Chemoenzymatic Synthesis of GAA-7 Glycan Analogues and Evaluation of Their Neuritogenic Activities.

Ganglioside GAA-7 exhibits higher neurite outgrowth than ganglioside GM1a and most echinodermatous gangliosides (EGs) when tested on neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of nerve growth factor (NGF). The unique structure of GAA-7 glycan, containing an uncommon sialic acid (8-O-methyl-N-glycolylneuraminic acid) and sialic acid-α-2,3-GalNAc linkage, makes it challenging to synthesize. We recently developed a streamlined method to chemoenzymatically synthesize GAA-7 glycan and employed this modular strategy to efficiently prepare a library of GAA-7 glycan analogues incorporating N-modified or 8-methoxyl sialic acids. Most of these synthetic glycans exhibited moderate efficacy in promoting neuronal differentiation of PC12 cells. Among them, the analogue containing common sialic acid shows greater potential than the GAA-7 glycan itself. This result reveals that methoxy modification is not essential for neurite outgrowth. Consequently, the readily available analogue presents a promising model for further biological investigations.

Diversity-Oriented Synthesis of a Molecular Library of Immunomodulatory α-Galactosylceramides with Fluorous-Tag-Assisted Purification and Evaluation of Their Bioactivities in Regard to IL-2 Secretion.

Structural variants of α-galactosylceramide (α-GalCer) that stimulate invariant natural killer T (iNKT) cells constitute an emerging class of immunomodulatory agents in development for numerous biological applications. Variations in lipid chain length and/or fatty acids in these glycoceramides selectively trigger specific pro-inflammatory responses. Studies that would link a specific function to a structurally distinct α-GalCer rely heavily on the availability of homogeneous and pure materials. To address this need, we report herein a general route to the diversification of the ceramide portion of α-GalCer glycolipids. Our convergent synthesis commences from common building blocks and relies on the Julia-Kocienski olefination as a key step. A cleavable fluorous tag is introduced at the non-reducing end of the sugar that facilitates quick purification of products by standard fluorous solid-phase extraction. The strategy enabled the rapid generation of a focused library of 61 α-GalCer analogs by efficiently assembling various lipids and fatty acids. Furthermore, when compared against parent α-GalCer in murine cells, many of these glycolipid variants were found to have iNKT cell stimulating activity similar to or greater than KRN7000. ELISA assaying indicated that glycolipids carrying short fatty N-acyl chains (1fc and 1ga), an unsubstituted (1fh and 1fi) or CF3-substituted phenyl ring at the lipid tail, and a flexible, shorter fatty acyl chain with an aromatic ring (1ge, 1gf, and 1gg) strongly affected the activation of iNKT cells by the glycolipid-loaded antigen-presenting molecule, CD1d. This indicates that the method may benefit the design of structural modifications to potent iNKT cell-binding glycolipids.

Evaluating caregivers' service quality perceptions: impact-range performance and asymmetry analyses.

BACKGROUND: This study aimed to analyze family caregivers' (FCs) dementia care service perceptions to identify the various attributes impacting FCs satisfaction and dissatisfaction. METHODS: This is a cross-sectional survey study using convenience sampling methods. A self-completion questionnaire was developed from the Service Quality scale and distributed using a convenience sampling method to family caregivers in community-based dementia care centers to determine their perceptions of service quality in dementia care. Both exploratory factor analysis and reliability analysis were conducted to confirm the validity and factor structure of the scale. This study employed Impact Range Performance Analysis (IRPA) and Impact Asymmetry Analysis (IAA) to analyze the data obtained from FCs across five attribute dimensions (Tangibles, Reliability, Responsiveness, Assurance, and Empathy). Priorities for service improvement were derived using a three-step analytical framework. RESULTS: This study reported that the overall perceived performance of service provided is high. The results indicated that practitioners should focus on attributes such as demand coordination, appropriate services, timely service, barrier-free environment, care-giving process, fire and safety compliance, professional knowledge, and reliable services, which have a higher range of impact on customer service and low impact-asymmetry and attribute performance scores. CONCLUSION: This study used expectation and perceived performance to suggest that the priorities for improvement and resource allocation in dementia care centers vary across different attributes. Thus, attentiveness toward satisfying user demand could improve patient care and caregiver satisfaction. The dimensions and attributes identified by our study can serve as basic data for future research on the long-term care system.

