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Abstract Background Maintenance of physical function, mobility, and independent living are important goals for older adults. However, concerns about falling (CaF) play a central role in the vicious cycle of CaF, inflammation, loss of muscle mass, and decreasing physical function ultimately resulting in negative health outcomes. CaF, like other states of chronic stress and anxiety, can be considered as enduring adverse stimuli affecting the stress systems and the inflammatory system. Therefore, the aim of this study is to investigate whether a reduction of CaF leads to a reduction of stress and therefore possibly reduces chronic low-grade inflammation. Understanding the role and directionality of the effects of inflammation on CaF increases our understanding of age-related loss of mobility and physical function. Methods In this study, community-dwelling older adults, aged 70 years and older, will be randomly assigned to either a 4-month, multi-component intervention with exercise training and cognitive-behavioral components or to a sham control group with light stretching exercises, cognitive training, and educational health lectures. For the operationalization of specific CaF, the Falls Efficacy Scale—International will be used. Stress and related psychological symptoms will be monitored using established self-reports and by measuring salivary cortisol. Concentrations of C-reactive protein, interleukin 6, interleukin 10, and tumor-necrosis-factor-alpha, as well as gene expression of selected inflammatory transcripts, will be used as surrogate parameters of the inflammatory status at baseline, after the 4-month intervention and 8-month follow-up. Discussion This study will be the first to test whether CaF are related with stress system activity or reactivity or with markers of inflammation in the context of a multi-component intervention with exercise training and cognitive-behavioral components addressing CaF. The reduction of specific CaF or general psychological symptoms should reverse alterations in stress systems, and / or slow down low-grade inflammation. Changes in activity, as well as psychological and biological pathways leading from CaF to muscle loss will be measured, to disentangle the individual contribution to sarcopenia, and to provide an additional pathway to break or slow-down the vicious cycle of CaF and sarcopenia. Trial registration German Clinical Trials Register (DRKS): DRKS00029171 . Registered 22 July 2022.

Background: Despite the emerging interest in phase angle (PhA), a non-invasive marker of cell hydration and nutritional status, no previous study has reported the prospective association between PhA and incident sarcopenia. Therefore, the aim of our study was to evaluate the association of baseline PhA in older subjects without sarcopenia with the development of new sarcopenia as outcome. Methods: Six-hundred ninety-six subjects without sarcopenia aged ≥75 years enrolled in an international multicenter observational study were included. Sarcopenia was assessed according to the revised EWGSOP2 criteria at baseline and in follow-up visits at 12 and 24 months. Muscle strength was assessed through the handgrip strength test using a hydraulic grip strength dynamometer, muscle mass was assessed by bioimpedance analysis (BIA) and appendicular skeletal muscle mass (ASMM) was estimated. Physical performance was assessed by Short Physical Performance Battery (SPPB). Results: Participants who developed sarcopenia were older, less educated, had higher prevalence of osteoporosis, and lower baseline cognitive function, SPPB, handgrip strength and ASMM than those without sarcopenia. Baseline PhA was significantly lower in subjects developing sarcopenia. Nevertheless, after adjusting for all potential covariates including baseline components of sarcopenia in multiple logistic regression, neither PhA as continuous variable nor different levels of PhA were any more significant predictors of sarcopenia. Conclusions: As an indicator of cells function, PhA could be a potential useful early marker in identifying older people at risk of developing sarcopenia but its practical applicability remains uncertain with the present data.

