Developing physical frailty specifications for investigation of frailty pathways in older people

Different frailty definitions are suitable for different purposes. When investigating its key multidimensional predictors and effects, narrower definitions of frailty that exclude these elements may be more desirable. For this purpose, candidate physical frailty specifications are constructed and then evaluated on their construct and concurrent validity. For 4638 participants aged 65 to 89 years from wave 2 (2004) of the English Longitudinal Study of Ageing, confirmatory factor analysis is performed to create physical frailty specifications with four indicators (slowness, weakness, exhaustion, and weight loss) and with three indicators (slowness, weakness, and either exhaustion or weight loss). Using derived factor scores, their convergent, discriminant, and concurrent validity are compared. For specifications with four indicators and with three indicators including exhaustion, slowness contributes dominantly to the physical frailty factor. However, with three indicators including weight loss, weakness contributes most. Where represented, weight loss only contributes minimally. Higher factor scores are significantly associated with chronic diseases, functional impairment, and poor self-rated health, although less so for the third specification. Factor scores for the first two specifications have low correlation with psychological and social frailty while those for the third have negligible correlation. Factor scores increase with higher Frailty Index although again less so for the third specification. Minor differences are seen across gender. On account of their convergent, discriminatory, and concurrent validity, physical frailty specifications with four indicators and with three indicators including exhaustion hold promise for use in investigation of frailty pathways involving multidimensional predictors and effects

Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects

Physical frailty in older people is an escalating health and social challenge. We investigate its physical, psychological, and social predictors, including how and for whom these conditions exert their effects. For 4,638 respondents aged 65 to 89 years from wave 2 of the English Longitudinal Study of Ageing, we examine prediction of future physical frailty by physical, psychological, and social conditions using latent growth curve analysis with multiple indicators. In addition, we explore their indirect effects through disease and physiologic decline, and repeat these analyses after stratification by gender, age group, and selected conditions which are possible moderators. We find that chronic disease, allostatic load, low physical activity, depressive symptoms, cognitive impairment, and poor social support all predict future physical frailty. Furthermore, chronic disease and allostatic load mediate the effects of low physical activity, depressive symptoms, and cognitive impairment on future physical frailty. Finally, although poor social integration is not a predictor of future physical frailty, this condition moderates the indirect effect of poor social support through chronic disease by rendering it stronger. By virtue of their roles as predictor, mediator, or moderator on pathways to physical frailty, chronic disease, allostatic load, low physical activity, cognitive impairment, depressive symptoms, poor social support, and poor social integration are potentially modifiable target conditions for population-level health and social interventions to reduce future physical frailty in older people

Pathways from physical frailty to activity limitation in older people: identifying moderators and mediators in the English longitudinal study of ageing

Physical frailty increases the risk of future activity limitation, which in turn, compromises independent living of older people and limits their healthspan. Thus, we seek to identify moderators and mediators of the effect of physical frailty on activity limitation change in older people, including gender- and age-specific effects. In a longitudinal study using data from waves 2, 4, and 6 of the English Longitudinal Study of Ageing, unique physical frailty factor scores of 4,638 respondents aged 65 to 89 years are obtained from confirmatory factor analysis of physical frailty, which is specified by three indicators, namely slowness, weakness, and exhaustion. Using a series of autoregressive cross-lagged models, we estimate the effect of physical frailty factor score on activity limitation change, including its moderation by social conditions, and indirect effects through physical and psychological conditions. We find that the effect of physical frailty on activity limitation change is significantly stronger with older age, while it has significant indirect effects through low physical activity, depressive symptoms, and cognitive impairment. In turn, indirect effects of physical frailty through low physical activity and cognitive impairment are stronger with older age. Sensitivity analyses suggest that these effects vary in their robustness to unmeasured confounding. We conclude that low physical activity, depressive symptoms, and cognitive impairment are potentially modifiable mediators on pathways from physical frailty to activity limitation in older people, including those who are very old. This evidence offers support for population-level interventions that target these conditions, to mitigate the effect of physical frailty on activity limitation, and thereby enhance healthspan

Parallel super-resolution imaging

Massive parallelization of scanning-based super-resolution imaging allows fast imaging of large fields of view

Preliminary Observations on the Effects In Vivo and In Vitro of Low Dose Laser on the Epithelia of the Bladder, Trachea and Tongue of the Mouse

The effects of low dose CW laser were studied by in vivo and in vitro systems. The experimental tissues that were used included bladders, tracheas and tongues as experimental tissues. Buddings (round surface projections) from the transitional epithelium of bladder were frequently observed 3 days after laser treatment in both in vivo and in vitro systems. The trachea and tongue were less affected. In both the in vivo and in vitro systems, some epithelial cells of the trachea showed decreased microvilli and cilia 3 days after treatment whereas the epithelial cells of the tongue revealed no response to laser treatment in both systems. Low dose laser, however, appeared to promote the rate of healing of experimental tongue ulcer: healing was about 1 day earlier in the laser treated than non-treated animals and vessel infiltration and epithelialization were detected earlier in the treated

Microbes control Drosophila germline stem cell increase and egg maturation through hormonal pathways

