The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

Sleep disturbances in an arctic population: The Tromsø Study

<p>Abstract</p> <p>Background</p> <p>Prevalence estimates for insomnia range from 10 to 50% in the adult general population. Sleep disturbances cause great impairment in quality of life, which might even rival or exceed the impairment in other chronic medical disorders. The economic implications and use of health-care services related to chronic insomnia represent a clinical concern as well as a pronounced public health problem. Hypnotics are frequently prescribed for insomnia, but alcohol and over-the-counter sleep aids seem to be more widely used by insomniacs than prescription medications. Despite the complex relationship between insomnia and physical and mental health factors, the condition appears to be underrecognized and undertreated by health care providers, probably due to the generally limited knowledge of the causes and natural development of insomnia.</p> <p>Methods/Design</p> <p>The Tromsø Study is an ongoing population-based cohort study with five previous health studies undertaken between 1974 and 2001. This protocol outlines a planned study within the sixth Tromsø Study (Tromsø VI), aiming at; 1) describing sleep patterns in a community-based sample representative of the general population of northern Norway, and 2) examining outcome variables of sleep disturbances against possible explanatory and confounding variables, both within a cross-sectional approach, as well as retrospectively in a longitudinal study – exploring sleep patterns in subjects who have attended two or more of the previous Tromsø studies between 1974 and 2009. First, we plan to perform a simple screening in order to identify those participants with probable sleep disturbances, and secondly to investigate these sleep disturbances further, using an extensive sleep-questionnaire. We will also collect biological explanatory variables, i.e. blood samples, weight, height and blood pressure. We plan to merge data on an individual level from the Tromsø VI Study with data from the Norwegian Prescription Database (NorPD), which is a national registry including data for all prescription drugs issued at Norwegian pharmacies. Participants with sleep disturbances will be compared with pair-matched controls without sleep disturbances.</p> <p>Discussion</p> <p>Despite ongoing research, many challenges remain in the characterization of sleep disturbances and its correlates. Future mapping of the biological dimensions, natural history, as well as the behavioral and drug-related aspects of sleep disturbances in a representative population samples is clearly needed.</p

KINETIC-ANALYSIS OF ZINC-METABOLISM IN HUMANS AFTER SIMULTANEOUS ADMINISTRATION OF ZN-65 AND ZN-70

Zinc kinetics were studied and compared after oral simultaneous administration of two tracers, radioactive (Zn-65) and stable (Zn-70) isotope, to four normal human volunteers. Both tracers and zinc concentration were measured in plasma, red blood cells (RBC), urine, and feces for up to 78 days. Radioactive zinc was also measured by external counting over whole body, liver, and thigh. Data from each individual were analyzed using a compartmental model for zinc metabolism. Values calculated for absorption, fractional zinc excretion in urine, exchange with RBC, and secretion into gut using Zn-70 data did not differ from values calculated using Zn-65 data. Results show that human zinc metabolism can be investigated using stable isotopes as tracers to determine parameters of whole body zinc metabolism, including zinc absorption, excretion, and secretion

Diabetes-induced vascular hypertrophy is accompanied by activation of Na+-H+ exchange and prevented by Na+-H+ exchange inhibition

Vascular disease often involves vessel hypertrophy with underlying cellular hypertrophy or hyperplasia. Experimental diabetes stimulates hypertrophy of the rat mesenteric vasculature, and we investigated the hypothesis that this hypertrophy is associated with activation of Na-H exchange (NHE) activity. We measured the NHE activity in isolated, intact blood vessels from control and streptozotocin-induced diabetic adult rats using concurrent myography and fluorescence spectroscopy. The role of inhibiting NHE activity in preventing the development of the mesenteric hypertrophy in streptozotocin-diabetic rats was investigated by administration of cariporide (100 mg/kg body weight per day in 3 doses by gavage) after induction of diabetes and subsequently determining vessel weight and structure. The weight of the mesenteric vasculature was not increased 1 week after streptozotocin treatment but was significantly increased by an average of 56% at 3 weeks NHE activity in mesenteric arteries showed an enhanced maximal velocity (V(max)) in diabetic vessels at 1 and 3 weeks (0.246±0.006 and 0.238±0.007 versus 0.198±0 007 pH U/min) with no change in the apparent K(m). Moreover, NHE-1 mRNA in mesenteric arterioles at 3 weeks after streptozotocin treatment was increased by >60% (55.8±6.4 versus 91 3±12.3 fg). Administration of cariporide significantly reduced mesenteric vascular weight, the wall/lumen ratio, and mesenteric extracellular matrix accumulation in the diabetic animals. Our study shows that diabetes in vivo correlates with elevated NHE activity and mRNA in the mesenteric vasculature and furthermore that inhibition of this system prevents the hypertrophic response. These data suggest that NHE may be a target for therapeutic modulation of vascular changes in diabetes

Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation

Slow waves are characteristic waveforms that occur during non-rapid eye movement (NREM) sleep that play an integral role in sleep quality and brain plasticity. Benzodiazepines are commonly used medications that alter slow waves, however, their effects may depend on the time of night and measure used to characterize slow waves. Prior investigations have utilized minimal scalp derivations to evaluate the effects of benzodiazepines on slow waves, and thus the topography of changes to slow waves induced by benzodiazepines has yet to be fully elucidated. This study used high-density electroencephalography (hdEEG) to evaluate the effects of oral temazepam on slow wave activity, incidence, and morphology during NREM sleep in 18 healthy adults relative to placebo. Temazepam was associated with significant decreases in slow wave activity and incidence, which were most prominent in the latter portions of the sleep period. However, temazepam was also associated with a decrease in the magnitude of high-amplitude slow waves and their slopes in the first NREM sleep episode, which was most prominent in frontal derivations. These findings suggest that benzodiazepines produce changes in slow waves throughout the night that vary depending on cortical topography and measures used to characterize slow waves. Further research that explores the relationships between benzodiazepine-induced changes to slow waves and the functional effects of these waveforms is indicated

The genome of the obligate intracellular parasite Trachipleistophora hominis : new insights into microsporidian genome dynamics and reductive evolution

The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome architecture in some, but not all, lineages.Publisher PDFPeer reviewe