ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension.

BACKGROUND: Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC. METHODS: RNA sequencing was applied to pulmonary arterial SMC (PASMC) from PAH patients with and without a BMPR2 (bone morphogenetic receptor 2) mutation versus control PASMC to uncover genes required for their heightened proliferation and glycolytic metabolism. Assessment of differentially expressed genes established metabolism as a major pathway, and the most highly upregulated metabolic gene in PAH PASMC was aldehyde dehydrogenase family 1 member 3 (ALDH1A3), an enzyme previously linked to glycolysis and proliferation in cancer cells and systemic vascular SMC. We determined if these functions are ALDH1A3-dependent in PAH PASMC, and if ALDH1A3 is required for the development of pulmonary hypertension in a transgenic mouse. Nuclear localization of ALDH1A3 in PAH PASMC led us to determine whether and how this enzyme coordinately regulates gene expression and metabolism in PAH PASMC. RESULTS: ALDH1A3 mRNA and protein were increased in PAH versus control PASMC, and ALDH1A3 was required for their highly proliferative and glycolytic properties. Mice with Aldh1a3 deleted in SMC did not develop hypoxia-induced pulmonary arterial muscularization or pulmonary hypertension. Nuclear ALDH1A3 converted acetaldehyde to acetate to produce acetyl coenzyme A to acetylate H3K27, marking active enhancers. This allowed for chromatin modification at NFYA (nuclear transcription factor Y subunit α) binding sites via the acetyltransferase KAT2B (lysine acetyltransferase 2B) and permitted NFY-mediated transcription of cell cycle and metabolic genes that is required for ALDH1A3-dependent proliferation and glycolysis. Loss of BMPR2 in PAH SMC with or without a mutation upregulated ALDH1A3, and transcription of NFYA and ALDH1A3 in PAH PASMC was ß-catenin dependent. CONCLUSIONS: Our studies have uncovered a metabolic-transcriptional axis explaining how dividing cells use ALDH1A3 to coordinate their energy needs with the epigenetic and transcriptional regulation of genes required for SMC proliferation. They suggest that selectively disrupting the pivotal role of ALDH1A3 in PAH SMC, but not endothelial cells, is an important therapeutic consideration.

The Protective Impact of Telemedicine on Persons With Dementia and Their Caregivers During the COVID-19 Pandemic.

OBJECTIVES: Social distancing under the COVID-19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable alternative to face-to-face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video-conferencing platforms could bring additional benefits to care-recipient with NCD and their spousal caregivers at home. PARTICIPANTS: Sixty older adults NCD-and-caregiver dyads were recruited through an activity center. DESIGN, INTERVENTION: The impact of additional services delivered to both care-recipient and caregiver through video conference (n = 30) was compared with telehealth targeted at caregivers by telephone only (n = 30), over 4 weeks in a pretest-post-test design. Interviews and questionnaires were conducted at baseline and study's end. MEASUREMENTS, RESULTS: Supplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone-only group (ηp2 = 0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL-AD, ηp2 = 0.23). Varying degrees of improvements in physical and mental health (Short-Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self-efficacy (Revised Caregiving Self-Efficacy Scale) were observed among caregivers in the video-conferencing group, which were absent in the telephone-only group (ηp2 = 0.23-0.51). CONCLUSION: Telemedicine by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehmedicine beyond the context of pandemic-related social distancing should be considered.

The validity, reliability and clinical utility of a performance-based executive function assessment in people with mild to moderate dementia.

Objective: Performance-based evaluation of executive function by using real-world daily living activities is an important area of study. This approach has been used extensively in evaluating patients after stroke or traumatic brain injury and patients with schizophrenia. Most important is the fact that until now, there has been no validated performance-based evaluation of executive function in people with dementia.Methods: To address that knowledge gap, this study recruited 80 patients diagnosed with dementia and 80 demographically matched healthy controls. The participants were administered tests for evaluating their performance-based executive function (Chinese Multiple Errands Test), their instrumental activities of daily living (Lawton Instrumental Activities of Daily Living Scale, Chinese Version), and their functional disability (Chinese Version of the Disability Assessment for Dementia), along with a cognitive screening test (Montreal Cognitive Assessment, Hong Kong Version) and a neuropsychological test of executive function (Trail-making Test).Results: The Chinese Multiple Errands Test demonstrated excellent inter-rater reliability, test-retest reliability and high internal consistency. Results revealed that the healthy controls out-performed the dementia patients in the performance-based executive function and cognitive screening, but not in the instrumental activities of daily living tests. Additionally, the performance efficiency scores of the older adults with dementia on the Chinese Multiple Errands Test correlated significantly with their performance results on the neuropsychological test of executive function and on the tests of functional disability and cognitive function.Conclusion: Our results indicated that the Chinese Multiple Errands Test is a reliable and valid instrument for assessing executive function in Chinese older people with dementia.

