司坦唑醇对促性腺激素释放激素拟似物处理后的青春期大鼠生长板软骨细胞IGF-1 mRNA表达及其蛋白合成、分泌的影响

目的研究司坦唑醇（stanozolol,ST）对促性腺激素释放激素拟似物（gonadotropin releasing hormone agonist,GnRHa）处理后的离体青春期大鼠生长板软骨细胞胰岛素样生长因子-1（insulin-like growth factor-1,IGF-1）mRNA表达及其蛋白合成、分泌的影响。方法将6只雌鼠的原代软骨细胞,分为时效组、量效组。根据是否用司坦唑醇干预,将时效组和量效组分为时效干预组,时效对照组;量效于预组,量效对照组,分别观察司坦唑醇的干预时限和剂量对促性腺激素释放激素拟似物处理后离体青春期大鼠生长板软骨细胞增殖的影响。采用软骨细胞增殖能力测定法（MTT）和免疫组化法检测不同剂量、不同时间点司坦唑醇处理的离体的青春期大鼠生长板软骨细胞的增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）表达,荧光实时定量RT—PCR检测软骨细胞的IGF-1 mRNA表达。酶联免疫吸附法（enzyme—linked immunosorbent assay,ELISA）测定胰岛素样生长因子-1的合成。结果司坦唑醇以时效和量效作用方式,对雌激素受抑的离体青春期大鼠生长板软骨细胞增殖呈双相型影响。在合适的剂量和疗程时,软骨细胞增殖效应可达最好效果。①司坦唑醇作用2h后,软骨细胞IGF-1 mRNA表达显著增加,与时效对照组基础值相比,差异有显著意义（P〈0．05）,并存在较强的时间依赖性;作用8h时,达最高峰（为时效对照组基础值的3．8倍）。司坦唑醇的作用在（10^-10～10^-5）mol／L时,与软骨细胞的细胞核抗原增殖效应存在明显的剂量依赖性（组间比较,差异有显著意义,P〈0．05）;在10^-7mol／L时,软骨细胞的增殖细胞核抗原表达达最高峰（为基础值的5．75倍）。②司坦唑醇作用自5h起,软骨细胞胰岛素样生长因子-1蛋白合成与时间点为0组比较,差异有显著意义（P=0．042）;5h-20h时,作用存在显著时间依赖性（P〈0．05）;作用20h时,达峰值（为量效对照组基础值的3．3倍）。与量效对照组比较,司坦唑醇自10^-10mol／L组,胰岛素样生长因子-1蛋白含量开始增加,并在10^-7mol／L组达峰值（P=0．000）。结论司坦唑醇可以量效、时效的作用方式,影响和增加对促性腺激素释放激素拟似物处理后的体外培养雌激素水平,促进青春期大鼠生长板软骨细胞IGF-1 mRNA的表达和胰岛素样生长因子-1的合成、分泌,推测司坦唑醇促进生长效应机制与生长板局部胰岛素样生长因子-1的自分泌、旁分泌增加有关。     

Relation Between Genetic Factors and Frailty in Older Adults

ObjectivesFrailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants.DesignLongitudinal population-based cohort of 2488 community-dwelling people from Toledo, Spain, aged 65 years or older.Setting and participantsWe obtained blood samples from 78 individuals with frailty and 74 nonfrail individuals who were nonfrail (according to Fried criteria) from the Toledo Study of Healthy Ageing and extracted DNA using the Chemagic DNA blood kit.MeasuresSample genotyping was carried out by means of Axiom Exome 319 Genotyping Array (Thermo Fisher Scientific), which contains 295,988 markers [single-nucleotide polymorphisms (SNPs) and rare variants], and transferred to the GeneTitan Instrument (Affymetrix).ResultsWe found 15 SNPs (P < .001), 18 genes (P < .005), and 4 pathways (P < .05) related to cytokine-cytokine receptor interaction, natural killer cell-mediated cytotoxicity, regulation of autophagy, and renin-angiotensin system as the most strongly associated with frailty.Conclusions/ImplicationsThe specific genetic features related to energy metabolism, biological processes regulation, cognition, and inflammation highlighted by this preliminary analysis offer useful insights for finding biologically meaningful biomarkers of frailty that allow early diagnosis and treatment. Further research is needed to confirm our novel findings in a larger population. Indeed, the EU-funded FRAILOMICS research effort will address this question.     

