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Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of 3 different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; aged 23 ± 3 years) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30 min; 65% peak oxygen consumption), high-intensity interval cycling exercise (10 × 1 min at 90% peak heart rate), and lower-load higher-repetition resistance exercise (25–35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p < 0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p < 0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. Novelty: We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an OGTT. Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.

Reproductive fitness and survival are enhanced by adaptive behaviors that are modulated by internal physiological states and external social contexts. The common bed bug, Cimex lectularius, is an obligate hematophagous ectoparasite that requires host blood for growth, development, and reproduction. We investigated how mating, starvation and social interactions affect host-seeking, blood feeding, oviposition, and survival of female bed bugs. The percentage of females that fed and the amount of blood they ingested were greater in mated females (90–100%) than in unmated females (48–60%). Mating state also modulated the female’s orientation towards human skin odor in an olfactometer; more mated (69%) than unmated (23%) females responded to human odors. The response rate of unmated females (60%) to skin odor increased with longer starvation period, while the opposite pattern was observed in mated females (20%). Although fecundity after a single blood meal was unaffected by long or short residence and interaction with males, females subjected to frequent copulation attempts had lower survivorship and lifespan than females housed with males for only 24 h. Taken together, these results indicate that by adaptively and coordinately expressing behaviors based on the internal physiological state, females maximize their survival and reproductive fitness.

Muscle disuse rapidly induces insulin resistance (IR). Despite a relationship between intramyocellular lipid (IMCL) content and IR, during muscle-disuse IR develops before IMCL accumulation, suggesting that IMCL are not related to disuse-induced IR. However, recent studies show that it is not total IMCL, but IMCL size and location that are related to IR. Changes in these IMCL parameters may occur prior to increases in IMCL content, thus contributing to disuse-induced IR. Omega-3 fatty acids may mitigate the effects of disuse on IR by preventing a decline in insulin signaling proteins. Twenty women (age 22±3 y) received either 5g·d-1 omega-3 fatty acid or isoenergetic sunflower oil for 4-weeks prior to, throughout 2-weeks of single-leg immobilization, and during 2-weeks of recovery. Changes in IMCL characteristics and insulin signaling proteins were examined in vastus lateralis samples taken prior to supplementation and immobilization, and following immobilization and recovery. Omega-3 supplementation had no effect. IMCL area density decreased in the subsarcolemmal region during immobilization and recovery (-19% and -56%, respectively, p=0.009). IMCL size increased in the central intermyofibrillar region during immobilization (43%, p=0.007), returning to baseline during recovery. PLIN5 and AKT increased during immobilization (87%, p=0.002; 30%, p=0.007, respectively). PLIN 5 remained elevated and AKT increased further (15%) during recovery. IRS1, AS160 and GLUT4 decreased during immobilization (-35%, p=0.001; -44%, p=0.03; -56%, p=0.02, respectively), returning to baseline during recovery. Immobilization alters IMCL storage characteristics while negatively affecting unstimulated insulin signaling protein content in young women.

Background Higher-protein (HP) diets are advocated for several reasons, including mitigation of sarcopenia, but their effects on kidney function are unclear. Objective This meta-analysis was conducted to determine the effect of HP intakes on kidney function in healthy adults. Methods We conducted a systematic review and meta-analysis of trials comparing HP (≥1.5 g/kg body weight or ≥20% energy intake or ≥100 g protein/d) with normal- or lower-protein (NLP; ≥5% less energy intake from protein/d compared with HP group) intakes on kidney function. Medline and EMBASE databases were searched. Randomized controlled trials comparing the effects of HP with NLP (>4 d duration) intakes on glomerular filtration rate (GFR) in adults without kidney disease were included. Results A total of 2144 abstracts were reviewed, with 40 articles selected for full-text review; 28 of these were analyzed and included data from 1358 participants. Data were analyzed using random-effects meta-analysis (RevMan 5; The Cochrane Collaboration), meta-regression (STATA; StataCorp), and dose-response analysis (Prism; GraphPad). Analyses were conducted using postintervention (post) GFR and the change in GFR from preintervention to post. The post-only comparison showed a trivial effect for GFR to be higher after HP intakes [standardized mean difference (SMD): 0.19; 95% CI: 0.07, 0.31; P = 0.002]. The change in GFR did not differ between interventions (SMD: 0.11; 95% CI: -0.05, 0.27; P = 0.16). There was a linear relation between protein intake and GFR in the post-only comparison (r = 0.332, P = 0.03), but not between protein intake and the change in GFR (r = 0.184, P = 0.33). The main limitation of the current analysis is the unclear risk of selection bias of the included trials. Conclusions Postintervention GFR comparisons indicate that HP diets result in higher GFRs; however, when changes in GFR were compared, dietary protein had no effect. Our analysis indicates that HP intakes do not adversely influence kidney function on GFR in healthy adults.