A cohort study on protocol-based nurse-led out-patient management of post-chemotherapy low-risk febrile neutropenia.

PURPOSE: International guidelines adopt risk stratification approach to manage patients with low-risk febrile neutropenia patients. We developed this out-patient program using shared-care model with professional input and patient empowerment, so as to reduce patients' psychological burden from hospitalization and to improve the cost-effectiveness of management. METHOD: This is a prospective cohort study to compare the efficacy and safeness of the out-patient program when compared with traditional in-patient care. Patients with solid tumors, developed febrile neutropenia with Multinational Association of Supportive Care in Cancer score of at least 21, and good performance status were included. After initial assessment and the first dose of oral antibiotics, patients were observed in the ambulatory center. Stable patients were discharged home after 4 h of observation and nurse counseling. Patients' condition and clinical progress were regularly reviewed by specialist nurses within the following week by telephone and nurse clinic follow-up. The primary objective of the study is success rate, which defined as the resolution of fever and infection, without hospitalization or any change in antibiotics. RESULTS: From September 2014 to December 2016, a total of 38 patients were enrolled. Majority were female with breast cancer (97%). Two patients required hospitalization due to persistent fever. The success rate of the out-patient program was not significantly different from the historical in-patient cohort (94.9 versus 97.4%, p = 0.053). No mortality was observed. Patients' compliance to the program was 100%, to telephone follow-up, nurse clinic visits, and daily temperature record. CONCLUSION: Out-patient management of patients with low-risk febrile neutropenia is effective and safe through implementation of a structured protocol with joint inputs and engagement from clinicians, oncology nurses, and patients.

Radiologically detected intranodal thyroid tissues in ipsilateral cervical lymph nodes after hemithyroidectomy in a pediatric patient.

This case report illustrates the presence of intranodal thyroid tissues in ipsilateral cervical lymph nodes after hemithyroidectomy for multinodular goiter in an adolescent patient. It highlights the rare radiological finding of thyroid tissues within cervical lymph nodes detected by ultrasonography and computed tomography, which is a great mimicker of nodal metastasis.

Usability of a virtual reality environment simulating an automated teller machine for assessing and training persons with acquired brain injury.

OBJECTIVE: This study aimed to examine the usability of a newly designed virtual reality (VR) environment simulating the operation of an automated teller machine (ATM) for assessment and training. DESIGN: Part I involved evaluation of the sensitivity and specificity of a non-immersive VR program simulating an ATM (VR-ATM). Part II consisted of a clinical trial providing baseline and post-intervention outcome assessments. SETTING: A rehabilitation hospital and university-based teaching facilities were used as the setting. PARTICIPANTS: A total of 24 persons in the community with acquired brain injury (ABI)--14 in Part I and 10 in Part II--made up the participants in the study. INTERVENTIONS: In Part I, participants were randomized to receive instruction in either an "early" or a "late" VR-ATM program and were assessed using both the VR program and a real ATM. In Part II, participants were assigned in matched pairs to either VR training or computer-assisted instruction (CAI) teaching programs for six 1-hour sessions over a three-week period. OUTCOME MEASURES: Two behavioral checklists based on activity analysis of cash withdrawals and money transfers using a real ATM were used to measure average reaction time, percentage of incorrect responses, level of cues required, and time spent as generated by the VR system; also used was the Neurobehavioral Cognitive Status Examination. RESULTS: The sensitivity of the VR-ATM was 100% for cash withdrawals and 83.3% for money transfers, and the specificity was 83% and 75%, respectively. For cash withdrawals, the average reaction time of the VR group was significantly shorter than that of the CAI group (p = 0.021). We found no significant differences in average reaction time or accuracy between groups for money transfers, although we did note positive improvement for the VR-ATM group. CONCLUSION: We found the VR-ATM to be usable as a valid assessment and training tool for relearning the use of ATMs prior to real-life practice in persons with ABI.

Home-based evaluation of executive function (Home-MET) for older adults with mild cognitive impairment.

