The efficacy of vigorous-intensity exercise as an aid to smoking cessation in adults with elevated anxiety sensitivity: study protocol for a randomized controlled trial

Background: Although cigarette smoking is a leading cause of death and disability in the United States (US), over 40 million adults in the US currently smoke. Quitting smoking is particularly difficult for smokers with certain types of psychological vulnerability. Researchers have frequently called attention to the relation between smoking and anxiety-related states and disorders, and evidence suggests that panic and related anxiety vulnerability factors, specifically anxiety sensitivity (AS or fear of somatic arousal), negatively impact cessation. Accordingly, there is merit to targeting AS among smokers to improve cessation outcome. Aerobic exercise has emerged as a promising aid for smoking cessation for this high-risk (for relapse) group because exercise can effectively reduce AS and other factors predicting smoking relapse (for example, withdrawal, depressed mood, anxiety), and it has shown initial efficacy for smoking cessation. The current manuscript presents the rationale, study design and procedures, and design considerations of the Smoking Termination Enhancement Project (STEP). Methods: STEP is a randomized clinical trial that compares a vigorous-intensity exercise intervention to a health and wellness education intervention as an aid for smoking cessation in adults with elevated AS. One hundred and fifty eligible participants will receive standard treatment (ST) for smoking cessation that includes cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT). In addition, participants will be randomly assigned to either an exercise intervention (ST+EX) or a health and wellness education intervention (ST+CTRL). Participants in both arms will meet 3 times a week for 15 weeks, receiving CBT once a week for the first 7 weeks, and 3 supervised exercise or health and wellness education sessions (depending on randomization) per week for the full 15-week intervention. Participants will be asked to set a quit date for 6 weeks after the baseline visit, and smoking cessation outcomes as well as putative mediator variables will be measured up to 6 months following the quit date. Discussion: The primary objective of STEP is to evaluate whether vigorous-intensity exercise can aid smoking cessation in anxiety vulnerable adults. If effective, the use of vigorous-intensity exercise as a component of smoking cessation interventions would have a significant public health impact. Specifically, in addition to improving smoking cessation treatment outcome, exercise is expected to offer benefits to overall health, which may be particularly important for smokers. The study is also designed to test putative mediators of the intervention effects and therefore has the potential to advance the understanding of exercise-anxiety-smoking relations and guide future research on this topic

Synthesis of Alkaline Earth Diazenides MAEN2 (MAE = Ca, Sr, Ba) by Controlled Thermal Decomposition of Azides under High Pressure

The alkaline earth diazenides MAEN2 with MAE = Ca, Sr and Ba were synthesized by a novel synthetic approach, namely, a controlled decomposition of the corresponding azides in a multianvil press at highpressure/ high-temperature conditions. The crystal structure of hitherto unknown calcium diazenide (space group I4/mmm (no. 139), a = 3.5747(6) Å, c = 5.9844(9) Å, Z = 2, wRp = 0.078) was solved and refined on the basis of powder X-ray diffraction data as well as that of SrN2 and BaN2. Accordingly, CaN2 is isotypic with SrN2 (space group I4/mmm (no. 139), a = 3.8054(2) Å, c = 6.8961(4) Å, Z = 2, wRp = 0.057) and the corresponding alkaline earth acetylenides (MAEC2) crystallizing in a tetragonally distorted NaCl structure type. In accordance with literature data, BaN2 adopts a more distorted structure in space group C2/c (no. 15) with a = 7.1608(4) Å, b = 4.3776(3) Å, c = 7.2188(4) Å, β = 104.9679(33)°, Z = 4 and wRp = 0.049). The N−N bond lengths of 1.202(4) Å in CaN2 (SrN2 1.239(4) Å, BaN2 1.23(2) Å) correspond well with a double-bonded dinitrogen unit confirming a diazenide ion [N2]2−. Temperature-dependent in situ powder X-ray diffractometry of the three alkaline earth diazenides resulted in formation of the corresponding subnitrides MAE2N (MAE = Ca, Sr, Ba) at higher temperatures. FTIR spectroscopy revealed a band at about 1380 cm−1 assigned to the N−N stretching vibration of the diazenide unit. Electronic structure calculations support the metallic character of alkaline earth diazenides

