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.

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.

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.

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.

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.

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.

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.

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.

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.