Peer support for physical activity adoption among breast cancer survivors: Do the helped resemble the helpers?

Interventions offering peer mentoring programmes promoting moderate-to-vigorous physical activity (MVPA) have shown improvements in MVPA and well-being from baseline; however, research is limited. The purpose of this study was to compare the physical activity (PA) levels and psychosocial well-being of coaches and participants at baseline and following a 12-week intervention. Breast cancer survivors (<5 years) were recruited and randomised into either exercise (Reach-to-Recovery (RTR) + PA) or control (RTR Control). Participants in both groups were individually assigned one of the 18 available coaches who delivered either the MVPA intervention or the control condition via telephone. PA (7-Day PA Recall), psychosocial well-being, fatigue and mood were assessed at baseline and intervention completion. Seventy-six breast cancer survivors (average age = 55.62 (±9.55)) were randomised. At baseline, all participants showed significantly lower MVPA (p = .001) and well-being (p < .05) as compared to coaches. However, post-intervention showed significant improvement in PA and well-being in RTR + PA, so that they were no longer significantly different from the coaches. Post-intervention, MVPA (p < .01), quality of life (p < .05) and fatigue (p < .05) remained significantly lower in RTR Controls compared to coaches. Future interventions should consider the behavioural patterns not only of the participants, but also of those who deliver the interventions.

Lifetime characteristics of participants and non-participants in a smoking cessation trial: implications for external validity and public health impact.

BACKGROUND: Detailed information about the characteristics of smokers who do and do not participate in smoking cessation treatment is needed to improve efforts to reach, motivate, and treat smokers. PURPOSE: The aim of this study is to explore a broad range of characteristics related to participation in a smoking cessation trial. METHODS: Eligible smokers were recruited from a longitudinal birth cohort. Participants and non-participants were compared on a broad range of sociodemographics, smoking, psychiatric and substance abuse disorders, personality, and prospective measures from early childhood. Eligible smokers were compared to a matched regional subsample of the Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: Few differences were observed, most of which were statistically significant but not clinically meaningful. Compared to non-participants, participants were more likely to be single, have lower income, be more nicotine-dependent, be more motivated to quit, and have higher levels of depressed mood and stress even after covariance of gender, income, and marital status. Sociodemographic differences between participants and the BRFSS sample reflect the skew toward lower socioeconomic status in the original birth cohort. CONCLUSIONS: The encouraging conclusion is that smokers who enroll in cessation trials may not differ much from non-participants. Information about treatment participants can inform the development of recruitment strategies, improve the tailoring of treatment to individual smoker profiles, help to estimate potential selection bias, and improve estimates of population impact.

Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives.

Inhibitors targeting pancreatic alpha-amylase and intestinal alpha-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an alpha-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective alpha-glucosidase inhibitors modeled after salacinol, a naturally occurring alpha-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity.

Synthesis of nitrogen analogues of salacinol and their evaluation as glycosidase inhibitors.

The syntheses of two nitrogen analogues (11 and 12) of the naturally occurring sulfonium ion, salacinol (7) are described. The latter compound is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of a 1,4-dideoxy-1,4-imino-D- or L-arabinitol at the least hindered carbon of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The nitrogen analogues bear a permanent positive charge and serve as mimics of the sulfonium ion. We reasoned that these ammonium derivatives should function in a manner similar to that of known glycosidase inhibitors of the alkaloid class such as castanospermine (4) and deoxynojirimycin (5). Enzyme inhibition assays indicate that salacinol (7) is a weak (K(i) = 1.7 mM) inhibitor of glucoamylase, whereas compounds 11 and 12 inhibit glucoamylase with K(i) values in the range approximately 10-fold higher. The nitrogen analogues 11 and 12 showed no significant inhibitory effect of either barley alpha-amylase (AMY1) or porcine pancreatic alpha-amylase (PPA) at concentrations of 5 mM. In contrast, salacinol (7) inhibited AMY1 and PPA in the micromolar range, with K(i) values of 15 +/- 1 and 10 +/- 2 microM, respectively.

Maintenance of physical activity following an individualized motivationally tailored intervention.