Abstract Background The risk of older adults being injured or killed in a bicycle accident increases significantly due to the age-related decline of physical function. Therefore, targeted interventions for older adults to improve safe cycling competence (CC) are urgently needed. Methods The “Safer Cycling in Older Age” (SiFAr) randomized controlled trial investigated if a progressive multi-component training program related to cycling improves CC of older adults. Between June 2020 and May 2022, 127 community-dwelling persons living in the area Nürnberg-Fürth-Erlangen, Germany aged 65 years and older were recruited, who are either (1) beginners with the e-bike or (2) feeling self-reported unsteadiness when cycling or (3) uptaking cycling after a longer break. Participants were either randomized 1:1 to an intervention group (IG; cycling exercise program, 8 sessions within 3 months) or an active control group (aCG; health recommendations). The CC as primary outcome was tested not blinded in a standardized cycle course prior and after the intervention period and after 6–9 months, which consists of variant tasks requiring skills related to daily traffic situations. Regression analyses with difference of errors in the cycling course as dependent variable and group as independent variable adjusted for covariates (gender, number of errors at baseline, bicycle type, age and cycled distance) were performed. Results 96 participants (73.4 ± 5.1 years; 59.4% female) were analyzed for primary outcome. Compared to the aCG (n = 49), the IG (n = 47) made an average of 2.37 fewer errors in the cycle course after the 3 months intervention period (p = 0.004). People with more errors at baseline had higher potential for improvement (B=-0.38; p

Abstract Background Fear of falling (FoF) is an important risk factor for falls among older people. The objectives of our investigations were: a.) to present characteristics of older community-dwelling (CD) fallers with persistent or transient FoF (P-FoF or T-FoF) over 12 months, and b.) to investigate clinical predictors of P-FoF and T-FoF and c.) to explore differences between P-FoF and T-FoF. Methods Our series consisted of 389 older people reporting a fall or injurious fall at baseline and during 24 months follow-up participating in a multicenter prospective study. T-FoF was defined as participants reported “not at all” at baseline and “somewhat/fairly/very concerned” at follow-up, or “not at all” at follow-up, and “somewhat/fairly/very concerned” at baseline, and P-FoF was defined as participants answered “somewhat/fairly/very concerned” in both assessments at baseline and at follow-up. The association between risk factors and T-FoF or P-FoF was investigated by logistic regression analysis. Results The mean age of fallers in our sample was 79.0 years (SD 6.0), and 54.2% were females. Out of 389 older adults with a fall history at baseline, 83 participants (21.3%) did not report any FoF over time, P-FoF and T-FoF were observed in 42.7% and 35.9% of participants, respectively. After adjusting for potential confounders (e.g. age, gender), osteoporosis (OR = 2.04, 95%CI = 1.03–4.05) and impaired physical performance (OR = 2.38, 95%CI = 1.12–5.03) were significant predictors of T-FoF vs No-FoF. Osteoporosis (OR = 2.68, 95%CI = 1.31–5.48), depressive symptoms (OR = 3.54, 95%CI = 1.23–10.1) and living alone (OR = 2.44, 95%CI = 1.17–5.06) were significantly associated with P-FoF vs No-FoF. When comparing T-FoF and P-FoF, female gender (OR = 1.95, 95%CI = 1.16–3.27), BMI (OR = 1.08, 95%CI = 1.02–1.14), overall comorbidity (OR = 1.07, 95%CI = 1.02–1.13) and depression (OR = 2.55, 95%CI = 1.33–4.88) were significant predictors of P-FoF. Conclusions T-FoF and P-FoF may be predicted by different sets of risk factors among older fallers. Thus, fallers should be screened for FoF especially when carrying specific risk factors, including female gender, osteoporosis, depression, living alone, impaired physical performance, BMI, comorbidity. These findings may be helpful in designing tailored intervention to blunt the risks related to consequence of FoF among older people experiencing falls. Trial registration The SCOPE study was registered prospectively at clinicaltrials.gov (NCT02691546; 25/02/2016).

