Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 58
Filter
1.
Eur J Nutr ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38693451

ABSTRACT

PURPOSE: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. METHODS: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. RESULTS: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. CONCLUSION: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

2.
Environ Pollut ; 349: 123908, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38570157

ABSTRACT

Paddy Crusts (PC) play a pivotal role in the migration and transformation of heavy metals within paddy ecosystems, situated at the critical intersection of air, water, and soil. This study focused on PC samples from heavy metal-contaminated rice paddies in six southern Chinese provinces. It's the first time we've screened and quantified the impact of nutrition, physicochemical properties, and heavy metals on bacterial diversity in PC. Our results highlight the significant influence of zinc, total nitrogen, and soil manganese on bacterial diversity. Using structural equation models, we identified the pathways through which these three types of environmental factors shape bacterial diversity. Heavy metal indicators and physical and chemical indicators exerted a direct negative effect on bacterial diversity in PC, while nutritional indicators had a direct and significant positive effect on bacterial diversity. Variance partitioning analysis revealed heavy metals had the most significant impact, accounting for 7.77% of the total effect. Moreover, the influence of heavy metals on bacterial diversity increased as diversity decreased, ranging from 3.81% to 42.09%. To remediate specific heavy metal pollution, our proposed method involves cultivating indigenous bacteria by controlling these environmental factors, based on an analysis of the interplay among bacterial diversity, environmental variables, and heavy metal bioconcentration factors. These findings enhance our understanding of PC and provide insights into rice field heavy metal pollution mitigation.


Subject(s)
Metals, Heavy , Oryza , Soil Microbiology , Soil Pollutants , Metals, Heavy/analysis , China , Soil Pollutants/analysis , Bacteria/drug effects , Environmental Monitoring/methods , Ecosystem , Soil/chemistry , Agriculture
3.
J Hazard Mater ; 465: 133524, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38232555

ABSTRACT

Utilizing an acid-resistant biological soil crust (BSC) species that we discovered, we developed a device capable of efficiently removing cadmium (Cd) from mine wastewater with varying levels of acidity. Our research has demonstrated that this particular BSC species adapts to acidic environments by regulating the balance of fatty acids and acid-resistant enzymes. At a Cd concentration of 5 mg/L, the BSC grew well. When the initial Cd concentration was 2 mg/L, and the flow rate was set at 1 mL/min (at pH levels of 3, 4, and 5), BSC had a high removal rate of Cd, and the removal rate increased with the increase of pH (from 90% to 97%). Chemisorption is the primary removal mechanism in the initial stage, where the functional groups and minerals on the surface of the BSC play a significant role. In addition, BSC also adapts to Cd stress by changing bacterial community structure. It was discovered through infrared spectroscopy and two-dimensional correlation analysis that hydrophilic groups, specifically phosphate and carboxyl groups, exhibited the highest reactivity during the Cd binding process. Protein secondary structure analysis confirmed that as the pH increased, the adsorption capacity of the BSC increased; making biofilm formation easier. This study presents a novel approach for the treatment of acidic wastewater.


Subject(s)
Cadmium , Wastewater , Cadmium/analysis , Soil/chemistry , Minerals , Adsorption , Hydrogen-Ion Concentration
4.
Front Nutr ; 10: 1227974, 2023.
Article in English | MEDLINE | ID: mdl-37706212

ABSTRACT

Background: Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. Methods: The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. Results: This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Conclusion: Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

5.
Cell Chem Biol ; 30(9): 1104-1114.e7, 2023 09 21.
Article in English | MEDLINE | ID: mdl-37164019

ABSTRACT

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.


Subject(s)
Gout , Hyperuricemia , Humans , Animals , Uric Acid/metabolism , Anaerobiosis , Drosophila melanogaster/metabolism , Gout/metabolism , Purines/metabolism , Escherichia coli/metabolism , Hydrolases/metabolism
6.
Clin Gerontol ; 46(1): 47-52, 2023.
Article in English | MEDLINE | ID: mdl-33308033