BACKGROUND Age-related sarcopenia is accelerated by physical inactivity. Low-load resistance exercise (LLRE) counters inactivity-induced muscle atrophy in older adults, but changes in muscle fibre morphology are unstudied. We aimed to determine the impact of LLRE during short-term inactivity (step-reduction) on muscle fibre size and capillarity as well as satellite cell (SC) content in older skeletal muscle. METHODS Fourteen older (~71 years) male adults underwent 14 days of step reduction (

Older women may not be consuming enough protein to maintain muscle mass. Augmentation of protein intake with leucine may enhance the muscle protein synthetic response in older women to aid in maintaining muscle mass.We measured the acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS) response to consumption of a high-quality mixed protein beverage compared with an isonitrogenous protein beverage with added leucine.In a parallel design, free-living, healthy older women (aged 65-75 y, n = 11/group) consumed a fixed, weight-maintaining diet with protein at 1.0 g · kg-1 · d-1 and were randomly assigned to twice-daily consumption of either 15 g milk protein beverage containing 4.2 g leucine (LEU) or 15 g mixed protein (milk and soy) beverage containing 1.3 g leucine (CON). Unilateral leg resistance exercise allowed a determination of acute ([13C6]-phenylalanine infusion, hourly rate) and integrated (deuterated water ingestion, daily rate) exercised and rested myoPS responses.Acute myoPS increased in response to feeding in the rested (CON: 13% ± 4%; LEU: 53% ± 5%) and exercised (CON: 30% ± 4%; LEU: 87% ± 7%) leg in both groups, but the increase was greater in LEU (P0.001). Integrated myoPS increased during the supplementation period in both legs (rested: 9% ±1%; exercised: 17% ± 2%; P0.001) in LEU, but in the exercised leg only (7% ± 2%; P0.001) in CON.A 15-g protein-containing beverage with ∼4 g leucine induced greater increases in acute and integrated myoPS than did an isonitrogenous, isoenergetic mixed-protein beverage. Declines in muscle mass in older women may be attenuated with habitual twice-daily consumption of a protein beverage providing 15 g protein and higher (4.2 g/serving) amounts of leucine. This trial was registered at clinicaltrials.gov as NCT02282566.

Exercise results in the rapid remodeling of skeletal muscle. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity vs. translational efficiency in contributing to muscular hypertrophy. We also examine whether high-intensity sprinting-type exercise promotes changes in protein turnover that lead to hypertrophy or merely a change in mitochondrial content. Finally, we propose novel areas for future study that will fill existing knowledge gaps in the fields of translational research and exercise science.

The prevalence of pre-diabetes (PD) and type II diabetes (T2D) has risen dramatically in recent years affecting an estimated 422 million adults worldwide. The risk of T2D increases with age, with the sharpest rise in diagnosis occurring after age 40. With age, there is also a progressive decline in muscle mass starting after the age of 30. The decline in muscle mass and function due to aging is termed sarcopenia and immediately precedes the sharp rise in T2D. The purpose of the current review is to discuss the role of protein to attenuate declines in muscle mass and insulin sensitivity to prevent T2D and sarcopenia in aging adults. The current recommended dietary allowance for protein consumption is set at 0.8 g/kg/day and is based on dated studies on young healthy men and may not be sufficient for older adults. Protein consumption upwards of 1.0–1.5 g/kg/day in older adults is able to induce improvements in glycemic control and muscle mass. Obesity, particularly central or visceral obesity is a major risk factor in the development of PD and T2D. However, the tissue composition of weight loss in older adults includes both lean body mass and fat mass and therefore may have adverse metabolic consequences in older adults who are already at a high risk of lean body mass loss. High protein diets have the ability to increase weight loss while preserving lean body mass therefore inducing “high-quality weight loss,” which provides favorable metabolic changes in older adults. High protein diets also induce beneficial outcomes on glycemic markers due to satiety, lowered post-prandial glucose response, increased thermogenesis, and the ability to decrease rates of muscle protein breakdown (MPB). The consumption of dairy specific protein consumption has also been shown to improve insulin sensitivity by improving body composition, enhancing insulin release, accelerating fat oxidation, and stimulating rates of muscle protein synthesis (MPS) in older adults. Exercise, specifically resistance training, also works synergistically to attenuate the progression of PD and T2D by further stimulating rates of MPS thereby increasing muscle mass and inducing favorable changes in glycemic control independent of lean body mass increases.

When you lift weights you get stronger and your muscles can get bigger, a process we call hypertrophy, and these changes can mean a big advantage in certain sports. We all ‘know’ that we need to consume supplemental protein when we lift weights to get bigger muscles, right? But what’s the real (science-based) answer? A meta-analysis is a way of looking at all of the studies that have been done in a particular area of science. In our study,1 we performed …

Background: Leucine co-ingestion with lower-protein (LP)–containing meals may overcome the blunted muscle protein synthetic response to food intake in the elderly but may be effective only in individuals who consume LP diets. Objective: We examined the impact of leucine co-ingestion with mixed macronutrient meals on integrated 3-d rates of myofibrillar protein synthesis (MyoPS) in free-living older men who consumed higher protein (HP) (1.2 g · kg–1 · d–1) or LP (0.8 g · kg–1 · d–1) in rested and resistance exercise (REX) conditions. Design: In a crossover design, 20 healthy older men [aged 65–85 y] were randomly assigned to receive LP or HP diets while ingesting a placebo (days 0–2) and Leu supplement (5 g leucine/meal; days 3–5) with their 3 main daily meals. A bout of unilateral REX was performed during the placebo and Leu treatments. Ingested 2H2O and skeletal muscle biopsies were used to measure the 3-d integrated rate of MyoPS during the placebo and Leu treatments in the rested and REX legs. Results: Leucinemia was higher with Leu treatment than with placebo treatment (P < 0.001). MyoPS was similar in LP and HP during both treatments (P = 0.39) but was higher with Leu treatment than with placebo treatment in the rested (pooled mean ± SD: Leu, 1.57% ± 0.11%/d; placebo, 1.48% ± 0.08%/d; main effect of treatment: P < 0.001) and REX (pooled mean: Leu, 1.87% ± 0.09%/d; placebo, 1.71 ± 0.10%/d; main effect of treatment: P < 0.001) legs. Conclusions: Leu co-ingestion with daily meals enhances integrated MyoPS in free-living older men in rested and REX conditions and is equally effective in older men who consume daily protein intakes greater than or equal to the RDA. This trial was registered at clinicaltrials.gov as NCT02371278.

