Having children with multiple partners is associated with reduced risk of malignant melanoma: an observation seeking a plausible explanation

Anne V Olesen1,2,3, Erik T Parner4, Preben B Mortensen5, Cecilia H Ramlau-Hansen6, Jørn Olsen71Institute of Public Health, Department of Epidemiology, University of Aarhus; 2Unit for Psychiatric Research, Aalborg Psychiatric Hospital; 3Department of Clinical Epidemiology, Aarhus University Hospital; 4Institute of Public Health, Department of Biostatistics; 5National Centre for Register-based Research; 6Department of Occupational Medicine, Aarhus University Hospital, Denmark; 7Department of Epidemiology, School of Public Health, University of California, Los Angeles, USAObjective: We examined the association between the number of partners that mothers and fathers have children with and occurrence of cutaneous malignant melanoma (CMM).Methods: We conducted a complete registry-based follow-up of all Danish mothers born after 1935 from the birth of their second child until CMM, death, emigration, or end of study in 2002. We conducted a similar follow-up of the corresponding fathers. Incidence rate ratios (IRR) and confidence intervals (CI) were estimated by Poisson regression.Results: This study corroborates that women having children with three or more men are half as likely to have CMM as women who have children with one man: incidence rate ratio (IRR) = 0.51, 95% CI: 0.29, 0.91; having children by two fathers reduces risk among women by 20%: IRR = 0.80, 95% CI: 0.70, 0.91. Fathers with multiple partners tend to face a similar risk reduction.Conclusion: The similar patterns of mothers and fathers challenge us to consider and propose likely mechanisms common to both sexes. The patterns of reduced risk have now been reported in two large independent complete population-based studies in Sweden and Denmark.Keywords: malignant melanoma, epidemiology, children with multiple partner

Momentum Distributions of Particles from Three--Body Halo Fragmentation: Final State Interactions

Momentum distributions of particles from nuclear break-up of fast three-body halos are calculated consistently, and applied to $^{11}$Li. The same two-body interactions between the three particles are used to calculate the ground state structure and the final state of the reaction processes. We reproduce the available momentum distributions from $^{11}$Li fragmentation, together with the size and energy of $^{11}$Li, with a neutron-core relative state containing a $p$-state admixture of 20\%-30\%. The available fragmentation data strongly suggest an $s$-state in $^{10}$Li at about 50 keV, and indicate a $p$-state around 500 keV.Comment: 11 pages (RevTeX), 3 Postscript figures (uuencoded postscript file attached at the end of the LaTeX file). To be published in Phys. Rev.

Coulomb-nuclear interference in the breakup of 11^{11}Be

Within a theory of breakup reactions formulated in the framework of the post form distorted wave Born approximation, we calculate contributions of the pure Coulomb and the pure nuclear breakup as well as those of their interference terms to a variety of cross sections in breakup reactions of the one-neutron halo nucleus $^{11}$Be on a number of target nuclei. In contrast to the assumption often made, the Coulomb-nuclear interference terms are found to be non-negligible in case of exclusive cross sections of the fragments emitted in this reaction on medium mass and heavy target nuclei. The consideration of the nuclear breakup leads to a better description of such data.Comment: 9 pages, latex, 2 figures, to be published in Phys. Rev. C (Rapid Communication

Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition

BACKGROUND: The tumor response to preoperative radiotherapy of locally advanced rectal cancer varies greatly, warranting the use of experimental models to assay the efficacy of molecular targeting agents in rectal cancer radiosensitization. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby remodeling of chromatin structure, may override cell cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell death. METHODS: Human colorectal carcinoma cell lines were exposed to ionizing radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as well as clonogenicity, were analyzed. RESULTS: In addition to G(2)/M phase arrest following irradiation, the cell lines displayed cell cycle responses typical for either intact or defective p53 function (the presence or absence, respectively, of radiation-induced expression of the cell cycle inhibitor p21 and subsequent accumulation of G(1 )phase cells). In contrast, histone acetylation was associated with complete depletion of the G(1 )population of cells with functional p53 but accumulation of both G(1 )and G(2)/M populations of cells with defective p53. The cellular phenotypes upon HDAC inhibition were consistent with the observed repression of Polo-like kinase-1, a regulatory G(2)/M phase kinase. Following pre-treatment with HDAC inhibitors currently undergoing clinical investigation, the inhibitory effect of ionizing radiation on clonogenicity was significantly amplified. CONCLUSION: In these experimental models, HDAC inhibition sensitized the tumor cells to ionizing radiation, which is in accordance with the concept of increased probability of tumor cell death when chromatin structure is modified

Dynamical description of the breakup of one-neutron halo nuclei 11Be and 19C

We investigate the breakup of the one-neutron halo nuclei 11Be and 19C within a dynamical model of the continuum excitation of the projectile. The time evolution of the projectile in coordinate space is described by solving the three-dimensional time dependent Schroedinger equation, treating the projectile-target (both Coulomb and nuclear) interaction as a time dependent external perturbation. The pure Coulomb breakup dominates the relative energy spectra of the fragments in the peak region, while the nuclear breakup is important at higher relative energies. The coherent sum of the two contributions provides a good overall description of the experimental spectra. Cross sections of the first order perturbation theory are derived as a limit of our dynamical model. The dynamical effects are found to be of the order of 10-15% for the beam energies in the range of 60 - 80 MeV/nucleon. A comparison of our results with those of a post form distorted wave Born approximation shows that the magnitudes of the higher order effects are dependent on the theoretical model.Comment: 15 pages, ReVTeX, 5 figures, typos corrected, accepted for publication in Physical Review

Supplement with whey protein hydrolysate in contrast to carbohydrate supports mitochondrial adaptations in trained runners

Background: Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified. The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners. Methods: Twenty-four trained runners (VO2max 60.7 ± 3.7 ml O2 kg− 1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3 g kg− 1) before and protein-carbohydrate beverage (0.3 g protein kg− 1 and 1 g carbohydrate kg− 1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6 K time trial (6 K TT) and a VO2max test pre, midway (only 6 K TT) and post intervention. Results: Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p < 0.05), with several other mitochondrial proteins (Succinate dehydrogenase (SDHA), Cytochrome C oxidase (COX-IV), Voltage-dependent anion channel (VDAC), Heat shock protein 60 (HSP60), and Prohibitin (PHB1)) following a similar, but non-significant pattern (p = 0.07–0.14). β-hydroxyacyl-CoA dehydrogenase (HAD) activity was significantly lower after training in the CHO group (p < 0.01), but not in the PRO-CHO group (p = 0.24). VO2max and 6 K TT was significantly improved after training with no significant difference between groups. Conclusion: Intake of whey PRO hydrolysate before and whey PRO hydrolysate plus CHO after each exercise session during a six-week endurance training period may augment training effects on specific mitochondrial proteins compared to intake of iso-caloric CHO but does not alter VO2max or 6 K TT performance

Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control.

BACKGROUND Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA). OBJECTIVE To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA. METHODS We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n = 140; severe, n = 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables. RESULTS The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity. CONCLUSIONS Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity