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The current retrospective cohort study uses Department of Veterans Affairs (VA) clinical and facility data of Veterans with heart failure enrolled in the VA Home Tele-health (HT) Program. General estimating equations with facility as a covariate were used to model percent average adherence at 1, 3, 6, and 12 months post-enrollment. Most HT patients were White, male, and of older age (mean = 71 years). Average adherence increased the longer patients remained in the HT program. Number of weekly reports of HT use, not having depression, and being of older age were all associated with higher adherence. Compared to White Veterans, Black and other non-White Veterans had lower adherence. These findings identify subgroups of patients (e.g., those with depression, of younger age, non-White) that may benefit from additional efforts to improve adherence to HT technologies. [ Journal of Gerontological Nursing, 46 (7), 26–34.]

A major goal of this pilot study was to quantify intramyocellular lipids (IMCL), extra-myocellular lipids (EMCL), unsaturation index (UI) and metabolites such as creatine (Cr), choline (Ch) and carnosine (Car), in the soleus muscle using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Ten subjects with type 2 diabetes (T2D), controlled by lifestyle management alone, and 9 healthy control subjects, were studied. In T2D patients only, the following measurements were obtained: body mass index (BMI); waist circumference (WC); abdominal visceral and subcutaneous fat quantified using breath-held magnetic resonance imaging (MRI); a fasting blood draw for assessment of glucose, insulin, and estimation of homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, and high-sensitivity c-reactive protein (hs-CRP). Analysis of the soleus muscle 2D L-COSY spectral data showed significantly elevated IMCL ratios with respect to Cr and decreased IMCL UI in T2D when compared to healthy subjects (P < 0.05). In T2D subjects, Pearson correlation analysis showed a positive correlation of IMCL/Cr with EMCL/Cr (0.679, P < 0.05) and HOMA-IR (0.633, P < 0.05), and a non-significant correlation of visceral and subcutaneous fat with magnetic resonance spectroscopy (MRS) and other metrics. Characterization of muscle IMCL and EMCL ratios, UI, and abdominal fat, may be useful for the noninvasive assessment of the role of altered lipid metabolism in the pathophysiology of T2D, and for assessment of the effects of future therapeutic interventions designed to alter metabolic dysfunction in T2D.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p < 0.001) was observed in the soleus muscle (predominantly type I fibers). These observations indicate unexpected differences in changes in myolipid metabolism in type I vs. type II rich muscle regions in obesity, perhaps related to IR, and warrant further investigation.

Significance Mitigating thermal stress through evolutionary adaptation or physiological plasticity is critical for species’ persistence in changing climates. Sparse knowledge of genetic and physiological architectures of thermal plasticity hampers our ability to predict organismal resilience to climate change. Understanding the independence of short- and long-term plasticity and constraints of basal thermotolerance on plasticity is important for understanding responses to climate change. We show heritable genetic variation for basal cold tolerance and plasticity in a midlatitude Drosophila melanogaster population. High long-term plasticity predicted high short-term plasticity, and basal cold tolerance constrained both plasticity measures. There was no overlap in SNPs associated with either plasticity type. Overlapping molecular function of SNPs suggests shared physiology between long- and short-term plasticity, despite distinct genetic architectures. Seasonal and daily thermal variation can limit species distributions because of physiological tolerances. Low temperatures are particularly challenging for ectotherms, which use both basal thermotolerance and acclimation, an adaptive plastic response, to mitigate thermal stress. Both basal thermotolerance and acclimation are thought to be important for local adaptation and persistence in the face of climate change. However, the evolutionary independence of basal and plastic tolerances remains unclear. Acclimation can occur over longer (seasonal) or shorter (hours to days) time scales, and the degree of mechanistic overlap is unresolved. Using a midlatitude population of Drosophila melanogaster , we show substantial heritable variation in both short- and long-term acclimation. Rapid cold hardening (short-term plasticity) and developmental acclimation (long-term plasticity) are positively correlated, suggesting shared mechanisms. However, there are independent components of these traits, because developmentally acclimated flies respond positively to short-term acclimation. A strong negative correlation between basal cold tolerance and developmental acclimation suggests that basal cold tolerance may constrain developmental acclimation, whereas a weaker negative correlation between basal cold tolerance and short-term acclimation suggests less constraint. Using genome-wide association mapping, we show the genetic architecture of rapid cold hardening and developmental acclimation responses are nonoverlapping at the SNP and corresponding gene level. However, genes associated with each trait share functional similarities, including genes involved in apoptosis and autophagy, cytoskeletal and membrane structural components, and ion binding and transport. These results indicate substantial opportunity for short-term and long-term acclimation responses to evolve separately from each other and for short-term acclimation to evolve separately from basal thermotolerance.

