Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer

<p>Abstract</p> <p>Background</p> <p>The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk^-1of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO_2peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO_2peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO_2peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks).</p> <p>Discussion</p> <p>EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO_2peakand other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy.</p> <p>Trial Registration</p> <p>NCT01186367</p

Fracture-fill calcite as a record of microbial methanogenesis and fluid migration: a case study from the Devonian Antrim Shale, Michigan Basin

The Devonian Antrim Shale is an organic-rich, naturally fractured black shale in the Michigan Basin that serves as both a source and reservoir for natural gas. A well-developed network of major, through-going vertical fractures controls reservoir-scale permeability in the Antrim Shale. Many fractures are open, but some are partially sealed by calcite cements that retain isotopic evidence of widespread microbial methanogenesis. Fracture filling calcite displays an unusually broad spectrum of δ 13 C values (+34 to −41‰ PDB), suggesting that both aerobic and anaerobic bacterial processes were active in the reservoir. Calcites with high δ 13 C values (>+15‰) record cementation of fractures from dissolved inorganic carbon (DIC) generated during bacterial methanogenesis. Calcites with low δ 13 C values (<−32‰) are solely associated with outcrop samples and record methane oxidation during cement precipitation. Fracture-fill calcite with δ 13 C values between −10 and −30‰ can be attributed to variable organic matter oxidation pathways, methane oxidation, and carbonate rock buffering. Identification of 13 C-rich calcite provides unambiguous evidence of biogenic methane generation and may be used to identify gas deposits in other sedimentary basins. It is likely that repeated glacial advances and retreats exposed the Antrim Shale at the basin margin, enhanced meteoric recharge into the shallow part of the fractured reservoir, and initiated multiple episodes of bacterial methanogenesis and methanotrophic activity that were recorded in fracture-fill cements. The δ 18 O values in both formation waters and calcite cements increase with depth in the basin (−12 to −4‰ SMOW, and +21 to +27‰ PDB, respectively). Most fracture-fill cements from outcrop samples have δ 13 C values between −41 and −15‰ PDB. In contrast, most cement in cores have δ 13 C values between +15 and +34‰ PDB. Radiocarbon and 230 Th dating of fracture-fill calcite indicates that the calcite formed between 33 and 390 ka, well within the Pleistocene Epoch.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75720/1/j.1468-8123.2002.00036.x.pd

A survey of canine tick-borne diseases in India

Background: There are few published reports on canine Babesia, Ehrlichia, Anaplasma, Hepatozoon and haemotropic Mycoplasma infections in India and most describe clinical disease in individual dogs, diagnosed by morphological observation of the microorganisms in stained blood smears. This study investigated the occurrence and distribution of canine tick-borne disease (TBD) pathogens using a combination of conventional and molecular diagnostic techniques in four cities in India. Results: On microscopy examination, only Hepatozoon gamonts were observed in twelve out of 525 (2.3%; 95% CI: 1.2, 4) blood smears. Using polymerase chain reaction (PCR), a total of 261 from 525 dogs (49.7%; 95% CI: 45.4, 54.1) in this study were infected with one or more canine tick-borne pathogen. Hepatozoon canis (30%; 95% CI: 26.0, 34.0) was the most common TBD pathogen found infecting dogs in India followed by Ehrlichia canis (20.6%; 95% CI: 17.2, 24.3), Mycoplasma haemocanis (12.2%; 95% CI: 9.5, 15.3), Anaplasma platys (6.5%; 95% CI: 4.5, 8.9), Babesia vogeli (5.5%, 95% CI: 3.7, 7.8) and Babesia gibsoni (0.2%, 95% CI: 0.01, 1.06). Concurrent infection with more than one TBD pathogen occurred in 39% of cases. Potential tick vectors, Rhipicephalus (most commonly) and/or Haemaphysalis ticks were found on 278 (53%) of dogs examined. Conclusions: At least 6 species of canine tick-borne pathogens are present in India. Hepatozoon canis was the most common pathogen and ticks belonging to the genus Rhipicephalus were encountered most frequently. Polymerase chain reaction was more sensitive in detecting circulating pathogens compared with peripheral blood smear examination. As co-infections with canine TBD pathogens were common, Indian veterinary practitioners should be cognisant that the discovery of one such pathogen raises the potential for multiple infections which may warrant different clinical management strategies

Research cardiac magnetic resonance imaging in end stage renal disease - incidence, significance and implications of unexpected incidental findings