Purpose:Self–myofascial release (SMR) is a common exercise and therapeutic modality shown to induce acute improvements in joint range of motion (ROM) and recovery; however, no long-term studies have been conducted. Static stretching (SS) is the most common method used to increase joint ROM and decrease muscle stiffness. It was hypothesized that SMR paired with SS (SMR+SS) compared with SS alone over a 4-wk intervention would yield greater improvement in knee-extension ROM and hamstring stiffness.Methods:19 men (22 ± 3 y) with bilateral reduced hamstring ROM had each of their legs randomly assigned to either an SMR+SS or an SS-only group. The intervention consisted of 4 repetitions of SS each for 45 s or the identical amount of SS preceded by 4 repetitions of SMR each for 60 s and was performed on the respective leg twice daily for 4 wk. Passive ROM, hamstring stiffness, rate of torque development (RTD), and maximum voluntary contraction (MVC) were assessed pre- and postintervention.Results:Passive ROM (P < .001), RTD, and MVC (P < .05) all increased after the intervention. Hamstring stiffness toward end-ROM was reduced postintervention (P = .02). There were no differences between the intervention groups for any variable.Conclusion:The addition of SMR to SS did not enhance the efficacy of SS alone. SS increases joint ROM through a combination of decreased muscle stiffness and increased stretch tolerance.

Indoor pests, and the allergens they produce, adversely affect human health. Surprisingly, however, their effects on indoor microbial communities have not been assessed. Bed bug (Cimex lectularius) infestations pose severe challenges in elderly and low-income housing. They void large amounts of liquid feces into the home environment, which might alter the indoor microbial community composition. In this study, using bed bug-infested and uninfested homes, we showed a strong impact of bed bug infestations on the indoor microbial diversity. Floor dust samples were collected from uninfested and bed bug-infested homes and their microbiomes were analyzed before and after heat interventions that eliminated bed bugs. The microbial communities of bed bug-infested homes were radically different from those of uninfested homes, and the bed bug endosymbiont Wolbachia was the major driver of this difference. After bed bugs were eliminated, the microbial community gradually shifted toward the community composition of uninfested homes, strongly implicating bed bugs in shaping the dust-associated environmental microbiome. Further studies are needed to understand the viability of these microbial communities and the potential risks that bed bug-associated microbes and their metabolites pose to human health.

Women and men store lipid differently within the body with men storing more fat in the android region and women storing more fat in the gynoid region. Fat is predominately stored in adipose tissue as triacylglycerides (TG); however, TG are also stored in other tissues including the liver and skeletal muscle. Excess hepatic TG storage, defined as a TG concentration >5% of liver weight and known as nonalcoholic fatty liver disease (NAFLD), is related to the metabolic syndrome. Similarly, elevated skeletal muscle TG, termed intramyocellular lipids (IMCL), are related to insulin resistance in obesity and type II diabetes. Men store more hepatic TG than women and, unsurprisingly, NAFLD is more prevalent in men than women. Women store more IMCL than men, yet type II diabetes risk is not greater, which is likely due to the manner in which women store TG within muscle. Sex-based differences in TG storage between men and women are underpinned by differences in messenger RNA expression, protein content, and enzyme activities of skeletal muscle and hepatic lipid metabolic pathways. Furthermore, women have a greater reliance on lipid during exercise because of upregulation of lipid oxidative pathways. The purpose of this review is to discuss the role of sex in mediating lipid storage and metabolism within skeletal muscle and the liver at rest and during exercise and its relationship with metabolic disease.

Background The German cockroach, Blattella germanica, is one of the most challenging pests to eradicate from indoor environments. Professional pest control is often prohibitively expensive, prompting low-income residents to turn to over-the-counter consumer products, including total release foggers (TRFs, “bug bombs”). Despite their widespread use, little is known regarding either the associated pesticide exposure risks or the efficacy of TRFs. Methods Cockroach-infested homes were recruited into the study. Wipe samples were collected from various surfaces before TRFs were discharged, immediately after, and one month later to determine pesticide exposure risks in 20 homes (divided equally among four different TRF products). Simultaneously, cockroach populations were monitored in all homes to assess the efficacy of TRFs. In parallel, 10 homes were treated with gel baits (divided equally between two bait products), to compare TRFs to a more targeted, low-risk, do-it-yourself intervention strategy. Results TRFs failed to reduce cockroach populations, whereas similarly priced gel baits caused significant declines in the cockroach populations. Use of TRFs resulted in significant pesticide deposits throughout the kitchen. Across all products, pesticides, and horizontal kitchen surfaces, pesticide residues following TRF discharge were 603-times (SEM ±184) higher than baseline, with a median increase of 85 times. Conclusions The high risks of pesticide exposure associated with TRFs combined with their ineffectiveness in controlling German cockroach infestations call into question their utility in the marketplace, especially because similarly priced and much safer bait products are highly effective in the indoor environment.

