Promoting More Modest Weight Losses: A Pilot Study

Objective: This pilot study assessed the short‐ and long‐term effects of a modified cognitive behavioral treatment designed to facilitate obese patients’ acceptance of a 5% to 10% reduction in initial weight. Research Methods and Procedures: Participants were 17 women with a mean age of 46.5 ± 9.7 years and BMI of 34.7 ± 2.9 kg/m². They participated in a 40‐week program that included four phases. The first discussed the benefits of modest weight losses and the potential adverse effects of unrealistic expectations. Phase II provided instruction in traditional cognitive behavioral methods of weight control Phase III focused on methods to improve body image and self‐esteem. Phase IV addressed skills for weight maintenance. Changes in weight, self‐esteem, body image, and quality of life were assessed at the end of treatment and 1 year later (week 92). Results: At week 40, participants lost an average of 5.7 ± 5.3% of initial weight, which was associated with significant improvements in body image, self‐esteem, and quality of life. Improvements in psychosocial status were maintained at week 92, although mean weight loss at this time had declined to 2.9 ± 5.6% of initial weight. Increased satisfaction with body weight at week 40 was associated with significantly better maintenance of weight loss at follow‐up (r = ?0.70; p = 0.02). Discussion: Having participants seek only modest initial weight losses does not appear to facilitate weight maintenance. However, increasing patients’ satisfaction with their body weight at the end of treatment may help improve weight maintenance. More research is needed on the relation between satisfaction with initial weight loss and long‐term success.     

Combining Behavioral and Pharmacological Treatments for Obesity

Weight‐loss medications are currently recommended for use only as an adjunct to diet, exercise, and behavior modification. Little, however, is known about the benefits of combining behavioral and pharmacological therapies or about the mechanisms that would make these combined approaches more effective than either used alone. This article reviews the effects of adding pharmacotherapy (i.e., principally sibutramine and orlistat) to a modest program of lifestyle modification. Studies revealed that the addition of medication typically improved short‐ and long‐term weight loss compared with lifestyle modification alone. The best results, however, were obtained when medications were combined with an intensive, group program of lifestyle modification. The two approaches may have additive effects; behavioral treatment seems to help obese individuals control the external (i.e., food‐related) environment, whereas pharmacotherapy may control the internal environment by reducing hunger, cravings, or nutrient absorption. The article examines possible methods of sequencing behavioral and pharmacological therapies and offers suggestions for future research.     

Effects of Endolithic Parasitism on Invasive and Indigenous Mussels in a Variable Physical Environment

Biotic stress may operate in concert with physical environmental conditions to limit or facilitate invasion processes while altering competitive interactions between invaders and native species. Here, we examine how endolithic parasitism of an invasive and an indigenous mussel species acts in synergy with abiotic conditions of the habitat. Our results show that the invasive Mytilus galloprovincialis is more infested than the native Perna perna and this difference is probably due to the greater thickness of the protective outer-layer of the shell of the indigenous species. Higher abrasion due to waves on the open coast could account for dissimilarities in degree of infestation between bays and the more wave-exposed open coast. Also micro-scale variations of light affected the level of endolithic parasitism, which was more intense at non-shaded sites. The higher levels of endolithic parasitism in Mytilus mirrored greater mortality rates attributed to parasitism in this species. Condition index, attachment strength and shell strength of both species were negatively affected by the parasites suggesting an energy trade-off between the need to repair the damaged shell and the other physiological parameters. We suggest that, because it has a lower attachment strength and a thinner shell, the invasiveness of M. galloprovincialis will be limited at sun and wave exposed locations where endolithic activity, shell scouring and risk of dislodgement are high. These results underline the crucial role of physical environment in regulating biotic stress, and how these physical-biological interactions may explain site-to-site variability of competitive balances between invasive and indigenous species.     