Patterns of home- and community-based services in older adults with dementia: an analysis of the long-term care system in Taiwan.

BACKGROUND: Understanding the specific characteristics of the patients with dementia is essential in developing services required to meet their needs. The purpose of this study was to investigate the patterns of use of home- and community-based services (HCBS) by patients with dementia and the factors influencing the utilisation of these services. METHODS: We analysed a dataset of patients with dementia receiving long-term care at a medical centre. All participating patients were required to complete a structured interview form every 6 months to assess their need for service utilisation. Between 2015 and 2018, a total of 822 patients fulfilled the criteria for dementia, and 737 people had assessment records, of whom 244 had used social services. Robust Poisson regression analyses were performed to estimate HCBS usage and the factors influencing service utilisation. RESULTS: The overall service utilisation rate was 33 %. Most patients used only one service, and assistive devices were used as the main service. Regarding the factors influencing service use, dementia concomitant with dependency increased the use of HCBS. These results suggest that patients with mild dependency might prefer to use community support services, whereas those with moderate to severe dependency being more likely to utilise in-home care services. CONCLUSIONS: This study provides empirical evidence regarding the use of long-term care resources by patients with dementia in the community. Providing customised HCBS, rather than a non-specialised service assumed to be suitable for every patient, is essential for ensuring good patient care. In addition, attention needs to be paid to patients with care needs who do not use HCBS.

Acceptor-mediated regioselective enzyme catalyzed sialylation: chemoenzymatic synthesis of GAA-7 ganglioside glycan.

Herein, we applied PmST1 (a sialyltransferase) to achieve acceptor-mediated regioselective sialylation (AMRS) on the nonreducing end GalNH2 or GalAz (2-azido-2-deoxy galactose). Thus, C5 and C8-modified sialic acid was efficiently assembled on GalNH2 (or GalAz) to achieve the synthesis of the GAA-7 (one of the echinodermatous gangliosides with higher neuritogenic activity) glycan moiety.

Factors Affecting Patients' Acceptance of and Satisfaction with Cloud-Based Telehealth for Chronic Disease Management: A Case Study in the Workplace.

OBJECTIVE: Understanding patients' acceptance of and satisfaction with telehealth use is important for workplace health promotion. In this study, we used a questionnaire to measure patients' usage behavior and satisfaction with cloud-based telehealth services in the workplace. We empirically investigated the factors that influence patients' usage and satisfaction based on data collected from 101 participants. METHODS: As its main research framework, this study utilized a revised version of the technology acceptance model 2 that was based on the telehealth services provided for chronic disease management. Through integrating a cross-sectional research design with an author-developed structured questionnaire that was assessed using reliability and validity tests, an anonymous survey was conducted on selected participants. The proposed research model and hypotheses were validated through path analysis using SPSS. RESULTS: We found that users believe telehealth services can promote their workplace health management; that job relevance, result demonstrability, and perceived ease of use (PEOU) positively affect the perceived usefulness (PU), which implies that cognitive instrumental processes have the most significant impact on the PU of cloud-based telehealth; and that both PEOU and PU positively affect the intention to use (IU), but PU has a bigger influence than PEOU on users' intentions to continue using telehealth. In particular, the IU and actual usage behavior were critical to the patients' satisfaction with telehealth services. CONCLUSION: This research contributes to the rapid developing field of technology acceptance research by examining workplace telemedicine engagement. Our results will provide researchers with useful advice and a user-centered strategy for promoting workplace health management, which benefits both health care providers and corporate managers.

Exploring a Path Model of Cognitive Impairment, Functional Disability, and Incontinence Among Male Veteran Home Residents in Southern Taiwan.

Most studies focusing on only one directional effect among cognitive health, physical function, and incontinence may miss potential paths. This study aimed to determine the pathway by analyzing the bidirectional effects of exposure (X) on outcome (Y) and explore the mediating effect (M) between X and Y. Secondary data analyses were performed in this study. The original data were collected from August to October 2013 in one VH in Tainan, Taiwan, and the final sample size was 144 older male veterans. Path analysis was performed to test the pathway sequence X → M → Y among the three outcome variables. Approximately 80% of the veterans were aged 81 or older, approximately 42% had a functional disability, 26% had cognitive impairment, and 20% had incontinence. The relationships between functional disability and incontinence and between functional disability and cognition impairment were bidirectional, and functional disability played a key mediating role in the relationship between cognitive impairment and incontinence. Physical more than cognitive training in order to improve or at least stabilize functional performance could be a way to prevent or reduce the process of developing incontinence.

Inequality in outpatient resource utilization among older adults during the 2007-2008 financial crisis: findings from Taiwan.

BACKGROUND: Equity in medical resource utilization is a crucial concern in countries with national health insurance systems. From the perspective of an active aging framework, public health insurance is one of the pillars of economic security, as suggested by the World Bank, to achieve the goal of social security for older adults. This study thus sought to quantify income-related inequality in national health insurance systems, especially during the global economic crisis of 2007-2008. METHODS: By employing the Taiwan National Health Interview Surveys (2005 and 2009) datasets, we analyzed the socioeconomic inequality of outpatient service utilization for older Taiwanese adults during the financial crisis of 2007-2008. We used corrected concentration indices (CCIs) to examine inequalities over time. Furthermore, we decomposed socioeconomic inequalities to reveal the contributions of determinant factors. The dependent variables related to whether participants had used outpatient services in the previous month, and the independent factors included individual's needs, enabling, predisposing, and environmental factors proposed by Andersen model. RESULTS: The sample consisted of 2415 observations in 2005 and 2554 observations in 2009. The income-related health care inequality was minor from pro-rich to pro-poor across the study duration, although the difference was insignificant (women: from a concentration index [CI] of 0.0256 in 2005 to a CI of - 0.0098 in 2009; men: from a CI of 0.0379 in 2005 to a CI of 0.0310 in 2009). We used a probit model to analyze the effect of explanatory factors on outpatient resource utilization by men and women. After other factors were controlled for, we found that that the income variable had a positive and significant effect on outpatient service utilization in 2009 and the absolute contribution of income to inequality notably increased from 0.0480 in 2005 to 0.3247 in 2009 for older women. CONCLUSIONS: In conclusion, Taiwan's National Health Insurance system guarantees the accessibility of health care services to older adults, but slight income-related inequality was maintained in the outpatient resource utilization of women during the 2007-2008 financial crisis. Close attention should be paid to the vulnerability of women during times of economic insecurity.

Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3 ß-Tetrapeptide Analogues.

A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal ß-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3 ß-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3 ß-tetrapeptide framework have been successfully synthesized.

The longitudinal relationship between mental health disorders and chronic disease for older adults: a population-based study.

OBJECTIVE: Although mental health disorders in older adults are common, their relationship with chronic disease and the influence of chronic disease on the development of mental health disorders over time is not well understood. This longitudinal study investigated the change in status of mental health disorders and chronic disease, as well as their interrelationships, over time. METHODS: Participants included community-dwelling older adults living in Taiwan, aged 65 years or older, who completed six waves of survey interviews. Mental health disorders were scored using the Short Psychiatric Evaluation Schedule, and chronic disease(s) status was recorded during consecutive biennial data collection waves. The autoregressive latent trajectory model and parallel latent growth curve model were used for data analysis. RESULTS: The study findings suggest that in older people pre-existing mental health disorders and/or chronic disease(s) will predispose them to developing significantly more mental health disorders and/or chronic diseases respectively. The study findings also suggest that pre-existing mental health disorders can significantly contribute to the development of chronic disease over time, and that pre-existing chronic disease(s) significantly can contribute to the development of mental health disorders over time, indicating a reciprocal interrelationship. CONCLUSIONS: Our study findings suggest that it in addition to monitoring and treating chronic disease(s) in older people, it is also important to monitor and treat their mental health disorders. Doing so will result in overall better health outcomes and will facilitate a better quality of life as they age. Copyright © 2016 John Wiley & Sons, Ltd.

