Telomeres and Telomerase Biology in Vertebrates: Progress Towards a Non-Human Model for Replicative Senescence and Ageing

Studies on telomere and telomerase biology are fundamental to the understanding of human ageing and age-related diseases such as cancer. However, human studies of whole body ageing are hampered by the lack of suitable fully reflective animal model systems, the wild-type mouse model being unsuitable due to differences in telomere biology. Here we summarise recent data on the biology of telomeres, telomerase, and the tumour suppressor protein p53 in various animals, and examine their possible roles in replicative senescence, ageing, and tumourigenesis. The advantages and disadvantages of various animals as model systems for whole body ageing in humans are discussed.     

Main partner factors associated with worse adherence to HAART among women in Baltimore, Maryland: a preliminary study

Compared to US men, US women have worse HAART and HIV health outcomes. The study examined main partner factors associated with women's HAART adherence. The community sample comprised 85% African-Americans; 63% had a main partner and 32% relied on their partner for emotional support. Adherence was highest (92%) among those without a main partner and lowest (57%) among those with an HIV seropositive main partner. In adjusted analysis, adherence was 75% less likely among women with an HIV seropositive main partner and 78% less likely among those relying on their partner for emotional support. Furthermore, HIV seropositive versus other serostatus main partners were most likely to provide medication taking assistance and to be preferred in helping participants deal with HIV, yet were no more likely to be nominated as the most helpful to them. Findings reveal women's perceived unmet support needs from HIV seropositive main partners in this population and the need for interventions to promote their HAART adherence. Seroconcordant couples-focused intervention that enhances mutual support of HAART adherence may be an effective approach to improving women's HAART adherence and reducing US gender disparities in HIV health outcomes.     

Replicative senescence in sheep fibroblasts is a p53 dependent process

Studies on telomere and telomerase biology are fundamental to the understanding of human ageing, and age-related diseases such as cancer. However, human studies are hampered by the lack of fully reflective animal model systems. Here we describe basic studies of telomere length and telomerase activity in sheep tissues and cells. Terminal restriction fragment lengths from sheep tissues ranged from 9 to 23 kb, with telomerase activity present in testis but suppressed in somatic tissues. Sheep fibroblasts had a finite lifespan in culture, after which the cells entered senescence. During in vitro growth the mean terminal restriction fragment lengths decreased in size at a rate of 210 and 350 bp per population doubling (PD). Senescent skin fibroblasts had increased levels of p53 and p21WAF1 compared to young cells. Incubation of senescent cells with siRNA duplexes specific for p53 suppressed p53 expression and allowed the cells to re-enter the cell cycle. Five PDs beyond senescence the siRNA-treated cells reached a second proliferative barrier. This study shows that telomere biology in sheep is similar to that in humans, with senescence in sheep GM03550 fibroblasts being a telomere-driven, p53-(p21WAF1)-dependent process. Therefore sheep may represent an alternative model system for studying telomere biology, replicative senescence, and by implication human ageing.     

Integrated Care: Treatment Initiation Following Positive Depression Screens

BACKGROUND

Primary Care-Mental Health Integration (PC-MHI) may improve mental health services access and continuity of care.

OBJECTIVE

To assess whether receipt of integrated PC-MHI services on the date of an initial positive depression screen influences receipt of depression treatment among primary care (PC) patients in the Veterans Health Administration.

DESIGN

Retrospective cohort study.

SUBJECTS

Thirty-six thousand, two hundred and sixty-three PC patients with positive depression screens between October 1, 2009 and September 30, 2010.

MAIN MEASURES

Subjects were assessed for depression diagnosis and initiation of antidepressants or psychotherapy on the screening day, within 12 weeks, and within 6 months. Among individuals with PC encounters on the screening day, setting of services received that day was categorized as PC only, PC-MHI, or Specialty Mental Health (SMH). Using multivariable generalized estimating equations (GEE) logistic regression, we assessed likelihood of treatment initiation, adjusting for demographic and clinical measures, including depression screening score.

