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1.
J Am Chem Soc ; 145(50): 27325-27335, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38069901

RESUMO

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides.


Assuntos
Produtos Biológicos , Ribossomos , Ribossomos/metabolismo , Peptídeos/química , Peptídeos Cíclicos/química , Sistema Enzimático do Citocromo P-450/metabolismo , Processamento de Proteína Pós-Traducional , Produtos Biológicos/química
2.
Clin Gerontol ; 46(1): 47-52, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-33308033

RESUMO

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.


Assuntos
Medo , Vida Independente , Humanos , Idoso , Medo/psicologia , Atividades Cotidianas
3.
Am J Occup Ther ; 76(3)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35616653

RESUMO

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.


Assuntos
Fragilidade , Idoso , Estudos de Viabilidade , Feminino , Fragilidade/prevenção & controle , Hábitos , Humanos , Estudos Prospectivos , Qualidade de Vida
4.
Angew Chem Int Ed Engl ; 61(33): e202205577, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35701881

RESUMO

Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton.


Assuntos
Diterpenos , Indenos , Diterpenos/química , Indenos/química , Norbornanos , Esqueleto
5.
J Aging Phys Act ; 29(4): 612-619, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361502

RESUMO

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.


Assuntos
Acidentes por Quedas , Área Carente de Assistência Médica , Acidentes por Quedas/prevenção & controle , Idoso , Exercício Físico , Terapia por Exercício , Humanos , Projetos Piloto
6.
Am J Occup Ther ; 75(5)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34780632

RESUMO

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.


Assuntos
Sobrecarga do Cuidador , Cuidadores , Idoso , Estudos de Viabilidade , Humanos , Autocuidado , Autoeficácia
7.
Aust Occup Ther J ; 67(5): 470-478, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648268

RESUMO

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.


Assuntos
Acidentes por Quedas/prevenção & controle , Terapia Ocupacional/organização & administração , Idoso , Humanos , Vida Independente , Fatores de Risco
8.
Am J Occup Ther ; 73(2): 7302205060p1-7302205060p8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915967

RESUMO

IMPORTANCE: Forty percent to 75% of community-dwelling older adults are not able to adhere to their medication routine. A medication management assessment can correctly identify the reasons for nonadherence and the barriers contributing to it. OBJECTIVE: To further develop the HOME-Rx, an in-home medication management assessment, by modifying scoring metrics, improving clinical utility, and establishing psychometric properties. DESIGN: In Phase 1, the scoring metrics were modified, and the clinical procedures were evaluated. In Phase 2, the psychometric properties were established. SETTING: The homes of older adults. PARTICIPANTS: Older adults who took three or more medications, managed their own medications, and lived in their own home were eligible. Older adults with cognitive impairment were ineligible. OUTCOMES AND MEASURES: We assessed concurrent validity with the Performance Assessment for Self-Care Skills (PASS) and Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and established interrater reliability. RESULTS: The PASS was positively correlated with the HOME-Rx Performance and Safety subscales; the MedMaIDE was negatively correlated with the HOME-Rx Performance subscale and positively correlated with the Barriers subscale. Interrater reliability was excellent (ICCs = .87-1.00). CONCLUSIONS AND RELEVANCE: All relationships were as predicted: The HOME-Rx is a valid and reliable performance-based assessment that provides clinicians and researchers with a measure of older adults' actual medication management ability in the home using their medications. The results can potentially be used to guide treatment planning and improve medication management. WHAT THIS ARTICLE ADDS: Occupational therapy practitioners can use the HOME-Rx to adequately determine performance problems, safety concerns, and environmental barriers and potentially to guide treatment planning and improve medication management for older adults.