Abstract Background Cycling has positive effects on health and the proportion of older cyclists is rising. However, the risk for older adults to be injured or killed by a bicycle accident increases. The aim of the ongoing project “Safer Cycling in Older Age (SiFAr)” is to promote safer cycling in community-dwelling older adults with a structured, multi-component exercise training. Methods SiFAr is a randomized, controlled trial with a duration of 3 months for the intervention and a 6–9 months follow-up. We address community-dwelling persons aged 65 years and older living in the area Nürnberg-Fürth-Erlangen (Germany) who are either 1) beginners with the e-bike or 2) feeling self-reported unsteadiness when cycling or 3) uptaking cycling after a longer break. Long-term, experienced cyclists without subjectively reported limitations or worries when cycling are excluded. Participants are either randomized 1:1 to an intervention group (IG; receiving multi-component exercise program related to cycling, MEPC) or an active control group (aCG; receiving health and bicycle-related presentations, HRP). The purpose of this study is to investigate if the cycling competence of the IG will improve compared to the aCG. The cycling competence as primary outcome is tested not blinded in a standardized cycle course prior and after the intervention period, which consists of variant tasks requiring motor and cognitive skills related to traffic situations in daily life. Additional assessments such as physical functioning, quality of life, fear of falling, questionnaires regarding cycling behavior are obtained. To investigate the primary objective, regression analyses with difference of errors in the cycling course as independent variable and group as dichotomous dependent variable adjusted for covariates (sex, bicycle type) will be performed. The trial design is described in the present manuscript, using the extended CONSORT checklist for reporting pragmatic trials. Discussion Since there is a lack of cycling-related interventions for older people, SiFAr aims to evaluate a standardized intervention to enhance cycling safety. The results of the SiFAr trial could contribute to the implementation of an evaluated cycling course concept promoting mobility and independence of older adults. Trial registration This study was registered with clinicaltrials.gov : NCT04362514 on April 27, 2020

Abstract Background SiFAr-Stress investigates the impact of cycling on stress levels in older adults. Uncertainty due to change to motorized bicycle or fear of falling can be perceived as stressors for cyclists. Stress activates different physiological signal cascades and stimulates the hypothalamic-pituitary-adrenal (HPA) axis, which leads to the release of the stress hormone cortisol and further effects such as the development of low-grade inflammation. Both can—in the long term—be associated with negative health outcomes. The aim of the study SiFAr-Stress is to analyze inflammatory processes as well as the activity of stress systems before and after a cycling intervention for older adults. Methods In this study, community-dwelling older adults aged 65 years and older will be randomly assigned to either a cycling or a control intervention in a parallel-group design. Objective HPA axis–related measures (saliva cortisol and hair cortisol) will be assessed before, after, and 6–9 months after the cycling and control intervention (T0, T1, and T2). Furthermore, changes in cortisol reactivity in response to the cycling intervention will be investigated at the second and seventh training lessons. Furthermore, secondary outcomes (fear of falling, perceived stress, salivary alpha amylase, and C-reactive protein) will be assessed at T0, T1, and T2. Discussion The study will be the first, in which stress- and health-related bio-physiological outcomes will be assessed in the context of a multicomponent exercise intervention, addressing cycling in older adults. It will enable us to better understand the underlying patho-physiological and psychological mechanisms and will help to improve interventions for this target group. Trial registration ClinicalTrials.gov NCT04362514 . Prospectively registered on 27 April 2020

Abstract Background Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79–1.14 for eGFR