Sex Difference in the Association Between Protein Intake and Frailty: Assessed Using the Kihon Checklist Indexes Among Older Adults

Background

Dietary protein intake is inversely associated with physical frailty risk. However, it is unknown whether an association exists between dietary protein intake and comprehensive frailty.

Examining the Association Between Health Literacy and Medication Adherence Among Older Adults

Health literacy plays a vital role in patients’ understanding of their prescribed medication instructions. To inform strategies to assist providers in communicating in a manner that is easily understood by patients, it would be beneficial to determine the relationship between health literacy and the day-to-day aspects of medication adherence. This study identified: 1) differences of health literacy levels in medication adherence; 2) the association between health literacy and medication adherence; and 3) and factors associated with medication adherence score. A convenience sample of older predominantly African-American patients (N = 389), over the age of 60, completed a cross-sectional survey. Chi-square analysis assessed health literacy differences in five aspects of medication adherence. Ordinary linear regression analysis determined factors associated with medication adherence score. Patients with limited health literacy were more likely to forget to take their medications and more likely to take less medication than instructed than patients with adequate health literacy (χ²(5) = 15.91, p = .007, χ²(5) = 10.31, p = .036, respectively). REALM score was also significantly associated with medication adherence score (β= .016, p < .001, β = .009, p = .033), respectively). Findings suggest that providers seeking to improve medication adherence in older adults, particularly African-American patients, should focus communication on assessing health literacy levels prior to discussing medication instructions.     

Association Between Bisphosphonates and Hospitalized Clostridioides difficile Infection Among Frail Older Adults

ObjectivesClostridioides difficile infection is a major source of morbidity and mortality among frail older adults, especially those in nursing homes (NHs). Safety reports have signaled that bisphosphonate use may be a contributing cause. We therefore evaluated the risk of C difficile hospitalization associated with oral bisphosphonate use in the NH.DesignObservational, retrospective new-user cohort study.SettingThe cohort included US NH residents aged ≥65 years who became a long-stay resident (>100 days in the NH) between January 1, 2008 and December 31, 2009.MethodsWe conducted a study of NH residents using linked Medicare claims and Minimum Data Set records. Residents were new users of an oral bisphosphonate 1:1 matched to new calcitonin users (“active” comparator) on propensity scores controlling for more than 100 covariates. The outcome was risk of hospitalization for C difficile infection in a Cox proportional hazards model adjusted for previous antibiotic and proton pump inhibitor use.ResultsOur final analytical cohort included 17,753 bisphosphonate and 5348 calcitonin users. In the matched cohort, 84/5209 (1.6%) vs 71/5209 (1.4%) C difficile–related hospitalizations occurred in bisphosphonate and calcitonin users, respectively. We observed no significant difference in the risk of hospitalization among bisphosphonate users (hazard ratio: 1.11, 95% confidence interval: 0.80-1.51). Antibiotic and proton pump inhibitor exposure before and after osteoporosis treatment was also similar between bisphosphonate and calcitonin users.Conclusions and ImplicationsC difficile infection should not be a consideration when prescribing bisphosphonates to frail older adults given the lack of a significant association.     

Association between Dysphagia and Frailty in Community Dwelling Older Adults

The journal of nutrition, health & aging - Dysphagia is described as a geriatric syndrome that occurs more frequently with aging. It is associated with the deterioration in functionality...     