Trajectories of disability and their relationship with health status and social service use.

UNLABELLED: BACKGROUND/STUDY CONTEXT: This longitudinal study was conducted between 1994 and 2004 in a cohort of southern Taiwan community-living older residents. The study aims to explore the trajectories of disability and how these patterns differed between respondents who survived and those who died during data collection phases; this study also investigated how health status change and social service use predicted the different trajectories of disability. METHODS: Disability, chronic disease, depression, and social service usage data were collected over six waves. Clusters of disability were used to define a categorical response variable. Baseline levels and new occurrences of chronic disease and depression and the frequency of social service use during this period were chosen as the predictors of disability trajectories. RESULTS: Changes in levels of disability during the aging process were identified. Different trajectories clearly reflected heterogeneity within disability clusters and between surviving and nonsurviving respondents. This study highlighted that hypertension and depression were predictors of increased disability among both surviving and nonsurviving respondents, whereas diabetes was only found to be a strong predictor of increased disability for the nonsurviving respondents. In addition, this study found that use of social services such as personal care, homemaker-household, and physical therapy were significantly associated with an increase in disability, whereas use of recreational services seemed to be associated with a decrease in disability. CONCLUSIONS: These findings identify disability to be a highly dynamic process, which can be characterized into different trajectory clusters (e.g., no, mild, and major disability clusters). A greater awareness of these trajectories could be used to better target strategies to prevent and/or manage disabilities in an aging population.

Health-related services use and the onset of functional disability: 10 year follow-up study.

This study aimed to examine the effect of health-related service use on the development of functional disability in an older adult Taiwanese cohort. The sample population consisted of 871 participants without Instrumental Activities of Daily Living (IADL) disabilities, 1061 participants without Activities of Daily Living (ADL) disabilities and 817 participants without IADL and ADL disabilities at baseline. The onset of IADL and ADL disabilities were estimated as the follow-up survey year that these functional disabilities were first noted, or the follow-up survey year that the participant was noted as having died. A Cox proportional hazards model, with time-dependent covariates, was used to analyze the association between the time of onset of the functional disabilities and the health-related service use, after controlling for age, gender, education, marital status and time varying chronic disease status. This study found that an increase in the number of services used by the participants resulted in fewer IADL and ADL disabilities. Furthermore, participants who attended recreational programs, regular health examinations, and who received the information assistance and meal preparation were significantly less likely to develop disabilities. Participants who used one or more services were 55-77% less likely to be IADL disabled, and were 54-81% less likely to be ADL disabled, and were also 59-89% less likely to develop IADL and ADL disabilities as compared to those who used none. In the present study therefore, as the number of health services used increased the likelihood of developing a functional disability decreased.

The longitudinal relationship between depressive symptoms and disability for older adults: a population-based study.

BACKGROUND: Although depressive symptoms in older adults are common, their relationship with disability and the influence of disability on the development of depressive symptoms over time is not well understood. This longitudinal study investigates the change trajectories of both depressive symptoms and disability, as well as their associations over time. METHODS: Participants included 442 community-dwelling older adults living in Taiwan, aged 65 years or older, who completed six waves of survey interviews. Depression was scored with the Short Psychiatric Evaluation Schedule and disability with the instrumental and physical activities of daily living measure during each consecutive data collection wave. The autoregressive latent trajectory model and parallel latent growth curve modeling were adopted for analysis of the data. RESULTS: The autoregressive latent trajectory model highlights that previous depressive symptoms (and disability) significantly contributed to the advancement of more severe depressive symptoms (and disability). This model also indicates that disability significantly contributed to the onset of depressive symptoms and vice versa. The parallel latent growth curve modeling highlights that the disability intercept had significant effects on the depressive symptoms intercept, as did the depressive symptoms on disability. Furthermore, the disability slope had significant effects on the slope of the depressive symptoms. CONCLUSIONS: These findings demonstrate that disability is a stronger predictor of depressive symptoms than depressive symptoms are of disability. In addition, the prior existence of a health condition will lead to further deterioration of health conditions and that they often coexist.