Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

Development of Pharmacotherapies for the Treatment of Sarcopenia.

Sarcopenia, the associated loss of skeletal muscle mass and strength and impaired physical function seen with aging, is a growing, global public health challenge in need of accepted, proven treatments that address the needs of a broad range of older adults. While exercise, primarily resistance training, and increased dietary protein have been shown to delay and even reverse losses in muscle mass, strength and physical function seen with aging, proven treatments that are accessible globally, cost effective and sustainable by patients are needed. While no drug has yet demonstrated the substantial safety and clinical value needed to be the first pharmacological therapy registered for muscle wasting or sarcopenia, the field is active. Several approaches to treating the muscle loss and subsequent functional decline are being studied in a variety of patient populations across every continent. We provide a review of the leading programs and approaches and available findings from recent studies. In addition, we briefly discuss several related issues needed to facilitate the development of a safe and efficacious pharmacotherapeutic that could be used as part of a treatment plan for older men and women with sarcopenia.

Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations.

An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials.

Antimicrobial resistance in some gram-negative bacteria isolated from the bovine ejaculate.

The bacterial load and degree of antibiotic resistance present in untreated and antibiotic-treated semen samples were investigated in five bulls standing at a cattle-breeding centre. Bacterial load was determined by colony counts from semen samples cultured on brain heart infusion and nutrient agar plates. Antibiotic resistance in these bacteria was assessed by measuring the diameter of bacterial growth inhibition zones around discs containing different concentrations of antibiotics. Representative antibiotic-resistant bacterial isolates were selected for identification. Untreated semen contained few culturable bacteria, and all were completely sensitive to gentamycin, spectinomycin and lincomycin: six of the isolates showed some resistance to tylosin. In semen to which antibiotics had been added as part of the routine production process, two isolates were sensitive to all of the antibiotics tested, and the remainder were resistant to all. Resistant Gram-negative isolates that were identified included Pseudomonas and Stenotrophomonas spp. both in the class Gammaproteobacteria and a Sphingomonas sp. which is in the class Alphaproteobacteria.

Short communication: Characterization of Shiga toxin 2-carrying bacteriophages induced from Shiga-toxigenic Escherichia coli isolated from Italian dairy products.

Forty samples of raw milk cheese and 25 samples of raw milk itself were subjected to enrichment culture for Shiga-toxigenic Escherichia coli (STEC), and a single Shiga toxin 2- (Stx(2)) positive strain was obtained from one of the cheese samples. Thus, aged cheeses in which the curd is subsequently heat treated (48°C) cannot be presumed to be STEC free. Infective Stx(2) bacteriophages were induced from 3 STEC strains isolated elsewhere from raw milk and 1 STEC strain from aged cheese sourced in Italy. Data on E. coli host range, morphology, genome size, and genetic variation determined by restriction fragment length polymorphism and multi-locus genotyping are presented. Although all 4 bacteriophages were found to be short-tailed Podoviridae, they exhibited considerable variation in both genome size and content. This extended to the Stx(2) genes themselves, whose sequences contained several point mutations, but these did not translate to amino acid substitutions.

Interrelationships among disablement concepts.

BACKGROUND: Understanding interrelationships among disablement concepts is critical to the design of future disability treatment and prevention interventions. METHODS: This study uses cross-sectional data to examine the relationships among physiologic impairments, functional limitations, and disability in a moderately disabled sample of 207 community-dwelling older adults. RESULTS: As hypothesized, the data revealed statistically significant curvilinear relationships of upper and lower extremity strength and balance with mobility in this older sample. Multivariate analyses further clarified the hypothesized causal mechanism among the disablement concepts by demonstrating that most of the association of muscle strength and balance with disability was through the intermediary role of mobility limitations. CONCLUSIONS: The findings from this study highlight the value of clinical trials that focus on prevention or treatment of mobility limitations as a means of preventing disability; our findings underscore the need for future research that examines the effects of other variables believed to influence disablement in late life.

