Unusual association of a unique CAG interruption in 5′ of DM1 CTG repeats with intergenerational contractions and low somatic mosaicism

Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that ～90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5′ of the CTG expansion in one family, whereas multiple 5′ CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet‐prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3′ of the interruptions for both families.     

Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues

To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient‐matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 18–25 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t‐tests. These results suggest that preferential selection of 18–25 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.     

关于社区健康促进项目评价设计的理论探讨

社区健康促进项目广泛开展,由于项目的复杂性,项目评价往往存在一些问题。结合社区项目评价实践,指出社区项目评价设计方面存在的主要问题以及解决思路,主要在项目评价设计时机、构建项目理论和抽样调查样本量计算等方面进行了理论探讨以及案例分析,以期对完善社区干预项目的评价设计提供参考。     

A Complementary Ecological Model of the Coordinated School Health Program

BACKGROUND: A complementary ecological model of the coordinated school health program (CSHP) reflecting 20 years of evolved changes is proposed. Ecology refers to the complex interrelationship between intrapersonal factors, interpersonal processes and primary groups, institutional factors, community factors, and public policy. METHODS: Public health and child development theories that incorporate the influence of personal and social environments on health behavior, along with models that incorporate the influence of ecology, were consulted. RESULTS: Concepts from several models were combined with the 8 components of CSHP to formulate an ecological model involving 6 program and services components in an inner circle surrounded by 4 concentric rings representing the healthy school environment, essential structures of CSHP, local school district governance, and family and community involvement. CONCLUSION: This complementary ecological model is intended to serve as an additional conceptual approach to CSHP practice, evaluation, and research, and should prove especially useful to practitioners and researchers who already have a fundamental understanding of CSHP.     

South Indian men with reduced CAG repeat length in the androgen receptor gene have an increased risk of prostate cancer

The androgen receptor (AR) gene possesses polymorphic CAG tandem repeats and the repeat length has been inversely related to the risk of prostate cancer (PCa). The distinct ethnic variation in the CAG repeat length may be correlated to differences in PCa risk in different populations. To evaluate the CAG repeat length in the AR gene and the implications for PCa, we screened 87 PCa patients and 120 control subjects from South India. The mean CAG repeat length in PCa patients was significantly smaller than that of controls (17.0 vs 20.7; P<0.001). Men with 19 CAG repeats had a significantly increased risk of cancer compared to those with >19 CAG repeats (age-adjusted OR=7.01; 95% CI=3.52–13.94; P<0.001). However, no significant association was observed between CAG repeats and age of onset or prostate-specific antigen levels. Although there was a trend towards shorter CAG repeat length in high grades of cancer, it was not significant (P=0.085). Thus, our results suggest an association between short CAG repeats in the AR gene and PCa risk in South Indian men. Further, we propose that CAG repeats could be used as a prognostic marker for PCa diagnosis.     

Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin

The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1–3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18 × 10⁵ inhabitants, with the remarkable figure of 141.66 × 10⁵ in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors.     

Factors Associated With Involvement in Marriage Preparation Programs

Abstract: Little is known empirically about the characteristics of couples who do and do not participate in marriage preparation. This study assessed the individual, couple, family, and sociocultural context variables that distinguish couples who become involved in marriage preparation from those who do not, using a sample of 7,331 couples. The results showed that the individual characteristics of valuing marriage, being kind and considerate, and being mature, and the couple context factor of perceived relationship problems, predicted involvement. Implications for increasing attendance in marriage preparation interventions include maximizing efforts to reach the “likely‐to‐attend group,” as identified in our findings. With this base of support for the value of interventions, we can then look to the less‐likely‐to‐attend group, who will take more resources of time, energy, and money to get to attend.     

Technical skills for weight loss: preliminary data from a randomized trial

BACKGROUND: Optimal behavioral interventions for sustainable weight loss are uncertain. We therefore conducted a study among overweight/obese women comparing conventional dietary counseling of individuals (counseling-based intervention) to a novel, group-based skill-building intervention. METHODS: Eighty subjects were randomly assigned to either the counseling-based or to the skill-building intervention. Outcomes included weight loss, dietitian hours per group and per unit weight loss, and dollars spent per group and per unit weight lost. RESULTS: Weight loss at 6 months (follow-up rate 61.3%) in the counseling-based group was 8.8 lb (P = 0.0001), and in the skill-building group was 3.8 lb (P = 0.01). A total of 160 dietitian hours were required for the counseling-based group, and 131 for the skilled-building group. The counseling-based group cost an average of $21 per pound lost, while the skill-building cost an average of $48 per pound lost (P = 0.16). CONCLUSIONS: At 6 months, individualized office-based counseling produced more weight loss than a skill-building approach and cost less than half as much per pound of weight loss. Longer-term follow-up is required to determine if, as hypothesized, the skill-building intervention produces more sustainable weight loss.     

Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1–3, 6 and 7 CAG expansions

Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders, six of which are caused by expansion of a polyglutamine-coding CAG repeats (SCA1- 3, 6, 7 and 17). In addition, expansions of a CAG triplet in the 5' region of a gene and a CTG triplet in an antisense RNA have been demonstrated in the SCA12 and SCA8 genes respectively. Our series of 134 ataxic patients (22 familial and 112 sporadic, tested negative for SCAI–3, 6, 7) was investigated for the presence of triplet expansions in the SCA8 and SCA12 genes. No SCA12 expansion was identified. A moderate SCA8 expansion (85–97 repeats) was found in two unrelated families with slowly progressive cerebellar ataxia. The frequency of SCA8 expansion accounts for ∼4.3 % of the whole pool of our ataxia families (2 out of 46), while none of the 127 controls screened carried > 35 CTG+CTA repeats. Our data suggest a possible pathogenetic role of this mutation, which at present is still controversial, and confirm the rarity of the SCA12 expansion in Italian patients. Received: 30 March 2001, Received in revised form: 20 November 2001, Accepted: 15 January 2002