This study examined predictors of exercise maintenance following completion of a physical activity intervention. Sedentary adults recruited through newspaper advertisements were randomly assigned to receive either (a) a motivation-matched intervention with feedback reports that were individually tailored (IT) to psychological variables from social cognitive theory and the Transtheoretical Model via computer expert system, or (b) a standard, print-based intervention (ST). The intervention phase of the study included mailed assessments and intervention materials at baseline, 1, 3, and 6 months. An assessment-only follow-up was conducted 6 months after the end of the intervention (Month 12). Participants were assessed for current physical activity participation, motivational readiness for physical activity, a number of psychological constructs posited to influence participation in physical activity (e.g., self-efficacy), and current affect. Significantly more participants in the IT condition met or exceeded exercise participation goals at the end of the intervention period and maintained this level of physical activity through the Month 12 follow-up compared to ST participants. Prospective analyses revealed significant differences in several psychological constructs both at program entry (baseline) and the end of the intervention period between individuals who maintained their physical activity participation through Month 12 and those who did not. Results suggest that the maintenance of physical activity following the end of an active intervention program may be influenced by attitudes and behaviors acquired along with increased participation in physical activity, as well as by preexisting characteristics that individuals bring into treatment.

Randomized trial of a "talking computer" to improve adults' eating habits.

PURPOSE: To assess efficacy of an intervention delivered by an interactive, computer-controlled telephone system to improve individuals' diets. DESIGN: Randomized controlled trial. SETTING: Large multispecialty group practice. SUBJECTS: Two hundred ninety-eight adults who were both sedentary and had suboptimal diet quality. INTERVENTION: Weekly communication for 6 months via a totally automated, computer-based voice system. Among intervention group subjects, the system monitored dietary habits and provided educational feedback, advice, and behavioral counseling. Control group subjects received physical activity promotion counseling. MEASURES: Daily intake of fruits, vegetables, red and processed meats, whole fat dairy foods, and whole grain foods estimated from a food frequency questionnaire. RESULTS: Mean age 45.9 years, 72% women, 45% white, and 45% African-American. Among participants who completed diet assessments, compared with the control group, the intervention raised fruit intake a mean of 1.1 servings per day (95% confidence interval [CI] .4, 1.7). On a 0 to 100 global diet quality score combining all five food groups, intervention participants improved their mean score 9 (95% CI 4, 13) points more than in the control group. The intervention also raised dietary fiber intake 4.0 g/d (95% CI .1, 7.8) and decreased saturated fat, as a proportion of energy intake, by 1.7% (95% CI -2.7, -.7). CONCLUSIONS: This computer-based telecommunications dietary behavior intervention helped improve participants' overall diet.

A new class of glycosidase inhibitor: synthesis of salacinol and its stereoisomers.

Salacinol (4) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheses of salacinol (4), the enantiomer of salacinol (5), and a diastereomer (7) are described. The synthetic strategy relies on the selective nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D- or L-arabinitol at C-1 of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The work serves to resolve the ambiguity about the exact structure of salacinol and establishes conclusively the structure of the natural product.

Physician-based activity counseling: intervention effects on mediators of motivational readiness for physical activity.

In theory-based interventions for behavior change, there is a need to examine the effects of interventions on the underlying theoretical constructs and the mediating role of such constructs. These two questions are addressed in the Physically Active for Life study, a randomized trial of physician-based exercise counseling for older adults. Three hundred fifty-five patients participated (intervention n = 181, control n = 174; mean age = 65.6 years). The underlying theories used were the Transtheoretical Model, Social Cognitive Theory and the constructs of decisional balance (benefits and barriers), self-efficacy, and behavioral and cognitive processes of change. Motivational readiness for physical activity and related constructs were assessed at baseline, 6 weeks, and 8 months. Linear or logistic mixed effects models were used to examine intervention effects on the constructs, and logistic mixed effects models were used for mediator analyses. At 6 weeks, the intervention had significant effects on decisional balance, self-efficacy, and behavioral processes, but these effects were not maintained at 8 months. At 6 weeks, only decisional balance and behavioral processes were identified as mediators of motivational readiness outcomes. Results suggest that interventions of greater intensity and duration may be needed for sustained changes in mediators and motivational readiness for physical activity among older adults.