ABSTRACT

OBJECTIVE: Determine whether race predicts fear of falling (FOF) in older adults with a history of previous fall(s) while controlling for mobility performance, activity of daily living (ADL) independence, age, gender, and education. METHODS: We examined predictors of FOF among community-dwelling older adults using data from two longitudinal randomized controlled trials that implemented fall prevention programs for community-dwelling older adults. RESULTS: Two hundred fifty-nine participants were included in the analysis; 145 reported low FOF, while 59 reported high FOF. After controlling for mobility performance, ADL independence, and sociodemographic factors, Black older adults were more likely to report FOF (OR = 2.17) compared to White older adults. Overall, older adults with lower mobility performance/functioning scores were more likely to have FOF (OR = 0.08). CONCLUSIONS: Older adults (aged ≥65 years) who are at higher risk, based on a prior history of fall(s), are more susceptible to developing FOF, as evidenced by the older adults within this study, due to limited mobility performance and functioning. CLINICAL IMPLICATIONS: Black older adults may be at greater risk of FOF than their White counterparts based on previous fall history and level of functional mobility. Incorporating measures of objective performance-based function along with measures of psychological factors are viable methods to identify and address FOF within Black older adult populations.


Subject(s)
Fear , Independent Living , Humans , Aged , Fear/psychology , Activities of Daily Living
7.
Redox Biol ; 59: 102578, 2023 02.
Article in English | MEDLINE | ID: mdl-36566738

ABSTRACT

Conventional techniques for in vitro cancer drug screening require labor-intensive formalin fixation, paraffin embedding, and dye staining of tumor tissues at fixed endpoints. This way of assessment discards the valuable pharmacodynamic information in live cells over time. Here, we found endogenous lipofuscin-like autofluorescence acutely accumulated in the cell death process. Its unique red autofluorescence could report the apoptosis without labeling and continuously monitor the treatment responses in 3D tumor-culture models. Lifetime imaging of lipofuscin-like red autofluorescence could further distinguish necrosis from apoptosis of cells. Moreover, this endogenous fluorescent marker could visualize the apoptosis in live zebrafish embryos during development. Overall, this study validates that lipofuscin-like autofluorophore is a generic cell death marker. Its characteristic autofluorescence could label-free predict the efficacy of anti-cancer drugs in organoids or animal models.


Subject(s)
Lipofuscin , Neoplasms , Animals , Lipofuscin/metabolism , Zebrafish/metabolism , Microscopy, Fluorescence , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Staining and Labeling
8.
J Gerontol B Psychol Sci Soc Sci ; 78(Suppl 1): S71-S80, 2023 03 13.
Article in English | MEDLINE | ID: mdl-36368018

ABSTRACT

OBJECTIVES: Social participation is known to enhance well-being. Caregiving responsibilities are more intense when caring for an older adult with than without dementia and may affect caregivers' ability for social participation. We estimate social participation restrictions among caregivers for older persons with versus without dementia, variation within racial/ethnic group, and the mediating effect of care hours. METHODS: We use the 2017 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) to study family caregivers for older adults. We estimate the prevalence of social participation (e.g., visiting family/friends, religious activities, group/club activities, going out) that were important to the caregiver but missed due to caregiving. We use logistic models to test for differences in restrictions by the older adult's dementia status overall and within race/ethnic group, adjusting for caregiver and care receiver characteristics. RESULTS: One-third of family caregivers for older adults with dementia reported restrictions due to caregiving, double the prevalence among caregivers of an older adult without dementia (33.3% vs 16.0%; p < .001). This doubling gap persisted in adjusted models (odds ratio [OR] = 2.4; p < .01) but mainly for White, non-Hispanic caregivers (OR = 3.2; p < .001). Substantially greater caregiving hours for people with versus without dementia was found (104 vs 60 hr per month), which is responsible for about 21% of the total difference in restrictions (p < .05). DISCUSSION: More time spent among caregivers of persons with versus without dementia may be an important factor undermining social participation, but hours only partially explain the gap. Future interventions should consider how to facilitate social participation among caregivers.


