Weight management personas of breast cancer patients undergoing chemotherapy in China: a multi-method study.

BACKGROUND: Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users' personal information and persona development for the design and implementation of mHealth interventions. METHODS: Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant's experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC. RESULTS: Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics. CONCLUSIONS: The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

The Effect of Exercise on Weight and Body Composition of Breast Cancer Patients Undergoing Chemotherapy: A Systematic Review.

BACKGROUND: Chemotherapy is a primary adjuvant treatment strategy for breast cancer patients, accompanied by weight gain and negative changes in body composition. However, it is unknown whether exercise is effective in preventing said weight gain and mitigating body composition changes of breast cancer patients undergoing treatment. OBJECTIVES: The current study used meta-analysis with trial sequential analysis to determine exercise effect on weight and body composition of breast cancer patients undergoing chemotherapy. METHODS: Cochrane Library, PubMed, EMBASE, EBSCO, Scopus, and SinoMed were searched (from the database start date up to August 16, 2021) for randomized controlled studies evaluating the effect of exercise on weight or body composition among breast cancer patients during chemotherapy. RevMan software and TSA Software were used to assess the risk of bias and analyze study results. RESULTS: In total, 13 studies comprising 1828 participants were included. Meta-analysis showed that exercise could lead to lower weight, body mass index (BMI), and percentage of body fat during chemotherapy for breast cancer patients, and muscular strength showed significant improvement. Trial sequential analysis showed that evidence of muscular strength was sufficient, but BMI evidence requires further confirmation. CONCLUSION: This meta-analysis found significant differences in body weight, BMI, percentage of body fat, and muscular strength between exercise intervention groups and control groups. IMPLICATIONS FOR PRACTICE: Exercise during chemotherapy is beneficial in preventing weight gain and negative changes in body composition. Medical practitioners should encourage patients to start exercising during chemotherapy. However, further studies are required because insufficient sample sizes meant that outcomes of body composition remain unconfirmed.

Adaptive Auricular Point Acupressure for Sleep Disturbance in Women with Breast Cancer: A Randomized Controlled Trial.

Objectives: The study aimed to evaluate the preliminary effect and efficacy of auricular point acupressure (APA) on the quality of sleep in women with breast cancer who were undergoing chemotherapy. Sample & Setting. We conducted a randomized controlled trial on 68 patients with breast cancer who reported poor sleep quality based on the Pittsburgh Sleep Quality Index (PSQI) scores (>7). Methods & Variables. Participants were randomly assigned to an APA treatment group or a control group. Patients in the APA group had magnetic pellets attached to selected auricular points and were instructed to apply pressure to these points 4×/day for three consecutive weeks. We objectively measured sleep quality using the Actiwatch Spectrum and the PSQI at the baseline and postintervention. Statistical analyses of changes in sleep data were performed using the t-test, a rank-sum test, and analyses of covariance. Results: In patients treated with APA, the PSQI total score and sleep onset latency had significantly decreased, while the total sleep time and sleep efficiency had significantly increased. Although the total PSQI score differed between groups at the baseline, ANCOVA results showed that the APA group had a significantly lower total PSQI score. Conclusion: APA could be an inexpensive and effective approach to improving sleep quality and reducing sleep disturbance in patients with breast cancer. Further research needs a larger sample size to verify our findings.

Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration.

Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models' response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.

Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or "dry" AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.

Subtypes of nurses' mental workload and interaction patterns with fatigue and work engagement during coronavirus disease 2019 (COVID-19) outbreak: A latent class analysis.

BACKGROUND: Nurses play critical roles when providing health care in high-risk situations, such as during the COVID-19 outbreak. However, no previous study had systematically assessed nurses' mental workloads and its interaction patterns with fatigue, work engagement and COVID-19 exposure risk. METHODS: A cross-sectional study was conducted via online questionnaire. The NASA Task Load Index, Fatigue Scale-14, and Utrecht Work Engagement Scale were used to assess nurses' mental workload, fatigue and work engagement, respectively. A total of 1337 valid questionnaires were received and analyzed. Nurses were categorized into different subgroups of mental workload via latent class analysis (LCA). Cross-sectional comparisons, analysis of covariance (ANCOVA), and multivariate (or logistic) regression were subsequently performed to examine how demographic variables, fatigue and work engagement differ among nurses belonging to different subgroups. RESULTS: Three latent classes were identified based on the responses to mental workload assessment: Class 1 - low workload perception & high self-evaluation group (n = 41, 3.1%); Class 2 - medium workload perception & medium self-evaluation group (n = 455, 34.0%); and Class 3 - high workload perception & low self-evaluation group (n = 841, `62.9%). Nurses belonging into class 3 were most likely to be older and have longer professional years, and displayed higher scores of fatigue and work engagement compared with the other latent classes (p < 0.05). Multivariate analysis showed that high cognitive workload increased subjective fatigue, and mental workload may be positively associated with work engagement. Group comparison results indicated that COVID-19 exposure contributed to significantly higher mental workload levels. CONCLUSIONS: The complex scenario for the care of patients with infectious diseases, especially during an epidemic, raises the need for improved consideration of nurses' perceived workload, as well as their physical fatigue, work engagement and personal safety when working in public health emergencies.

Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype.

Identification of Distinct Profiles of Cancer-Related Fatigue and Associated Risk Factors for Breast Cancer Patients Undergoing Chemotherapy: A Latent Class Analysis.

BACKGROUND: Cancer-related fatigue is a complex, multidimensional, subjective experience that affects patients physically, emotionally, and mentally. The interindividual variability in symptoms of cancer-related fatigue merits further exploration. OBJECTIVE: Our objective was to identify distinct profiles of cancer-related fatigue experienced by breast cancer patients undergoing chemotherapy and to evaluate how subgroups vary demographically in clinical characteristics and in modifiable factors such as physical activity, sleep quality, and exercise self-efficacy. METHODS: Fatigue was assessed with the Chinese Cancer-Related Fatigue Scale, and a latent class analysis was performed to identify subgroups of patients with distinct fatigue profiles. RESULTS: A total of 427 breast cancer patients were included in the data analyses. Five different fatigue profiles were identified: all low-risk fatigue, all high-risk fatigue, high-risk physical fatigue, high-risk emotional fatigue, and high-risk mental fatigue. Patients in different subgroups were characterized by different risk factors. For example, patients in the high-risk emotional fatigue group had less education, lower monthly household incomes, lower exercise self-efficacy scores, less sedentary behavior, poorer sleep, and poorer quality-of-life outcomes compared with those in the all low-risk fatigue group. CONCLUSION: These findings reveal that breast cancer patients undergoing chemotherapy show significant heterogeneity in their experience of cancer-related fatigue. IMPLICATIONS FOR PRACTICE: Characteristics associated with different fatigue profiles, in particular the high-risk profiles, can be used by clinicians to target patients at greater risk of poorer symptom and quality-of-life outcomes to provide interventions tailored to their different needs.

Physical activity in the context of advanced breast cancer: An integrative review.

AIMS: To describe and synthesize diverse empirical evidence regarding physical activity (PA) in the context of advanced breast cancer (ABC). DESIGN: Integrative review guided by the work of Whittemore and Knafl (2005). DATA SOURCES: Six electronic databases were systematically searched to identify relevant literature published between January 2007-June 2019. REVIEW METHODS: Abstracts of papers that met the inclusion criteria were reviewed by two researchers and full texts of eligible papers were assessed. Data were extracted by two independent researchers and inter-rater reliability of data extraction established. Quality of papers was evaluated using the Mixed Methods Appraisal Tool. Data were organized according to comprehensive thematic analysis and the biobehavioural model for the study of exercise interventions. RESULTS: Of the 532 abstracts, 18 studies met the inclusion criteria which included six randomized controlled trials, one quantitative non-randomized study, seven quantitative descriptive studies, three mixed method studies and one qualitative study. Results from studies enrolled fell into four domains: PA performance and its influence on survival; barriers and preferences for PA; interventions to enhance PA; perceived benefits of PA from qualitative feedback. CONCLUSION: Evidence suggests that ABC patients are physically inactive. Main barriers of PA are less aerobic fitness and heavy symptom burden. Simple, tailored and specialist-supervised PA is preferred by ABC patients. Form of joint self-instructed and group accompanying is advocated as well. PA intervention programmes identified in this review vary on type, intensity, duration and frequency, while generally, are found to be feasible, safe and beneficial to patients' physical and psychosocial well-being. IMPACT: The results propose tailored, supervised, group-based PA programmes are in urgent need for ABC patients. Clinical professionals should manage more feasible and safer PA interventions to help improve patients' overall health. More research with rigorous methodology design is warranted to explore PA's effect on long-term health outcomes.