Objectives: Left ventricular mass (LVM) at cardiac magnetic resonance imaging (CMR) is a frequent end point in clinical trials in nephrology. Trial participants with end stage renal disease (ESRD) may have a greater frequency of incidental findings (IF). We retrospectively investigated prevalence of IF in previous research CMR and reviewed their subsequent impact on participants. Methods: Between 2002 and 2006, 161 ESRD patients underwent CMR in a transplant assessment study. Images were used to assess LV mass and function. In the current study a radiologist reviewed the scans for IF. Review of patient records determined the subsequent clinical significance of IF. Results: There were 150 IF in 95 study participants. Eighty-four (56 %) were new diagnoses. One hundred and two were non-cardiac. Fifteen were suspicious of malignancy. There was a clinically significant IF for 14.9 % of the participants. In six cases earlier identification of an IF may have improved quality of life or survival. Conclusions: Without radiology support clinically important IF may be missed on CMR. Patients undergoing CMR in trials should be counselled about the frequency and implications of IF. Patients with ESRD have a higher prevalence of IF than reported in other populations. Nephrology studies require mechanisms for radiologist reporting and strategies for dealing with IF

Temporal Dissociation between Myeloperoxidase (MPO)-Modified LDL and MPO Elevations during Chronic Sleep Restriction and Recovery in Healthy Young Men

OBJECTIVES: Many studies have evaluated the ways in which sleep disturbances may influence inflammation and the possible links of this effect to cardiovascular risk. Our objective was to investigate the effects of chronic sleep restriction and recovery on several blood cardiovascular biomarkers. METHODS AND RESULTS: Nine healthy male non-smokers, aged 22-29 years, were admitted to the Sleep Laboratory for 11 days and nights under continuous electroencephalogram polysomnography. The study consisted of three baseline nights of 8 hours sleep (from 11 pm to 7 am), five sleep-restricted nights, during which sleep was allowed only between 1 am and 6 am, and three recovery nights of 8 hours sleep (11 pm to 7 am). Myeloperoxidase-modified low-density lipoprotein levels increased during the sleep-restricted period indicating an oxidative stress. A significant increase in the quantity of slow-wave sleep was measured during the first recovery night. After this first recovery night, insulin-like growth factor-1 levels increased and myeloperoxidase concentration peaked. CONCLUSIONS: We observed for the first time that sleep restriction and the recovery process are associated with differential changes in blood biomarkers of cardiovascular disease

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Protist-Type Lysozymes of the Nematode Caenorhabditis elegans Contribute to Resistance against Pathogenic Bacillus thuringiensis

Pathogens represent a universal threat to other living organisms. Most organisms express antimicrobial proteins and peptides, such as lysozymes, as a protection against these challenges. The nematode Caenorhabditis elegans harbours 15 phylogenetically diverse lysozyme genes, belonging to two distinct types, the protist- or Entamoeba-type (lys genes) and the invertebrate-type (ilys genes) lysozymes. In the present study we characterized the role of several protist-type lysozyme genes in defence against a nematocidal strain of the Gram-positive bacterium Bacillus thuringiensis. Based on microarray and subsequent qRT-PCR gene expression analysis, we identified protist-type lysozyme genes as one of the differentially transcribed gene classes after infection. A functional genetic analysis was performed for three of these genes, each belonging to a distinct evolutionary lineage within the protist-type lysozymes (lys-2, lys-5, and lys-7). Their knock-out led to decreased pathogen resistance in all three cases, while an increase in resistance was observed when two out of three tested genes were overexpressed in transgenic lines (lys-5, lys-7, but not lys-2). We conclude that the lysozyme genes lys-5, lys-7, and possibly lys-2 contribute to resistance against B. thuringiensis, thus highlighting the particular role of lysozymes in the nematode's defence against pathogens

Discovery of the inhibitory effect of a phosphatidylinositol derivative on P-glycoprotein by virtual screening followed by <i>in vitro</i> cellular studies

P-glycoprotein is capable of effluxing a broad range of cytosolic and membrane penetrating xenobiotic substrates, thus leading to multi-drug resistance and posing a threat for the therapeutic treatment of several diseases, including cancer and central nervous disorders. Herein, a virtual screening campaign followed by experimental validation in Caco-2, MDKCII, and MDKCII mdr1 transfected cell lines has been conducted for the identification of novel phospholipids with P-gp transportation inhibitory activity. Phosphatidylinositol-(1,2-dioctanoyl)-sodium salt (8∶0 PI) was found to significantly inhibit transmembrane P-gp transportation in vitro in a reproducible-, cell line-, and substrate-independent manner. Further tests are needed to determine whether this and other phosphatidylinositols could be co-administered with oral drugs to successfully increase their bioavailability. Moreover, as phosphatidylinositols and phosphoinositides are present in the human diet and are known to play an important role in signal transduction and cell motility, our finding could be of substantial interest for nutrition science as well

Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions

Background: Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions. Methods: A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, child’s educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months. Results: A higher child’s education level was associated with better memory (p = 0.03), attention (p = 0.005) and spatial learning scores over the 24 months (p = 0.05); higher nutrition scores predicted better visual spatial processing (p = 0.002) and spatial learning scores (p = 0.008); and a higher home environment score predicted a better memory score (p = 0.03). Conclusion: Cognition in Ugandan children is predicted by child’s education, nutritional status and the home environment