INTRODUCTION: Executive function helps older adults maintain their activities of daily living by making plans, setting goals, and carrying them out successfully. It is important for their independence in community living. METHODS: With a carefully match-group of 80 mild cognitive impaired with 80 health control subjects. The home-based evaluation of executive function (Home-MET) was validated in subjects' own living environment. RESULTS: This Home-MET showed significant correlation in the assessment of attention control that was assessing by Test of Everyday Attention (TEA) (r = .86, p < .01), with working memory that was assessed with Trail Making Test (TMT) (r = .72, p < .01), with inhibitory control that was assessing with Stroop Test (r = .86, p < .01), with individuals' functional disability was assessed by Chinese Disability Assessment of Dementia (CDAD) (r = .77, p < .01) and cognitive assessment was assessed by Hong Kong Montreal Cognitive Assessment (HK-MoCA) (r = .88, p < .01). By benchmarking with the validated performance-based executive function assessment, the Home-MET shows significant correlation (r = .92, p < .05) with the executive function test in a standard environment in hospital, i.e. the Chinese Multiple Errands Test (the Chinese-MET). The two-stage hierarchical linear regression model with backward method showed functional disability was a marginally significant predictor (p < .059) for the Home-MET with regression model showed with R2 = .93. CONCLUSION: Results indicated the Home-MET, can provide an objective measure of executive function for subjects with mild cognitive impairment in participants' own home environment.

A randomized control trial of activity scheduling for caring for older adults with dementia and its impact on their spouse care-givers.

INTRODUCTION: Participating in meaningful activities is important for any individual's wellbeing. Activity scheduling enables older adults with dementia and their spouse caregivers to structure their activities in accordance with the things they value. METHODS: In examining the effectiveness of activity scheduling, this report details the results of a 12-week single-blinded randomized control trial using a parallel group experimental design. RESULTS: From August 2018 to August 2019, 100 community-dwelling older adults with mild to moderate dementia and their spouses completed this study. The experimental group (n = 50) practicing activity scheduling showed improvements than in control group (n = 50), with respect to alleviating the impact of the caregiving role, reducing the behavioural and psychological symptoms of dementia, decreasing the caring demand and generally improving the quality of life, with Cohen's d = .61, .45, .50 and 43 respectively. Moreover, there were significant differences between the groups indicated that over time, the experimental group showed an improvement with regard to alleviating the role of caring, with Cohen's d = .64, and alleviating disruptive and depressive behavior, with an effect size of .45 and .50 respectively. The number of caring hours needed dropped from 6.98 to 5.98 h in the experimental group. DISCUSSION & CONCLUSION: There were more activities that older adults with dementia and their spouse caregivers would like to do, and could participate in, than we had expected. Activity scheduling can facilitate their participation. This is a very important topic as non-pharmacological interventions are needed for this even-growing segment of the population.

Reliability, validity, and clinical utility of a self-reported screening tool in the prediction of fall incidence in older adults.

Background: The Chinese HomeFAST self-reported screening tool was developed to measure the number of hazards and the risk of home falls and other accidents for community-living older adults.Methods: This reliability, validity, and clinical utility study consisted of three phases. The tool's linguistic validity was established in the first phase of study, with a panel of domiciliary healthcare experts. In the second phase, the instrument yielded inter-rater reliability between community-living older adults and a group of experienced occupational therapists. Furthermore, in the third phase of study, factor analysis of the Chinese Home-FAST self-reported screening tool was conducted.Results: There was good linguistic validity, test-retest reliability and good to excellent internal consistency of the Chinese Home-FAST self-reported screening tool among older adults living in the community. Moreover, a structure with three factors - namely "Home Environment and Furniture," "Capability in Activities of Daily Living," and "Use of Devices" - was yielded from categorical principal components analysis. Clinically, the incidence of falls among this group of recruited older adults in a six-month period was 18%. The identification of seven or more hazards was associated with prediction of unplanned fall-related hospital admission with sensitivity of 83.33% and specificity of 95.83%. Conclusion: The Chinese HomeFAST self-reported screening tool is thus demonstrated to be a valid and reliable tool for measuring home hazards and can predict home falls in Chinese-speaking older adults.Implications for rehabilitationTo develop an easily understandable screening tool for older adults.Older adults can perform home safety screening on their own, and can identify potential risk of falls and other accidents at home.This can serve as a communication tool between older adults and healthcare professionals.Identified hazards can be reported to healthcare professionals for further intervention.This validated instrument can help healthcare professionals to identify higher-risk older adults in the community and thus to better prioritize their provision of professional services.