Skeletal muscle is the largest and most important site of capillary-tissue exchange, especially during high-energy demand tasks such as exercise; however, information regarding the role of the microcirculation in maintaining skeletal muscle health is limited. Changes in microcirculatory function, as observed with aging, chronic and cardiovascular diseases, and exercise, likely precede any alterations that arise in larger vessels, although further investigation into these changes is required. One of the main barriers to addressing this knowledge gap is the lack of methodologies for quantifying microvascular function in vivo; the utilization of valid and noninvasive quantification methods would allow the dynamic evaluation of microvascular flow during periods of clinical relevance such as during increased demand for flow (exercise) or decreased demand for flow (disuse). Contrast-enhanced ultrasound (CEUS) is a promising noninvasive technique that has been used for diagnostic medicine and more recently as a complementary research modality to investigate the response of the microcirculation in insulin resistance, diabetes, and aging. To improve the reproducibility of these measurements, our laboratory has optimized the quantification protocol associated with a bolus injection of the contrast agent for research purposes. This brief report outlines the assessment of microvascular flow using the raw time-intensity curve incorporated into gamma variate response modeling. CEUS could be used to compliment any macrovascular assessments to capture a more complete picture of the aging vasculature, and the modified methods presented here provide a template for the general analysis of CEUS within a research setting.

Resuscitative thoracotomy has been extensively described in the civilian trauma literature and has a high mortality rate, due largely to the nature of the injuries leading to arrest. The survival rates are generally highest (10-30%) for penetrating truncal injuries and patients who arrive with vital signs and proceed to arrest or who have impending arrest. They are significantly lower (less than 5%) for blunt trauma victims, particularly those who arrest in the field or during transport (1% or less). In addition, the likelihood of survival with intact neurologic function is significantly lower than the overall survival rates, particularly for blunt trauma victims and for prehospital arrest.

An age-associated loss of muscle mass and strength – sarcopenia – begins at around the fifth decade of life, with mass being lost at ~0.5-1.2% per year and strength at ~3% per year. Sarcopenia can contribute to a variety of negative health outcomes, including an increased risk for falls and fractures, the development of metabolic diseases like type 2 diabetes mellitus, and increase the chance of requiring assisted living. Linear sarcopenic declines in muscle mass and strength are, however, punctuated by transient periods of muscle disuse that can accelerate losses of muscle and strength, which could result in increased risk for the aforementioned conditions. Muscle disuse is recognizable with bed rest or immobilization (for example, due to surgery or acute illness requiring hospitalization); however, recent work has shown that even a relative reduction in ambulation (reduced daily steps) results in significant reductions in muscle mass, strength and possibly an increase in disease risk. Although reduced ambulation is a seemingly “benign” form of disuse, compared to bed rest and immobilization, reports have documented that 2-3 weeks of reduced daily steps may induce: negative changes in body composition, reductions in muscle strength and quality, anabolic resistance, and decrements in glycemic control in older adults. Importantly, periods of reduced ambulation likely occur fairly frequently and appear more difficult to fully recover from, in older adults. Here we explore the consequences of muscle disuse due to reduced ambulatory activity in older adults, with frequent comparisons to established models of disuse: bed rest and immobilization.

What is the topic of this review? The topic is how sex influences carbohydrate and fat metabolism during exercise and whether this influences adaptation to nutritional and exercise regimens aiming to improve health and performance. What advances does it highlight? Women respond differently to certain nutritional and training regimens aimed at improving health and performance. Few studies have included women in trials and thus we are unsure how women respond to nutritional and training strategies aimed at improving health and performance. Sex-based differences in substrate metabolism during moderate-intensity endurance exercise (END) have been well established. Specifically, during END of the same relative intensity women have a lower respiratory exchange ratio than men, indicative of a lesser reliance on carbohydrate oxidation to support fuel requirements for exercise. In fact, compared with men, women show a lesser reliance on both liver and muscle glycogen during END. Sex-based differences in intramyocellular lipid (IMCL) utilization during END are controversial. However, women have a larger depot of IMCL available to support END fuel needs and a greater percentage of IMCL in contact with mitochondria after a bout of END compared with men, suggestive of a greater capacity to use IMCL. These sex-based differences in metabolism during END are known to be mediated by oestrogen. Despite the well-recognized sexual dimorphisms in substrate metabolism during END, there is a paucity of research examining the effects of exercise and nutritional regimens aimed to enhance performance and/or health in women. Furthermore, the evidence that does exist is suggestive of discordance in the effectiveness of nutritional and exercise regimens between the sexes. The focus of this review is to provide an overview of the well-established sex-based differences in metabolism during END and how they relate to the physiological responses to nutritional and exercise strategies intended to improve exercise performance and/or health.

Skeletal muscle is an integral body tissue playing key roles in strength, performance, physical function, and metabolic regulation. It is essential for athletes to ensure that they have optimal amounts of muscle mass to ensure peak performance in their given sport. However, the role of maintaining muscle mass during weight loss and as we age is an emerging concept, having implications in chronic disease prevention, functional capacity, and quality of life. Higher-protein diets have been shown to: (1) promote gains in muscle mass, especially when paired with resistance training; (2) spare muscle mass loss during caloric restriction; and (3) attenuate the natural loss of muscle mass that accompanies aging. Protein quality is important to the gain and maintenance of muscle mass. Protein quality is a function of protein digestibility, amino acid content, and the resulting amino acid availability to support metabolic function. Whey protein is one of the highest-quality proteins given its amino acid content (high essential, branched-chain, and leucine amino acid content) and rapid digestibility. Consumption of whey protein has a robust ability to stimulate muscle protein synthesis. In fact, whey protein has been found to stimulate muscle protein synthesis to a greater degree than other proteins such as casein and soy. This review examines the existing data supporting the role for protein consumption, with an emphasis on whey protein, in the regulation of muscle mass and body composition in response to resistance training, caloric restriction, and aging.

Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust). Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment.

Bed bugs (Cimex lectularius) provide a unique opportunity to understand speciation and host-associated divergence in parasites. Recently, two sympatric but genetically distinct lineages of C. lectularius were identified: one associated with humans and one associated with bats. We investigated two mechanisms that could maintain genetic differentiation in the field: reproductive compatibility (via mating crosses) and aggregation fidelity (via two-choice sheltering assays). Effects were assessed at the intra-lineage level (within human-associated bed bugs), inter-lineage level (between human- and bat-associated bed bugs), and inter-species level (between C. lectularius and Cimex pipistrelli [bat bug]). Contrary to previous reports, bed bugs were found to be reproductively compatible at both the intra- and inter-lineage levels, but not at the inter-species level (although three hybrids were produced, one of which developed into an adult). Lineage- and species-specific aggregation fidelity was only detected in 8% (4 out of 48) of the aggregation fidelity assays run. These results indicate that under laboratory conditions, host-associated lineages of bed bugs are reproductively compatible, and aggregation pheromones are not capable of preventing gene flow between lineages.

Introduction: Advances in cancer detection and treatment have substantially increased the survival rate for breast cancer patients. Chemotherapeutic drugs, particularly anthracyclines, have potentially toxic side effects in the brain- impacting memory, processing time and verbal fluency. More than 30% of patients undergoing chemotherapy for breast cancer report cognitive deficits during and after treatment. Despite the high incidence and significant impact on quality of life, little is known about the cause of the cognitive deficits and no effective treatment currently exists. Our hypothesis is that chemotherapy-induced neuroinflammation impairs cognition. Methods: Adult female BALB/C mice were ovariectomized and then two weeks later injected intravenous (IV) with a single dose of chemotherapy (45 mg/m2 doxorubicin + 450 mg/m2 cyclophosphamide) or vehicle (n = 10–12/group). The mice were trained for three trials per day across six days in the Barnes Maze, a well-characterized spatial memory task. Results: Both the chemotherapy-treated and vehicle-treated mice were able to acquire the task by the final day of training. However, the vehicle-treated mice reached asymptotic performance after fewer training sessions than the chemotherapy-treated mice. Furthermore, the chemotherapy-treated mice took significantly longer to find the escape box than the vehicle-treated mice on training days 2–5 (p < 0.05). In contrast, there were no group differences in overall locomotor activity level, suggesting that the observed difference in maze performance was not due to a fatigue. (p > 0.05) In addition, chemotherapy increased proinflammatory cytokine expression (TNF-α, IL-1β, and IL-6) in the hippocampus (p < 0.05), a region of the brain that is critical for spatial learning and memory. Likewise, microglia from chemotherapy-treated mice exhibited increased expression of MHCII and CD80 relative to vehicle-treated mice (p < 0.05), thereby suggesting a proinflammatory phenotype. Conclusions: Together, these data suggest that the administration of doxorubicin and cyclophosphamide in doses that are approximately 25% lower than the typical dose for women treated for breast cancer, produce neuroinflammation, including microglia activation, increased proinflammatory cytokine expression and concomitant cognitive deficits in female mice. Additional studies will establish whether a causal relationship exists between chemotherapy-induced neuroinflammation and cognitive deficits. Identifying the mechanism through which chemotherapy induces cognitive deficits is the first step toward designing therapeutic interventions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-04.

Proteins that coat the lipid droplets (also known as PAT proteins or perilipin (PLIN) family proteins) have diverse functions that are not well elucidated in many tissues. In skeletal muscle, there is even less known about the functions or characteristics of these proteins or how they might change in response to perturbations that alter both intramyocellular lipid (IMCL) content and fat utilization and oxidation. Therefore, the purpose of this study was to examine the human muscle content and gene expression of the four skeletal muscle PLIN proteins in both lean and obese men and women and how this was changed following a 12-week endurance training protocol. PLIN2–PLIN5 proteins were all more abundant in women than in men (p = 0.037 and p < 0.0001, respectively), consistent with higher IMCL content observed in female skeletal muscle. PLIN5 (previously known as OXPAT) is of particular interest because it has previously been associated primarily with oxidative tissues that rely heavily on fat oxidation for energy production. Although PLIN5 was not different between lean and obese subjects, it was the only PLIN protein to increase in response to endurance training in both sexes. PLIN5 correlated with IMCL volume (p < 0.0001), but in general, the other PLIN proteins did not correlate well with IMCL volume, suggesting that the relationship between lipid accumulation and PLIN family protein content is not a simple one. Although more work is necessary, it is clear that PLIN5 likely plays an important role in IMCL accumulation and oxidation, both of which increase with endurance training in human skeletal muscle.