Assuntos
Tratamento Farmacológico/psicologia , Vida Independente , Cooperação do Paciente , Psicometria/estatística & dados numéricos , Autocuidado/psicologia , Inquéritos e Questionários/normas , Idoso , Humanos , Terapia Ocupacional , Reprodutibilidade dos Testes
9.
Am J Occup Ther ; 72(1): 7201205020p1-7201205020p10, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29280722

RESUMO

OBJECTIVE: The aim of this study was to conduct a process evaluation to examine the implementation of a randomized controlled trial of home modifications designed to reduce the risk of falls and improve daily activity performance among community-dwelling older adults. METHOD: A process evaluation was conducted alongside a blinded, randomized sham-controlled trial (n = 92). Participants were followed for 1 yr after intervention. The process evaluation was framed using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. RESULTS: The treatment group improved daily activity performance over 12 mo compared with the sham control group (F = 4.13; p = .024). The intervention elements and dose were delivered with greater than 90% accuracy. Participants reported a 91% adherence rate at 12 mo. CONCLUSION: The complex intervention of home modifications examined in this study is acceptable to older adults, is feasible, and can be delivered with high fidelity for frail, community-dwelling older adults.


Assuntos
Acidentes por Quedas/prevenção & controle , Atividades Cotidianas , Casas de Saúde , Avaliação de Resultados da Assistência ao Paciente , Idoso , Estudos de Viabilidade , Serviços de Saúde para Idosos , Humanos , Terapia Ocupacional , Avaliação de Processos em Cuidados de Saúde
10.
BMC Geriatr ; 17(1): 90, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28427336

RESUMO

BACKGROUND: Falls remain the leading cause of injury, long-term disability, premature institutionalization, and injury-related mortality in the older adult population. Home modifications, when delivered by occupational therapists, can reduce falls among high-risk community-dwelling older adults by 39%. However, home-modification implementation is not standard practice in the United States. The goal of the Home Hazard Removal Program (HARP) study is to implement an evidence-based home modification intervention for older adults designed to reduce the incidence of falls through an aging services network. METHODS: We will conduct a hybrid effectiveness/implementation trial of 300 older adults at risk for a fall who are randomized and followed for 12 months. Participants who are randomized to treatment will receive the home modification intervention provided by an occupational therapist in addition to usual care, defined as continued services from the area agency on aging. We will compare the effectiveness of the program and usual care using survival analysis with the time to the first fall over 12 months as the primary outcome of interest. Secondary outcomes include daily activity performance, fall self-efficacy, and health-related quality of life. Fidelity, dose, adherence, safety, cost, and health care utilization will also be examined in the implementation component of this study. DISCUSSION: This intervention targets an underserved, difficult to reach population of older adults. The tailored approach of the study intervention is a strength in improving adherence, as each recommendation is individualized to be acceptable to the participant. The effectiveness/implementation design of the study allows for rapid dissemination of results and implementation of the intervention in a United States social services agency. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02392013 . Retrospectively registered on March 5, 2015.


Assuntos
Acidentes por Quedas/prevenção & controle , Atividades Cotidianas , Envelhecimento , Terapia por Exercício/métodos , Serviços de Assistência Domiciliar/normas , Qualidade de Vida , Autoeficácia , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
11.
Am J Occup Ther ; 71(4): 7104190020p1-7104190020p7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28661381

RESUMO

OBJECTIVE: This study assessed the initial psychometric properties of a novel in-home, performance-based instrument for older adults called the In-Home Medication Management Performance Evaluation (HOME-Rx). METHOD: Content validity of the HOME-Rx was determined through the multistep content validity index (CVI) process. Content experts provided qualitative and quantitative judgment of the instrument's ability to measure medication management. The assessment's target population provided qualitative feedback. CVI outcomes informed instrument revisions. RESULTS: Content experts (n = 7) were in agreement that the overall instrument was valid for measuring medication management (scale-level CVI = .95). Six items were deleted because of low agreement (item-level CVI <.80). Twenty-nine minor edits were made to the order of questions and language. Older adult participants (n = 5) reported the instrument was relevant, acceptable, and easy to understand. CONCLUSION: The HOME-Rx appears to be a relevant and valid method to assess performance barriers to medication management in the home.