Subject(s)
Caregivers , Dementia , Humans , Aged , Aged, 80 and over , Dementia/therapy
10.
Am J Occup Ther ; 76(3)2022 May 01.
Article in English | MEDLINE | ID: mdl-35616653

ABSTRACT

IMPORTANCE: Frailty is common, detrimental, and costly in later life. Interventions can reduce the risk for frailty. OBJECTIVE: To assess the feasibility of a frailty prevention intervention. DESIGN: A two-arm, prospective randomized controlled trial with blinded participant allocation and data collection at baseline and 1 wk postintervention by data collectors blinded to participant assignment. SETTING: Community. PARTICIPANTS: Thirty community-dwelling, English-speaking, older African-Americans who were classified as prefrail were randomly recruited from a university research subject registry. INTERVENTION: The habit formation treatment was delivered face to face during 12 weekly home-based sessions approximately 45 min in length. OUTCOMES AND MEASURES: We assessed feasibility as reflected in participant recruitment, retention, session attendance, and program satisfaction. Clinical outcomes included sedentary time and dietary quality (primary) as well as frailty status, physical activity, physical function, depression, quality of life, and anthropometry (secondary). Habit formation (mechanism of change) was assessed in the treatment group only. RESULTS: Twenty women (M age = 73.5 yr) completed the study. The recruitment rate was 69.8%, and we retained 95.2% of participants through the end of the study, with session attendance rates of 98.1% and 88.6% for the treatment and control groups, respectively, and mean acceptability scores of 30.3 and 28.0 for the treatment and control groups, respectively. Changes in primary and secondary clinical outcomes were largely in the expected direction. CONCLUSIONS AND RELEVANCE: The intervention was feasible to deliver. Although future efficacy studies are needed, our preliminary data suggest the potential of an occupational therapy intervention to reduce frailty risk. What This Article Adds: Although it may be possible to slow or prevent the progression to frailty by modifying existing habits and occupations, few occupational therapy interventions address frailty. Our data provide new and much-needed insights about the potential feasibility of an occupational therapy intervention to reduce frailty risk.


Subject(s)
Frailty , Aged , Feasibility Studies , Female , Frailty/prevention & control , Habits , Humans , Prospective Studies , Quality of Life
11.
Front Genet ; 13: 832582, 2022.
Article in English | MEDLINE | ID: mdl-35444682

ABSTRACT

Background and Aims: Antithrombin (AT) is the most important physiological inhibitor in vivo, and coagulation factor II (FII) or prothrombin is a coagulation factor vital to life. The purpose of our research was to illustrate the connection between gene mutations and the corresponding deficiencies of AT and FII. Methods: Functional and molecular analyses were performed. The possible impact of the mutation was analyzed by online bioinformatics software. ClustalX-2.1-win and PyMol/Swiss-Pdb Viewer software were used for conservative analyses and to generate molecular graphic images, respectively. Results: The proband showed a lower limb venous thrombosis and acute pulmonary embolism infarction with reduced AT activity (50%). His mother, with subcutaneous ecchymosis, had reduced activities of AT and FII, of 44 and 5%, respectively. Molecular analysis showed that both the proband and his mother carried c.964A > T (p.Lys322stop) heterozygotes in SERPINC1. The difference was that his mother carried homozygous c.494C > T (p.Thr165Met) in F2, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein. Conclusion: This study identified a novel mutation of SERPINC1 and a missense mutation of F2, which may be the molecular mechanism leading to AT and FII deficiency in this family. It will help genetic diagnosis and counseling for thrombotic families.

12.
Int J Pharm ; 616: 121568, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35150845

ABSTRACT

It is becoming clear that the human gut microbiome is critical to health and well-being, with increasing evidence demonstrating that dysbiosis can promote disease. Increasingly, precision probiotics are being investigated as investigational drug products for restoration of healthy microbiome balance. To reach the distal gut alive where the density of microbiota is highest, oral probiotics should be protected from harsh conditions during transit through the stomach and small intestines. At present, few probiotic formulations are designed with this delivery strategy in mind. This study employs an emerging machine learning (ML) technique, known as active ML, to predict how excipients at pharmaceutically relevant concentrations affect the intestinal proliferation of a common probiotic, Lactobacillus paracasei. Starting with a labelled dataset of just 6 bacteria-excipient interactions, active ML was able to predict the effects of a further 111 excipients using uncertainty sampling. The average certainty of the final model was 67.70% and experimental validation demonstrated that 3/4 excipient-probiotic interactions could be correctly predicted. The model can be used to enable superior probiotic delivery to maximise proliferation in vivo and marks the first use of active ML in microbiome science.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Probiotics , Dysbiosis , Humans , Supervised Machine Learning
13.
Am J Occup Ther ; 75(5)2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34780632