Tissue Transglutaminase Is a Negative Regulator of Monomeric Lacritin Bioactivity

PURPOSE. Molar accounting of bioactive fluids can expose new regulatory mechanisms in the growing proteomic focus on epithelial biology. Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role. Although optimal bioactive levels in cell culture are 1 to 10 nM over a biphasic dose optimum, ELISA suggests a sustained tear lacritin concentration in the midmicromolar range in healthy adults. Here we identify a reconciling mechanism. METHODS. Monoclonal anti-lacritin 1F5 antibody was generated, and applied together with a new anti-C-terminal polyclonal antibody to tear and tissue Western blotting. In vitro tissue transglutaminase (Tgm2) cross-linking was monitored and characterized by mass spectrometry. RESULTS. Blotting for lacritin in human tears or saliva surprisingly detected immunoreactive material with a higher molecular weight and prominence equal or exceeding the~23 to 25 kDa band of monomeric glycosylated lacritin. Exogenous Tgm2 initiated lacritin cross-linking within 1 minute and was complete by 90 minutes-even with as little as 0.1 nM lacritin, and involved the donors lysine 82 and 85 and the acceptor glutamine 106 in the syndecan-1 binding domain. Lacritin spiked into lacritin-depleted tears formed multimers, in keeping with~0.6 lM TGM2 in tears. Cross-linking was absent when Tgm2 was inactive, and cross-linked lacritin, unlike recombinant monomer, bound syndecan-1 poorly. Enhanced TGM2 expression correlates with reduced cell viability, caspase activation, TNF receptor clustering, 7 and mitochondrial dysfunction 8 associated with hyperosmolar stress in dry eye. 14 Could TGM2 in tears regulate ocular surface biology? Lacritin is a 12.3 kDa tear prosecretory mitogen 15 with glutamine and lysine residues suitable for TGM2 catalyzed cross-linking. Lacritin promotes corneal epithelial cell survival (Zimmerman K, et al. IOVS 2012;53:ARVO E-Abstract 4231) and proliferation

Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome

The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response

Challenges and opportunities for improved understanding of regional climate dynamics

Dynamical processes in the atmosphere and ocean are central to determining the large-scale drivers of regional climate change, yet their predictive understanding is poor. Here, we identify three frontline challenges in climate dynamics where significant progress can be made to inform adaptation: response of storms, blocks and jet streams to external forcing; basin-to-basin and tropical–extratropical teleconnections; and the development of non-linear predictive theory. We highlight opportunities and techniques for making immediate progress in these areas, which critically involve the development of high-resolution coupled model simulations, partial coupling or pacemaker experiments, as well as the development and use of dynamical metrics and exploitation of hierarchies of models

Large-scale integration of cancer microarray data identifies a robust common cancer signature

<p>Abstract</p> <p>Background</p> <p>There is a continuing need to develop molecular diagnostic tools which complement histopathologic examination to increase the accuracy of cancer diagnosis. DNA microarrays provide a means for measuring gene expression signatures which can then be used as components of genomic-based diagnostic tests to determine the presence of cancer.</p> <p>Results</p> <p>In this study, we collect and integrate ~ 1500 microarray gene expression profiles from 26 published cancer data sets across 21 major human cancer types. We then apply a statistical method, referred to as the <it>T</it>op-<it>S</it>coring <it>P</it>air of <it>G</it>roups (TSPG) classifier, and a repeated random sampling strategy to the integrated training data sets and identify a common cancer signature consisting of 46 genes. These 46 genes are naturally divided into two distinct groups; those in one group are typically expressed less than those in the other group for cancer tissues. Given a new expression profile, the classifier discriminates cancer from normal tissues by ranking the expression values of the 46 genes in the cancer signature and comparing the average ranks of the two groups. This signature is then validated by applying this decision rule to independent test data.</p> <p>Conclusion</p> <p>By combining the TSPG method and repeated random sampling, a robust common cancer signature has been identified from large-scale microarray data integration. Upon further validation, this signature may be useful as a robust and objective diagnostic test for cancer.</p

