables included the change in MMSE scores from T0 to T1 and MMSE scores at T0 and T1. RESULTS: The mean MMSE score was 29 across the three time points. A one-point decrease in MMSE score from T0 to T1 was associated with 79% (95% confidence interval: 1.62, 1.97) higher odds of an increase in MMSE score from T1 to T2 and 28% (1.17, 1.40) higher odds of attrition at T2. A one-point decrement in the MMSE score at T0 and T1 was also associated with an increase in the MMSE score from T1 to T2 and attrition at T2. CONCLUSION: Focusing on cognitive fluctuation for 2 years, rather than cognitive function at a point in time, would have no remarkable advantage when focusing on future cognitive function and attrition. Our results emphasize the need for further studies to identify factors that distinguish between those who continue to attend follow-up surveys and show improvements in cognitive test scores and those who drop out.

Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C.

The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles.

Association of dietary variety with the risk for dementia: the Yabu cohort study.

OBJECTIVE: The consumption of various foods is internationally recommended in healthy diet although the association between dietary variety and incident dementia is unknown. We aimed to examine the association between dietary variety and the incidence of disabling dementia in older Japanese adults. DESIGN: We conducted a prospective cohort study. Dietary variety was assessed based on the Dietary Variety Score (DVS). DVS was assessed by counting the number of ten food components (meat, fish/shellfish, eggs, milk, soyabean products, green/yellow vegetables, potatoes, fruit, seaweed and fats/oils) that were consumed almost daily using a FFQ. Participants were categorised into low (0-2 points), middle (3-4 points) and high (5-10 points) groups based on the DVS. Data on newly diagnosed disabling dementia were retrieved from the public long-term care insurance database. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95 % CI. SETTING: Yabu cohort study, Japan. PARTICIPANTS: A total of 4972 community-dwelling adults aged 65 years or older. RESULTS: During the median follow-up of 6·8 years, 884 participants were newly diagnosed with disabling dementia. After adjusting for confounders, the multivariable-adjusted HR for incident disabling dementia was 0·82 (95 % CI, 0·69, 0·97) for participants in the highest DVS category compared with those in the lowest DVS category (Pfor trend = 0·019). CONCLUSIONS: A higher dietary variety is associated with a reduced risk of disabling dementia in older Japanese adults. These results have potential implications for the development of effective public nutritional approaches to prevent dementia in older adults.

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.