Common fall-risk indicators are not associated with fall prevalence in a high-functioning military population with lower limb trauma.

BACKGROUND: Persons with lower limb trauma are at high risk for falls. Although there is a wide range of measures used to assess stability and fall-risk that include performance measures, temporal-spatial gait parameters, and nonlinear dynamic stability calculations, these measures are typically derived from fall-prone populations, such as older adults. Thus, it is unclear if these commonly used fall-risk indicators are effective at evaluating fall-risk in a younger, higher-functioning population of Service members with lower limb trauma. METHODS: Twenty-one Service members with lower limb trauma completed a battery of fall-risk assessments that included performance measures (e.g., four-square-step-test), and gait parameters (e.g., step width, step length, step time) and dynamic stability measures (e.g., local divergence exponents) during 10 min of treadmill walking. Participants also reported the number of stumbles and falls over the previous 4 weeks. Negative Binomial and Quasibinomial Regressions were used to evaluate the strength of associations between fall-risk indicators and self-reported falls. FINDING: Participants reported on average stumbling 6(4) times and falling 2(3) times in the previous 4 weeks. At least one fall was reported by 62% of the participants. None of the fall-risk indicators were significantly associated with fall prevalence in this population of Service members with lower limb trauma (p > 0.1). INTERPRETATION: Despite the high number of reported falls in this young active population, none of the fall-risk indicators investigated effectively captured and quantified the fall-risk. Further research is needed to identify appropriate fall-risk assessments for young, high-functioning individuals with lower limb trauma.

Acacia Fiber Protects the Gut from Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli Colonization Enabled by Antibiotics.

Novel approaches to combating antibiotic resistance are needed given the ever-continuing rise of antibiotic resistance and the scarce discovery of new antibiotics. Little is known about the colonization dynamics and the role of intrinsic plant-food characteristics in this process. We sought to determine whether plant fiber could alter colonization dynamics by antibiotic-resistant bacteria in the gut. We determined that ingestion of antibiotics in mice markedly enhanced gut colonization by a pathogenic extended-spectrum beta-lactamase-producing Escherichia coli strain of human origin, E. coli JJ1886 (ST131-H30Rx). Furthermore, ingestion of soluble acacia fiber before and after antibiotic exposure significantly reduced pathogenic E. coli colonization. 16S rRNA analysis and ex vivo cocultures demonstrated that fiber protected the microbiome by serving as a prebiotic, which induced native gut E. coli to inhibit pathogenic E. coli via colicin M. Fiber may be a useful prebiotic with which to administer antibiotics to protect human and livestock gut microbiomes against colonization from antibiotic-resistant, pathogenic bacteria. IMPORTANCE A One Health-based strategy-the concept that human health and animal health are interconnected with the environment-is necessary to determine the drivers of antibiotic resistance from food to the clinic. Moreover, humans can ingest antibiotic-resistant bacteria on food and asymptomatically, or "silently," carry such bacteria in the gut long before they develop an opportunistic extraintestinal infection. Here, we determined that fiber-rich foods, in particular acacia fiber, may be a new, promising, and inexpensive prebiotic to administer with antibiotics to protect the mammalian (i.e., human and livestock) gut against such colonization by antibiotic-resistant, pathogenic bacteria.

Assessments of trunk postural control within a fall-prevention training program for service members with lower limb trauma and loss.

BACKGROUND: Trunk postural control (TPC) is critical in maintaining balance following perturbations (i.e., avoiding falls), and impaired among persons with lower extremity trauma, contributing to elevated fall risk. Previously, a fall-prevention program improved TPC in individuals with unilateral transtibial amputation following trip-inducing perturbations. However, it is presently unclear if these improvements are task specific. RESEARCH QUESTION: Do improvements to TPC gained from a fall-prevention program translate to another task which assesses TPC in isolation (i.e., unstable sitting)? Secondarily, can isolated TPC be used to identify who would benefit most from the fall-prevention program? METHODS: Twenty-five individuals (21 male/4 female) with lower extremity trauma, who participated in a larger fall-prevention program, were included in this analysis. Trunk flexion and flexion velocity quantified TPC following perturbation; accelerometer-based sway parameters quantified TPC during unstable sitting. A generalized linear mixed-effects model assessed training-induced differences in TPC after perturbation; a generalized linear model assessed differences in sway parameters following training. Spearman's rho related training-induced changes to TPC following perturbation (i.e., the difference in TPC measures at pre- and post-training assessments) with pre- vs. post-training changes to sway parameters during unstable sitting (i.e., the difference in sway parameters at pre- and post-training assessments) as well as pre-training sway parameters with the pre- vs. post-training differences in TPC following perturbation. RESULTS: Following training, trunk flexion angles decreased, indicating improved TPC; however, sway parameters did not differ pre- and post-training. In addition, pre- vs. post-training differences in TPC following perturbation were neither strongly nor significantly correlated with sway parameters. Moreover, pre-training sway parameters did not correlate with pre- vs. post-training differences in trunk flexion/flexion velocity. SIGNIFICANCE: Overall, these results indicate that improvements to TPC gained from fall-prevention training are task-specific and do not translate to other activities. Moreover, isolated TPC measures are not able to identify individuals that benefit most from the fall-prevention program.

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.

Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. It is conserved in animals and is both neuroprotective and cytoprotective. Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.

The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus.

Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age-specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner.

MicroRNAs Circulate in the Hemolymph of Drosophila and Accumulate Relative to Tissue microRNAs in an Age-Dependent Manner.

In mammals, extracellular miRNAs circulate in biofluids as stable entities that are secreted by normal and diseased tissues, and can enter cells and regulate gene expression. Drosophila melanogaster is a proven system for the study of human diseases. They have an open circulatory system in which hemolymph (HL) circulates in direct contact with all internal organs, in a manner analogous to vertebrate blood plasma. Here, we show using deep sequencing that Drosophila HL contains RNase-resistant circulating miRNAs (HL-miRNAs). Limited subsets of body tissue miRNAs (BT-miRNAs) accumulated in HL, suggesting that they may be specifically released from cells or particularly stable in HL. Alternatively, they might arise from specific cells, such as hemocytes, that are in intimate contact with HL. Young and old flies accumulated unique populations of HL-miRNAs, suggesting that their accumulation is responsive to the physiological status of the fly. These HL-miRNAs in flies may function similar to the miRNAs circulating in mammalian biofluids. The discovery of these HL-miRNAs will provide a new venue for health and disease-related research in Drosophila.

Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction.

MicroRNAs (miRNAs) function to modulate gene expression, and through this property they regulate a broad spectrum of cellular processes. They can circulate in blood and thereby mediate cell-to-cell communication. Aging involves changes in many cellular processes that are potentially regulated by miRNAs, and some evidence has implicated circulating miRNAs in the aging process. In order to initiate a comprehensive assessment of the role of circulating miRNAs in aging, we have used deep sequencing to characterize circulating miRNAs in the serum of young mice, old mice, and old mice maintained on calorie restriction (CR). Deep sequencing identifies a set of novel miRNAs, and also accurately measures all known miRNAs present in serum. This analysis demonstrates that the levels of many miRNAs circulating in the mouse are increased with age, and that the increases can be antagonized by CR. The genes targeted by this set of age-modulated miRNAs are predicted to regulate biological processes directly relevant to the manifestations of aging including metabolic changes, and the miRNAs themselves have been linked to diseases associated with old age. This finding implicates circulating miRNAs in the aging process, raising questions about their tissues of origin, their cellular targets, and their functional role in metabolic changes that occur with aging.