Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.

Background: We have previously shown that a structured in-hospital and outpatient heart failure (HF) program reduces clinical events over a 3-month period following hospital discharge. Aims: This prospective randomized controlled study examines the additional benefits of extending the standard 3-month HF program to 6 months on death and readmission over a 2-year follow-up period. Methods: Of 161 patients admitted with NYHA class IV HF who completed the standard 3-month HF program, 130 consenting patients (mean age 69.9F12.2 years, 65% male) were randomized to the extended 6-month HF program (EP; n=62) or standard care (SP; n=68). The primary endpoint was death and/or unplanned rehospitalization for HF at 2 years postrandomization. Results: In the 2-year follow-up period, there were eight people with unplanned hospitalizations for HF and 16 deaths in the EP group (event rate 38.7%) compared to seven people with unplanned HF readmissions and 14 deaths in the SP group (event rate 30.9%, p=0.348 versus EP). Kaplan-Meier survival analysis demonstrated no difference in outcome between standard and extended program ( p=0.315). There were no differences between the groups in terms of unscheduled clinic visits or non-HF-related readmissions in the 2-year follow-up period. Conclusions: There is no measured clinical advantage in terms of death and/or HF readmission in extending a structured hospital-based disease management program for HF beyond 3 months postdischarge. However, it appears that patients continue to need access to the service to help abort clinical deteriorations, and this may have implication for the optimal organisation of such programs.

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Background: Heart failure (HF) impacts 1.7 million Americans between the ages of 20 and 59 years, but limited research exists addressing the issues unique to this age group. Objective: The aim of this study was to investigate the experiences of younger persons living with HF. Methods: Semistructured interviews (n = 18) were analyzed using a qualitative thematic analysis. Results: Six themes emerged: (1) role fulfillment: participants who perceived their roles as a parent, caregiver, spouse, employee, and friend have been negatively affected by HF; (2) autonomy: participants frequently linked their well-being to a sense of independence, productivity, and purpose; (3) financial impact: most of the sample expressed financial instability further complicated by existing disability policies; (4) perception of self: recurrent statements revealed participants feeling judged because of their HF diagnosis and younger age; (5) retrospective life changes: participants reflected on past decisions and often blamed themselves for their current health; and (6) symptom burden: participants reported higher levels of psychosocial symptoms, such as depression, anxiety, and fatigue. Conclusions: Younger individuals living with HF reported overwhelmingly poor health-related quality of life that was linked to the 6 themes identified previously. The effect of HF was seen on numerous life events that traditionally occur earlier in the life course such as establishing a career, meaningful relationships, family, and financial security. This directly impacted health-related quality of life by disrupting what each individual perceived as important to them, which took a toll on their overall mental health. To provide holistic care to younger patients living with HF, interventions that address the heavy burden of psychosocial symptoms and policy changes associated with financial burden and disability laws must be developed.

Exposure to chemosensory signals from unfamiliar males can terminate pregnancy in recently mated female mice. The number of tyrosine hydroxylase-positive neurons in the main olfactory bulb has been found to increase following mating and has been implicated in preventing male-induced pregnancy block during the post-implantation period. In contrast, pre-implantation pregnancy block is mediated by the vomeronasal system, and is thought to be prevented by selective inhibition of the mate’s pregnancy blocking chemosignals, at the level of the accessory olfactory bulb. The objectives of this study were firstly to identify the level of the vomeronasal pathway at which selective inhibition of the mate’s pregnancy blocking chemosignals occurs. Secondly, to determine whether a post-mating increase in tyrosine hydroxylase-positive neurons is observed in the vomeronasal system, which could play a role in preventing pre-implantation pregnancy block. Immunohistochemical staining revealed that mating induced an increase in tyrosine-hydroxylase positive neurons in the arcuate hypothalamus of BALB/c females, and suppressed c-Fos expression in these neurons in response to mating male chemosignals. This selective suppression of c-Fos response to mating male chemosignals was not apparent at earlier levels of the pregnancy-blocking neural pathway in the accessory olfactory bulb or corticomedial amygdala. Immunohistochemical staining revealed an increase in the number of tyrosine hydroxylase-positive neurons in the accessory olfactory bulb of BALB/c female mice following mating. However, increased dopamine-mediated inhibition in the accessory olfactory bulb is unlikely to account for the prevention of pregnancy block to the mating male, as tyrosine hydroxylase expression did not increase in females of the C57BL/6 strain, which show normal mate recognition. These findings reveal an association of mating with increased dopaminergic modulation in the pregnancy block pathway and support the hypothesis that mate recognition prevents pregnancy block by suppressing the activation of arcuate dopamine release.