Abstract Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR

Whole-body electromyostimulation (WB-EMS) induces high-intense stimuli to skeletal muscles with low strain on joints and the autonomic nervous system and may thus be suitable for frail, older people. However, if trained at very high intensities, WB-EMS may damage muscles and kidneys (rhabdomyolysis). This study aimed at investigating the feasibility, safety and preliminary efficacy of WB-EMS in frail, older people. Seven frail (81.3 ± 3.5 years), 11 robust (79.5 ± 3.6 years), 10 young (29.1 ± 6.4 years) participants completed an eight-week WB-EMS training (week 1–4: 1x/week; week 5–8: 1.5x/week) consisting of functional exercises addressing lower extremity strength and balance. Feasibility was assessed using recruitment, adherence, retention, and dropout rates. The satisfaction with WB-EMS was measured using the Physical Activity Enjoyment Scale for older adults (PACES-8). In week 1, 3, and 8 creatine kinase (CK) was assessed immediately before, 48 and 72 h after WB-EMS. Symptoms of rhabdomyolysis (muscle pain, muscle weakness, myoglobinuria) and adverse events were recorded. Functional capacity was assessed at baseline and after 8 weeks using the Short Physical Performance Battery (SPPB), Timed Up-and-Go Test (TUG), Choice Stepping Reaction Time Test (CSRT), 30-second Chair-Stand Test (30-STS), maximum isometric leg strength and handgrip strength. The recruitment rate of frail individuals was 46.2%, adherence 88.3% and the dropout rate 16.7%. All groups indicated a high satisfaction with WB-EMS. CK activity was more pronounced in young individuals with significant changes over time. Within older people CK increased borderline-significantly in the frail group from baseline to week 1 but not afterwards. In robust individuals CK increased significantly from baseline to week 1 and 3. No participant reached CK elevations close to the threshold of ≥5,000 U/l and no symptoms of rhabdomyolysis were observed. With the exception of the TUG (p = 0.173), frail individuals improved in all tests of functional capacity. Compared to the young and robust groups, frail individuals showed the greater improvements in the SPPB, handgrip strength, maximum isokinetic hip-/knee extension and flexion strength. WB-EMS is feasible for frail older people. There were no clinical signs of exertional rhabdomyolysis. WB-EMS proved to be sufficiently intense to induce meaningful changes in functional capacity with frail individuals showing greater improvements for several measures.

Aging is associated with reduced appetite as well as a slight increase in pro-inflammatory status, which both might contribute to the development of malnutrition. We aimed to evaluate the association between inflammation based on serum C-reactive protein (CRP), and appetite in healthy community-dwelling older adults. In this cross-sectional study of 158 healthy and non-smoking persons (aged 75–85 years), appetite was assessed in personal interviews by a single question with five answer categories. As nobody reported (very) poor appetite, the remaining three categories were dichotomised into “(very) good” and “moderate” appetite. Fasting serum CRP was analysed according to standard procedures, values ≥ 5.0 mg/L were considered as inflammation. The association between inflammation and appetite was examined by binary logistic regression, unadjusted and adjusted for age, sex, waist circumference, leptin, depressive mood, number of medications, interleukin-6 and tumor necrosis factor-α. Appetite was very good in 27.8%, good in 58.9%, and moderate in 13.3% of participants. Inflammation was present in 10.8% overall, in 8.8% of those with (very) good and in 23.8% of those with moderate appetite (p = 0.038). In the unadjusted model, participants with inflammation were 3.2 times more likely to have moderate appetite (95%CI: 1.01–10.44, p = 0.047). In the adjusted model, the odds of having moderate appetite was 3.7 times higher in participants with inflammation, but no longer significant (95%CI: 0.77–18.55, p = 0.102). In healthy older people, we found hints for a potential association between increased levels of CRP and a slightly reduced appetite. More studies in larger samples are needed.

Abstract Background Obesity is a risk factor for chronic kidney disease (CKD). While the exact mechanisms remain unclear, inflammation may be a consequence of obesity that directly impacts the kidneys. The aim of this study was to examine the inflammatory status of the kidneys and potential ongoing renal damage, i.e., tubular damage and fibrosis after long-term obesity maintained through persistent consumption of a high-fat diet (HFD). Results Twenty-four-week-old male Long-Evans (LEV) rats were continuously fed a control diet (CD) or HFD for 51 weeks. The mean body weight was higher in HFD-fed rats than in control diet-fed rats and markedly elevated during the last 24 weeks. Blood analyses revealed no substantial alterations in renal functional parameters by HFD consumption but a substantial increase in creatine kinase, a muscle loss marker. Magnetic resonance imaging (MRI) was utilized to quantify rat quadriceps muscle mass. The data showed that HFD-induced obesity in LEV rats was accompanied by minor decreases in muscle mass and strength at 75 weeks of age. Rat kidney inflammatory status was evaluated using histological and immunohistological techniques. The number of foci with immune cell infiltrates and infiltrating monocytes/macrophages was significantly increased in HFD-fed rat kidneys at week 75. Renal fibrosis parameters, including glomerulosclerosis and tubular damage, were also markedly increased in renal tissues from HFD-fed rats compared to the controls. The significant increase in tubular protein casts in HFD-fed rat tissues indicated that renal function was already disturbed. Rat kidney inflammatory status was further evaluated using the simultaneous profiling of twenty-two inflammatory markers in kidney tissue extracts. Consistently, MCP-1 and eotaxin (CCL11) levels were elevated in obese LEV rat kidneys. Conclusions Compared to CD-fed rats, HFD-fed obese LEV rats show significant damage of renal structures with aging. These subtle changes may sensitize the kidneys to the development of progressive CKD.