BACKGROUND Brain metastases (BM) are frequently diagnosed in patients (pts) with Her2-positive metastatic breast cancer (BC); a rising incidence was also reported in triple-negative disease. We hypothesized that pts with triple-negative or Her2-positive tumours had shorter BMFS as compared to other BC subtypes. Therefore, we aimed to compare BMFS in pts with Her2-positive, estrogen receptor (ER) positive and triple-negative BC treated at the Medical University of Vienna from 1999–2009. In Her2-positive tumours, we further investigated the influence of ER co-expression on BMFS, as Her2-positive / ER-positive tumours were reported to express less aggressive biological properties. METHODS BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic BC until diagnosis of BM. A total of 168 pts were identified from a breast cancer database. 34 pts were excluded from this analysis as brain was the first site of disease progression; hence complete datasets from 134 pts were available (69 Her2-positive; 33 triple-negative; 32 ER-positive). Her2 status was analyzed by immunohistochemistry (IHC) and reanalyzed by FISH if a score of 2+ was gained. ER was analyzed by IHC; ER negative tumours were defined by a cut-off value of RESULTS Median BMFS in triple-negative pts was 14 months (m) (95% CI 12.17−15.83), as compared to 25 m (95% CI 13.37−36.62) in Her2-positive (p=0.001) and 35 m (95% CI 19.79−50.22) in ER-positive pts (p In Her2-positive pts, prior trastuzumab treatment for metastatic disease prolonged median BMFS (29 vs. 11 m; p ER-expression (HR 2.03; 95%CI 1.22−3.36; p CONCLUSIONS BMFS in triple-negative disease is significantly shorter as compared to Her2-positive or ER-positive tumours, mirroring the aggressiveness of this breast cancer subtype. Probably due to improved systemic disease control, trastuzumab significantly prolonged BMFS in Her2-positive pts. Longer BMFS in ER/Her2 co-positive disease reflects a less aggressive subtype of Her2-positive breast cancer which is less likely to benefit from strategies of BM screening or prevention. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-05.

Background: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. Methods: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. Results: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). Interpretation: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ⩾70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.

We present an unusual case of right lower lobe intralobar pulmonary sequestration in a previously healthy and physical active 27-year-old U.S. Marine, who presented with new onset hemoptysis after doing push-ups. Diagnosis was obtained by chest X-ray and contrast computed tomography scan. Preoperatively the patient underwent fluoroscopy-guided embolization of the aberrant systemic artery supplying the sequestration. The segmental resection of the sequestration was then successfully performed through a muscle-sparing thoracotomy.

The physiological link between neuropathic pain and depression remains unknown despite a high comorbidity between these two disorders. A mouse model of spared nerve injury (SNI) was used to test the hypothesis that nerve injury precipitates depression through the induction of inflammation in the brain, and that prior exposure to stress exacerbates the behavioral and neuroinflammatory consequences of nerve injury. As compared with sham surgery, SNI induced mechanical allodynia, and significantly increased depressive-like behavior. Moreover, SNI animals displayed increased interleukin-1beta (IL-1beta) gene expression within the frontal cortex and concurrent increases in the expression of glial fibrillary acidic protein (GFAP) within the periaqueductal grey (PAG). Additionally, exposure to chronic restraint stress for 2 weeks before SNI exacerbated mechanical allodynia and depressive-like behavior, and resulted in an increase in IL-1beta gene expression in the frontal cortex and brain-derived neurotrophic factor (BDNF) gene expression in PAG. Treatment with metyrapone (MET), a corticosteroid synthesis inhibitor, before stress eliminated deleterious effects of chronic stress on SNI. Finally, this study showed that interference with IL-1beta signaling, through administration of IL-1 receptor antagonist (IL-1ra), ameliorated the effects of neuropathic pain on depressive-like behavior. Taken together, these data suggest that peripheral nerve injury leads to increased cytokine expression in the brain, which in turn, contributes to the development of depressive-like behavior. Furthermore, stress can facilitate the development of depressive-like behavior after nerve injury by promoting IL-1beta expression.

This report details the life and contributions of William Ray Rumel, an early cardiovascular surgeon known for his innovations, particularly the "Rumel tourniquet," and the ability to repair the diseased mitral valve without replacing it.

Evaluating the critical thermal maximum (CTmax) in insects has provided a number of challenges. Visual observations of endpoints (onset of spasms, loss of righting response, etc.) can be difficult to measure consistently, especially with smaller insects. To resolve this problem, Lighton and Turner (2004) developed a new technique: thermolimit respirometry (TLR). TLR combines real time measurements of both metabolism (V·CO2) and activity to provide two independent, objective measures of CTmax. However, several questions still remain regarding the precision of TLR and how accurate it is in relation to traditional methods. Therefore, we evaluated CTmax of bed bugs using both traditional (visual) methods and TLR at three important metabolic periods following feeding (1d, 9d, and 21d). Both methods provided similar estimates of CTmax, although traditional methods produced consistently lower values (0.7-1°C lower than TLR). Despite similar levels of precision, TLR provided a more complete profile of thermal tolerance, describing changes in metabolism and activity leading up to the CTmax, not available through traditional methods. In addition, feeding status had a significant effect on bed bug CTmax, with bed bugs starved 9d (45.19[±0.20]°C) having the greatest thermal tolerance, followed by bed bugs starved 1d (44.64[±0.28]°C), and finally bed bugs starved 21d (44.12[±0.28]°C). Accuracy of traditional visual methods in relation to TLR is highly dependent on the selected endpoint; however, when performed correctly, both methods provide precise, accurate, and reliable estimations of CTmax.

In vitro studies have pointed to the collapsin response mediator proteins (CRMPs) as key regulators of neurite outgrowth and axonal differentiation. CRMP3 is expressed mostly in the nervous system during development but remains at high levels in the hippocampus of adults. To explore CRMP3 function in vivo, we generated mice with targeted disruption of the CRMP3 gene. Immunohistochemistry and Golgi staining of CA1 showed abnormal dendrite and spine morphogenesis in the hippocampus of CRMP3-deficient mice. Apical dendrites displayed an increase in undulation and a reduction in length and branching points. Basal dendrites also exhibited a reduction in length with an alteration in soma stem distribution and an increased number of thick dendrites localized in stratum oriens (SO). Long-term potentiation (LTP) was impaired in this area. These data indicate an important role for CRMP3 in dendrite arborization, guide-posts navigation, and neuronal plasticity.—Quach, T. T., Massicotte, G., Belin, M. F., Honnorat, J...

