Association of Klotho with physical performance and frailty in middle-aged and older adults: A systematic review

Abstract Ageing is an inevitable process of physical deterioration that impairs functional autonomy and quality of life, becoming a public health issue. Since the percentage of people over 60 years is increasing worldwide, the use of easily detectable biomarkers of ageing is a relevant tool for monitoring of the ageing process and treatment. Among them, Klotho, an ageing suppressor gene because its deficiency leads to ageing like phenotype, seems particularly promising. This systematic review includes the last 10 years clinical studies that evaluated the association between plasma Klotho and body composition, physical performance and frailty in both sedentary and active middle-aged and older adults. Sixteen studies have been found: nine regarding the association between Klotho and body composition, two the association of Klotho and frailty and finally five concerning the effects of physical activity on Klotho. The results of these studies, albeit with some exceptions, point out that Klotho is positively associated with muscle strength and negatively with osteoporosis, frailty, disability and mortality while physical activity generally increases Klotho levels. Moreover, even if there are still few clinical studies, Klotho might be positively associated with bone mineral density, muscle strength, longevity, mobility and robustness during ageing

Periosteal derived cells and bone tissue regenerative medicine

Mesenchymal stem cells (MSCs), showing a high capacity of self-renewal and differentiation into various lineages, have primarily used for the biological repair of cartilage and bone. Even though MSCs have been identified in different organ tissues, cells from different sources may show phenotypic heterogeneity, different in vivo results and specific functions of graft regions after transplantation. Therefore, a correct selection of MSC source is crucial to obtain a more efficient treatment for regeneration of injured osteochondral tissues. Periosteum Derived Progenitor Cells (PDPCs), which possesses multipotency at single cell level and can form cartilage and bone in vitro and in vivo may represent as an interesting cell resource for bone tissue engineering. Aim of the present study is the isolation and characterization of human PDPCs and the evaluation of their ability to grow on bioresorbable composite scaffolds for bone tissue engineering applications. PDCPs were obtained from periosteal tissue harvested from healthy subjects undergoing surgery for orthopedic trauma. Prior to cells seeding cell were phenotipically characterized. Three composite scaffolds, differing in weight ratios between the components were tested. The scaffolds were coded as CEL2/POL 0/100, 40/60 and 70/30 where CEL2 is a bioglass and POL the organic component based on chitosan and gelatin. Cells were cultured for 14 and 21 days. Our culture conditions favour the selection of a mesenchymal stem cells population. The obtained PDPCs displayed a good ability to interact with the different tested scaffolds. Morphological and biochemical analysis performed showed that cells maintain their metabolic activity and ability to proliferate on the scaffolds. Differentiation over proliferation that occurred to PDCPs at the increase of bioactive glass concentration proves the capacity of these scaffolds to modulate osteogenic properties. This strengthens the hypothesis of periosteum as stem cell source for an osteochondral tissue regenerative medicine based on in situ cell recruitment. This work was supported by RBAP10MLK7 FIRB project

Development and characterization of a novel human 3D model of bone metastasis from breast carcinoma in vitro cultured

Breast cancer frequently metastasizes to the skeleton causing significant morbidity. Here, we set-up a novel and advanced ex vivo model by using fresh tissue from human vertebral bone metastasis from breast carcinoma patients able to retain the tumor microenvironment and tumor cells heterogeneity

Influenza vaccination coverage among medical residents: An Italian multicenter survey

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P < 0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. © 2014 Landes Bioscience

Multimorbidity and Polytherapy in Patients with Femoral Neck Fracture: A Retrospective Observational Study

