A minimal observable length is a common feature of theories that aim to merge quantum physics and gravity. Quantum mechanically, this concept is associated with a nonzero minimal uncertainty in ...position measurements, which is encoded in deformed commutation relations. In spite of increasing theoretical interest, the subject suffers from the complete lack of dedicated experiments and bounds to the deformation parameters have just been extrapolated from indirect measurements. As recently proposed, low-energy mechanical oscillators could allow to reveal the effect of a modified commutator. Here we analyze the free evolution of high-quality factor micro- and nano-oscillators, spanning a wide range of masses around the Planck mass mP (≈ 22 μg). The direct check against a model of deformed dynamics substantially lowers the previous limits on the parameters quantifying the commutator deformation.
A minimal observable length is a common feature of theories that aim to merge quantum physics and gravity. Quantum mechanically, this concept is associated to a nonzero minimal uncertainty in ...position measurements, which is encoded in deformed commutation relations. In spite of increasing theoretical interest, the subject suffers from the complete lack of dedicated experiments and bounds to the deformation parameters are roughly extrapolated from indirect measurements. As recently proposed, low-energy mechanical oscillators could allow to reveal the effect of a modified commutator. Here we analyze the free evolution of high quality factor micro- and nano-oscillators, spanning a wide range of masses around the Planck mass \(m_{\mathrm{P}}\) (\({\approx 22\,\mu\mathrm{g}}\)), and compare it with a model of deformed dynamics. Previous limits to the parameters quantifying the commutator deformation are substantially lowered.
The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and ...vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J
mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.
Advanced glycation end-products (AGEs) and their interaction with the receptor for advanced glycation end-products (RAGE) play a pivotal role in the development and progression of type 2 diabetes. In ...this retrospective cohort study, we explored the association of circulating levels of soluble RAGE (sRAGE) isoforms, i.e., endogenous secretory esRAGE and cleaved cRAGE, AGEs and their respective ratios with 15-year all-cause mortality in type 2 diabetes.
Baseline AGEs and sRAGE isoforms concentration were measured by ELISA in 362 patients with type 2 diabetes and in 125 age- and gender-matched healthy control subjects (CTR). Independent predictors of mortality were determined using Cox proportional-hazards models and used to build and validate a nomogram for all-cause mortality prediction in type 2 diabetes.
AGEs, total sRAGE, cRAGE and the AGEs/sRAGE and AGEs/esRAGE ratios were significantly increased in patients with type 2 diabetes compared to CTR (p < 0.001). In CTR subjects, but not in type 2 diabetes patients, a significant negative correlation between cRAGE and age was confirmed (p = 0.003), whereas the AGEs/sRAGE (p = 0.032) and AGEs/cRAGE (p = 0.006) ratios were positively associated with age. At an average follow-up of 15 years (4,982 person-years), 130 deaths were observed. The increase in the AGEs/cRAGE ratio was accompanied by a higher risk of all-cause mortality in patients with type 2 diabetes (HR per each SD increment = 1.30, 95% CI 1.15-1.47; p < 0.001). Moreover, sRAGE was associated with the development of major adverse cardiovascular events (MACE) in type 2 diabetes patients without previous MACE (OR for each SD increase: 1.48, 95% CI 1.11-1.89). A nomogram based on age, sex, HbA1c, systolic blood pressure, and the AGEs/cRAGE ratio was built to predict 5-, 10- and 15-year survival in type 2 diabetes. Patients were categorized into quartiles of the monogram scores and Kaplan-Meier survival curves confirmed the prognostic accuracy of the model (log-rank p = 6.5 × 10
).
The ratio between AGEs and the cRAGE isoform is predictive of 15-year survival in patients with type 2 diabetes. Our data support the assessment of circulating AGEs and soluble RAGE isoforms in patients with type 2 diabetes as predictors of MACE and all-cause mortality.
: Physical activity is an important predictor of quality of life in older adults with type 2 diabetes (T2D). Unfortunately, most T2D adults adopt a sedentary lifestyle. The randomized, controlled ...TRIPL-A trial aims to verify the effect of a personalized, discontinuous exercise program on a sedentary lifestyle of T2D older adults.
