Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system.

Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Starting from published single-cell transcriptomic data, we report that (FKH) is endogenously expressed in neurons, whereas (FOXO) is expressed in glial cells.

Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.

Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5.

Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila.

High-sugar diets cause thirst, obesity, and metabolic dysregulation, leading to diseases including type 2 diabetes and shortened lifespan. However, the impact of obesity and water imbalance on health and survival is complex and difficult to disentangle. Here, we show that high sugar induces dehydration in adult Drosophila, and water supplementation fully rescues their lifespan.

The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity.

Identifying the molecular mechanisms that underlie aging and their pharmacological manipulation are key aims for improving lifelong human health. Here, we identify a critical role for Ras-Erk-ETS signaling in aging in Drosophila. We show that inhibition of Ras is sufficient for lifespan extension downstream of reduced insulin/IGF-1 (IIS) signaling.

New graduate nurses' transition to home healthcare: an integrative review.

This article is a review of relevant literature exploring the factors that contribute to new graduate nurses' transition to home healthcare nursing. The results revealed themes that include introducing the nurse to home healthcare nursing, knowledge and confidence, and developing the professional role. The review findings suggest that home healthcare leaders should consider recruiting new graduate nurses to home healthcare nursing and provide a structured orientation program in a supportive and welcoming work environment.

Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila.

The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1. We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster.

Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies.

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster.

Sex hormones differentially influence voluntary running activity, food intake and body weight in aging female and male rats.

The aim of this study was to examine the longer-term effects of reduced gonadal hormones on food intake, food efficiency, voluntary running activity and body weight in mature male and female rats, compared to age-matched controls. We hypothesized that hormonal effects would differ for rats that were not rapidly growing and our results are consistent with this hypothesis. 6-8 month male and female rats were divided into four groups: Female and male control groups and a female and male experimental group.

A rehabilitation exercise program to remediate skeletal muscle atrophy in an estrogen-deficient organism may be ineffective.

To determine rehabilitation exercise program effects under hormone deficient (ovariectomy or OVX) and hormone supplemented [OVX + 17-beta estradiol (E2)] conditions. Mature female rats (n = 123) were assigned to OVX or OVX + E2-supplemented groups. OVX and OVX + E2 groups were allocated to one of four conditions: (1) control, (2) hindlimb unweighted (HLU) for 4 weeks to induce muscle atrophy, (3) cage Recovery for 2 weeks after HLU, and (4) Recovery with 2 weeks of rehabilitation exercise program after 4 weeks of HLU.

dFOXO-independent effects of reduced insulin-like signaling in Drosophila.

The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles in growth control, metabolic homeostasis, stress responses, reproduction, and lifespan. Genetic manipulations that reduce IIS in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have been shown not only to produce substantial increases in lifespan but also to ameliorate several age-related diseases. In C.

Comparison of passive transfer of immunity in neonatal dairy calves fed colostrum or bovine serum-based colostrum replacement and colostrum supplement products.

Objective: To compare serum total protein (sTP) and serum IgG (sIgG) concentrations In neonatal calves administered colostrum or a bovine serum-based colostrum replacement (CR) product followed by a bovine serum-based colostrum supplement (CS) product.

Design: Randomized controlled clinical trial.

Animals: 18 Jersey and 269 Holstein neonatal heifer calves.

Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data.

Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster.

The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants.

The effect of ovariectomy combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats.

Objective: To determine the effect of loss of ovarian function and mechanical loading (ie, inactivity) alone or in combination on bone mass and strength.

Design: Mature (aged 6 mo) rats were ovariectomized to induce loss of ovarian function and bone. Hindlimb unloading (HLU) was used to determine the effect of mechanical unloading and reloading on bone mass and strength.

Classification of adverse events occurring in a surgical intensive care unit.

Introduction: We aimed to describe the preventability and provider specificity of surgical intensive care unit (SICU) deaths and complications compared with those in a cohort of trauma patients.

Methods: Data were collected on all trauma and SICU admissions from July 1, 2001, to June 30, 2004, from administrative (Trauma Base and Project Impact) and morbidity databases. Services were protocol driven and staffed by in-house attendings.

Amelioration of increased intensive care unit service readmission rate after implementation of work-hour restrictions.

Unlabelled: In July 2003, we reallocated our resident workforce to address mandated duty-hour restrictions. In the subsequent academic year (AY), surgical intensive care unit (SICU) service readmission rates (RR) doubled. We hypothesized that a targeted intervention could reduce SICU service RR in academic year (AY) 2004-05.

Ovariectomy, hindlimb unweighting, and recovery effects on skeletal muscle in adult rats.

Introduction: The effect of female sex hormones on skeletal muscle is unclear. Reports suggest that female sex hormones have an anabolic effect, have no effect, or are detrimental to skeletal muscle.

Methods: To amplify ovarian hormones' potential effects on skeletal muscle, 6-mo-old virgin intact (sham), ovariectomized (OVX), and ovariectomized plus estrogen (OVX + E2) rats were hindlimb unweighted (HLU) for 4 wk.

Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass.

The recovery of atrophied muscle mass in animals is thought to be dependent on a number of factors including hormones, cytokines, and/or growth factor expression. The Akt/mammalian target of rapamycin (mTOR) signaling pathway is believed to be activated by these various factors, resulting in skeletal muscle growth through the initiation of protein synthesis. It was hypothesized that surgical removal of the ovaries (Ovx) may alter activation of the Akt/mTOR signaling pathway, a mechanism necessary for muscle regrowth.

Use of corporate Six Sigma performance-improvement strategies to reduce incidence of catheter-related bloodstream infections in a surgical ICU.

Background: Corporate performance-improvement methodologies can outperform traditional ones in addressing ICU-based adverse events. My colleagues and I used Six Sigma methodology to address our catheter-related bloodstream infection (CR-BSI) rate, which considerably exceeded the nationally established median over a 9-year period. We hypothesized that use of Six Sigma methodology would result in a substantial and sustainable decrease in our CR-BSI rate.