Fractures of the femoral neck are one of the most common reasons for admission to an orthopedic institute. These patients also show multimorbidity (&ge;2 chronic conditions) and polytherapy (&ge;5 drugs). Multimorbidity and polytherapy are associated with a high risk of hospitalization and a reduction in quality of life. The present retrospective observational study was conducted to evaluate the prevalence of multimorbidity and polytherapy in patients aged &ge;65 years and surgically treated for femoral neck fractures at an orthopedic institute over 3 years. Multimorbidity was evaluated with Elixhauser&rsquo;s comorbidity measure and polytherapy was obtained from the patient&rsquo;s medical record. This study identified 917 patients (84 &plusmn; 7.6 years); most of them were females. Most patients presented &ge;2 chronic conditions, the most frequent of which was uncomplicated hypertension, and most patients used &ge;5 drugs, of which antithrombotic ones were the most frequently taken. No significant gender and age differences were found between the presence or not of multimorbidity or polytherapy. Multimorbidity and polytherapy were statistically associated with an increased and decreased risk of 1-year mortality, respectively. This retrospective study has evaluated the variables required for the establishment of a minimum core of descriptors of the prevalence of polytherapy and multimorbidity in the orthopedic field

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1&beta;, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up- and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease

Ageing and Osteoarthritis Synergically Affect Human Synoviocyte Cells: An In Vitro Study on Sex Differences

Osteoarthritis is a chronic inflammatory disease that affects all of the joints, especially those of the elderly. Aging is a natural and irreversible biological process implicated in the pathophysiology of many chronic diseases, such as osteoarthritis. Inflammation and oxidative stress are the main factors involved in osteoarthritis and aging, respectively, with the production of several pro-inflammatory cytokines such as Interleukin 1β (IL1β) and reactive oxygen species. The aim of the study was to set-up an in vitro model of osteoarthritis and aging, focusing on the sex differences by culturing male and female fibroblast-like synoviocytes (FLSs) with IL1β, hydrogen peroxide (H2O2), IL1β+H2O2 or a growth medium (control). IL1β+H2O2 reduced the cell viability and microwound healing potential, increased Caspase-3 expression and reactive oxygen species and IL6 production; IL1β increased IL6 production more than the other conditions did; H2O2 increased Caspase-3 expression and reactive oxygen species production; Klotho expression showed no differences among the treatments. The FLSs from female donors demonstrated a better response capacity in unfavorable conditions of inflammation and oxidative stress than those from the male donors did. This study developed culture conditions to mimic the aging and osteoarthritis microenvironment to evaluate the behavior of the FLSs which play a fundamental role in joint homeostasis, focusing on the sex-related aspects that are relevant in the osteoarthritis pathophysiology

Increased Chondrogenic Potential of Mesenchymal Cells From Adipose Tissue Versus Bone Marrow-Derived Cells in Osteoarthritic In Vitro Models

Primarily, to compare the behavior of human mesenchymal stem cells (MSCs) derived from bone marrow (hBMSCs) and adipose tissue (hADSCs) in an osteoarthritic (OA) microenvironment; secondly, to investigate the reaction of these cell types in two alternative in vitro culture systems, obtained by using TNFα and/or IL1β as inflammation mediators, or by using synovial fluid harvested by OA patients (OSF) to simulate the complex inflamed knee microenvironment. 3D micromass cultures of hBMSCs or hADSCs were grown in chondrogenic medium (CTR), in the presence of TNFα and/or IL1β, or synovial fluid from OA patients. After 1 month of culture, the chondrogenic differentiation of micromasses was evaluated by gene expression, matrix composition, and organization. Both hMSCs types formed mature micromasses in CTR, but a better response of hADSCs to the inflammatory environment was documented by micromass area and Bern score evaluations. The addition of OSF elicited a milder reaction than with TNFα and/or IL1β by both cell types, probably due to the presence of both catabolic and protective factors. In particular, SOX9 and ACAN gene expression and GAG synthesis were more abundant in hADSCs than hBMSCs when cultured in OSF. The expression of MMP1 was increased for both hMSCs in inflammatory conditions, but in particular by hBMSCs. hADSCs showed an increased chondrogenic potential in inflammatory culture systems, suggesting a better response of hADSCs in the OA environment, thus underlining the importance of appropriate in vitro models to study MSCs and potential advantages of using these cells for future clinical applications. J. Cell. Physiol. 9999: 1-11, 2016. © 2016 Wiley Periodicals, Inc