: A total of 305 T2D patients (mean age ± SD: 68.8 ± 3.3 years) were divided into a control arm receiving only behavioral counseling and an intervention arm of an 18-month supervised discontinuous exercise program (ERS). The primary outcomes were the changes in sitting time (ST) and metabolic equivalent (MET) values, both evaluated by the International Physical Activity Questionnaire short form. A repeated measures ANOVA with Bonferroni correction for multiple comparisons was used to compare study outcomes.
: The ST and MET differed significantly during the study compared to the control group (
= 0.028 and
= 0.004, respectively). In the intervention group, a decrease from baseline in ST at 6 months (
= 0.01) and an increase in MET values at 6 months (
= 0.01) up to 12 months (
< 0.01) were found. No significant differences were found for the other variables.
: Beneficial lifestyle changes were found within the first year of intervention. These results align with the theory of change.
Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary ...lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle.
A randomized controlled design will be used, and an ERS, supported by a WBA, will be implemented. 300 physically inactive T2D patients (aged 65-74 years) will be assigned to either an intervention or control arm. Control arm patients will only receive behavioral counseling on physical activity and diet, while intervention arm patients will also undergo an 18-month (3 day/week), discontinuously supervised aerobic exercise training program. The trial will be divided into six three-month periods: during first, third and fifth period, an exercise specialist will supervise the training sessions and, using the WBA, prescribe exercise progression and monitor exercise adherence. Patients will exercise on their own in the other periods. Patients' sedentary behaviors (primary outcome), PA level, fitness status, metabolic profile, psychological well-being, quality of life, and use of health care services (secondary outcomes) will be assessed at baseline and at 6, 12, and 18 months from baseline. Repeated measure ANCOVAs will be used to compare the intervention and control arm with respect to each study outcome measure.
Primary and secondary outcome results will allow us to evaluate the effectiveness of an ERS, specifically designed for the management of T2D clinical conditions and supported by a WBA, in promoting PA within Italian primary care settings.
This trial is retrospectively registered under the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12618001164280 ; registered 13 July 2018).
Parkinson's disease (PD) is one of the most frequent causes of disability among older people, characterized by motor disorders, rigidity, and balance problems. Recently, dance has started to be ...considered an effective exercise for people with PD. In particular, Irish dancing, along with tango and different forms of modern dance, may be a valid strategy to motivate people with PD to perform physical activity. The present protocol aims to implement and evaluate a rehabilitation program based on a new system called "SI-ROBOTICS," composed of multiple technological components, such as a social robotic platform embedded with an artificial vision setting, a dance-based game, environmental and wearable sensors, and an advanced AI reasoner module.
For this study, 20 patients with PD will be recruited. Sixteen therapy sessions of 50 min will be conducted (two training sessions per week, for 8 weeks), involving two patients at a time. Evaluation will be primarily focused on the acceptability of the SI-ROBOTICS system. Moreover, the analysis of the impact on the patients' functional status, gait, balance, fear of falling, cardio-respiratory performance, motor symptoms related to PD, and quality of life, will be considered as secondary outcomes. The trial will start in November 2021 and is expected to end by April 2022.
The study aims to propose and evaluate a new approach in PD rehabilitation, focused on the use of Irish dancing, together with a new technological system focused on helping the patient perform the dance steps and on collecting kinematic and performance parameters used both by the physiotherapist (for the evaluation and planning of the subsequent sessions) and by the system (to outline the levels of difficulty of the exercise).
The study was approved by the Ethics Committee of the IRCCS INRCA. It was recorded in ClinicalTrials.gov on the number NCT05005208. The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.
Abstract
Background
age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD ...stage at which mortality increases among older people.
Methods
our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index.
Results
overall, mortality was found to increase starting from eGFR = 30–44.9 ml/min/1.73 m2 (hazard ratio HR = 3.28, 95% confidence interval CI = 1.81–5.95) to ACR = 30–300 mg/g (HR = 1.96, 95%CI = 1.23–3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45–59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78–0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71–0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function.
Conclusions
physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild–moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function.
Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with ...DM.
A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses.
A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes 887 (80.31%) vs. 227 (72.1%), p = 0.002, highlighting higher percentages of severe sarcopenia in participants with diabetes 27 (8.6%) vs. 58 (5.2%), p = 0.028. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios OR, 1.17; 95% confidence interval CI, 1.08-1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71-0.89 were associated with the presence of sarcopenia.
One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.
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