Biomarkers shared by frailty and sarcopenia in older adults: A systematic review and meta-analysis

Background: Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted. Results: Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60–88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68–87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts. Conclusions: A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia

Extracellular vesicles and pancreatic cancer: Insights on the roles of mirna, lncrna, and protein cargos in cancer progression

Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. Although mutations of key oncogenes and oncosuppressor involved in tumor growth and in immunosurveillance escape are known, the underlying mechanisms that orchestrate PC initiation and progression are poorly understood or still under debate. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. Literature data report that these nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. In this review, we have summarized and discussed principal cargos of extracellular vesicles characterized in PC, such as miRNAs, lncRNAs, and several proteins, to offer a systematic overview of their function in PC progression. The study of extracellular vesicles is allowing to understand that investigation of their secretion and analysis of their content might represent a new and potential diagnostic and prognostic tools for PC

Amino acid profiles in older adults with frailty. Secondary analysis from MetaboFrail and BIOSPHERE studies

An altered amino acid metabolism has been described in frail older adults which may contribute to muscle loss and functional decline associated with frailty. In the present investigation, we compared circulating amino acid profiles of older adults with physical frailty and sarcopenia (PF&S, n = 94), frail/pre-frail older adults with type 2 diabetes mellitus (F-T2DM, n = 66), and robust non-diabetic controls (n = 40). Partial least squares discriminant analysis (PLS–DA) models were built to define the amino acid signatures associated with the different frailty phenotypes. PLS–DA allowed correct classification of participants with 78.2 ± 1.9% accuracy. Older adults with F-T2DM showed an amino acid profile characterized by higher levels of 3-methylhistidine, alanine, arginine, ethanolamine, and glutamic acid. PF&S and control participants were discriminated based on serum concentrations of aminoadipic acid, aspartate, citrulline, cystine, taurine, and tryptophan. These findings suggest that different types of frailty may be characterized by distinct metabolic perturbations. Amino acid profiling may therefore serve as a valuable tool for frailty biomarker discovery

Effects of combined resistance and power training on cognitive function in older women: A randomized controlled trial

The present study compared the effects of traditional resistance training (TRT) and combined power training (PT) and TRT (PTRT) on cognitive parameters and serum brain-derived neurotrophic factor (BDNF) levels in non-demented, well-functioning, community-dwelling older women. Forty-five older women were randomized into one of three experimental groups: TRT, PTRT, and control group (CG). Cognitive tests explored global cognitive function, short-term memory, and dual-task performance. Serum BDNF levels were assessed at baseline and after the intervention. Exercise sessions were performed twice a week over 22 weeks. In TRT, exercise sessions were based on three sets of 8\u201310 repetitions at \u201cdifficult\u201d intensity. In PTRT, the first session was based on PT (three sets of 8 1210 repetitions at \u201cmoderate\u201d intensity), while the second session was similar to the TRT. Our analyses indicated that overall cognitive function, short-term memory, and dual-task performance were similarly improved after TRT and PTRT. Serum BDNF concentrations were not altered by any training protocol. In conclusion, the two RT programs tested in the present trial improved global cognitive function, short-term memory and dual task performance in non-demented, well-functioning, community-dwelling older women. In addition, our findings suggest that mechanisms other than BDNF may be associated with such improvements

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID

The full-length prototype of the KLOE drift chamber

The main goal of the KLOE experiment is the study of CP violation in the K mesons system, with an accuracy of 10(-4) in the measurement of Re(epsilon'/epsilon). This task imposes strong constraints on the design and operation of the drift chamber, which must reconstruct the charged decays of low momentum K-L's and K-S's with high efficiency and high resolution, full-length prototype of the chamber has been built and tested on a 50 GeV/c beam. The analysis of the large sample of data has allowed a detailed study of the time to distance relations as a function of the track parameters and of the peculiar geometry of the drift cell, The detector performance, in terms of efficiency, spatial resolutions and dE/dx resolution, is illustrated and discussed

Black Girls Speak STEM: Counterstories of Informal and Formal Learning Experiences

This study presents the interpretations and perceptions of Black girls who participated in I AM STEM – a community-based informal science, technology, engineering, and mathematics (STEM) program. Using narrative inquiry, participants generated detailed accounts of their informal and formal STEM learning experiences. Critical race methodology informed this research to portray the dynamic and complex experiences of girls of color, whose stories have historically been silenced and misrepresented. The data sources for this qualitative study included individual interviews, student reflection journals, samples of student work, and researcher memos, which were triangulated to produce six robust counterstories. Excerpts of the counterstories are presented in this article. The major findings of this research revealed that I AM STEM ignited an interest in STEM learning through field trips and direct engagement in scientific phenomena that allowed the girls to become agentic in continuing their engagement in STEM activities throughout the year. This call to awaken the voices of Black girls to speak casts light on their experiences and challenges as STEM learners ⎯ from their perspectives. The findings confirm that when credence and counterspaces are given to Black girls, they are poised to reveal their luster toward STEM learning. This study provided a space for Black girls to reflect on their STEM learning experiences, formulate new understandings, and make connections between the informal and formal learning environments within the context of their everyday lives, thus offering a more holistic approach to STEM learning that occurs across settings and over a lifetime

Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: The EURODIAB Prospective Complications Study

Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes

Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

The diversion of MHC class II-restricted thymocytes into the regulatory T (Treg) cell lineage, similarly to clonal deletion, is driven by intrathymic encounter of agonist self-antigens. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and those that are diverted into the Treg cell lineage. Here, we discuss how thymocyte-intrinsic and -extrinsic determinants may specify the choice between these two fundamentally different T cell fates

Self-tolerance in multiple sclerosis

During the last decade, several defects in self-tolerance have been identified in multiple sclerosis. Dysfunction in central tolerance leads to the thymic output of antigen-specific T cells with T cell receptor alterations favouring autoimmune reactions. In addition, premature thymic involution results in a reduced export of naïve regulatory T cells, the fully suppressive clone. Alterations in peripheral tolerance concern costimulatory molecules as well as transcriptional and epigenetic mechanisms. Recent data underline the key role of regulatory T cells that suppress Th1 and Th17 effector cell responses and whose immunosuppressive activity is impaired in patients with multiple sclerosis. Those recent observations suggest that a defect in self-tolerance homeostasis might be the primary mover of multiple sclerosis leading to subsequent immune attacks, inflammation and neurodegeneration. The concept of multiple sclerosis as a consequence of the failure of central and peripheral tolerance mechanisms to maintain a self-tolerance state, particularly of regulatory T cells, may have therapeutic implications. Restoring normal thymic output and suppressive functions of regulatory T cells appears an appealing approach. Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56bright natural killer cells