Prevalence and Incidence of Frailty Among Community-dwelling Older Adults in Slovenia

IntroductionFrailty is recognized as one of the most important global health challenges as the population is aging. The aim of this study was to evaluate prevalence and incidence of frailty, and associated factors, among the population of older adults in Slovenia compared to other European countries.MethodsThe prevalence and 4-year incidence of frailty among older adults (≥65 years) were evaluated using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). Frailty was defined by the SHARE operationalization of Frailty phenotype. Multiple logistic regression model was used to explore factors associated with frailty.ResultsAge-standardized prevalence (95% CI) of frailty and pre-frailty in Slovenia were 14.9% (13.3-16.5) and 42.5% (39.8-45.2), respectively. Factors (OR, 95% CI) associated with increased frailty in Slovenia included age (7584 years: 5.03 (3.08-8.22); ≥85 years 21.7 (10.6-44.7) vs. 65-74 years), self-rated health (fair: 4.58 (2.75-7.61), poor: 54.6 (28.1-105.9) vs. excellent/very good/good), number of chronic diseases (1.20 (1.03-1.40)), and polypharmacy (yes: 3.25 (1.93-5.48) vs. no). Female gender and lower education were significantly associated with pre-frailty, but not frailty, in the adjusted model. Independently of these characteristics, age-standardized prevalence of frailty varied among geographical regions. Age-standardized 4-year incidence of frailty and pre-frailty in Slovenia were 6.6% (3.0-10.1) and 40.2% (32.7-47.6), respectively.ConclusionAmong the Slovenian population of older adults aged 65 years and older, the age-standardized prevalence of frailty is 15% and 4-year incidence of frailty is 7%. Regional differences in Slovenia show the lowest prevalence in central Slovenian regions and the highest in northeastern Slovenian regions.     

The Association between Frailty and Healthcare Expenditure among Chinese Older Adults

ObjectivesThe purpose of this study was to examine whether frailty could explain variability in healthcare expenditure beyond multimorbidity and disability among Chinese older adults.DesignCross-sectional.Setting and ParticipantsParticipants were 5300 community-dwelling adults age at least 60 years from the China Health and Retirement Longitudinal Study.MethodsFrailty was identified by the physical frailty phenotype approach that has been created and validated among Chinese older adults. Five criteria were used: slowness, weakness, exhaustion, inactivity, and shrinking. Persons were classified as “nonfrail” (0 criteria), “prefrail” (1‒2 criteria), or “frail” (3‒5 criteria). Healthcare expenditure was measured based on participants’ self-report and was classified into 3 types: outpatient expenditure, inpatient expenditure, and self-treatment expenditure. The association of frailty and healthcare expenditure was analyzed using a 2-part regression model to account for excessive zero expenditures.ResultsFrailty was associated with higher odds of incurring outpatient, inpatient, and self-treatment expenditure. Among persons with non-zero expenditure, prefrail and frail persons, on average, had US $30.62 [95% confidence interval (CI) 8.41, 52.82] and US $60.60 (95% CI 5.84, 115.36) higher outpatient expenditure than the nonfrail, adjusting for sociodemographics, multimorbidity, and disability. After adjustment for all covariates, prefrail persons, on average, had US $3.34 (95% CI 0.54, 6.13) higher self-treatment expenditure than the nonfrail.Conclusions and ImplicationsFrailty is an independent predictor of higher healthcare expenditure among older adults. These findings suggest that timely screening and recognition of frailty are important to reduce healthcare expenditure among older adults.     

Daily Physical Activity Predicts Frailty Development Among Community-Dwelling Older Japanese Adults

ObjectivesThis study examined the association between frailty development and physical activity including the number of steps, the time of light-intensity physical activity (LPA) with <3.0 metabolic equivalents (METs), and the time of moderate- to vigorous-intensity physical activity (MVPA) with ≥3.0 METs in community-dwelling older Japanese adults.Design, setting, and participantsStudy subjects were 401 older adults at the baseline examination (April 2000–May 2002) who participated at least once in the follow-up examination of the longitudinal study of aging. Their 1787 cumulative data points (mean number of repeat visits, 3.5) were used for analysis.MeasuresThe number of steps, time of LPA, and time of MVPA were recorded at baseline using a uniaxial accelerometer. Frailty was defined according to 5 frailty criteria: shrinking, exhaustion, low physical activity, low grip strength, and slow gait speed.ResultsThe fully adjusted odds ratio for frailty among subjects walking <5000 steps was 1.85 [95% confidence interval (CI), 1.10-3.11]. The fully adjusted odds ratio for frailty among subjects with MVPA for <7.5 minutes was 1.80 (95% CI, 1.05-3.09). No significant association was observed between frailty and LPA.Conclusions and ImplicationsThe risk for developing frailty was substantially lower in older people walking ≥5000 steps/d or exercising for at least 7.5 minutes/d at an intensity >3.0 METs. These data could be applicable to the community interventions that aim to prevent frailty.     