Relationships of physical activity with dietary behaviors among adults.

BACKGROUND: Physical activity and diet are important influences on health, but few data are available about the relationship between these two factors. The purpose of this study was to examine relationships between physical activity and dietary quality and to identify determinants of the combination of sedentary behavior and suboptimal diet. METHODS: The design of this study was cross-sectional. The setting was a large managed-care organization and the participants were 1,322 racially diverse men and women ages 25-91 years. We categorized subjects' physical activity into vigorous, moderate, and sedentary based on answers to two validated interviewer-administered questions about intensity and duration of specified activities. Dietary assessment was by means of a validated short food frequency questionnaire. We defined suboptimal diet as consuming unhealthful quantities of at least two of the following five food groups: fruits, vegetables, whole grain foods, whole-fat dairy foods, and red and processed meats. RESULTS: Seven hundred fifty-four (57%) subjects were sedentary and 617 (47%) consumed a suboptimal diet. Using multiple linear regression, we found that sedentary individuals consumed smaller amounts of foods and nutrients considered to be healthful, such as fruits and vegetables, fiber, calcium, folate, and vitamins A, C, and E, than more active participants. For nutrients considered to be harmful, such as saturated fat, trans fat, and dietary cholesterol, the association with physical activity was inverse. In multiple logistic regression analyses, the strongest sociodemographic correlates of the joint presence of inactivity and poor diet were less education [odds ratio for 1-year decrease 1.14 (95% confidence interval 1.06, 1.22)], nonwhite race [1.48 (1.05, 2.07)], and nonmarried status [1.49 (1.06, 2.10)]. CONCLUSIONS: Physical activity and diet quality are correlated behaviors. Suboptimal diet and sedentary behavior tend to cluster in individuals who are less educated, not married, and of nonwhite race. Programs that target diet and activity together, informed by their joint determinants, may attain enhanced outcomes.

Conformational preferences in glycosylamines. implications for the exo-anomeric effect.

The conformational preferences about the C-N bond in N-(4-methoxyphenyl)-2,3,4,6-tetra-O-acetyl-alpha (1) and beta-D-glucopyranosylamine (2), in the solid state and in solution, have been investigated. The crystal structure of the axially substituted alpha anomer (1) indicates a conformational preference about the C-1-N bond in which nN-->sigma*C-O exo-anomeric interactions may be expressed, although this conformational preference is not displayed in solution. The solution conformation relieves steric interactions that result from expression of the exo-anomeric effect in the solid-state conformation. The conformational preference in the equatorially substituted beta anomer (2) both in solution and in the solid state is similar and permits expression of nN-->sigma*C-O exo-anomeric interactions. The structural data for 1 and 2 indicate significant differences in O-5-C-1-N-1 bond angles but insignificant differences in each of the O-5-C-1 or C-1-N-1 bond lengths. The J(C-1-H-1 coupling constants in 1 and 2 indicate a greater coupling constant for the alpha anomer that is consistent with a dominant nO-->sigma*C-H orbital interaction in the beta anomer that weakens the C-1-H-1 bond.

Synthesis of thio-linked disaccharides by 1-->2 intramolecular thioglycosyl migration: oxacarbenium versus episulfonium ion intermediates.

The conversion of 1,1'-thio-linked glucopyranosyl alpha-D-mannopyranosides to 1,2-thio-linked methyl sophorosides or methyl kojibiosides is described. The method involves the 1-->2-migration of the thioglucopyranosyl portion of the nonreducing disaccharide with inversion of configuration at C-2 of the mannopyranose ring and concomitant formation of the methyl glucopyranoside. The thioglucosyl migration does not occur when electron-withdrawing benzoate protecting groups are present. The rearrangement occurs with retention of configuration in the migrating thioglucoside but the methyl glycoside is formed as a mixture of alpha- and beta-isomers. This is attributed to a mechanism involving an oxacarbenium-ion intermediate rather than an episulfonium-ion intermediate. The relevance of this work to recent theoretical predictions concerning the relative stability of such intermediates is discussed.