Automating Human Induced Pluripotent Stem Cell Culture and Differentiation of iPSC-Derived Retinal Pigment Epithelium for Personalized Drug Testing.

Derivation and differentiation of human induced pluripotent stem cells (hiPSCs) provide the opportunity to generate medically important cell types from individual patients and patient populations for research and the development of potential cell therapies. This technology allows disease modeling and drug screening to be carried out using diverse population cohorts and with more relevant cell phenotypes than can be accommodated using traditional immortalized cell lines. However, technical complexities in the culture and differentiation of hiPSCs, including lack of scale and standardization and prolonged experimental timelines, limit the adoption of this technology for many large-scale studies, including personalized drug screening. The entry of reproducible end-to-end automated workflows for hiPSC culture and differentiation, demonstrated on commercially available platforms, provides enhanced accessibility of this technology for both research laboratories and commercial pharmaceutical testing. Here we have utilized TECAN Fluent automated cell culture workstations to perform hiPSC culture and differentiation in a reproducible and scalable process to generate patient-derived retinal pigment epithelial cells for downstream use, including drug testing. hiPSCs derived from multiple donors with age-related macular degeneration (AMD) were introduced into our automated workflow, and cell lines were cultured and differentiated into retinal pigment epithelium (RPE). Donor hiPSC-RPE lines were subsequently entered in an automated drug testing workflow to measure mitochondrial function after exposure to "mitoactive" compounds. This work demonstrates scalable, reproducible culture and differentiation of hiPSC lines from individuals on the TECAN Fluent platform and illustrates the potential for end-to-end automation of hiPSC-based personalized drug testing.

Teaching Health Assessment Symptomatology Using a Flipped Classroom Combined With Scenario Simulation.

BACKGROUND: Symptom assessment is difficult to understand and be retained by second-year bachelor's nursing students. A flipped classroom combined with scenario simulation (FCSS) is a new potential teaching model. This study compares the teaching effect and knowledge retention between the FCSS approach and the traditional flipped classroom (FC) approach. METHOD: Second-year bachelor's nursing students were selected as research participants. One group (n = 59) adopted an FCSS approach, whereas the other group (n = 68) adopted an FC approach. We evaluated student mastery and retention of knowledge through two tests: one before the next class, the other after 2 months. RESULTS: Regarding knowledge mastery, the FC group had a higher score than the FCSS group both in total score (66.29 ± 15.27 versus 59.42 ± 10.76) and group learning score (46.06 ± 13.25 versus 38.47 ± 8.22) in the first test (p < .05). The retention of knowledge in the FCSS group was better than that in the FC group (p < .001), represented by the variable of test score difference before and after 2 months. CONCLUSION: When teaching symptomatology, FCSS is helpful to enhance self-learning and improve student long-term memory. [J Nurs Educ. 2020;59(8):448-452.].

Multimedia Appendix Correction: mHealth Supportive Care Intervention for Parents of Children With Acute Lymphoblastic Leukemia: Quasi-Experimental Pre- and Postdesign Study.

[This corrects the article DOI: 10.2196/mhealth.9981.].

Relationship Between the Efficacy of Cardiac Cell Therapy and the Inhibition of Differentiation of Human iPSC-Derived Nonmyocyte Cardiac Cells Into Myofibroblast-Like Cells.

RATIONALE: Myofibroblasts are believed to evolve from precursor cells; however, whether noncardiomyocyte cardiac cells (NMCCs; ie, endothelial cells, smooth muscle cells, pericytes, and fibroblasts) that have been derived from human-induced pluripotent stem cells (hiPSCs) can transdifferentiate into myofibroblast-like cells, and if so, whether this process reduces the efficacy of hiPSC-NMCC therapy, is unknown. OBJECTIVE: To determine whether hiPSC-NMCCs can differentiate to myofibroblast-like cells and whether limiting the transdifferentiation of hiPSC-NMCCs can improve their effectiveness for myocardial repair. METHODS AND RESULTS: When endothelial cells, smooth muscle cells, pericytes, and fibroblasts that had been generated from hiPSCs were cultured with TGF-ß (transforming growth factor-ß), the expression of myofibroblast markers increased, whereas endothelial cell, smooth muscle cell, pericyte, and fibroblast marker expression declined. TGF-ß-associated myofibroblast differentiation was accompanied by increases in the signaling activity of Smad, Snail, and mTOR (mammalian target of rapamycin). However, measures of pathway activation, proliferation, apoptosis, migration, and protein expression in hiPSC-endothelial cell-derived, smooth muscle cell-derived, pericyte-derived, and fibroblast-derived myofibroblast-like cells differed. Furthermore, when hiPSC-NMCCs were transplanted into the hearts of mice after myocardial infarction, ≈21% to 35% of the transplanted hiPSC-NMCCs expressed myofibroblast markers 1 week later, compared with <7% of transplanted cells ( P<0.01, each cell type) in animals that were treated with both hiPSC-NMCCs and the TGF-ß inhibitor galunisertib. Galunisertib coadministration was also associated with significant improvements in fibrotic area, left ventricular dilatation, vascular density, and cardiac function. CONCLUSIONS: hiPSC-NMCCs differentiate into myofibroblast-like cells when cultured with TGF-ß or when transplanted into infarcted mouse hearts, and the phenotypes of the myofibroblast-like cells can differ depending on the lineage of origin. TGF-ß inhibition significantly improved the efficacy of transplanted hiPSC-NMCCs for cardiac repair, perhaps by limiting the differentiation of hiPSC-NMCCs into myofibroblast-like cells.