Social Frailty Predicts Incident Disability and Mortality Among Community-Dwelling Japanese Older Adults

Objective

To determine the prevalence of social frailty and its relation to incident disability and mortality in community-dwelling Japanese older adults.

Transitions in Frailty States Among Community-Living Older Adults and Their Associated Factors

BackgroundFrailty renders older individuals more prone to adverse health outcomes. Little has been reported about the transitions between the different frailty states. We attempted to examine the rate of these transitions and their associated factors.MethodsWe recruited 3018 Chinese community-living adults 65 years or older. Frailty status was classified according to the Fried criteria in 2 visits 2 years apart. Demographic data, medical conditions, hospitalizations, and cognition were recorded. Rates of transitions and associated factors were studied.ResultsAt baseline, 850 (48.7%) men and 884 (52.6%) women were prefrail. Among these, 23.4% men and 26.6% women improved after 2 years; 11.1% of men and 6.6% of women worsened. More men than women (P < .001) deteriorated into frailty. Hospitalizations, older age, previous stroke, lower cognition, and osteoarthritis were risk factors for decline among prefrail participants. Having diabetes was associated with 50% lower chance of improvement in women. Among the robust, older age and previous cancer, hospitalizations, chronic lung diseases, and stroke were risk factors for worsening. Higher socioeconomic status was protective. Previous stroke reduced the chance of improvement by 78% in frail men. Only younger age was associated with improvement in frail women.ConclusionWomen were less likely to decline in frailty status than men. Hospitalizations, older age, previous stroke, lower cognitive function, diabetes, and osteoarthritis were associated with worsening or less improvement. Older age, previous cancer, hospitalizations, lung diseases, and stroke were risk factors for worsening in the robust and higher socioeconomic status was protective.     

Association Between Disability Trajectory and Health Care Service Utilization Among Older Adults in China

ObjectivesThis study aimed to identify the heterogeneous disability trajectories among older Chinese adults and examine the association between disability trajectories and health care service utilization.DesignProspective cohort study.Setting and ParticipantsA community-based study including older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey.MethodsDisability was assessed by the difficulties in activities of daily living and instrumental activities of daily living between 2002 and 2018. Health care utilization was measured by the expenditures on outpatient and inpatient services in 2018. Growth mixture modeling was conducted to estimate heterogeneous disability trajectories. A 2-part model was used to analyze the association of disability trajectories and health care utilization. Covariates were included based on Andersen's behavioral model.ResultsThree classes of disability trajectories were identified: the progressive (7.9%), late-onset (13.7%), and normal classes (78.4%). Older adults who followed the late-onset trajectory of disability were more likely to use inpatient services compared with the normal class (odds ratio = 1.47, P < .010), after controlling potential confounders. Compared with the normal class, the progressive class on average spent US$145.94 more annually (45.2% higher) on outpatient services (P < .010) and $738.99 more annually (72.6% higher) on inpatient services (P < .001); the late-onset class reported higher annual expenditures on outpatient and inpatient services of $215.94 (66.9% higher) and $1405.00 (138.0% higher), respectively (all P < .001).Conclusions and ImplicationsHeterogeneous disability trajectories exhibited distinct health care service utilization patterns among older Chinese adults. Older adults affected by late-onset disability incurred the highest health care needs. These findings provide valuable policy-relevant evidence for reducing health care burden among older adults.     