Health behavior changes after a cancer diagnosis: what do we know and where do we go from here?

Survival rates for certain types of cancer have improved over the past few decades. Changing unhealthy behaviors such as smoking, poor diet, and sedentary life-style among individuals who have been diagnosed with cancer may help to reduce cancer treatment sequelae, possibly reduce risk of recurrence for specific types of cancer, and reduce risk for other common diseases such as cardiovascular disease, obesity, and hypertension. This article reports the prevalence of each of these behaviors among those diagnosed with cancer and reviews interventions that have targeted these risk behaviors. There is considerable variation in the type of research questions asked, the methodologic quality of the research, sample sizes, and the outcomes observed across studies focusing on changing the three health risk behaviors. In the final section, we provide guidelines for researchers in developing health behavior interventions for individuals diagnosed with cancer and highlight challenges that should be addressed.

Novel 4-thiogalactofuranosyl-containing disaccharides with nitrogen in the interglycosidic linkage.

The syntheses of three novel disaccharides containing a 4-thiogalactofuranosyl residue as the non-reducing unit and a nitrogen in the interglycosidic linkage are described. Acid-catalyzed condensation reactions of 4-thio-alpha/beta-D-galactofuranose with either methyl 3-amino-3-deoxy-alpha-D-mannopyranoside, methyl 2-amino-2-deoxy-alpha-D-mannopyranoside, or methyl 2-acetamido-6-amino-2,6-dideoxy-beta-D-glucopyranoside gave methyl 3-amino-3-deoxy-3-N-(4-thio-alpha/beta-D-galactofuranosyl)-alpha-D-manno pyranoside, methyl 2-amino-2-deoxy-2-N-(4-thio-alpha/beta-D-galactofuranosyl)-alpha-D-manno pyranoside, or methyl 2-acetamido-6-amino-2,6-dideoxy-6-N-(4-thio-alpha/beta-D-galactofuranosy l)-beta-D-glucopyranoside.

Synthesis of galactofuranosyl-containing oligosaccharides corresponding to the glycosylinositolphospholipid of Trypanosoma cruzi.

The oligosaccharide beta-D-Galf-(1-->3)-alpha-D-Manp-(1-->2)-[beta-D-Galf- (1-->3)]-alpha-D-Manp-(1-->2)-alpha-D-Manp corresponds to the terminal end of the glycosylinositolphospholipid oligosaccharide of the protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. Syntheses of methyl or ethylthio glycosides of the terminal disaccharide, trisaccharide, tetrasaccharide, and pentasaccharide corresponding to this structure are described. These syntheses employ the selective activation of a phenyl 1-selenogalactofuranoside or a phenyl 1-selenomannopyranoside donor over ethyl 1-thioglycoside acceptors with NIS-TfOH.

Bivalency and epitope specificity of a high-affinity IgG3 monoclonal antibody to the Streptococcus group A carbohydrate antigen. Molecular modeling of a Fv fragment.

The binding of Strep 9, a mouse monoclonal antibody (mAb) of the IgG3 subclass directed against the cell-wall polysaccharide of Group A Streptococcus (GAS), has been characterized. The intact antibody and proteolytic fragments of Strep 9 bind differently to GAS: the intact mAb and F(ab)2' have greater affinity for the carbohydrate epitope than the monomeric Fab or F(ab)'. A mode of binding in which Strep 9 binds bivalently to portions of the polysaccharide on adjacent chains on GAS is proposed. A competitive ELISA protocol using a panel of carbohydrate inhibitors shows that the branched trisaccharide, beta-D-GlcpNAc-(1-->3)-[alpha-L-Rhap-(1-->2)]-alpha-L-Rhap, and an extended surface are key components of the epitope recognized by Strep 9. Microcalorimetry measurements with the mAb and two synthetic haptens, a tetrasaccharide and a hexasaccharide, show enthalpy-entropy compensation as seen in other oligosaccharide-protein interactions. Molecular modeling of the antibody variable region by homology modeling techniques indicates a groove-shaped combining site that can readily accommodate extended surfaces. Visual docking of an oligosaccharide corresponding to the cell-wall polysaccharide into the site provides a putative model for the complex, in which a heptasaccharide unit occupies the site and the GlcpNAc residues of two adjacent branched trisaccharide units occupy binding pockets within the groove-shaped binding site.