Step-reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding-induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate muscle anabolic resistance accompanying SR. We used a unilateral leg model to compare older subjects’ who had undergone SR to a loaded condition of SR plus RT (SR + RT). Thirty older men (70 ± 1 years) underwent 14 days of SR (

The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation.

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.

The G93A transgenic mouse has a mutation in copper/zinc superoxide dismutase (CuZnSOD) that results in oxidative stress and motor neuron loss. Endurance exercise training is known to increase antioxidant capacity in skeletal muscle. Therefore, we hypothesized that endurance training may extend onset of disease or survival in the G93A mouse. We examined the effects of high-intensity endurance exercise training (45 min/day, 5 times/week, progressive increase from 9 to 22 m/min) on disease onset and survival in G93A mice. Endurance training did not affect clinical onset, although it hastened death in male mice (P < 0.05). Endurance-trained males had a statistically significant decrease in rotarod performance at 112 days (P < 0.05), whereas sedentary males decreased at 119 days (P < 0.05). Endurance-trained and sedentary females decreased at 126 days and 129 days, respectively (P < 0.05). Female mice lived longer than males (P < 0.05), and there was a trend for hastened clinical onset in males (P = 0.062). We conclude that high-intensity endurance exercise training does not affect onset of clinical symptoms in G93A mice but hastens a decrease in motor performance and death following onset of clinical symptoms in male mice only. In light of a recent report describing increased survival following low-intensity endurance training, it appears that training intensity is an important determinant of survival in the G93A mouse.

The bed bug (Cimex lectularius L.) is a common hematophagous pest in the urban environment and is capable of surviving extended periods of starvation. However, the relationship between starvation and metabolism in bed bugs is not well understood. To better understand this relationship, we measured the metabolism of all life stages for900 h after feeding (starvation) using closed-system respirometry. Measurements were made around molting for the immature life stages, which occurs only after a blood meal. In addition, both mated and unmated adults were measured. Starvation and molting had significant effects on the metabolism of the bed bug. Mass-specific metabolic rate (V(O2); mL g(-1) h(-1)) declined in a curvilinear fashion with the period of starvation for adults and with the postmolting period for immature bed bugs (used to standardize all immature life stages). A standard curve was developed to depict the generalized pattern of metabolic decline observed in all life stages that molted. Individual metabolic comparisons among life stages that molted revealed some differences in metabolic rate between unmated males and females. In addition, the mass scaling coefficient was found to decline with starvation time (postmolting time) for all life stages that molted. In most life stages, the ratio of V(CO2) to V(O2) (respiratory exchange ratio) declined over time, indicating a change in metabolic substrate with starvation. Finally, daily percent loss in body mass declined in a pattern similar to that of V(O2). The observed patterns in metabolic decline are evaluated in relation to the life history of bed bugs. In addition, the evolutionary development of these patterns is discussed. The metabolic pattern after feeding was also found to share several similarities with that of other ectothermic species.

Age-related sarcopenia and dynapenia have negative effects on strength and the ability to perform activities of daily living. Resistance training (RT) increases muscle mass and strength in older adults and is an established countermeasure for sarcopenia and dynapenia, and creatine may enhance this effect. We aimed to determine whether the addition of Cr to RT increased gains in muscle mass, strength, and function in older adults over RT alone by conducting a systematic review and meta-analysis.PubMed and Healthstar databases were searched. Randomized, placebo-controlled trials that involved older adults supplemented with Cr and included RT regimens (6 wk) were included. Data were analyzed using fixed or random (if data were heterogeneous) effects meta-analysis using RevMan 5.The meta-analysis comprised 357 older adults (average ± SD Cr: 63.6 ± 5.9 yr, Pl: 64.2 ± 5.4 yr) with 12.6 ± 4.9 wk of RT. Cr + RT increased total body mass (P = 0.004) and fat-free mass (P0.0001) with no effect on fat mass as compared with RT alone. Cr + RT increased chest press (P = 0.004) and leg press (P = 0.02) one-repetition maximum to a greater extent than RT alone, with no difference in the effect on knee extension or biceps curl one-repetition maximum, isokinetic or isometric knee extension peak torque. Cr + RT had a greater effect than RT alone on the 30-s chair stand test (P = 0.03).Retention of muscle mass and strength is integral to healthy aging. The results from this meta-analysis are encouraging in supporting a role for Cr supplementation during RT in healthful aging by enhancing muscle mass gain, strength, and functional performance over RT alone; however, the limited number of studies indicates further work is needed.

A 17-year-old male patient presented to his primary care provider with heart failure symptoms and was transferred to our hospital with the diagnosis of idiopathic cardiomyopathy. His workup identified a large mediastinal mass with right ventricular outflow obstruction, which was resected. The pathology of the mass was a low-grade chondrosarcoma. The patient currently remains disease free at 4 years.

Nontropical rodents may experience large fluctuations in both food availability and energetic demands. The energy required for thermoregulation is high during the winter when energy availability is usually low. Winter conditions can induce a state of energetic stress that elevates circulating glucocorticoid levels and compromises immune function. Exposure to short days enhances immune function; the adaptive function of short-day enhancement of immune function may be to counteract the effects of stress-induced immunocompromise. To examine the role of energy availability in immune function, female deer mice were housed in either long (16:8-h light-dark cycle) or short (8:16-h light-dark cycle) days for 8 wk and then injected with either saline or 2-deoxy-D-glucose (2-DG), a glucose analog that inhibits cellular utilization of glucose and induces energetic stress. Long-day mice injected with 2-DG exhibited elevated corticosterone levels and reduced splenocyte proliferation compared with control mice. Short days buffered the animals against glucoprivation stress. Neither corticosterone levels nor splenocyte proliferation differed between 2-DG injected and control mice housed in short days. These data are consistent with the hypothesis that short days provide a buffer against metabolic stress.