The Association Between Psychological Resilience and Physical Function Among Older Adults With Hip Fracture Surgery

ObjectivesTo examine the associations of prefracture psychological resilience and prefracture general mental health with physical function among older adults with hip fracture surgery.DesignSingle-center observational study.InterventionNone.Setting and participantsPatients aged ≥50 years who underwent first hip fracture surgery between January 2017 and December 2017 (N = 152).MethodsWe used data collected prospectively from the hospital's hip fracture registry. We performed generalized estimating equations to examine the associations of prefracture psychological resilience (10-item Connor-Davidson Resilience Scale) and prefracture general mental health (Short Form–36 mental health subscale) with physical function (Short Form–36 physical functioning subscale) at 4 time points—prefracture (based on recall), and 1.5, 3, and 6 months after surgery.ResultsPrefracture psychological resilience had an association with physical function; a 1-unit increase in psychological resilience score was associated with 1.15 units [95% confidence interval (CI) 0.71, 1.59] higher physical function score across 4 time points. In contrast, the association between general mental health and physical function varied over time; a 1-unit increase in general mental health score was associated with 0.42 units (95% CI 0.18, 0.66) higher physical function score at prefracture, 0.02 units (95% CI –0.18, 0.22) lower at 1.5 months, 0.23 units (95% CI –0.03, 0.49) higher at 3 months, and 0.39 units (95% CI 0.09, 0.68) higher at 6 months after surgery.Conclusions and implicationsPsychological resilience is associated with physical function among older adults with hip fracture surgery, independent from general mental health. Our findings suggest the potential for interventions targeting psychological resilience for these patients and call for more studies on psychological factors affecting physical function recovery after hip fracture surgery.     

The Prevalence of Social Frailty Among Older Adults: A Systematic Review and Meta-Analysis

ObjectiveTo report the overall prevalence of social frailty among older people and provide information for policymakers and authorities to use in developing policies and social care.DesignA systematic review and meta-analysis.Setting and participantsWe searched 4 databases (PubMed, Embase, Web of Science, and Google Scholar) to find articles from inception to July 30, 2022. We included cross-sectional and cohort studies that provided the prevalence of social frailty among adults aged 60 years or older, in any setting.MethodsThree researchers independently reviewed the literature and retrieved the data. A risk of bias tool was used to assess each study’s quality. A random-effect meta-analysis was performed to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression.ResultsFrom 761 records, we extracted 43 studies with 83,907 participants for meta-analysis. The pooled prevalence of social frailty in hospital settings was 47.3% (95% CI: 32.2%–62.4%); among studies in community settings, the pooled prevalence was 18.8% (95% CI: 14.9%–22.7%; P < .001). The prevalence of social frailty was higher when assessed using the Tilburg Frailty Indicator (32.3%; 95% CI: 23.1%–41.5%) than the Makizako Social Frailty Index (27.7%; 95% CI: 21.6%–33.8%) or Social Frailty Screening Index (13.4%; 95% CI: 8.4%–18.4%). Based on limited community studies in individual countries using various instruments, social frailty was lowest in China (4.9%; 95% CI: 4.2%–5.7%), followed by Spain (11.6%; 95% CI: 9.9%–13.3%), Japan (16.2%; 95% CI: 12.2%–20.3%), Korea (26.6%; 95% CI: 7.1%–46.1%), European urban centers (29.2%; 95% CI: 27.9%–30.5%), and the Netherlands (27.2%; 95% CI: 16.9%–37.5%). No other subgroup analyses showed any statistically significant prevalence difference between groups.Conclusion and ImplicationsThe prevalence of social frailty among older adults is high. Settings, country, and method for assessing social frailty affected the prevalence. More valid comparisons will await consensus on measurement tools and more research on geographically representative populations. Nevertheless, these results suggest that public health professionals and policymakers should seriously consider social frailty in research and program planning involving older adults.     

Residential Greenness and Frailty Among Older Adults: A Longitudinal Cohort in China

ObjectivesFrailty is an accumulation of deficits characterized by reduced resilience to stressors and increased vulnerability to adverse outcomes. There is evolving evidence on the health benefits of residential greenness, but little is known about its impact on frailty.DesignA longitudinal cohort study.Setting and participantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with a 12-year follow-up.MethodsWe assessed residential greenness by calculating the Normalized Difference Vegetation Index (NDVI) in the 500 m radius around participants' residence. We used 39 self-reported health items to construct a frailty index (FI) as a proportion of accumulated deficits. We defined an FI of ≤0.21 as nonfrail and prefrail, and an FI of >0.21 as frail. We used the mixed effects logistic regression models to examine the association between residential greenness and frailty, adjusted for a number of covariates.ResultsWe had 16,238 participants, with a mean age of 83.0 years (standard deviation: 11.5). The mean baseline NDVI and FI were 0.40, and 0.12, respectively. Compared to the participants living in the lowest quartile of residential greenness, those in the highest quartile had a 14% [odds ratio (OR): 0.86, 95% confidence interval (CI): 0.77, 0.97] lower odds of frailty. The association was stronger among urban vs rural residents. Additionally, each 0.1-unit increase in annual average NDVI was related to a 2% higher odds of improvement in the frailty status (OR: 1.02, 95% CI: 1.00, 1.04).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are related to a lower likelihood of frailty, specifically in urban areas.     

Association between Dysphagia and Frailty in Older Adults: A Systematic Review and Meta-Analysis

Background: Increasing bodies of epidemiological evidence indicate potential associations between dysphagia and the risk of frailty in older adults. We hypothesized that older adults with symptoms of dysphagia might have a higher prevalence of frailty or prefrailty than those without dysphagia. Methods: We systematically searched the PubMed, Embase, and Cochrane Library databases for relevant studies published through 20 April 2022. Cross-sectional and longitudinal studies that examined the associations between dysphagia and the existence of frailty or prefrailty in community-dwelling, facility-dwelling, or hospitalized adults aged 50 years or older were synthesized. The Newcastle–Ottawa Scale was used to evaluate study quality. Results: The meta-analysis comprised 12 cohorts, including 5,503,543 non-frailty participants and 735,303 cases of frailty or prefrailty. Random-effect meta-analysis demonstrated a significant association between dysphagia and the risk of frailty and prefrailty (OR, 3.24; 95% CI, 2.51–4.20). In addition, we observed consistent results across the subgroups and heterogeneity assessments. Conclusions: We propose including dysphagia assessment as a critical factor in the cumulative deficit model for identifying frailty in older adults. Understanding dysphagia and the potential role of nutritional supplements in older adults may lead to improved strategies for preventing, delaying, or mitigating frailty.     

The Prevalence of Frailty Among Older Adults Living With Dementia: A Systematic Review

ObjectivesTo investigate the prevalence of frailty in older adults living with dementia and explore the differences in medication use according to frailty status.DesignSystematic review of published literature from inception to August 20, 2020.Setting and ParticipantsAdults age ≥65 years living with dementia in acute-care, community and residential care settings.MethodsA systematic search was performed in Embase, Medline, International Pharmaceutical Abstracts, APA PscyInfo, CINAHL, Scopus, and Web of Science. Two reviewers independently screened records and conducted quality assessment using the Newcastle-Ottawa Scale.ResultsSixteen articles met the inclusion criteria, with 7 studies conducted in acute care setting and 9 studies in community-dwelling adults. Five studies recruited people with dementia exclusively, and 11 studies were conducted in older populations that included individuals with dementia diagnosis. Among studies conducted in acute care setting, the prevalence of frailty ranged from 50.8% to 91.8% compared with studies in community-dwelling setting, which reported a prevalence of 24.3% to 98.9%. With respect to medication exposure, 3 studies documented medication use according to frailty status but not dementia status. Higher medications use, measured as total number of medications was reported in frail [7.0 ± 4.0 (SD) ?12.0 ± 9.0 (SD)] compared with nonfrail participants [6.1 ± 3.1(SD) ?10.4 ± 3.8 (SD)].Conclusions and ImplicationsCurrent data suggests a wide range of frailty prevalence in individuals with dementia. Future studies should systematically document frailty in adults living with dementia and its impact on medication use.     

Serum SIRT1 is Associated with Frailty and Adipokines in Older Adults

The journal of nutrition, health & aging - Because frailty is a major health concern among older patients, identifying frailty-related biomarkers will help in the early detection and prevention...