Due to the demographic changes and the increasing awareness of the role of physical function, mobility in older age is becoming an important topic. Mobility limitations have been reported as increasingly prevalent in older persons affecting about 35% of persons aged 70 and the majority of persons over 85 years. Mobility limitations have been associated with increased fall risk, hospitalization, a decreased quality of life, and even mortality. As concepts of mobility are multifactorial and complex, in this narrative review, definitions, physical factors, and their age-related changes associated with mobility will be presented. Also, areas of cognitive decline and their impact on mobility, as well as neuromuscular factors related to mobility will be addressed. Another section will relate psychological factors such as Fall-related psychological concerns and sedentary behavior to mobility. Assessment of mobility as well as effective exercise interventions are only shortly addressed. In the last part, gaps and future work on mobility in older persons are discussed.

Repurposing of approved drugs that target host functions also important for virus replication promises to overcome the shortage of antiviral therapeutics. Mostly, virus biology including initial screening of antivirals is studied in conventional monolayer cells. The biology of these cells differs considerably from infected tissues. 3D culture models with characteristics of human tissues may reflect more realistically the in vivo events during infection. We screened first, second, and third generation epidermal growth factor receptor (EGFR)-inhibitors with different modes of action and the EGFR-blocking monoclonal antibody cetuximab in a 3D cell culture infection model with primary human keratinocytes and cowpox virus (CPXV) for antiviral activity. Antiviral activity of erlotinib and osimertinib was nearly unaffected by the cultivation method similar to the virus-directed antivirals tecovirimat and cidofovir. In contrast, the host-directed inhibitors afatinib and cetuximab were approx. 100-fold more efficient against CPXV in the 3D infection model, similar to previous results with gefitinib. In summary, inhibition of EGFR-signaling downregulates virus replication comparable to established virus-directed antivirals. However, in contrast to virus-directed inhibitors, in vitro efficacy of host-directed antivirals might be seriously affected by cell cultivation. Results obtained for afatinib and cetuximab suggest that screening of such drugs in standard monolayer culture might underestimate their potential as antivirals.

Studies of virus–host interactions in vitro may be hindered by biological characteristics of conventional monolayer cell cultures that differ from in vivo infection. Three-dimensional (3D) cell cultures show more in vivo-like characteristics and may represent a promising alternative for characterisation of infections. In this study, we established easy-to-handle cell culture platforms based on bioprinted 3D matrices for virus detection and characterisation. Different cell types were cultivated on these matrices and characterised for tissue-like growth characteristics regarding cell morphology and polarisation. Cells developed an in vivo-like morphology and long-term cultivation was possible on the matrices. Cell cultures were infected with viruses which differed in host range, tissue tropism, cytopathogenicity, and genomic organisation and virus morphology. Infections were characterised on molecular and imaging level. The transparent matrix substance allowed easy optical monitoring of cells and infection even via live-cell microscopy. In conclusion, we established an enhanced, standardised, easy-to-handle bioprinted 3D-cell culture system. The infection models are suitable for sensitive monitoring and characterisation of virus–host interactions and replication of different viruses under physiologically relevant conditions. Individual cell culture models can further be combined to a multicellular array. This generates a potent diagnostic tool for propagation and characterisation of viruses from diagnostic samples.

In this article, the author presents some common areas for the categories of power and security. Diagnosis of the security environment of a political unit should include both A qualitative and quantitative approach to the assessment of its power and that of neighbouring countries. Such comparisons of balance of power between the countries give the security assessment a broader range. it may be used, in addition, by design for the foreign and security policy of a state.