Health-related motivational and behavioral processes associated with DNA methylation of the TNF gene

Objective: Epigenetics has been described as one of the most exciting areas of contemporary biology, and research has begun to explore whether epigenetic modifications are influenced by psychological processes. The present research explored the associations of health-related motivation and behavior with the DNA methylation of tumor necrosis factor (TNF) gene. Method: Participants (N = 88) completed questionnaires examining engagement with health-related behavior (i.e., physical activity, diet, and smoking) and health-related motivation from the perspective of self-determination theory. They also provided a capillary blood sample for DNA extraction and analysis of four CpG sites via bisulfite conversion within Exon 1 of TNF. Results: Health-related autonomous motivation was weakly but positively associated with TNF methylation (β = .18, ρ = .08). Indirect effects were identified in a subsequent step; autonomous motivation was positively associated with fruit consumption (β = .29, ρ = .004), negatively associated with smoking (β = .22, ρ = .03), but not associated with physical activity (β = .10, ρ = .34). Moreover, TNF methylation was positively associated with lifetime physical activity (β = .18, ρ = .08) and negatively associated with smoking (β = .23, ρ = .03). Direct effects of autonomous motivation on DNA methylation did not persist when these indirect effects were included (β = .09, ρ = .43). Conclusions: Results support the idea that autonomous motivation is associated with DNA methylation, albeit indirectly through tobacco consumption

Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study

BACKGROUND: Spices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an experimental study was conducted in normal male mice. METHODS: The extracts (50% ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate). RESULTS: The extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity. CONCLUSION: The extracts (50% ethanolic) of nutmeg and clove enhanced the sexual behaviour of male mice

Benefit from preoperative radiotherapy in rectal cancer treatment: disease-free patients' and oncologists' preferences

Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer patients prefer PRT followed by surgery to surgery alone, and how oncologists and patients value various treatment outcomes. Sixty-six disease-free patients and 60 oncologists (surgical, radiation, medical) were interviewed. Minimally desired benefit from PRT (local control) was assessed using the Treatment Tradeoff Method. Importance of survival, local control, faecal incontinence, and sexual dysfunction in determining treatment outcome preferences was assessed using Adaptive Conjoint Analysis. The range of required benefit from PRT varied widely within participant groups. Seventeen percent of patients would choose PRT at a 0% benefit; 11% would not choose PRT for the maximum benefit of 11%. Mean minimally desired benefit excluding these two groups was 4%. For oncologists, the required benefit was 5%. Also, how strongly participants valued treatment outcomes varied widely within groups. Of the four outcomes, participants considered incontinence most often as most important. Relative treatment outcome importance differed between specialties. Patients considered sexual functioning more important than oncologists. Large differences in treatment preferences exist between individual patients and oncologists. Oncologists should adequately inform their patients about the risks and benefits of PRT, and elicit patient preferences regarding treatment outcomes

Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4+CD25+Foxp3+ regulatory T cells in COPD

<p>Abstract</p> <p>Background</p> <p>Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4⁺CD25⁺Foxp3⁺regulatory T cells (Foxp3⁺Tregs) after SFC therapy.</p> <p>Methods</p> <p>Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3⁺Tregs in the total CD4⁺T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3⁺Tregs was analyzed by statistical analysis.</p> <p>Results</p> <p>After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3⁺Tregs in the total CD4⁺T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3⁺Tregs in CD4⁺T cells.</p> <p>Conclusion</p> <p>SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3⁺Tregs in COPD.</p> <p>Trial registration</p> <p>This study was registered with <url>http://www.chictr.org</url> (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270</p

A randomized, double-blind, placebo-controlled trial to assess the efficacy of topiramate in the treatment of post-traumatic stress disorder

<p>Abstract</p> <p>Background</p> <p>Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD.</p> <p>Methods and design</p> <p>Seventy-two adult outpatients with DSM-IV-diagnosed PTSD will be recruited from the violence program of Federal University of São Paulo Hospital (UNIFESP). After informed consent, screening, and a one week period of wash out, subjects will be randomized to either placebo or topiramate for 12 weeks. The primary efficacy endpoint will be the change in the Clinician-administered PTSD scale (CAPS) total score from baseline to the final visit at 12 weeks.</p> <p>Discussion</p> <p>The development of treatments for PTSD is challenging due to the complexity of the symptoms and psychiatric comorbidities. The selective serotonin reuptake inhibitors (SSRIs) are the mainstream treatment for PTSD, but many patients do not have a satisfactory response to antidepressants. Although there are limited clinical studies available to assess the efficacy of topiramate for PTSD, the findings of prior trials suggest this anticonvulsant may be promising in the management of these patients.</p> <p>Trial Registration</p> <p>NCT 00725920</p