KEY RESULTS

Patients who received same-day PC-MHI services were more likely to initiate psychotherapy (OR: 8.16; 95 % CI: 6.54–10.17) and antidepressant medications (OR: 2.33, 95 % CI: 2.10–2.58) within 12 weeks than were those who received only PC services on the screening day.

CONCLUSIONS

Receipt of same-day PC-MHI may facilitate timely receipt of depression treatment.     

Links between the organization of the family home environment and child obesity: a systematic review

Due to increasingly high rates of child overweight and obesity, it is important to identify risk and protective factors that may inform more effective prevention and intervention. The degree of organization in the family home environment is a studied, but not well‐specified, factor that may impact child weight. Prior research on household organization has examined an array of constructs, including family routines, limit setting, household chaos, crowding and the broad home environment. This study systematically reviews literature on organization within the family home environment and weight among children ages 2–12. Six hundred thirty‐seven studies were reviewed by four coders for eligibility, and 32 studies were included in the final synthesis. Overall, 84% of studies provided evidence for relations between at least one indicator of organization within the family home environment and child weight. Studies provided compelling evidence across several constructs, suggesting that the relevance of household organization to child weight extends beyond a single indicator. Directions for future work include (i) examining the mediating role of health behaviours, (ii) examining the moderating role of socioeconomic factors, (iii) broadening this evidence base across cultures and nationalities and (iv) integrating constructs to develop a comprehensive model of organization within the home environment.     

Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants

Deficiency in the collectin mannose-binding lectin (MBL) increases the risk for pulmonary and systemic infections and its complications in children and adults. The aim of this prospective cohort study was to determine the genetic association of sequence variations within the MBL gene with systemic infections and pulmonary short- and long-term complications in preterm infants below 32 weeks gestational age (GA). Three single-nucleotide polymorphisms (SNPs) in the coding region and one SNP in the promotor region of MBL2 were genotyped by direct sequencing and with sequence-specific probes in 284 newborn infants <32 weeks GA. Clinical variables were comprehensively monitored. An association was found between two SNPs and the development of bronchopulmonary dysplasia (BPD), defined as persistent oxygen requirement at 36 weeks postmenstrual age, adjusting for covariates GA, grade of respiratory distress syndrome and days on mechanical ventilation (rs1800450 (exon 1 at codon 54, B variant): odds ratio dominant model (OR)=3.59, 95% confidence interval (CI)=1.62-7.98; rs7096206 (-221, X variant): OR=2.40, 95% CI=1.16-4.96). Haplotype analyses confirmed the association to BPD, and a single haplotype (frequency 56%) including all SNPs in their wild-type form showed a negative association with the development of BPD. We detected no association between the MBL gene variations and the development of early-onset infections or further pulmonary complications. Frequent variants of the MBL gene, leading to low MBL concentrations, are associated with the diagnosis of BPD in preterm infants. This provides a basis for potential therapeutic options and further genetic and proteomic analysis of the function of MBL in the resistance against pulmonary long-term complications in preterm infants.     

Racial (vs. self) affirmation as a protective mechanism against the effects of racial exclusion on negative affect and substance use vulnerability among black young adults

Affirming one’s racial identity may help protect against the harmful effects of racial exclusion on substance use cognitions. This study examined whether racial versus self-affirmation (vs. no affirmation) buffers against the effects of racial exclusion on substance use willingness and substance use word associations in Black young adults. It also examined anger as a potential mediator of these effects. After being included, or racially excluded by White peers, participants were assigned to a writing task: self-affirmation, racial-affirmation, or describing their sleep routine (neutral). Racial exclusion predicted greater perceived discrimination and anger. Excluded participants who engaged in racial-affirmation reported reduced perceived discrimination, anger, and fewer substance use cognitions compared to the neutral writing group. This relation between racial-affirmation and lower substance use willingness was mediated by reduced perceived discrimination and anger. Findings suggest racial-affirmation is protective against racial exclusion and, more generally, that ethnic based approaches to minority substance use prevention may have particular potential.