Complexes of glucoamylase with maltoside heteroanalogues: bound ligand conformations by use of transferred NOE experiments and molecular modeling.

Transferred nuclear Overhauser effect (trNOE) experiments have been performed to investigate the conformations of the competitive inhibitors, methyl 5'-thio-4-N-alpha-maltoside 3a and methyl 5'-thio-4-S-alpha-maltoside 4 when bound to the catalytic subunit of the enzyme glucoamylase. These NMR data suggest that, although each of the free ligands populates two conformational families, both heteroanalogues are bound by the enzyme in conformations in the area of the global energy minimum. These conformations have been used as initial points for docking into the active site of the enzyme taken from a X-ray crystal structure of the related glucoamylase-D-gluco-dihydroacarbose 2 complex. Minimization of the resulting complexes has yielded structures for the bound complexes. Corroboration of the structures is provided by fast T(1)(rho)-relaxation effects for certain ligand protons as a result of close contacts with protons in the enzyme active site. The results auger well for the combined use of transferred NOE spectroscopy and molecular modeling based on X-ray crystal structures of complexes of suitable congeners for the rapid analysis of ligand-receptor interactions.

Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy.

The determination of the bound solution conformation of D-gluco-dihydroacarbose (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by glucoamylase is described. Transferred NOE NMR experiments and line-broadening effects indicate that GAC is bound in a conformation resembling that observed in the crystal structure. This contrasts with the predominant conformation of GAC when free in solution. The NMR results also suggest regions on the carbohydrate that are in close contact with the protein. The determination of the bound solution conformation of GAC by glucoamylase using transferred NOE (trNOE) measurements is a significant achievement given the high affinity constant (Ka = 3 x 10(7) M(-1)) for this receptor-ligand pair. It is striking that the off-rate for complexation is still sufficiently high to permit observation of trNOEs.

Synthesis and glycosidase inhibitory activity of 5-thioglucopyranosylamines. Molecular modeling of complexes with glucoamylase.

The synthesis of a series of 5-thio-D-glucopyranosylarylamines by reaction of 5-thio-D-glucopyranose pentaacetate with the corresponding arylamine and mercuric chloride catalyst is reported. The products were obtained as anomeric mixtures of the tetraacetates which can be separated and crystallized. The tetraacetates were deprotected to give alpha/beta mixtures of the parent compounds which were evaluated as inhibitors of the hydrolysis of maltose by glucoamylase G2 (GA). A transferred NOE NMR experiment with an alpha/beta mixture of 7 in the presence of GA showed that only the alpha isomer is bound by the enzyme. The Ki values, calculated on the basis of specific binding of the alpha isomers, are 0.47 mM for p-methoxy-N-phenyl-5-thio-D-glucopyranosylamine (7), 0.78 mM for N-phenyl-5-thio-D-glucopyranosylamine (8), 0.27 mM for p-nitro-N-phenyl-5-thio-D-glucopyranosylamine (9) and 0.87 mM for p-trifluoromethyl-N-phenyl-5-thio-D-glucopyranosylamine (10), and the K(m) values for the substrates maltose and p-nitrophenyl alpha-D-glucopyranoside are 1.2 and 3.7 mM, respectively. Methyl 4-amino-4-deoxy-4-N-(5'-thio-alpha-D-glucopyranosyl)-alpha-D-glucopyrano side (11) is a competitive inhibitor of GA wild-type (Ki 4 microM) and the active site mutant Trp120-->Phe GA (Ki 0.12 mM). Compounds 7, 8, and 11 are also competitive inhibitors of alpha-glucosidase from brewer's yeast, with Ki values of 1.05 mM, > 10 mM, and 0.5 mM, respectively. Molecular modeling of the inhibitors in the catalytic site of GA was used to probe the ligand-enzyme complementary interactions and to offer insight into the differences in inhibitory potencies of the ligands.