Palliative chemotherapy or best supportive care? A prospective study explaining patients' treatment preference and choice

Item does not contain fulltextIn palliative cancer treatment, the choice between palliative chemotherapy and best supportive care may be difficult. In the decision-making process, giving information as well as patients' values and preferences become important issues. Patients, however, may have a treatment preference before they even meet their medical oncologist. An insight into the patient's decision-making process can support clinicians having to inform their patients. Patients (n=207) with metastatic cancer, aged 18 years or older, able to speak Dutch, for whom palliative chemotherapy was a treatment option, were eligible for the study. We assessed the following before they consulted their medical oncologist: (1) socio-demographic characteristics, (2) disease-related variables, (3) quality-of-life indices, (4) attitudes and (5) preferences for treatment, information and participation in decision-making. The actual treatment decision, assessed after it had been made, was the main study outcome. Of 207 eligible patients, 140 patients (68%) participated in the study. At baseline, 68% preferred to undergo chemotherapy rather than wait watchfully. Eventually, 78% chose chemotherapy. Treatment preference (odds ratio (OR)=10.3, confidence interval (CI) 2.8-38.0) and a deferring style of decision-making (OR=4.9, CI 1.4-17.2) best predicted the actual treatment choice. Treatment preference (total explained variance=38.2%) was predicted, in turn, by patients' striving for length of life (29.5%), less striving for quality of life (6.1%) and experienced control over the cause of disease (2.6%). Patients' actual treatment choice was most strongly predicted by their preconsultation treatment preference. Since treatment preference is positively explained by striving for length of life, and negatively by striving for quality of life, it is questionable whether the purpose of palliative treatment is made clear. This, paradoxically, emphasises the need for further attention to the process of information giving and shared decision-making

Improving topological cluster reconstruction using calorimeter cell timing in ATLAS

Clusters of topologically connected calorimeter cells around cells with large absolute signal-to-noise ratio (topo-clusters) are the basis for calorimeter signal reconstruction in the ATLAS experiment. Topological cell clustering has proven performant in LHC Runs 1 and 2. It is, however, susceptible to out-of-time pile-up of signals from soft collisions outside the 25 ns proton-bunch-crossing window associated with the event’s hard collision. To reduce this effect, a calorimeter-cell timing criterion was added to the signal-to-noise ratio requirement in the clustering algorithm. Multiple versions of this criterion were tested by reconstructing hadronic signals in simulated events and Run 2 ATLAS data. The preferred version is found to reduce the out-of-time pile-up jet multiplicity by ∼50% for jet pT ∼ 20 GeV and by ∼80% for jet pT 50 GeV, while not disrupting the reconstruction of hadronic signals of interest, and improving the jet energy resolution by up to 5% for 20 < pT < 30 GeV. Pile-up is also suppressed for other physics objects based on topo-clusters (electrons, photons, τ -leptons), reducing the overall event size on disk by about 6% in early Run 3 pileup conditions. Offline reconstruction for Run 3 includes the timing requirement

Software Performance of the ATLAS Track Reconstruction for LHC Run 3

Charged particle reconstruction in the presence of many simultaneous proton–proton (pp) collisions in the LHC is a challenging task for the ATLAS experiment’s reconstruction software due to the combinatorial complexity. This paper describes the major changes made to adapt the software to reconstruct high-activity collisions with an average of 50 or more simultaneous pp interactions per bunch crossing (pileup) promptly using the available computing resources. The performance of the key components of the track reconstruction chain and its dependence on pile-up are evaluated, and the improvement achieved compared to the previous software version is quantified. For events with an average of 60 pp collisions per bunch crossing, the updated track reconstruction is twice as fast as the previous version, without significant reduction in reconstruction efficiency and while reducing the rate of combinatorial fake tracks by more than a factor two

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √ s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Performance and calibration of quark/gluon-jet taggers using 140 fb⁻¹ of pp collisions at √s=13 TeV with the ATLAS detector

The identification of jets originating from quarks and gluons, often referred to as quark/gluon tagging, plays an important role in various analyses performed at the Large Hadron Collider, as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced background. This paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration, using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb-1 collected by the ATLAS experiment. Two taggers with high performances in rejecting jets from gluon over jets from quarks are studied: one tagger is based on requirements on the number of inner-detector tracks associated with the jet, and the other combines several jet substructure observables using a boosted decision tree. A method is established to determine the quark/gluon fraction in data, by using quark/gluon-enriched subsamples defined by the jet pseudorapidity. Differences in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points