Efficient and rapid assessment of multiple aspects of frailty using the Kyoto Frailty Scale, developed from the Edmonton Frail Scale

[Purpose] Global aging has led to a dramatic increase in the number of frail people, who are likely to become bedridden. Since frailty can be partially reversed, early intervention would be beneficial for patients, family members, and clinicians. This study was designed to develop a screening tool for an accurate and comprehensive assessment of frailty by modulating the Edmonton Frail Scale (EFS). [Participants and Methods] The EFS, covering multiple domains, is one of the major diagnostic tools for frailty. Frail and non-frail participants (n=67) were evaluated for each diagnostic item of the EFS to identify the most efficient combination of questions by evaluating its sensitivity and specificity. [Results] The Kyoto Frailty Scale (KFS) was developed as a rapid frailty scale, based on the EFS. The KFS comprises nine questions about health status, polypharmacy, hospitalization, living with a reliable caregiver, shopping, transportation, housework, money management, and forgetting to take medicine. The KFS has an excellent negative predictive value (100%) for screening frailty and a positive predictive value (97%) for screening prefrailty and frailty if we regard KFS ≥4 as a test positive. [Conclusion] The KFS permits clinician to rapidly and accurately screen for frailty and prefrailty, or exclude frailty

Senescence induction; a possible cancer therapy

Cellular immortalization is a crucial step during the development of human cancer. Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli: they have altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. During immortalization, cells acquire genetic alterations that override senescence. Tumor suppressor genes and oncogenes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screening to search for genes involved in senescence, several candidate oncogenes and putative tumor suppressor genes have been recently isolated, including subtypes of micro-RNAs. These findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy

Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty

Due to global aging, frailty and sarcopenia are increasing. Sarcopenia is defined as loss of volume and strength of skeletal muscle in elderlies, while frailty involves multiple domains of aging-related dysfunction, impaired cognition, hypomobility, and decreased social activity. However, little is known about the metabolic basis of sarcopenia, either shared with or discrete from frailty. Here we analyzed comprehensive metabolomic data of human blood in relation to sarcopenia, previously collected from 19 elderly participants in our frailty study. Among 131 metabolites, we identified 22 sarcopenia markers, distinct from 15 frailty markers, mainly including antioxidants, although sarcopenia overlaps clinically with physical frailty. Notably, 21 metabolites that decline in sarcopenia or low SMI are uremic compounds that increase in kidney dysfunction. These comprise TCA cycle, urea cycle, nitrogen, and methylated metabolites. Sarcopenia markers imply a close link between muscle and kidney function, while frailty markers define a state vulnerable to oxidative stress

Editorial: How Do Metabolism, Angiogenesis, and Hypoxia Modulate Resistance?

Resistència al càncer; Cèl·lules mare cancerígenes; TeràpiaResistencia al cáncer; Células madre cancerosas; TerapiaCancer resistance; Cancer stem cell; TherapyMetabolic alterations were among the first discovered hallmarks of cancer. They were first described 90 years ago when Otto Warburg realized that cancer cells in culture had a relatively increased metabolic rate (the Warburg hypothesis). It has been proposed that the drastic changes seen in cancer metabolism are in part attributed to mutations in the mtDNA, metabolic reprogramming, or mitochondrial dysfunction. However, novel players in cancer metabolism are emerging.This work was supported by ISCIII (Instituto de Salud Carlos III) Ref. FIS PI15/01262 (MELL), co-financed by the European Regional Development Fund (ERDF) and AECC Project GEC Ref. GC16173720CARR (MELL)

Whole Blood Metabolomics in Aging Research

Diversity is observed in the wave of global aging because it is a complex biological process exhibiting individual variability. To assess aging physiologically, markers for biological aging are required in addition to the calendar age. From a metabolic perspective, the aging hypothesis includes the mitochondrial hypothesis and the calorie restriction (CR) hypothesis. In experimental models, several compounds or metabolites exert similar lifespan-extending effects, like CR. However, little is known about whether these metabolic modulations are applicable to human longevity, as human aging is greatly affected by a variety of factors, including lifestyle, genetic or epigenetic factors, exposure to stress, diet, and social environment. A comprehensive analysis of the human blood metabolome captures complex changes with individual differences. Moreover, a non-targeted analysis of the whole blood metabolome discloses unexpected aspects of human biology. By using such approaches, markers for aging or aging-relevant conditions were identified. This information should prove valuable for future diagnosis or clinical interventions in diseases relevant to aging

Theoretical Analysis of a Ridged-Waveguide Mounting Structure

The driving-point impedance of a single-gap thin conductor strip, a model of the ribbon-and-pedestal of diode package, mounted across the gap of a ridged waveguide has been derived using the induced EMF method. The dyadic Green\u27s function for the ridged waveguide is derived to facilitate the analysis. An equivalent circuit is developed which involves an infinite array of transformers representing the couplings between the conductor strip and the waveguide normal modes. Numerical results for a typical example are presented to discuss the validity of the analytical results and also to demonstrate a remarkably smooth behavior of the driving-point impedance of the mount over a frequency range from 5.4 to 25.4 GHz