From Frailty to Gerastenia

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Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier.

The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses the gain of the 'cochlear amplifier' in each ear. Such efferent feedback is important for promoting discrimination of sounds in background noise, sound localization and protecting the cochleae from acoustic overstimulation. However, the sensory driver for the olivocochlear reflex is unknown. Here, we resolve this longstanding question using a mouse model null for the gene encoding the type III intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral ganglion neuron innervation of the outer hair cells, whereas innervation of the inner hair cells by type I spiral ganglion neurons was normal. Compared with Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent-mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice, demonstrating that outer hair cells and their type II afferents constitute the sensory drive for the olivocochlear efferent reflex

Performance Evaluation of a UWB Positioning System Applied to Static and Mobile Use Cases in Industrial Scenarios

Indoor positioning systems are essential in the industrial domain for optimized production and safe operation of mobile elements, such as mobile robots, especially in the presence of static machinery and human operators. In this paper, we assess the performance of a commercial UWB radio-based positioning system deployed in a realistic industrial scenario, considering both static and mobile use cases. Our goal is to characterize the accuracy of this system in the context of industrial use cases and applications. For the static case, an extensive analysis was presented based on measurements performed at 72 measurement positions at 3 different heights (above, at similar a level to, and below the average clutter level) in different industrial clutter conditions (open and cluttered spaces). The extensive analysis in the mobile case considered several runs of a route covered by an autonomous mobile robot equipped with multiple tags in different positions. The results indicate that a similar degree of accuracy with a median 2D positioning error smaller than 20 cm is possible in both static and mobile conditions with an optimized anchor deployment. The paper provides a complete statistical characterization of the system’s accuracy and addresses the multiple deployment trade-offs and system dynamics observed for the different configurations

Towards developing a Core Outcome Set for malnutrition intervention studies in older adults: a scoping review to identify frequently used research outcomes

Purpose: To conduct a scoping review to provide a systematic overview of outcomes used in nutritional intervention studies focused on the treatment of protein-energy malnutrition in older adults. // Methods: A systematic search of four electronic databases (Medline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve randomized controlled trials (RCTs), published until March 9, 2020, that evaluated the effect of nutritional interventions to treat protein-energy malnutrition in older adults and those at risk for malnutrition. Two authors screened titles, abstracts and full texts independently. One author extracted data that were cross-checked by another author. // Results: Sixty-three articles reporting 60 RCTs were identified. Most frequently used outcomes included body weight/body mass index (75.0% of RCTs), dietary intake (61.7%), functional limitations (48.3%), handgrip strength (46.7%), and body circumference (40.0%). The frequencies differed by setting (community, hospital and long-term care). For some outcomes there was a preferred assessment method (e.g., Barthel index for functional limitations), while for other outcomes (e.g., functional performance) a much greater variation was observed. // Conclusion: A large variation in outcomes, not only across but also within settings, was identified in nutritional intervention studies in malnourished older adults and those at risk. Furthermore, for many outcomes there was a large variation in the used assessment method. These results highlight the need for developing a Core Outcome Set for malnutrition intervention studies in older adults to facilitate future meta-analyses that may enhance our understanding on the effectiveness of treatment

a scoping review to identify frequently used research outcomes

© 2022. The Author(s).PURPOSE: To conduct a scoping review to provide a systematic overview of outcomes used in nutritional intervention studies focused on the treatment of protein-energy malnutrition in older adults. METHODS: A systematic search of four electronic databases (Medline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve randomized controlled trials (RCTs), published until March 9, 2020, that evaluated the effect of nutritional interventions to treat protein-energy malnutrition in older adults and those at risk for malnutrition. Two authors screened titles, abstracts and full texts independently. One author extracted data that were cross-checked by another author. RESULTS: Sixty-three articles reporting 60 RCTs were identified. Most frequently used outcomes included body weight/body mass index (75.0% of RCTs), dietary intake (61.7%), functional limitations (48.3%), handgrip strength (46.7%), and body circumference (40.0%). The frequencies differed by setting (community, hospital and long-term care). For some outcomes there was a preferred assessment method (e.g., Barthel index for functional limitations), while for other outcomes (e.g., functional performance) a much greater variation was observed. CONCLUSION: A large variation in outcomes, not only across but also within settings, was identified in nutritional intervention studies in malnourished older adults and those at risk. Furthermore, for many outcomes there was a large variation in the used assessment method. These results highlight the need for developing a Core Outcome Set for malnutrition intervention studies in older adults to facilitate future meta-analyses that may enhance our understanding on the effectiveness of treatment.publishersversionepub_ahead_of_prin

Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer’s Disease: A Randomized Controlled Trial—The OmegAD Study

Background: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer’s disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD. / Objective: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE). / Methods: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n  =  18) or placebo (n  =  15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. / Results: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable. / Conclusion: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score. / Trial registration: clinicaltrial.gov Identifier: NCT00211159

A vitamin D, calcium and leucine-enriched whey protein nutritional supplement improves measures of bone health in sarcopenic non-malnourished older adults: The PROVIDE study

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status

Open Access ArticleBACKGROUND: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. RESULTS: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. CONCLUSIONS: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.European CommissionAlzheimer’s Research UKJohn and Lucille van Geest FoundationNational Institute for Health Research (NIHR)European Medical Information Framework (EMIF)Medical Research Council (MRC)Wallenberg FoundationKarolinska InstitutetSwedish Medical Research CouncilSwedish Society for Medical Research (SSMF