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1.
Geriatr Gerontol Int ; 20(10): 980-987, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32886834

RESUMO

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Extremidade Inferior/fisiopatologia , Força Muscular/fisiologia , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Fragilidade , Força da Mão , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Estudos de Tempo e Movimento , Velocidade de Caminhada/fisiologia
2.
Support Care Cancer ; 28(8): 3965-3977, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32335732

RESUMO

INTRODUCTION: Although the chemotherapy-induced sarcopenia has some explanatory presence in clinical practice, the mechanisms underlying this phenomenon have not been clearly distinguished in patients with cancer. Therefore, we aimed with this study to investigate the role of inflammation by examining the inflammatory markers in the physiopathology of adjuvant chemotherapy-induced sarcopenia in patients with gastrointestinal tract cancer. MATERIAL AND METHOD: To detect the presence of sarcopenia, patients' body composition measurements were assessed using the BIA, and their muscular strength was assessed with a handgrip dynamometer in both pre- and post-adjuvant chemotherapy. At the same time, we examined the baseline and post-adjuvant chemotherapy anthropometric measurements and inflammatory markers in serum (Hs-CRP, IL8, and TNF-α). Patients were divided in three groups. Group 1 consisted of patients who presented post-treatment sarcopenia although they did not have it prior to the treatment, group 2 included the patients who had no pre- or post-treatment sarcopenia, and group 3 was comprised of patients who presented pre-treatment sarcopenia. Each group included 30 patients. RESULTS: A total of 90 patients were included in the study. Fifty-one of them were female patients. Median age was 60.5 (range 27-83). The patients consisted of cases with colorectal and gastric cancers. In group 1, Wilcoxon signed-rank test revealed a significant difference between scores of IL-8 (pg/mL), TNF-α (pg/mL) and Hs-CRP (mg/dL) given for the post-chemotherapy compared with the pre-chemotherapy ((Z 3.61, p < 0.001), (Z 3.254, p = 0.001), (Z 3.319, p = 0.001)). The post-chemotherapy median scores of IL-8 (pg/mL), TNF-α (pg/mL), and Hs-CRP were 76.31, 7.34, and 1.55, respectively, which remained on the levels of 12.25, 1.6, and 0.51 for the pre-chemotherapy. For group 2, a Wilcoxon signed-rank test indicated no significant difference between scores of the same markers given for the post-chemotherapy compared with the pre-chemotherapy. In all patients (including groups 1, 2, and 3), a comparison of the patients with pre-treatment sarcopenia (n = 30) and non-sarcopenic patients (n = 60) in terms of baseline IL-8, TNF-α, and Hs-CRP mean levels, IL-8 and Hs-CRP were found to be statistically different (146.02 (SD 311.96) vs. 47.24 (SD 66.3) (p = 0.009), 3.91 (SD 4.26) vs. 0.75 (SD 1.08) (p < 0.001), respectively). CONCLUSIONS: The present prospective observational study suggested an association of chemotherapy-induced sarcopenia with inflammatory markers Hs-CRP, IL8, and TNF-α. Inflammation may play a role in chemotherapy-induced sarcopenia in newly diagnosed non-metastatic patients.


Assuntos
Mediadores da Inflamação/sangue , Inflamação/sangue , Sarcopenia/sangue , Sarcopenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Proteína C-Reativa/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Inflamação/patologia , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sarcopenia/diagnóstico , Sarcopenia/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Fator de Necrose Tumoral alfa/sangue
3.
Ann Thorac Surg ; 110(2): 374-382, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278754

RESUMO

BACKGROUND: Although both sarcopenia and systemic inflammation reportedly affect long-term outcomes of esophageal carcinoma (EC) patients, their reciprocal associations with survival outcomes have yet to be investigated. This study aimed to evaluate the survival impact of sarcopenia combined with the neutrophil-to-lymphocyte ratio (NLR) in EC patients undergoing esophagectomy. METHODS: In total, 378 EC patients were retrospectively reviewed. The cutoff value for NLR was set at the NLR median of the cohort. Sarcopenia was determined based on decreased skeletal muscle index calculated from computed tomography obtained before surgery. Univariate and multivariate Cox hazards models were applied to determine independent predictors of poor overall survival and cancer-specific survival. RESULTS: Sarcopenia was more common in the high-NLR group (2.57 or greater) than in the low-NLR group (less than 2.57; P = .01). In the high-NLR group, patients with sarcopenia had significantly poorer overall and cancer-specific survival than those without sarcopenia (P < .001). In contrast, there was no survival impact of sarcopenia in the low-NLR group. Patients with both high NLR and sarcopenia exhibited poor overall and cancer-specific survival (5-year overall survival = 44.4%, 5-year cancer-specific survival = 57.0%). Sarcopenia was independently associated with poor overall survival (hazard ratio = 1.95; P = .007) and poor cancer-specific survival (hazard ratio = 2.66; P = .002) as well as pathological stage III disease and noncurative resection in the high-NLR group. CONCLUSIONS: The survival and oncological impact of sarcopenia was noteworthy only when present with elevated NLR. The combination of 2 factors is rational for identifying EC patients likely to have poor survival outcomes.