ABSTRACT

IMPORTANCE: Informal caregivers often receive limited training and support, especially in providing assistance with toileting, a physically and emotionally demanding activity of daily living. This increases caregivers' risk for physical injury and burnout and jeopardizes older adults' ability to age in place. OBJECTIVE: To assess the feasibility, acceptability, and preliminary efficacy of a toileting intervention using an automated bidet to reduce the amount of physical assistance required from caregivers. DESIGN: Randomized wait-list control feasibility study. SETTING: Caregiver's home. PARTICIPANTS: Ten informal caregivers. INTERVENTION: An occupational therapy intervention to educate and train caregiving dyads to use an automated bidet system. Outcomes and Measures: Feasibility was measured in terms of recruitment and retention, bidet installation, ability to operate the bidet, acceptability (a process evaluation), preliminary efficacy (physical barriers and impact on caregiver outcomes of performance, satisfaction, and self-efficacy), and adverse events. RESULTS: All bidets were installed successfully. All caregivers reported that the intervention made toileting easier and increased their confidence. Physical barriers decreased for the treatment group. The bidet had a large effect on self-efficacy for the treatment group. CONCLUSIONS AND RELEVANCE: The results suggest that the automated bidet intervention is feasible and acceptable and can have a positive impact on caregiver outcomes when assisting with toileting. What This Article Adds: A toileting intervention using an automated bidet is feasible and acceptable for caregivers of older adults and can reduce the amount of physical assistance required from caregivers.


Subject(s)
Caregiver Burden , Caregivers , Aged , Feasibility Studies , Humans , Self Care , Self Efficacy
14.
JAMA Netw Open ; 4(8): e2122044, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34463746

ABSTRACT

Importance: Falls are the leading preventable cause of morbidity, mortality, and premature institutionalization for community-dwelling older adults. Objective: To test the effectiveness of a behavioral intervention on fall risk among older adults receiving services from an Area Agency on Aging. Design, Setting, and Participants: This randomized clinical trial examined a home hazard removal intervention in the community using a race- and sex-stratified randomization design. Older adults receiving services from the Area Agency on Aging in urban St Louis, Missouri, were assigned to a home hazard removal intervention delivered over 2 weeks with a 6-month booster or usual care control. Eligible participants were adults aged 65 years or older who did not have dementia, were at high risk for falling, and resided in the community. Enrollment occurred from January 2015 to September 2016; 12-month follow-up occurred from February 2016 to October 2017. Data were analyzed from February 2019 to July 2021. Interventions: The intervention was a home hazard removal program delivered by an occupational therapist in the home that included a comprehensive clinical assessment and a tailored hazard removal plan. Usual care control consisted of annual assessments and community referral. Main Outcomes and Measures: The primary outcome was the hazard of a fall over 12 months. Prespecified secondary outcomes included the rate of falls over 12 months, daily activity performance, falls self-efficacy, and self-reported quality of life. Results: A total of 310 participants (mean [SD] age, 75 [7.4] years; 229 [74%] women; 161 Black participants [52%]) were randomized, with 155 participants assigned to the intervention and 155 participants assigned to usual care. Retention was 127 participants (82%) in the intervention group and 126 participants (81%) in the control group. There was no difference for our primary outcome of fall hazard (hazard ratio, 0.90; 95% CI, 0.66-1.27). There was a 38% reduction in the rate of falling in the intervention group compared with the control group (relative risk, 0.62; 95% CI, 0.40-0.95; P = .03). At 12 months, the rate of falls per person-year was 1.5 (95% CI, 1.32-1.75) in the intervention group and 2.3 (95% CI, 2.08-2.60) in the control group. There was no difference in daily activity performance (adjusted difference, -0.20; 95% CI, -0.95 to 0.55; P = .60), falls self-efficacy (adjusted difference, -0.12; 95% CI, -1.25 to 1.01; P = .84), or quality of life (adjusted difference, 0.84; 95% CI, -0.95 to 2.64; P = .35). Conclusions and Relevance: This randomized clinical trial found that a brief home hazard removal program did not reduce the hazard of falls among community-dwelling older adults at high risk for falling. The intervention was effective in achieving a reduced rate of falls, a prespecified secondary outcome. This effectiveness study has the potential for delivery through the national aging services network. Trial Registration: ClinicalTrials.gov Identifier: NCT02392013.