Assuntos
Adesão à Medicação , Preparações Farmacêuticas , Autocuidado , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas
12.
J Gerontol B Psychol Sci Soc Sci ; 78(Suppl 1): S71-S80, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36368018

RESUMO

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.


Assuntos
Cuidadores , Demência , Humanos , Idoso , Idoso de 80 Anos ou mais , Demência/terapia
13.
Chem Sci ; 14(13): 3661-3667, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37006697

RESUMO

Terpenoids comprise the most chemically and structurally diverse family of natural products. In contrast to the huge numbers of terpenoids discovered from plants and fungi, only a relatively small number of terpenoids were reported from bacteria. Recent genomic data in bacteria suggest that a large number of biosynthetic gene clusters encoding terpenoids remain uncharacterized. In order to enable the functional characterization of terpene synthase and relevant tailoring enzymes, we selected and optimized an expression system based on a Streptomyces chassis. Through genome mining, 16 distinct bacterial terpene biosynthetic gene clusters were selected and 13 of them were successfully expressed in the Streptomyces chassis, leading to characterization of 11 terpene skeletons including three new ones, representing an ∼80% success rate. In addition, after functional expression of tailoring genes, 18 novel distinct terpenoids were isolated and characterized. This work demonstrates the advantages of a Streptomyces chassis which not only enabled the successful production of bacterial terpene synthases, but also enabled functional expression of tailoring genes, especially P450, for terpenoid modification.

14.
Clin Exp Rheumatol ; 30(2): 197-201, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22325420

RESUMO

OBJECTIVES: AMG623, also known as A-623, is an antagonist of B-cell activating factor (BAFF). The present study was to evaluate the effects of AMG623 on murine models of autoimmune diseases. METHODS: AMG623 was generated through phage library. Inhibitory activities of AMG623 against human and murine BAFF were measured by biacore binding and BAFF-mediated B-cell proliferation assay. Pharmacological effects of AMG623 were studied in BALB/c mice, collagen-induced arthritis model (CIA) and in the NZBxNZW F1 lupus model. RESULTS: AMG623 binds to both soluble and cell surface BAFF. AMG623 blocks both human murine BAFF binding to the receptors. Treatment of AMG623 resulted in B-cell number reduction, and improvement of arthritis and lupus development in mice. CONCLUSIONS: AMG623 is a novel modality of BAFF antagonist. AMG623 is a potential therapeutic agent for the treatment of SLE, rheumatoid arthritis, and other B-cell-mediated autoimmune diseases.


Assuntos
Artrite Experimental/tratamento farmacológico , Fator Ativador de Células B/antagonistas & inibidores , Linfócitos B/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Animais , Artrite Experimental/imunologia , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Proliferação de Células/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Fatores de Tempo , Transfecção
15.
Chem Sci ; 13(43): 12892-12898, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36519048

RESUMO

Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1). Through genetic and biochemical studies, we elucidated the biosynthetic pathway of 1, which involves a complex glycosylation process. Our work discloses nature's huge capacity to generate diverse tetracyclines and expands the chemical diversity of tetracyclines.

16.
J Immunol ; 182(3): 1421-8, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19155489

RESUMO

Autoimmune diseases are marked by the presence of class-switched, high-affinity autoantibodies with pathogenic potential. Costimulation plays an important role in the activation of T cells and the development of T cell-dependent B cell responses. ICOS plays an indispensable role in the development of follicular helper T cells (T(FH) cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of T(FH) cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F(1) mouse model of systemic lupus erythematosus and the collagen-induced arthritis model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP-1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations and leads to a decrease in T(FH) cells and GC B cells as well as an overall decrease in the frequency of ICOS(+) T cells. Coculture experiments of Ag-primed B cells with CXCR5(+) or CXCR5(-) T cells show that blocking B7RP-1 does not directly impact the production of IgG by B cells. These findings further support the role of ICOS in autoimmunity and suggest that the expansion of the T(FH) cell pool is an important mechanism by which ICOS regulates Ab production.