Assuntos
Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/mortalidade , Inflamação/complicações , Sarcopenia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Inflamação/sangue , Contagem de Leucócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos , Sarcopenia/sangue , Taxa de Sobrevida
4.
Transplantation ; 104(7): e188-e198, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32150034

RESUMO

BACKGROUND: Cystatin C (CysC) is an early biomarker of renal dysfunction scarcely studied in patients awaiting liver transplantation (LT). Sarcopenia is frequent in cirrhosis and impacts prognosis. We aimed to assess the capability of these factors to predict survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT outcomes. METHODS: Single-center study that included all cirrhotic patients listed for LT between 2014 and 2017. Competing risk regression analysis was used to evaluate the capability of liver-, kidney-, and global status-related variables at waitlist (WL) inclusion to predict WL mortality and ACLF. Variables associated with post-LT outcomes were evaluated with logistic regression analysis. RESULTS: One-hundred-and-eighty patients were included. Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died. In the adjusted competing risk regression analysis, CysC ≥ 1.5 mg/L, sarcopenia and MELD-Na were independent predictors of ACLF in the WL, while CysC ≥ 1.5 mg/L, sarcopenia and albumin were independent predictors of mortality. The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in patients with sarcopenia and CysC ≥1.5 mg/L. An estimated glomerular filtration rate by chronic kidney disease (CKD)-EPI-CysC-creatinine <60 mL/min/1.73 m at WL inclusion was an independent predictor of the need for renal replacement therapy (RRT) in the first month post-LT. CONCLUSIONS: Higher levels of CysC and sarcopenia are strongly associated with the ACLF and mortality in WL. The assessment of both risk factors may improve the prognostic evaluation and allow identifying a group of patients with a very high risk of poor outcomes while awaiting LT.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Cistatina C/sangue , Doença Hepática Terminal/mortalidade , Cirrose Hepática/mortalidade , Transplante de Fígado/efeitos adversos , Sarcopenia/embriologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Insuficiência Hepática Crônica Agudizada/epidemiologia , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , Idoso , Biomarcadores/sangue , Creatinina/sangue , Doença Hepática Terminal/sangue , Doença Hepática Terminal/complicações , Doença Hepática Terminal/diagnóstico , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/etiologia , Índice de Gravidade de Doença , Listas de Espera/mortalidade
5.
Nutrients ; 12(2)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979011

RESUMO

Sarcopenia and malnutrition are commonly occurring conditions in the elderly that frequently coexist, leading to substantial effects on morbidity/mortality. Evidence established muscle-specific microRNAs (miRNAs) or myomiRs as essential regulators of skeletal muscle processes, from myogenesis to muscle homeostasis. This study aimed to evaluate the association between myomiRs and sarcopenia and explore the potential of nutrition in mediating this association. qPCR was employed to characterize the myomiR-1, -133a/b, -206, -208b, and -499 expression profiles of 109 non-sarcopenic and 109 sarcopenic subjects. In our sample, the proportion malnourished or at-risk subjects was higher in sarcopenia (p < 0.001). Among the detected myomiRs (miR-133a/b and miR-206), lower levels of miR-133b was significantly associated with the presence of sarcopenia (p = 0.006); however, this relationship was not independent from nutritional status in multivariate analysis, suggesting a mediating effect of nutrition on the relationship between miR-133b and sarcopenia. Correlation analyses showed that lower miR-133b levels were associated with poor nutritional status (Mini Nutritional Assessment Long Form (MNA-LF) score, p = 0.005); furthermore, correlations with albumin, ferritin, and iron were found. Similar results were obtained for miR-206. Statistically more significant correlations were observed in subjects with sarcopenia. In conclusion, our findings highlight a nutrient-miR-133b/miR-206 pathway having a potential role in the age-related muscle decline.