Synergistic ecoclimate teleconnections from forest loss in different regions structure global ecological responses

ABSTRACT: Forest loss in hotspots around the world impacts not only local climate where loss occurs, but also influences climate and vegetation in remote parts of the globe through ecoclimate teleconnections. The magnitude and mechanism of remote impacts likely depends on the location and distribution of forest loss hotspots, but the nature of these dependencies has not been investigated. We use global climate model simulations to estimate the distribution of ecologically-relevant climate changes resulting from forest loss in two hotspot regions: western North America (wNA), which is experiencing accelerated dieoff, and the Amazon basin, which is subject to high rates of deforestation. The remote climatic and ecological net effects of simultaneous forest loss in both regions differed from the combined effects of loss from the two regions simulated separately, as evident in three impacted areas. Eastern South American Gross Primary Productivity (GPP) increased due to changes in seasonal rainfall associated with Amazon forest loss and changes in temperature related to wNA forest loss. Eurasia’s GPP declined with wNA forest loss due to cooling temperatures increasing soil ice volume. Southeastern North American productivity increased with simultaneous forest loss, but declined with only wNA forest loss due to changes in VPD. Our results illustrate the need for a new generation of local-to-global scale analyses to identify potential ecoclimate teleconnections, their underlying mechanisms, and most importantly, their synergistic interactions, to predict the responses to increasing forest loss under future land use change and climate change

The roles of static stability and tropical – extratropical interactions in the summer interannual variability of the North Atlantic sector

Summer seasonal forecast skill in the North Atlantic sector is lower than winter skill. To identify potential controls on predictability, the sensitivity of North Atlantic baroclinicity to atmospheric drivers is quantified. Using ERA-INTERIM reanalysis data, North Atlantic storm-track baroclinicity is shown to be less sensitive to meridional temperature-gradient variability in summer. Static stability shapes the sector’s interannual variability by modulating the sensitivity of baroclinicity to variations in meridional temperature gradients and tropopause height and by modifying the baroclinicity itself. High static stability anomalies at upper levels result in more zonal extratropical cyclone tracks and higher eddy kinetic energy over the British Isles in the summertime. These static stability anomalies are not strongly related to the summer NAO; but they are correlated with the suppression of convection over the tropical Atlantic and with a poleward-shifted subtropical jet. These results suggest a non-local driver of North Atlantic variability. Furthermore, they imply that improved representations of convection over the south-eastern part of North America and the tropical Atlantic might improve summer seasonal forecast skill

Inside the guts of wood-eating catfishes: can they digest wood?

To better understand the structure and function of the gastrointestinal (GI) tracts of wood-eating catfishes, the gross morphology, length, and microvilli surface area (MVSA) of the intestines of wild-caught Panaque nocturnus, P. cf. nigrolineatus “Marañon”, and Hypostomus pyrineusi were measured, and contrasted against these same metrics of a closely related detritivore, Pterygoplichthys disjunctivus. All four species had anatomically unspecialized intestines with no kinks, valves, or ceca of any kind. The wood-eating catfishes had body size-corrected intestinal lengths that were 35% shorter than the detritivore. The MVSA of all four species decreased distally in the intestine, indicating that nutrient absorption preferentially takes place in the proximal and mid-intestine, consistent with digestive enzyme activity and luminal carbohydrate profiles for these same species. Wild-caught Pt. disjunctivus, and P. nigrolineatus obtained via the aquarium trade, poorly digested wood cellulose (<33% digestibility) in laboratory feeding trials, lost weight when consuming wood, and passed stained wood through their digestive tracts in less than 4 h. Furthermore, no selective retention of small particles was observed in either species in any region of the gut. Collectively, these results corroborate digestive enzyme activity profiles and gastrointestinal fermentation levels in the fishes’ GI tracts, suggesting that the wood-eating catfishes are not true xylivores such as beavers and termites, but rather, are detritivores like so many other fishes from the family Loricariidae