Subject(s)
Accidental Falls/prevention & control , Equipment Safety/standards , Guidelines as Topic , Independent Living , Safety Management/standards , Aged , Aged, 80 and over , Female , Humans , Male , Missouri
15.
J Aging Phys Act ; 29(4): 612-619, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33361502

ABSTRACT

The Lifestyle-integrated Functional Exercise Program (LiFE) is proven to have high adherence rates and can significantly reduce falls, but it has not yet been implemented for diverse older adults residing in urban medically underserved (MU) areas. An exploratory sequential mixed methods study was conducted to adapt LiFE and test the adapted program's preliminary feasibility. Focus groups with MU older adults and service providers were conducted to identify modifications. The new adapted program, Diverse Older Adults Doing LiFE (DO LiFE), was then evaluated with older adults. Thematic analysis revealed health literacy and lack of racial representation as barriers to implementing LIFE in this population. The pilot study showed that DO LiFE was feasible with good retention (89%) and high adherence (81.27%) rates. DO LiFE demonstrated preliminary feasibility for diverse MU older adults. Researchers should proceed to larger studies for translating DO LiFE from research to the community.


Subject(s)
Accidental Falls , Medically Underserved Area , Accidental Falls/prevention & control , Aged , Exercise , Exercise Therapy , Humans , Pilot Projects
16.
Aust Occup Ther J ; 67(5): 470-478, 2020 10.
Article in English | MEDLINE | ID: mdl-32648268

ABSTRACT

INTRODUCTION: Comprehensive evaluation and intervention provided by occupational therapists is effective in reducing the presence of fall hazards in the homes of older adults. The purpose of this study was to document known environmental hazards and to update a previous content analysis. A secondary goal reviewed a framework for evaluation and practice. METHODS: A comprehensive scoping review of published academic articles was performed from 1996 to 2019 to answer: What environmental hazards have been associated with falls in the homes of community-dwelling older adults? Data was extracted in a standardised critical appraisal worksheet and content analysis was conducted. A review of a conceptual framework for assessment and intervention was conducted by international experts (n = 6) in face-to-face interviews. RESULTS: Fourteen studies met the inclusion criteria for the scoping study. The studies reported 17 in-home environmental hazards: throw rugs/carpets, clutter, cords/wires, poorly placed light switches, items placed too low, items placed too high, no grab bars, toilet seats too low, uneven floor surfaces, slippery/wet surfaces, snowy/icy surfaces, backless/unsupportive shoes, unsteady stairs, inadequate lighting, inadequate heating/cooling, step stools without railings, and pets. CONCLUSION: A comprehensive list of specific fall hazards in and around the homes of older adults and a guiding framework offers occupational therapists an evidence-based foundation for fall prevention efforts.


Subject(s)
Accidental Falls/prevention & control , Occupational Therapy/organization & administration , Aged , Humans , Independent Living , Risk Factors
17.
Front Immunol ; 11: 1106, 2020.
Article in English | MEDLINE | ID: mdl-32582190

ABSTRACT

Among all T and NK cell subsets, regulatory T (Treg) cells typically respond to the lowest concentrations of IL-2 due to elevated surface expression of the IL-2R alpha chain (IL2RA; CD25) and the high affinity IL-2 receptor (IL-2R) complex. This enhanced sensitivity forms the basis for low-dose (LD) IL-2 therapy for the treatment of inflammatory diseases, where efficacy correlates with increased Treg cell number and expression of functional markers. Despite strong preclinical support for this approach, moderate and variable clinical efficacy has raised concerns that adequate Treg selectivity still cannot be achieved with LD IL-2, and/or that doses are too low to stimulate effective Treg-mediated suppression within tissues. This has prompted development of IL-2 variants with greater Treg selectivity, achieved through attenuated affinity for the signaling chains of the IL-2R complex (IL2RB or CD122 and IL2RG or CD132) and, consequently, greater reliance on high CD25 levels for full receptor binding and signaling. While certain IL-2 variants have advanced to the clinic, it remains unknown if the full range of IL-2R signaling potency and Treg-selectivity observed with low concentrations of wildtype IL-2 can be sufficiently recapitulated with attenuated IL-2 muteins at high concentrations. Using a panel of engineered IL-2 muteins, we investigated how a range of IL-2R signaling intensity, benchmarked by the degree of STAT5 phosphorylation, relates to biologically relevant Treg cell responses such as proliferation, lineage and phenotypic marker expression, and suppressor function. Our results demonstrate that a surprisingly wide dynamic range of IL-2R signaling intensity leads to productive biological responses in Treg cells, with negligible STAT5 phosphorylation associating with nearly complete downstream effects such as Treg proliferation and suppressor activity. Furthermore, we show with both in vitro and humanized mouse in vivo systems that different biological responses in Treg cells require different minimal IL-2R signaling thresholds. Our findings suggest that more than minimal IL-2R signaling, beyond that capable of driving Treg cell proliferation, may be required to fully enhance Treg cell stability and suppressor function in vivo.