Assuntos
Desnutrição/sangue , MicroRNAs/sangue , Estado Nutricional/genética , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Avaliação Geriátrica , Humanos , Masculino , Desnutrição/complicações , Força Muscular , Músculo Esquelético/metabolismo , Avaliação Nutricional , Sarcopenia/complicações
6.
Sci Rep ; 10(1): 1260, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988356

RESUMO

To investigate the association of the sarcopenia index (SI, serum creatinine value/cystatin C value × 100) with 3-year mortality and readmission among older inpatients, we reanalyzed a prospective study in the geriatric ward of a teaching hospital in western China. Older inpatients aged ≥ 60 years with normal kidney function were included. Survival status and readmission information were assessed annually during the 3-year follow-up. We applied Cox regression models to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) of sarcopenia for predicting mortality and readmission. We included 248 participants (mean age: 81.2 ± 6.6 years). During the follow-up, 57 participants (23.9%) died, whereas 179 participants (75.2%) were readmitted at least one time. The SI was positively correlated with body mass index (BMI) (r = 0.214, p = 0.001), calf circumference (CC) (r = 0.253, p < 0.001), handgrip strength (r = 0.244, p < 0.001), and gait speed (r = 0.221, p < 0.001). A higher SI was independently associated with a lower risk of 3-year all-cause mortality after adjusting for potential confounders (HR per 1-SD = 0.80, 95% CI: 0.63-0.97). The SI was not significantly associated with readmission (HR per 1-SD = 0.97, 95% CI: 0.77-1.25). In conclusion, the SI is associated with 3-year all-cause mortality but not readmission in a study population of hospitalized older patients.


Assuntos
Creatinina/sangue , Cistatina C/sangue , Sarcopenia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , China/epidemiologia , Creatinina/análise , Cistatina C/análise , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/fisiopatologia
7.
J Gerontol A Biol Sci Med Sci ; 75(1): 175-180, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874790

RESUMO

BACKGROUND: Growth and differentiation factor 15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical performance in adults has not been well characterized. METHODS: Plasma GDF-15, grip strength, 6-m gait speed, 400-m walking test time, lower extremity physical performance score, appendicular lean mass, and fat mass were measured in 194 healthy adult participants, aged 22-93 years, of the Baltimore Longitudinal Study of Aging. RESULTS: Plasma GDF-15 concentrations increased with age (p < .001) and were higher in whites compared with blacks and Asians (p = .04). Adults with higher plasma GDF-15 had slower 6-m gait speed, longer 400-m walking time, and lower physical performance score in multivariable analyses adjusting for age and race. Plasma GDF-15 was not associated with grip strength, appendicular lean mass, or fat mass. CONCLUSIONS: Elevated plasma GDF-15 is associated with slower gait speed, higher 400-m walking time, and lower physical performance in very healthy community-dwelling adults. The relationship between plasma GDF-15 and sarcopenia-related outcomes may be stronger in the population not selected to be healthy, and this hypothesis should be tested in a representative population.


Assuntos
Envelhecimento/fisiologia , Marcha/fisiologia , Avaliação Geriátrica/métodos , Fator 15 de Diferenciação de Crescimento/sangue , Vida Independente , Sarcopenia/sangue , Velocidade de Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Estudos Prospectivos , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Adulto Jovem
8.
J Nutr Health Aging ; 23(10): 979-986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781728

RESUMO

OBJECTIVES: (i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. DESIGN: Cross-sectional study. SETTING: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. PARTICIPANTS: 200 subjects aged 50 years and older residing in the community. MEASUREMENTS: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). RESULTS: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). CONCLUSION: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.