mHealth Supportive Care Intervention for Parents of Children With Acute Lymphoblastic Leukemia: Quasi-Experimental Pre- and Postdesign Study.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Caring for children with ALL is challenging for parents. A mobile health (mHealth) supportive care intervention was developed to meet parents' needs. OBJECTIVE: This study aims to evaluate the potential effectiveness of this mHealth supportive care intervention on emotional distress, social support, care burden, uncertainty in illness, quality of life, and knowledge. METHODS: We conducted a quasi-experimental pre- and postdesign study from June 2015 to January 2016. In total, 101 parents were enrolled in the study, with 50 in the observation group and 51 in the intervention group. Parents in the observation group received the standard health education and were observed for 3 months. Parents in the intervention group received the mHealth supportive care intervention, in addition to the standard health education. The intervention consisted of 2 parts-an Android smartphone app "Care Assistant (CA)" and a WeChat Official Account. The CA with 8 modules (Personal Information, Treatment Tracking, Family Care, Financial and Social Assistance, Knowledge Center, Self- Assessment Questionnaires, Interactive Platform, and Reminders) was the main intervention tool, whereas the WeChat Official Account was supplementary to update information and realize interaction between parents and health care providers. Data of parents' social support, anxiety, depression, care burden, uncertainty in illness, quality of life, their existing knowledge of ALL and care, and knowledge need were collected before and after the 3-month study period in both groups. For the intervention group, parents' experience of receiving the intervention was also collected through individual interviews. RESULTS: Overall, 43 parents in the observation group and 49 in the intervention group completed the study. Results found that the intervention reduced parents' anxiety (Dint(Post-Pre)=-7.0 [SD 13.1], Dobs(Post-Pre)=-0.4 [SD 15.8], t90=-2.200, P=.03) and uncertainty in illness (Dint(Post-Pre)=-25.0 [SD 8.2], Dobs(Post-Pre)=-19.8 [SD 10.1], t90=-2.761, P=.01), improved parents' social function (Dint(Post-Pre)=9.0 [SD 32.8], Dobs(Post-Pre)=-7.5 [SD 30.3], t90=2.494, P=.01), increased parents' knowledge of ALL and care (Dint(Post-Pre)=28.4 [SD 12.4], Dobs(Post-Pre)=17.2 [SD 11.9], t90=4.407, P<.001), and decreased their need for knowledge (Dint(Post-Pre)=-9.9 [SD 11.6], Dobs(Post-Pre)=-1.9 [SD 6.4], t90=-4.112, P<.001). Qualitative results showed that parents were satisfied with the intervention and their role in the caregiving process. CONCLUSIONS: The mHealth intervention in supporting parents of children with ALL is effective. This study is informative for other future studies on providing mHealth supportive care for parents of children with cancer.

Mobile Physical Activity Intervention for Breast Cancer Patients During Chemotherapy.

Breast cancer patients showed low engagement in physical activity (PA) during chemotherapy. Evidence showed regular PA has potential to reduce mortality and risks of cancer recurrence, relieve psychological distress, manage symptoms and improve quality of life. Mobile health intervention displays a great advantage to deliver cancer care timely and remotely. A Mobile Physical Activity Program was constructed in a mobile phone application. The application contained 5 modes: information delivering, disease tracking, events reminders, online interaction, health behavior recording (daily walking steps, sleeping time and body weight) and self-reported assessment. Both applications and web-based administration portal were developed by engineers.