Assuntos
Anticorpos Bloqueadores/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Autoanticorpos/biossíntese , Antígeno B7-1/imunologia , Diferenciação Celular/imunologia , Centro Germinativo/imunologia , Transdução de Sinais/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/fisiologia , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Experimental/terapia , Autoanticorpos/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Antígeno B7-1/fisiologia , Feminino , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Ligante Coestimulador de Linfócitos T Induzíveis , Proteína Coestimuladora de Linfócitos T Induzíveis , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Camundongos Endogâmicos NZB , Distribuição Aleatória , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia
17.
JAMA Netw Open ; 4(8): e2122044, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34463746

RESUMO

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.


Assuntos
Acidentes por Quedas/prevenção & controle , Segurança de Equipamentos/normas , Guias como Assunto , Vida Independente , Gestão da Segurança/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Missouri
18.
Chem Sci ; 12(8): 2925-2930, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34164059

RESUMO

Nonribosomal peptide synthetases (NRPSs) are modular enzymes that use a thiotemplate mechanism to assemble the peptide backbones of structurally diverse and biologically active natural products in bacteria and fungi. Unlike these canonical multi-modular NRPSs, single-module NRPS-like enzymes, which lack the key condensation (C) domain, are rare in bacteria, and have been largely unexplored to date. Here, we report the discovery of a gene cluster (gup) encoding a NRPS-like megasynthetase through genome mining. Heterologous expression of the gup cluster led to the production of two unprecedented alkaloids, guanipiperazines A and B. The NRPS-like enzyme activates two l-tyrosine molecules, reduces them to the corresponding amino aldehydes, and forms an unstable imine product. The subsequent enzymatic reduction affords piperazine, which can be morphed by a P450 monooxygenase into a highly strained compound through C-O bond formation. Further intermolecular oxidative coupling forming the C-C or C-O bond is catalyzed by another P450 enzyme. This work reveals the huge potential of NRPS-like biosynthetic gene clusters in the discovery of novel natural products.

19.
Gerontol Geriatr Med ; 6: 2333721420904234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076629

RESUMO

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.
Gerontologist ; 60(7): 1353-1363, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31688909

RESUMO

BACKGROUND AND OBJECTIVES: Older African Americans are at high risk for becoming frail in later life. Interventions can reverse or delay frailty, yet African Americans have largely been excluded from such research. Many interventions are also time- and resource-intensive, and thus inaccessible to socially disadvantaged older African Americans. We evaluated the feasibility of a low-dose frailty prevention intervention integrated with primary care among 60 community-dwelling, prefrail older African Americans aged 55+ recruited from a primary care clinic. RESEARCH DESIGN AND METHODS: We conducted a 2-arm randomized control trial. Participants were assigned to a 4-session intervention (1 session per month), delivered by an occupational therapist, or enhanced usual care. Feasibility criteria were set a priori at 75% for participant retention (including attrition due to death/hospitalization), 80% for session engagement, 2 participants/week for mean participant accrual, and 90% for program satisfaction. RESULTS: Participants were 65% female with an average age of 76.6 years, 51.7% lived alone and 39.1% reported <$10,000 in yearly income. Feasibility metrics were met. The study recruited, a mean of, 2.5 participants per week and retained 75% of participants who attended 95% of scheduled sessions. The mean satisfaction score was 29.75 (range = 0-32; SD .25). Changes in physical activity and dietary habit formation as well as changes in secondary outcomes were largely in the expected direction. DISCUSSION AND IMPLICATIONS: The intervention was feasible to deliver. Qualitative findings from exit interviews suggested changes to the program dose, structure, and content that could improve it for future use.


Assuntos
Fragilidade , Hábitos , Negro ou Afro-Americano , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto
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