Assuntos
Biomarcadores/sangue , Fragilidade/diagnóstico , Fator de Crescimento Insulin-Like I/metabolismo , Miostatina/sangue , Sarcopenia/diagnóstico , Idoso , Estudos Transversais , Feminino , Fragilidade/sangue , Identidade de Gênero , Humanos , Vida Independente , Estudos Longitudinais , Masculino , Estudos Prospectivos , Sarcopenia/sangue
9.
Nutr Metab Cardiovasc Dis ; 29(12): 1390-1399, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31668791

RESUMO

BACKGROUND AND AIMS: A progressive decrease in muscle mass until full-blown sarcopenia may occur in patients on peritoneal dialysis (PD) and worsen their life quality and expectancy. Here we investigate the prevalence of obesity and obesity-associated muscle wasting in PD patients. PATIENTS AND METHODS: The study design was observational, cross sectional. Body composition was assessed with BIA and BIVA in 88 PD patients (53.4 ± 13.1 years; 67% male). Patients with obesity and/or with reduced muscle mass were identified using FMI and SM/BW cutoff values, respectively. Inflammatory status was assessed by measuring CRP and fibrinogen blood levels. RESULTS: A total of 44.3% of the patients showed a reduced muscle mass (37.5% moderate and 6.8% severe). The prevalence of obesity was 6.1%, 81.8%, and 100% in patients with normal, moderately, and severely reduced muscle mass, respectively (p < 0.05). Of the total, 15.2% of the patients with normal muscle mass, 18.4% of those with moderately reduced muscle mass, and 66.7% of those with severely reduced muscle mass had diabetes. The prevalence of severe muscle mass loss was higher in those with diabetes than in those without diabetes (22.2% vs. 2.8%, p < 0.05). Patients with obesity-associated muscle wasting showed higher fibrinogen (613.9 ± 155.1 vs. 512.9 ± 159.5 mg/dL, p < 0.05) and CPR (1.4 ± 1.3 vs. 0.6 ± 0.8 mg/dL, p < 0.05) blood concentrations than those with normal body composition. CONCLUSION: Obesity and diabetes were strongly associated with muscle mass loss in our PD patients. It remains to be established whether prevention of obesity with nutritional interventions can halt the occurrence of muscle mass loss in patients on PD.


Assuntos
Falência Renal Crônica/terapia , Obesidade/epidemiologia , Diálise Peritoneal/efeitos adversos , Sarcopenia/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Composição Corporal , Proteína C-Reativa , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Fibrinogênio , Humanos , Mediadores da Inflamação/sangue , Itália/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Prevalência , Medição de Risco , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia
10.
Thromb Res ; 183: 36-44, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31614293

RESUMO

INTRODUCTION: Sarcopenia is attracting increasing attention due to its harmful impacts on health. Chronic inflammation is proposed to be a major cause of sarcopenia. Here, we aimed to identify whether white blood cell (WBC) and platelet count have independent roles in sarcopenia occurrence. METHOD AND MATERIALS: This cross-sectional study analyzed 10,092 adults (4293 men and 5799 women) from the 2008-2011 Korea National Health and Nutrition Survey. Cut-off values for sarcopenia were defined as a skeletal muscle mass index <0.789 for men and <0.512 for women. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression analysis after adjusting for confounding variables. ROC curve analysis was used to evaluate the ability of platelet count and white blood cell count to discriminate the presence of sarcopenia. RESULTS: After adjusting for possible confounders, the OR (95% CI) for sarcopenia occurrence according to platelet counts was 1.62 (1.20-2.19) for the T3 group in men and 1.72 (1.28-2.31) for the T3 group in women, relative to the lowest platelet count tertile. After adjusting for same confounders, the ORs (95% CI) for sarcopenia occurrence according to WBC counts was 1.86 (1.35-2.57) for the T3 group in men, and 2.36 (1.77-3.13) for the T3 group in women, relative to the lowest WBC count tertile. We also found independent significant associations between platelet count, WBC count, and sarcopenia. CONCLUSIONS: Higher platelet and WBC counts within the normal range are each independently associated with sarcopenia in Korean men and women. The inclusion of platelet, WBC, or combined platelet and WBC counts significantly improved the power to discriminate sarcopenia.


Assuntos
Contagem de Leucócitos/métodos , Contagem de Plaquetas/métodos , Sarcopenia/sangue , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Cachexia Sarcopenia Muscle ; 10(6): 1295-1306, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31508907