Ecological genomics of mutualism decline in nitrogen-fixing bacteria

Anthropogenic changes can influence mutualism evolution; however, the genomic regions underpinning mutualism that are most affected by environmental change are generally unknown, even in well-studied model mutualisms like the interaction between legumes and their nitrogen (N)-fixing rhizobia. Such genomic information can shed light on the agents and targets of selection maintaining cooperation in nature. We recently demonstrated that N-fertilization has caused an evolutionary decline in mutualistic partner quality in the rhizobia that form symbiosis with clover. Here, population genomic analyses of N-fertilized versus control rhizobium populations indicate that evolutionary differentiation at a key symbiosis gene region on the symbiotic plasmid (pSym) contributes to partner quality decline. Moreover, patterns of genetic variation at selected loci were consistent with recent positive selection within N-fertilized environments, suggesting that N-rich environments might select for less beneficial rhizobia. By studying the molecular population genomics of a natural bacterial population within a long-term ecological field experiment, we find that: (i) the N environment is indeed a potent selective force mediating mutualism evolution in this symbiosis, (ii) natural variation in rhizobium partner quality is mediated in part by key symbiosis genes on the symbiotic plasmid, and (iii) differentiation at selected genes occurred in the context of otherwise recombining genomes, resembling eukaryotic models of adaptation.     

Competition between Intramolecular and Intermolecular Interactions in an Amyloid-Forming Protein

Despite much progress in understanding the folding and the aggregation processes of proteins, the rules defining their interplay have yet to be fully defined. This problem is of particular importance since many diseases are initiated by protein unfolding and hence the propensity to aggregate competes with intramolecular collapse and other folding events. Here, we describe the roles of intramolecular and intermolecular interactions in defining the length of the lag time and the apparent rate of elongation of the 100-residue protein human β₂-microglobulin at pH 2.5, commencing from an acid-denatured state that lacks persistent structure but contains significant non-random hydrophobic interactions. Using a combination of site-directed mutagenesis, quantitative kinetic analysis and computational methods, we show that only a single region of about 10 residues in length, determines the rate of fibril formation, despite the fact that other regions exhibit a significant intrinsic propensity for aggregation. We rationalise these results by analysing the effect of incorporating the conformational properties of acid-unfolded β₂-microglobulin and its variants at pH 2.5 as measured by NMR spectroscopy into the Zyggregator aggregation prediction algorithm. These results demonstrate that residual structure in the precursor state modulates the intrinsic propensity of the polypeptide chain to aggregate and that the algorithm developed here allows the key regions for aggregation to be more clearly identified and the rates of their self-association to be predicted. Given the common propensity of unfolded chains to form non-random intramolecular interactions as monomers and to self-assemble subsequently into amyloid fibrils, the approach developed should find widespread utility for the prediction of regions important in amyloid formation and their rates of self-assembly.     

Prevalence of asthma in Melbourne schoolchildren: changes over 26 years.

OBJECTIVES--To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago. DESIGN--A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design. SETTING--Government and non-government schools in the greater Melbourne area, Australia. SUBJECTS--10,981 children. Parents completed questionnaires for 3324 children aged 7, 2899 aged 12, and 2968 aged 15. The overall response rate was 90%. MAIN OUTCOME MEASURES--History of wheeze or asthma in the past 12 months and in lifetime. RESULTS--The prevalences of wheeze in the past 12 months were 23.1%, 21.7%, and 18.6% for 7, 12, and 15 year olds respectively. A history of wheeze was more common in boys than in girls at age 7 (443/1711 v 324/1614) and 12 (418/1767 v 322/1718) but not at age 15. Overall, 78% (1548) of those reporting wheeze also reported a history of asthma and 83% (1611) had used a bronchodilator. The prevalence of a history of asthma among 7 year olds was 46% compared with 19.1% in the 1964 survey, an increase of 141%. CONCLUSIONS--The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years.     

Isolation of Highly Suppressive CD25+FoxP3+ T Regulatory Cells from G-CSF-Mobilized Donors with Retention of Cytotoxic Anti-Viral CTLs: Application for Multi-Functional Immunotherapy Post Stem Cell Transplantation

Previous studies have demonstrated the effective control of cytomegalovirus (CMV) infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T). Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from unrelated donors. This approach may therefore simplify the clinical application of adoptive immunotherapy and broaden the approach for manufacturing multi-functional T cells.