Gauging the Effects of Self-efficacy, Social Support, and Coping Style on Self-management Behaviors in Chinese Cancer Survivors.

BACKGROUND: Better self-management control in cancer survivors would benefit their functional status, quality of life, and health service utilization. Factors such as self-efficacy, social support, and coping style are important predictors of self-management behaviors of cancer survivors; however, the impact of these factors on self-management behaviors has not yet been empirically tested in Chinese cancer survivors. OBJECTIVES: The aim of this study was to examine how self-efficacy, social support, and coping style affect specific self-management behaviors. METHODS: A secondary data analysis was completed from a cross-sectional study. A total of 764 cancer survivors were recruited in the study. Validated instruments were used to assess patients' self-efficacy, social support, and coping style. Structural equation modeling (SEM) was used to test the hypothesis. RESULTS: The SEM model fits the data very well, with root mean square error of approximation (RMSEA) of 0.034; close-fit test cannot reject the hypothesis of root mean square error of approximation of 0.05 or less, comparative fit index of 0.91, Tucker-Lewis index of 0.90, and weighted root mean square residual of 0.82. For the measurement models in the SEM, all items loaded highly on their underlying first-order factors, and the first-order factors loaded highly on their underlying second-order factors (self-efficacy and social support, respectively). The model demonstrated that self-efficacy and social support directly and indirectly, via coping style, affect 3 self-management behaviors (ie, communication, exercise, and information seeking). CONCLUSION: Our results provide evidence that self-efficacy and social support impose significant direct effects, as well as indirect effects via copying style, on the self-management of cancer survivors. IMPLICATIONS FOR PRACTICE: Our findings may help nurses to further improve their care of cancer survivors in terms of their self-management behaviors, specifically communication, exercise, and information seeking.

Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells.

RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs. METHODS AND RESULTS: Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L+) medium or in standard (L-) medium. Compared with the L- medium, the L+ medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for NDRG (N-myc downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested that the L+ medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L+-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.

Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE) underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo. Using the Seahorse Extracellular Flux Analyzer to measure bioenergetics, we observed RPE from donors with AMD exhibited reduced mitochondrial and glycolytic function compared with healthy donors. RPE from AMD donors were also more resistant to oxidative inactivation of these two energy-producing pathways and were less susceptible to oxidation-induced cell death compared with cells from healthy donors. Investigation of the potential mechanism responsible for differences in bioenergetics and resistance to oxidative stress showed RPE from AMD donors had increased PGC1α protein as well as differential expression of multiple genes in response to an oxidative challenge. Based on our data, we propose that cultured RPE from donors phenotyped for the presence or absence of AMD provides an excellent model system for studying "AMD in a dish". Our results are consistent with the ideas that (i) a bioenergetics crisis in the RPE contributes to AMD pathology, and (ii) the diseased environment in vivo causes changes in the cellular profile that are retained in vitro.

Development of a Smartphone Application to Monitor Pediatric Patient-Reported Outcomes.

Patient-reported outcomes are increasingly emphasized in clinical trials and population health studies. Our research team developed a smartphone app to track patient-reported outcomes of children with chronic diseases. The purpose of this study is to develop a patient-reported outcome reporting app and evaluate its usability. A multidisciplinary research team including health services researchers, pediatric nurses, and software engineers worked collaboratively in developing the patient-reported outcome app and administration portal. Group discussions and several rounds of feedback and modification were used. Ten pediatric patients with cancer, five parents, and two nurses participated in the usability study. We conducted content analyses in app development and usability evaluation. The app collected demographic information and patient-reported outcomes. Patient-reported outcomes were collected by Chinese versions of pediatric Patient-Reported Outcomes Measurement Information System Short Forms and Patient-Reported Outcomes Measurement Information System Parent Proxy Report Scales for Children. Pediatric patients aged 8 to 17 years and parents with a 5- to 7-year-old pediatric child used different age-appropriate questionnaires. The Web-based administration portal helped to manage demographic information, questionnaires, administrators, and survey-conducting organizations. The users liked the app. All participants felt that this app was easy to use and the interfaces were friendly to children. Nurses thought the administration portal interfaces were simple and the data were convenient to download for further analysis. We conclude that the app and its administration portal meet researchers and clinical nurses' demand and have potential to promote patient-reported outcomes in assessing quality of life and symptoms of pediatric patients.