RESUMO

BACKGROUND: Sarcopenia is characterized by progressive decreases in muscle mass, muscle strength, and muscle function with ageing. Although many studies have investigated the mechanisms of sarcopenia, its connection with epigenetic factors, such as DNA methylation, still remains poorly understood. The aim of this study was to explore sarcopenia-related DNA methylation differences in blood samples between age-matched sarcopenic and non-sarcopenic older women. METHODS: A sarcopenic group (n = 24) was identified and selected from a set of 247 older Caucasian women (aged 65-80 years) based on cut-off points of skeletal muscle index at 6.75 kg/m2 and grip strength at 26 kg (the lower quintile of grip strength in the set). A non-sarcopenic group (n = 24) was created with a similar age distribution as that of the sarcopenic group. DNA methylation patterns of whole blood samples from both groups were analysed using Infinium MethylationEPIC BeadChip arrays. Differentially methylated cytosin-phosphate-guanine sites (dmCpGs) were identified at a P value threshold of 0.01 by comparing methylation levels between the sarcopenic and non-sarcopenic groups at each CpG site. dmCpG-related genes were annotated based on Homo sapiens hg19 genome build. The functions of these genes were further examined by GO and KEGG pathway enrichment analysis. RESULTS: The global methylation level of all analysed CpG sites (n = 788 074) showed no significant difference between the sarcopenic and non-sarcopenic groups (0.812), while the average methylation level of dmCpGs (n = 6258) was significantly lower in the sarcopenic group (0.004). The sarcopenic group had significantly higher methylation levels in TSS200 (the region from transcription start site to 200 nucleotides upstream of the site) and lower methylation levels in gene body and 3'UTR regions. In respect of CpG regions, CpG islands in promoters and some intragenic regions showed greater levels of methylation in the sarcopenic group. dmCpG-related KEGG pathways were mainly associated with muscle function, actin cytoskeleton regulation, and energy metabolism. Seven genes (HSPB1, PBX4, CNKSR3, ORMDL3, MIR10A, ZNF619, and CRADD) were found with the same methylation direction as previous studies of blood sample methylation during ageing. Fifty-four genes were shared with previous studies of resistance training. CONCLUSIONS: Our results improve understanding of epigenetic mechanisms of sarcopenia by identifying sarcopenia-related DNA methylation differences in blood samples of older women. These methylation differences suggest underlying alterations of gene expression and pathway function, which can partially explain sarcopenia-related muscular changes.


Assuntos
Envelhecimento/genética , Metilação de DNA , Redes Reguladoras de Genes , Sarcopenia/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Estudos de Casos e Controles , Ilhas de CpG , Epigênese Genética , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Sarcopenia/sangue
12.
BMC Geriatr ; 19(1): 233, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455238

RESUMO

BACKGROUND: Chronic inflammation is considered to affect physical performance, muscle strength and muscle mass, i.e. measures of sarcopenia. We need to identify a marker of inflammation that is univocally associated with measures of sarcopenia. We aimed to associate three markers of inflammation, erythrocyte sedimentation rate, albumin and white blood cell count, with measures of sarcopenia in geriatric outpatients. METHODS: Data from the Centre Of Geriatrics Amsterdam cohort was used. Geriatric outpatients at the VU university medical centre in Amsterdam were recruited based on referral between January 1st 2014 and the 31st of December 2015. Erythrocyte sedimentation rate, albumin and white blood cell count were assessed from venous blood samples. Measures of sarcopenia included physical performance by measuring gait speed with the 4 meter walk test, duration of the timed up and go test and of the chair stand test, muscle strength by assessing handgrip strength using handheld dynamometry and skeletal muscle mass by performing bioelectrical impedance analysis. Multivariable linear regression analyses were performed to assess the associations between erythrocyte sedimentation rate, albumin, white blood cell count and measures of sarcopenia. RESULTS: A total of 442 patients (mean age 80.8 years, SD 6.7, 58.1% female) were included. A higher erythrocyte sedimentation rate was significantly associated with lower gait speed (ß = - 0.005; 95% CI = - 0.007, - 0.003), longer duration of timed up and go test (Ln ß = 0.006; 95% CI = 0.003, 0.010), longer duration of chair stand test (Ln ß = 0.005; 95% CI = 0.002, 0.008), lower handgrip strength (ß = - 0.126; 95% CI = - 0.189, - 0.063) and lower relative skeletal muscle mass (ß = - 0.179; 95% CI = - 0.274, - 0.084). Lower albumin levels were significantly associated with lower gait speed (ß = - 0.020; 95% CI = - 0.011, - 0.028) and handgrip strength (ß = - 0.596; 95% CI = - 0.311, - 0.881). Associations remained significant after adjustment for age, sex and number of morbidities. No significant associations were found for white blood cell count and measures of sarcopenia. CONCLUSIONS: In geriatric outpatients, erythrocyte sedimentation rate was associated with all three measures of sarcopenia, underpinning the potential role of inflammation in sarcopenia.