When ectotherms are exposed to low temperatures, they enter a cold-induced coma (chill coma) that prevents resource acquisition, mating, oviposition, and escape from predation. There is substantial variation in time taken to recover from chill coma both within and among species, and this variation is correlated with habitat temperatures such that insects from cold environments recover more quickly. This suggests an adaptive response, but the mechanisms underlying variation in recovery times are unknown, making it difficult to decisively test adaptive hypotheses. We use replicated lines of Drosophila melanogaster selected in the laboratory for fast (hardy) or slow (susceptible) chill-coma recovery times to investigate modifications to metabolic profiles associated with cold adaptation. We measured metabolite concentrations of flies before, during, and after cold exposure using nuclear magnetic resonance (NMR) spectroscopy to test the hypotheses that hardy flies maintain metabolic homeostasis better during cold exposure and recovery, and that their metabolic networks are more robust to cold-induced perturbations. The metabolites of cold-hardy flies were less cold responsive and their metabolic networks during cold exposure were more robust, supporting our hypotheses. Metabolites involved in membrane lipid synthesis, tryptophan metabolism, oxidative stress, energy balance, and proline metabolism were altered by selection on cold tolerance. We discuss the potential significance of these alterations.

Metabolic cold adaptation is a pattern where ectotherms from cold, high-latitude, or -altitude habitats have higher metabolic rates than ectotherms from warmer habitats. When found, metabolic cold adaptation is often attributed to counter-gradient selection, wherein short, cool growing seasons select for a compensatory increase in growth rates and development times of ectotherms. Yet, ectotherms in high-latitude and -altitude environments face many challenges in addition to thermal and time constraints on lifecycles. In addition to short, cool growing seasons, high-latitude and - altitude environments are characterized by regular exposure to extreme low temperatures, which cause ectotherms to enter a transient state of immobility termed chill coma. The ability to resume activity quickly after chill coma increases with latitude and altitude in patterns consistent with local adaptation to cold conditions. We show that artificial selection for fast and slow chill coma recovery among lines of the fly Drosophila melanogaster also affects rates of respiratory metabolism. Cold-hardy fly lines, with fast recovery from chill coma, had higher respiratory metabolic rates than control lines, with cold-susceptible slow-recovering lines having the lowest metabolic rates. Fast chill coma recovery was also associated with higher respiratory metabolism in a set of lines derived from a natural population. Although their metabolic rates were higher than control lines, fast-recovering cold-hardy lines did not have faster growth rates or development times than control lines. This suggests that raised metabolic rates in high-latitude and -altitude species may be driven by adaptation to extreme low temperatures, illustrating the importance of moving “Beyond the Mean”.

Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. A long history of population genetic studies suggest that selection on core metabolic enzymes may shape life histories by altering metabolic flux. However, the direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested. We investigated flexibility of nutrient catabolism during cold stress in Drosophila melanogaster artificially selected for fast or slow recovery from chill coma (i.e. cold-hardy or -susceptible), specifically testing the hypothesis that stress adaptation increases metabolic turnover. Using 13C-labelled glucose, we first showed that cold-hardy flies more rapidly incorporate ingested carbon into amino acids and newly synthesized glucose, permitting rapid synthesis of proline, a compound shown elsewhere to improve survival of cold stress. Second, using glucose and leucine tracers we showed that cold-hardy flies had higher oxidation rates than cold-susceptible flies before cold exposure, similar oxidation rates during cold exposure, and returned to higher oxidation rates during recovery. Additionally, cold-hardy flies transferred compounds among body pools more rapidly during cold exposure and recovery. Increased metabolic turnover may allow cold-adapted flies to better prepare for, resist and repair/tolerate cold damage. This work illustrates for the first time differences in nutrient fluxes associated with cold adaptation, suggesting that metabolic costs associated with cold hardiness could invoke resource-based trade-offs that shape life histories.