The accumulation of intramyocellular lipids (IMCLs) and mitochondrial dysfunction in skeletal muscle have been associated with insulin resistance in obesity. Endurance training (ET) increases mitochondrial content/activity and IMCL content in young, active men and women. We have previously shown that ET alters the size, number, and physical juxtaposition of IMCLs and mitochondria.The purpose of this study was to determine the effects of obesity and ET on mitochondrial function, IMCL content, and IMCL-mitochondria juxtaposition in sedentary lean and obese women. DESIGN, SETTING, SUBJECTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Obese (n = 11) and lean (n = 12), sedentary women were recruited using local advertisements and underwent 12 weeks of ET in our training facility at McMaster University. Blood and muscle biopsy samples (vastus lateralis) were collected before and after ET to measure IMCL and mitochondrial ultrastructure, mitochondrial oxidative capacity, lipid oxidation capacity, and lipid metabolism by-products.Obese women were insulin resistant (homeostasis model assessment of insulin resistance) compared with lean women. ET did not change body weight but increased mitochondrial oxidative and β-oxidation capacity in both groups. ET mediated reorganization of the muscle architecture, whereby IMCL content in the subsarcolemmal region was reduced with a concomitant increase in intermyofibrillar IMCLs. ET increased the percentage of IMCLs in direct contact with mitochondria and did not alter diacylglycerol and ceramide content in either group.ET mediated positive changes in mitochondrial function and lipid oxidation and induced intracellular IMCL reorganization, which is reflective of greater IMCL turnover capacity in both lean and obese women.

Prairie voles (Microtus ochrogaster) are monogamous rodents that form pair bonds characterized by a preference for a familiar social partner. In male prairie voles, exposure to either the stress of swimming or exogenous injections of corticosterone facilitate the development of a social preference for a female with which the male was paired after injection or swimming. Conversely, adrenalectomy inhibits partner preference formation in males and the behavioral effects of adrenalectomy are reversed by corticosterone replacement. In female prairie voles, swim stress interferes with the development of social preferences and corticosterone treatments inhibit the formation of partner preferences, while adrenalectomized females form preferences more quickly than adrenally intact controls. Because sex differences in both behavior and physiology are typically reduced in monogamous species, we initially predicted that male and female prairie voles would exhibit similar behavioral responses to corticosterone. However, our findings suggest an unanticipated sexual dimorphism in the physiological processes modulating social preferences. This dimorphic involvement of stress hormones in pair bonding provides a proximate mechanism for regulating social organization, while permitting males and females to adapt their reproductive strategies in response to environmental challenges.

The purpose of this report is to record some of the recent accomplishments of the Surgery Interest Group (SIG) at the Uniformed Services University of the Health Sciences, and to provide a framework for others to follow, with the goal of encouraging students to become interested in the exciting field of surgery. We will outline some of the events that our SIG planned and carried out in order to provide a quality experience to its members.

Glucocorticoid levels in animals may respond to and influence the development of social attachments. This hypothesis was tested in prairie voles (Microtus ochrogaster), monogamous rodents that form long-term heterosexual pair bonds. In socially naive female prairie voles, cohabitation with an unfamiliar male resulted in a dramatic decline in serum corticosterone levels. When corticosterone levels were reduced via adrenalectomy, females developed partner preferences after 1 h of cohabitation, while sham-operated and untreated females required 3 h or more of nonsexual cohabitation to establish a partner preference. In adrenalectomized and intact females, exogenous injections of corticosterone, given prior to social exposure, prevented the development of preferences for the cohabitating male. Although corticosterone inhibited the development of partner preferences, it did not interfere with the expression of previously established social preferences. These results suggest that social stimuli can modulate adrenal activity and that adrenal activity, in turn, is capable of influencing the formation of adult social preferences in female prairie voles. The involvement of the adrenal axis in the formation of partner preferences and the subsequent development of pair bonds provides a mechanism through which environmental and social factors may influence social organization in this species.

Background Endocrine therapy is the preferred treatment for hormone-receptor (HR) positive metastatic breast cancer. In premenopausal patients, ovarian function suppression with goserelin in combination with anastrozole yielded promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields high rates of disease stabilisation in postmenopausal women. Therefore, we investigated the feasibility and safety of fulvestrant plus goserelin in premenopausal women with HR-positive metastatic breast cancer. Methods Premenopausal patients with metastatic breast cancer eligible for endocrine treatment received fulvestrant 250 mg and goserelin 3.6 mg every four weeks as first- to fourth-line therapy. Clinical benefit rate (CBR; response rate plus disease stabilisation ⩾6 months) was defined as the primary study end-point. Time to progression (TTP) and overall survival (OS) were estimated using the Kaplan–Meier product limit method. Findings Twenty-six patients received treatment as scheduled. 81% were pre-treated with tamoxifen and 69% had received prior aromatase inhibitors in combination with goserelin. The majority of patients (69%) presented with visceral metastases. Complete response was observed in a single patient, partial response in three and disease stabilisation ⩾6 months in eleven patients, resulting in a CBR of 58%. Median TTP was 6 months (95% confidence interval (CI), 2.4–9.6) and OS 32 months (95% CI, 14.28–49.72), respectively. Interpretation Results suggest that the combination of fulvestrant and goserelin offers promising activity in premenopausal patients and further investigation is warranted.