Assuntos
Força Muscular/fisiologia , Sarcopenia/sangue , Sarcopenia/epidemiologia , Albumina Sérica Humana/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Sedimentação Sanguínea , Estudos de Coortes , Estudos Transversais , Feminino , Força da Mão/fisiologia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Países Baixos/epidemiologia , Equilíbrio Postural/fisiologia , Sarcopenia/diagnóstico , Estudos de Tempo e Movimento , Velocidade de Caminhada/fisiologia
13.
Transplant Proc ; 51(6): 1874-1879, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31262437

RESUMO

BACKGROUND: Patients on a waiting list for liver transplantation frequently show core muscle wasting, referred to as sarcopenia, which results in poor prognosis. To date, there has been a lack of research on the association between inflammation mediators, including cytokines, and loss of core muscle mass in cirrhotic patients scheduled for living donor liver transplantation (LDLT). METHODS: Cytokines in serum, such as interleukin (IL)-2, IL-6, IL-10, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α, were retrospectively investigated in 234 LDLT patients 1 day before surgery. The psoas muscle area was measured using abdominal computed tomography within 1 month before surgery and used to calculate the psoas muscle index (PMI = psoas muscle area/height2). The study population was classified into 2 groups according to the interquartile range of PMI: a non-sarcopenia group (> 25th quartile) and a sarcopenia group (≤ 25th quartile) in each sex. RESULTS: In both sexes, IL-10 and TNF-α levels were significantly higher in the sarcopenia group than the non-sarcopenia group. In a univariate analysis, male patients showed that serum IL-10 and TNF-α levels were potentially associated with sarcopenia. Serum TNF-α was independently associated with sarcopenia in a multivariate analysis. In female patients, TNF-α was significantly associated with sarcopenia in both univariate and multivariate analyses. Male patients with a PMI ≤ 25th quartile had significantly higher TNF-α levels than those in other quartile ranges, and female patients with a PMI ≤ 25th quartile had a significantly higher TNF-α level than those with a PMI > 75th quartile. CONCLUSIONS: Serum levels of TNF-α are inversely associated with skeletal muscle wasting in both male and female patients scheduled for LDLT.


Assuntos
Hepatopatias/sangue , Transplante de Fígado , Sarcopenia/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Adulto , Citocinas/sangue , Feminino , Humanos , Hepatopatias/complicações , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Músculos Psoas/patologia , Estudos Retrospectivos , Sarcopenia/etiologia , Sarcopenia/patologia , Tomografia Computadorizada por Raios X , Listas de Espera
14.
Can J Gastroenterol Hepatol ; 2019: 8182195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183339

RESUMO

Sarcopenia is a common complication of cirrhosis with a negative impact on posttransplant outcome, health-related quality of life (HRQOL), and patient survival. Studies in experimental animals and in patients demonstrate that ammonia is directly implicated in the pathogenesis of sarcopenia in cirrhosis via mechanisms involving increased expression of myostatin and of autophagy markers such as LC3 lipidation and p62 leading to muscle dysmetabolism and sarcopenia. Paradoxically, skeletal muscle replaces liver as the primary ammonia-detoxifying site as a result of the modification of genes coding for key proteins implicated in ammonia-lowering pathways in cirrhosis. Thus, a vicious cycle occurs whereby hyperammonemia causes severe muscle damage and sarcopenia that, in turn, limits the capacity of muscle to remove excess blood-borne ammonia and the cycle continues. Randomized clinical trials and meta-analyses confirm that L-ornithine L-aspartate (LOLA) is an effective ammonia-lowering agent currently employed for the treatment of hepatic encephalopathy (HE) that stimulates both urea synthesis by residual hepatocytes and muscle glutamine synthesis together with putative hepatoprotective actions. Treatment of cirrhotic patients with LOLA limits ammonia-induced sarcopenia by improving muscle protein synthesis and function. It is conceivable that the antisarcopenic action of LOLA contributes to its efficacy for the treatment of HE in cirrhosis.


