SummaryIn the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared by day 4, mutation was not observed in germinal center B cells until day 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated until day 14. During this period, strong phenotypic selection on the mutant B lymphocytes was inferred from progressively biased distributions of mutations within the Ig variable region, the loss of crippling mutations, decreased relative clonal diversity, and increasingly restricted use of canonical gene segments. The period of most intense selection on germinal center B cell populations preceded significant levels of mutation and may represent a physiologically determined restriction on B ceUs permitted to enter the memory pathway. Noncanonical Ig genes recovered from germinal centers were mostly unmutated although they probably came from antigen-reactive cells. Together, these observations demonstrate that the germinal center microenvironment is rich and temporally complex but may not be constitutive for somatic hypermutation. ,•ter immunization with immunogenic conjugates of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP), 1 Ig hypermutation and selection take place in germinal centers (GC) (1), specialized histologic structures of secondary lymphoid tissues (2-4). Splenic GC support oligodonal B cell populations (2, 4, 5) that result from colonizing migration by antigen-activated (6) lymphocytes from the region of the periarteriolar lymphoid sheath (PALS) (4, 6, 7). Nonmigrating sister cells remain associated with the PALS, establishing large loci of antibody-forming cells (4, 6, 7). Interestingly, although focus and GC B cell populations arise from common founders, Ig hypermutation is not evident in loci (1, 6) and presumably is dependent upon the GC microenvironment.Despite intensive study, our understanding of somatic Ig mutation and selection remains elementary. Mutations are introduced into rearranged V regions of transcriptionally active Igh-and -I loci (8, 9) at the rate of 10 -3 mutations/bp per cell/generation (10). Mutations are predominately single nucleotide substitutions (90-95%) although small deletions 1 Abbreviations used in this paper: CG, chicken gamma globulin; FW, framework region; GC, germinal center; NP, (4-hydroxy-3-nitrophenyl)-acetyl; PALS, periarteriolar lymphoid sheath; PNA, peanut agglutinin. and insertions also have been noted (11-15). These mutations are distributed asymmetrically within an "~2-kbp region whose 5' boundary is defined by the V. promoter sequence (15, 16); the focus of this distribution is the rearranged V(D)J elements (15). Although mutation is believed to be approximately random (11-14), strand biases (17) and mutational hot spots (11, 18) have been reported. The mechanism oflg hypermutation i...
Mindful eating offers promise as an effective approach for weight management and glycemic control in people with diabetes. Diabetes self-management education (DSME) is an essential component of effective self-care. Yet, little research has compared the effect of mindful eating to DSME-based treatment. This study compared the impact of these two interventions in adults with type 2 diabetes mellitus (T2DM). A prospective randomized controlled trial with two parallel interventions was employed. Participants included adults aged 35–65 with T2DM for ≥ 1 year, body mass index (BMI) ≥ 27.0, and A1c ≥ 7.0% who were randomly assigned to a 3-month mindful eating (MB-EAT-D; n=27) or Smart Choices (SC) DSME-based (n=25) intervention. Follow-up occurred 3-months following intervention completion. Dietary intake, physical activity, weight, glycemia, and fasting insulin were assessed using repeated measures ANOVA with contrast analysis. There was no significant difference between groups in the change in weight or glycemia at study end. Significant difference occurred between groups in the change in dietary intake/1000 kcal of trans fats, total fiber, and sugars (all P<0.05). Mean (±SE) reduction in weight (−2.92 ± 0.54 kg for SC vs. −1.53 ± 0.54 kg for MB-EAT-D) and A1c (−0.67 ± 0.24% for SC and −0.83 ± 0.24% for MB-EAT-D) were significant (P<0.01). Significant reduction in energy intake and glycemic load occurred (all P<0.0001) for both groups. Training in mindful eating and diabetes self-management facilitate improvement in dietary intake, modest weight loss, and glycemic control. The availability of effective treatments allows diabetes patients choices in meeting their self-care needs.
One of the most challenging diabetes-related behavior changes is adhering to a healthful diet. Drawing on the social cognitive theory and social support literature, this qualitative study explores how spousal support influences dietary changes following a diagnosis of type 2 diabetes in middle-aged and older adults. The purpose of this study was to determine how aspects of the spousal relationship translate into behavior changes, specifically adherence to a healthful diet. Analyses revealed five core themes related to dietary adherence: control over food, dietary competence, commitment to support, spousal communication, and coping with diabetes. The themes can be categorized within two key social cognitive theory constructs: reinforcement and self-efficacy. Implications from the focus group data can inform the development of more effective, targeted nutrition messages and programs to provide specific knowledge and skills.
Mindful eating may be an effective intervention for increasing awareness of hunger and satiety cues, improving eating regulation and dietary patterns, reducing symptoms of depression and anxiety, and promoting weight loss. Diabetes self-management education (DSME), which addresses knowledge, self-efficacy, and outcome expectations for improving food choices, also may be an effective intervention for diabetes self-care. Yet few studies have compared the impact of mindful eating to a DSME-based treatment approach on patient outcomes. Adults 35 to 65 years old with type 2 diabetes for ≥1 year not requiring insulin therapy were recruited from the community and randomly assigned to treatment group. The impact of a group-based 3-month mindful eating intervention (MB-EAT-D; n = 27) to a group-based 3-month DSME “Smart Choices” (SC) intervention (n = 25) postintervention and at 3-month follow-up was evaluated. Repeated-measures ANOVA with contrast analysis compared change in outcomes across time. There was no significant difference between groups in weight change. Significant improvement in depressive symptoms, outcome expectations, nutrition and eating-related self-efficacy, and cognitive control and disinhibition of control regarding eating behaviors occurred for both groups (all p < .0125) at 3-month follow-up. The SC group had greater increase in nutrition knowledge and self-efficacy than the MB-EAT-D group (all p < .05) at 3-month follow-up. MB-EAT-D had significant increase in mindfulness, whereas the SC group had significant increase in fruit and vegetable consumption at study end (all p < .0125). Both SC and MB-EAT-D were effective treatments for diabetes self-management. The availability of mindful eating and DSME-based approaches offers patients greater choices in meeting their self-care needs.
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