Home-based resistance training: predictors of participation and adherence.

This study identified factors associated with exercise participation and adherence in a sample of 102 sedentary, functionally limited, community-dwelling adults aged 60 to 94 years who participated in a home-based resistance training program. Stepwise regression analyses revealed that baseline physical factors (i.e., higher levels of mobility, weaker muscle strength, and fewer numbers of new medical conditions) were associated with higher rates of participation in the home program. Positive attitudes and a sense of control toward exercise, lower levels of confusion and depressive moods, and the development of fewer new medical problems during the program were related to higher levels of adherence to the program. Findings revealed that although physical health variables were the primary indicators of an older person's overall participation in the program, it was the psychological factors that were most important to adherence to this home-based program.

Self-paced resistance training and walking exercise in community-dwelling older adults: effects on neuromotor performance.

BACKGROUND: Resistance-training intervention studies have demonstrated meaningful health benefits in older adults; however, most have used exercises performed at specific intensities on expensive equipment, which limit their widespread applicability. We tested whether two self-paced, less expensive exercise protocols could be effective and safe for modifying neuromotor performance and functional capacity in community-dwelling adults 65-95 years of age. METHODS: One hundred and thirty-one subjects were randomized to a novel resistance training, walking, or control group. Subjects determined their level of resistance or walking intensity (self-paced) on a session-by-session basis. Muscle strength, balance, reaction time, stair climbing speed, and a timed pen pickup task were measured before and after the intervention period. Exercisers met three times per week for 10 months. RESULTS: Significant improvements in tandem stance and single-legged stance with eyes open times and stair climbing speed were seen in both exercise groups. In addition, resistance trainers improved their muscle strength and ability to pick up an object from the floor and reduced the number of missteps taken during tandem walking, and walkers reduced tandem walking time. Controls showed no significant improvement in any variable. CONCLUSIONS: The two self-paced exercise protocols were effective at improving neuromotor performance and functional capacity in the study sample and show promise as a safe, effective, cost-efficient, acceptable exercise model for primary and secondary prevention in the general population of community-dwelling older adults.

Geometric variables from DXA of the radius predict forearm fracture load in vitro.

The purpose of this investigation was to determine the cross-sectional geometry of the radius in female and male cadaveric specimens using dual-energy X-ray absorptiometry (DXA), to measure the accuracy of this technique compared with a digitizing procedure, and to measure the correlation between these DXA-based geometric variables and the load required to produce a forearm fracture. Paired intact forearms were scanned at a distal site and at a site approximately 30% of the forearm length from the distal end. The cross-sectional area and the moments of inertia of two sections at 10 and 30% of the forearm length were computed from the X-ray attenuation data. One member of each pair was then sectioned at the 30% location, which is mostly cortical bone, and the section was traced on a digitizing pad. The other forearm was loaded to failure in a servohydraulic materials test system. The DXA-based area and moment of inertia at 30% correlated significantly with the digitized results (r2 = 0.93 for area; r2 = 0.95 for moment; P < 0.001). The conventional bone mineral density from DXA did not associate significantly with failure load, but the minimum moment of inertia and the cross-sectional area at 10% correlated in a strong and significant manner with the forearm fracture force (r2 = 0.67 for area; r2 = 0.66 for moment; P < 0.001). The determination of radial bone cross-sectional geometry, therefore, should have better discriminatory capabilities than bone mineral density in studies of bone fragility and fracture risk.

Musculoskeletal assessment and training: the young athlete.

The primary purpose of a preparticipation physical examination is to identify risk factors that may predispose an athlete to physical and/or psychological injury. Inclusion of a physiological assessment complements the more traditional preparticipation health examination by contributing valuable information toward the specific physical strengths and weaknesses of the young athlete. This information when combined with the orthopedic and medical components of a preparticipation examination can dramatically enhance the safety of sports participation.