Assuntos
Dipeptídeos/uso terapêutico , Doença Hepática Terminal/sangue , Sarcopenia/tratamento farmacológico , Amônia/sangue , Doença Hepática Terminal/complicações , Humanos , Hiperamonemia/tratamento farmacológico , Hiperamonemia/etiologia , Fígado/metabolismo , Sarcopenia/sangue , Sarcopenia/etiologia , Resultado do Tratamento
15.
BMC Musculoskelet Disord ; 20(1): 276, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31164134

RESUMO

BACKGROUND: Understanding interactions between bone and muscle based on endocrine factors may help elucidate the relationship between osteoporosis and sarcopenia. However, whether the abundance or activity of these endocrine factors is affected by age and sex or whether these factors play a causal role in bone and muscle formation and function is unclear. We aimed to evaluate the association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults. METHODS: In all, 254 residents (97 men, 157 women) participated in this cross-sectional study conducted in Japan. The calcaneal speed of sound (SOS) was evaluated by quantitative ultrasound examination. Skeletal muscle mass index (SMI) was calculated by bioelectrical impedance analysis. Grip strength was measured using a dynamometer. Gait speed was measured by optical-sensitive gait analysis. Serum sclerostin, osteocalcin (OC), insulin-like growth factor-1 (IGF-1), myostatin, and tartrate-resistant acid phosphatase-5b (TRACP-5b) concentrations were measured simultaneously. The difference by sex was determined using t test. Correlations between serum bone- and muscle-derived factors and age, BMI, SOS, SMI, grip strength, gait speed, and TRACP-5b in men and women were determined based on Pearson's correlation coefficients. Multiple regression analysis was performed using the stepwise method. RESULTS: There was no significant difference with regard to age between men (75.0 ± 8.9 years) and women (73.6 ± 8.1 years). Sclerostin was significantly higher in men than in women and tended to increase with age in men; it was significantly associated with SOS and TRACP-5b levels. OC was significantly higher in women than in men and was significantly associated with TRACP-5b levels and age. IGF-1 tended to decrease with age in both sexes and was significantly associated with SOS and body mass index. Myostatin did not correlate with any assessed variables. CONCLUSIONS: Sclerostin was significantly associated with sex, age, and bone metabolism, although there was no discernable relationship between serum sclerostin levels and muscle function. There was no obvious relationship between OC and muscle parameters. This study suggests that IGF-1 is an important modulator of muscle mass and function and bone metabolism in community-dwelling middle-aged and elderly adults.


Assuntos
Osso e Ossos/fisiologia , Vida Independente , Músculo Esquelético/fisiologia , Desempenho Físico Funcional , Proteínas Adaptadoras de Transdução de Sinal , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Composição Corporal/fisiologia , Proteínas Morfogenéticas Ósseas/sangue , Estudos Transversais , Feminino , Marcadores Genéticos , Força da Mão/fisiologia , Humanos , Fator de Crescimento Insulin-Like I/análise , Japão , Masculino , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/fisiopatologia , Sarcopenia/sangue , Sarcopenia/fisiopatologia , Fatores Sexuais , Velocidade de Caminhada/fisiologia
16.
Clin Nutr ESPEN ; 32: 88-95, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31221297

RESUMO

BACKGROUNDS & AIMS: Obesity and sarcopenia are independent illnesses associated with contemporary dietary and physical activity behaviors, aggravated by aging. Their coexistence is termed sarcopenic obesity (SO). Hence, increasing protein intake and resistance training (RT) are interventions that could counteract these illnesses. The objective of this investigation was to analyze the effects of whey protein (WP) supplementation associated with RT on body composition, muscular strength, functional capacity, and plasma-metabolism biomarkers in older women with SO. METHODS: Twenty six sarcopenic (appendicular lean soft tissue ALST < 15.02 kg) obese (body fat mass ≥ 35%) older women were randomly assigned to receive daily, either 35 g of WP (WP group) or placebo (PLA group), combined with supervised RT (8 exercises, 3 × 8-12 rep, 3 times a week), during a 12-week protocol. Blood samples, blood pressure, dietary intake, functional capacity tests, the one repetition maximum (1RM) test, and body composition were assessed before and after the intervention period. Two-way analysis of variance for repeated measures was applied for comparisons. RESULTS: The WP group presented greater (P < 0.05) increases in ALST (WP = 6.0% vs. PLA = 2.5%) and decreases in (P < 0.05) total (-3.3% vs. -0.3%) and trunk fat mass (WP = -5.1% vs. PLA = -1.1) and IL-6 (WP = -34.6% vs. PLA = 9.3%) compared with the PLA group. Both groups demonstrated improved (P < 0.05) scores for muscular strength, waist-hip ratio, functional capacity, and other plasma-metabolism biomarkers without significant differences between conditions. CONCLUSION: Whey protein combined with RT increased ALST, and decreased total and trunk fat mass, improving sarcopenia and decreasing SO in older women, with a limited impact on inflammation. Registered under ClinicalTrials.gov Identifier n° NCT03752359.