Suyama R., Cetraro N., Yew J.Y., et al. Microbes control Drosophila germline stem cell increase and egg maturation through hormonal pathways. Communications Biology 6, 1287 (2023); https://doi.org/10.1038/S42003-023-05660-X.Reproduction is highly dependent on environmental and physiological factors including nutrition, mating stimuli and microbes. Among these factors, microbes facilitate vital functions for host animals such as nutritional intake, metabolic regulation, and enhancing fertility under poor nutrition conditions. However, detailed molecular mechanisms by which microbes control germline maturation, leading to reproduction, remain largely unknown. In this study, we show that environmental microbes exert a beneficial effect on Drosophila oogenesis by promoting germline stem cell (GSC) proliferation and subsequent egg maturation via acceleration of ovarian cell division and suppression of apoptosis. Moreover, insulin-related signaling is not required; rather, the ecdysone pathway is necessary for microbe-induced increase of GSCs and promotion of egg maturation, while juvenile hormone contributes only to increasing GSC numbers, suggesting that hormonal pathways are activated at different stages of oogenesis. Our findings reveal that environmental microbes can enhance host reproductivity by modulating host hormone release and promoting oogenesis

Stimulation of Collagen Formation in the Intestinal Anastomosis by Low Dose He-Ne Laser

The effect of low dose He-Ne laser on the healing of intestinal anastomosis was studied in the albino rat. A small piece of jejunum was removed from each rat and the ends sutured back with a simple interrupted pattern. In the experimental animal, the anastomosis was Irradiated through an optic fiber with a He-Ne laser (1 mW) for 15 minutes whereas in the control animal, the anastomosis was not irradiated. The differences between the two groups were compared by histology, transmission electron microscopy, scanning electron microscopy and autoradiography 3 and 7 days after operation. The laser treated experimental animals demonstrated thicker collagen fibers and an increased quantity of collagen at the junction of the anastomosis compared to control animals. Increased uptake of labelled proline was also evident in the laser treated animals. These observations all point to a possible enhancement of collagen synthesis triggered by laser irradiation

Wide-field two-photon microscopy with temporal focusing and HiLo background rejection

Scanningless depth-resolved microscopy is achieved through spatial-temporal focusing and has been demonstrated previously. The advantage of this method is that a large area may be imaged without scanning resulting in higher throughput of the imaging system. Because it is a widefield technique, the optical sectioning effect is considerably poorer than with conventional spatial focusing two-photon microscopy. Here we propose wide-field two-photon microscopy based on spatio-temporal focusing and employing background rejection based on the HiLo microscope principle. We demonstrate the effects of applying HiLo microscopy to widefield temporally focused two-photon microscopy

Responses of Astrocytes in Culture After Low Dose Laser Irradiation

The effect of Helium-Neon low dose laser on astrocytes was investigated in cultures of isolated astrocytes from albino neonatal rats. The laser appeared to inhibit the growth of astrocytes as exemplified by the smaller sizes of the cells and the decreased leucine uptake in each cell after treatment. Temporary decrease in the number of mitoses was also observed, but this trend was reversed soon after. Electron microscopic studies revealed an increase in buddings from cell bodies and processes (branches) after irradiation

Relationship between Renal Function, Fibrin Clot Properties and Lipoproteins in Anticoagulated Patients with Atrial Fibrillation

Background: Mechanisms by which chronic kidney disease (CKD) influences fibrin clot properties in atrial fibrillation (AF) remain ill-defined. We aimed to investigate the effects of AF and CKD on fibrin clot properties and lipoproteins, and determine the relationship between these factors. Methods: Prospective cross-sectional study of patients recruited from cardiology services in Liverpool between September 2019 and October 2021. Primary groups consisted of anticoagulated AF patients with and without CKD in a 1:1 ratio. Control group comprised anticoagulated patients without AF or CKD. Fibrin clot properties were analysed using turbidity and permeation assays. Detailed lipoprotein characteristics, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL and oxidised LDL, were measured. Results: Fifty-six anticoagulated patients were enrolled (median age 72.5; 34% female); 46 with AF (23 with CKD and 23 without CKD) and 10 controls. AF was associated with changes in three indices of fibrin clot properties using PTT (T(lag) 314 vs. 358 s, p = 0.047; Abs(peak) 0.153 vs. 0.111 units, p = 0.031; T(lysis50%) 884 vs. 280 s, p = 0.047) and thrombin reagents (T(lag) 170 vs. 132 s, p = 0.031; T(max) 590 vs. 462 s, p = 0.047; T(peak50%) 406 vs. 220 s, p = 0.005) while the concomitant presence of CKD led to changes in fibrin clot properties using kaolin (T(lag) 1072 vs. 1640 s, p = 0.003; T(max) 1458 vs. 1962 s, p = 0.005; T(peak50%) 1294 vs. 2046, p = 0.008) and PPP reagents (T(lag) 566 vs. 748 s, p = 0.044). Neither of these conditions were associated with changes in fibrin clot permeability. Deteriorating eGFR was significantly correlated to the speed of clot formation, and CKD was independently associated with unfavourable clot properties (T(lag) −778, p = 0.002; T(max) −867, p = 0.004; T(peak50%) −853, p = 0.004 with kaolin reagent). AF alone was not associated with changes in lipoprotein distribution while AF patients with CKD had lower total cholesterol, LDL-C and small dense LDL due to the presence of other risk factors. No significant relationship was observed between fibrin clot properties and lipoprotein distribution. Conclusions: There are important changes that occur in fibrin clot properties with AF and CKD that may account for the increased risk of thromboembolic complications. However, these changes in fibrin clot properties were not attributable to alterations in lipoprotein distribution