Subject(s)
Interleukin-2/immunology , Lymphocyte Activation/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Humans , Interleukin-2/metabolism , Mice , Protein Binding , Protein Engineering , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Structure-Activity Relationship
18.
Front Psychol ; 11: 305, 2020.
Article in English | MEDLINE | ID: mdl-32174870

ABSTRACT

This study reported on development and evaluation of a learning program that integrated a multidimensional diagnostic assessment with two different learning interventions with the aim to diagnose and improve three-dimensional mental rotation skills. The multidimensional assessment was built upon the Diagnostic Classification Model (DCM) framework that can report the binary mastery on each specific rotation skill. The two learning interventions were designed to train students to use a holistic rotation strategy and a combined analytic and holistic strategy, respectively. The program was evaluated through an experiment paired with multiple exploratory and confirmatory statistical analysis. Particularly, the recently proposed joint models for response times and response accuracy within dynamic DCM framework is applied to assess the effectiveness of the learning interventions. Compared with the traditional assessment on spatial skills, where the tests are timed and number correct is reported as a measure for test-takers' performances, the developed dynamic diagnostic assessment can provide an informative estimate of the learning trajectory for each participant in terms of the strengths and weaknesses in four fine-grained spatial rotation skills over time. Compared with an earlier study that provided initial evidence of the effectiveness of building a multidimensional diagnostic assessment with training tools, the present study improved the assessment and learning intervention design. Using both response times and response accuracy, thus current study additionally evaluated the newly developed program by investigating the effectiveness of two interventions across gender, country and rotation strategy.

19.
Gerontol Geriatr Med ; 6: 2333721420904234, 2020.
Article in English | MEDLINE | ID: mdl-32076629

ABSTRACT

We examined the level of agreement between subjective frailty assessments (SFA) and frailty classifications derived from the validated Paulson-Lichtenberg Frailty Index (PLFI). Clinic patients (n = 202) were classified as healthy, prefrail, or frail first by screening using the PLFI and later by two geriatric nurses and two geriatricians according to SFA. Of the 202 participants (mean age = 76.7 ± 8.6), 52 (26%) were prefrail and 57 (28%) were frail based on the PLFI. Geriatrician SFA aligned with the PLFI in 43.0% of prefrail and 65.7% of frail cases. Nurse SFA aligned with the PLFI in 43.9% of prefrail and 17.0% of frail cases. There was slight-to-fair agreement between SFA and PLFI (geriatrician: Cohen's κ = .23; 95% confidence interval (CI) = [.11, .35], p < .001; nurse: Cohen's κ = .20; 95% CI = [.08, .33], p = .001). Clinician SFA did not align well with PLFI classifications.

20.
OTJR (Thorofare N J) ; 40(2): 99-112, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31642394

ABSTRACT

Intervening to change clients' habits in the course of their everyday occupations could improve health. Habit formation interventions are an emerging area of science, however, and there is a need to better understand the current state of habit intervention research. The objective of this study is to examine the evidence related to habit formation interventions to modify health habits among adults. We performed a scoping review of peer-review articles published since January 1, 2008. The majority of the 18 studies included in the review were randomized control trials using one of two measures to assess habit change. Studies targeted a range of habits. Trial results were mixed but supportive of habit formation approaches. Through habit formation interventions, a range of everyday behaviors can become a habit. Occupational therapy professionals can use data and results generated from this review to inform the development of occupation-based habit formation treatments.


Subject(s)
Behavior Therapy/methods , Habits , Health Behavior , Health Promotion , Occupational Therapy/methods , Adult , Humans
SELECTION OF CITATIONS
SEARCH DETAIL
...