Assuntos
Obesidade , Sarcopenia/terapia , Proteínas do Soro do Leite/administração & dosagem , Idoso , Biomarcadores/metabolismo , Composição Corporal , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Treinamento de Resistência , Sarcopenia/sangue , Resultado do Tratamento
17.
Calcif Tissue Int ; 105(2): 173-182, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31069442

RESUMO

Effects of low serum 25OHD on age-related changes in muscle mass and function remain unclear. Our aims were to explore associations of baseline 25OHD levels with prevalent and incident sarcopenia and changes in muscle parameters, and to examine the role of parathyroid hormone (PTH) therein. Cross-sectional (n = 975) and prospective analyses (n = 702) of older adults aged 65-93 years participating in the KORA-Age study. Sarcopenia was defined using the 2010 European Working Group on Sarcopenia in Older People (EWGSOP) criteria as low muscle mass combined with low grip strength or low physical performance. Associations with baseline 25OHD were examined in multiple regression analyses. Low vitamin D status was linked to increased odds of prevalent sarcopenia. Over three years, low baseline 25OHD < 25 vs. ≥ 50 nmol/L were associated with greater loss of muscle mass and increased time for the Timed Up and Go test. The risk for developing incident sarcopenia was not significantly elevated in individuals with low baseline 25OHD but when including death as combined outcome alongside incident sarcopenia, there was a strong positive association in multivariable analysis [OR (95% CI) 3.19 (1.54-6.57) for 25OHD < 25 vs. ≥ 50 nmol/L]. There was no evidence for a PTH-mediating effect. Low baseline 25OHD levels were associated with unfavorable changes in muscle mass and physical performance, but not with incident sarcopenia. Future randomized trials are needed to assess causality and to address the issue of competing risks such as mortality in older cohorts.


Assuntos
Envelhecimento , Hormônio Paratireóideo/sangue , Sarcopenia/sangue , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Estudos Prospectivos , Vitamina D/sangue
19.
Aging Clin Exp Res ; 31(6): 845-854, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049877

RESUMO

BACKGROUND: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. AIM: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. METHODS: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4-9) and a body mass index of 20-30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. RESULTS: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.


Assuntos
Leucina/uso terapêutico , Sarcopenia/tratamento farmacológico , Vitamina D/uso terapêutico , Proteínas do Soro do Leite/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-6/sangue , Leucina/farmacologia , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Músculo Esquelético/efeitos dos fármacos , Sarcopenia/sangue , Vitamina D/farmacologia , Proteínas do Soro do Leite/farmacologia
20.
J Cachexia Sarcopenia Muscle ; 10(3): 536-548, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31091026

RESUMO

BACKGROUND: Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell-to-cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. METHODS: We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre-operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR-203 expression levels in CRC tissues and pre-operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR-203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. RESULTS: A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35-89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well-established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour-node-metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log-rank test) and disease-free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log-rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19-10, P = 0.0001) and disease-free survival (hazard ratio: 2.33, 95% CI: 1.14-4.77, P = 0.021) in CRC patients. Serum miR-203 expression negatively correlated with pre-operative PMI level (P = 0.0001, ρ = -0.25), and multivariate logistic regression analysis revealed that elevated serum miR-203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8-14.8, P = 0.002). Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via down-regulation of BIRC5 (survivin) expression in human SkMC line. CONCLUSIONS: Assessment of serum miR-203 expression could be used for risk assessment of myopenia, and miR-203 might be a novel therapeutic target for inhibition of myopenia in CRC.


Assuntos
MicroRNA Circulante/sangue , Neoplasias Colorretais/complicações , MicroRNAs/sangue , Sarcopenia/diagnóstico , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular , Proliferação de Células/genética , MicroRNA Circulante/metabolismo , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Doença , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/metabolismo , Músculos Psoas/patologia , Reto/patologia , Reto/cirurgia , Medição de Risco/métodos , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/genética , Survivina/genética , Tomografia Computadorizada por Raios X
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