Bronchopulmonary Dysplasia and Pulmonary Hypertension. The Role of Smooth Muscle adh5.

Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification, airway hyperreactivity, and pulmonary hypertension. In our BPD model, we have investigated the metabolism of the bronchodilator and pulmonary vasodilator GSNO (S-nitrosoglutathione). We have shown the GSNO catabolic enzyme encoded by adh5 (alcohol dehydrogenase-5), GSNO reductase, is epigenetically upregulated in hyperoxia. Here, we investigated the distribution of GSNO reductase expression in human BPD and created an animal model that recapitulates the human data. Blinded comparisons of GSNO reductase protein expression were performed in human lung tissues from infants and children with and without BPD. BPD phenotypes were evaluated in global (adh5-/-) and conditional smooth muscle (smooth muscle/adh5-/-) adh5 knockout mice. GSNO reductase was prominently expressed in the airways and vessels of human BPD subjects. Compared with controls, expression was greater in BPD smooth muscle, particularly in vascular smooth muscle (2.4-fold; P = 0.003). The BPD mouse model of neonatal hyperoxia caused significant alveolar simplification, airway hyperreactivity, and right ventricular and vessel hypertrophy. Global adh5-/- mice were protected from all three aspects of BPD, whereas smooth muscle/adh5-/- mice were only protected from pulmonary hypertensive changes. These data suggest adh5 is required for the development of BPD. Expression in the pulmonary vasculature is relevant to the pathophysiology of BPD-associated pulmonary hypertension. GSNO-mimetic agents or GSNO reductase inhibitors, both of which are currently in clinical trials for other conditions, could be considered for further study in BPD.

Knowledge, attitudes, and behavior toward concussion in adult cyclists.

OBJECTIVE: To determine knowledge, attitudes, and behavior toward concussion in cyclists and to identify predictors of concussion knowledge. METHODS: Cycling organizations sent members a web link to online information about the study and a questionnaire. Anyone aged >16 years, living in New Zealand and engaged in a cycling activity was invited to participate. The 36-item questionnaire included sociodemographics, knowledge about concussion, helmet use, and personal concussion history. Data were collected between 15/05/19 and 30/06/19. A multiple linear regression model identified factors associated with levels of concussion knowledge. RESULTS: The questionnaire was completed by 672 participants aged between 16 and 82 years (x̄ = 48.6 years). Knowledge of concussion was high. However, knowledge that helmets are not able to prevent concussion was low and time to return to sport after injury was variable. Knowledge did not always translate to seeking of medical attention or replacement of helmet behavior. Younger age and having sustained at least one prior concussion were associated with higher levels of concussion knowledge F(df = 3) = 8.81, p < .001. CONCLUSIONS: Knowledge and attitudes toward concussion were positive. However, knowledge gaps and discrepancies between attitudes and behavior were identified. Consistent, clear messages are needed around return to sport timeframes.

Absence of leptin signaling allows fat accretion in cystic fibrosis mice.

Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low body-growth phenotype. As low body weight and body mass index strongly correlate with poor lung health and survival of patients with CF, improving energy balance is an important clinical goal (e.g., high-fat diet). CF mouse models also exhibit negative energy balance (growth retardation and high energy expenditure), independent from exocrine pancreatic insufficiency, lung disease, and malnutrition. To improve energy balance through increased caloric intake and reduced energy expenditure, we disrupted leptin signaling by crossing the db/db leptin receptor allele with mice carrying the R117H Cftr mutation. Compared with db/db mice, absence of leptin signaling in CF mice (CF db/db) resulted in delayed and moderate hyperphagia with lower de novo lipogenesis and lipid deposition, producing only moderately obese CF mice. Greater body length was found in db/db mice but not in CF db/db, suggesting CF-dependent effect on bone growth. The db/db genotype resulted in lower energy expenditure regardless of Cftr genotype leading to obesity. Despite the db/db genotype, the CF genotype exhibited high respiratory quotient indicating elevated carbohydrate oxidation, thus limiting carbohydrates for lipogenesis. In summary, db/db-linked hyperphagia, elevated lipogenesis, and morbid obesity were partially suppressed by reduced CFTR activity. CF mice still accrued large amounts of adipose tissue in contrast to mice fed a high-fat diet, thus highlighting the importance of dietary carbohydrates and not simply fat for energy balance in CF. NEW & NOTEWORTHY We show that cystic fibrosis (CF) mice are able to accrue fat under conditions of carbohydrate overfeeding, increased lipogenesis, and decreased energy expenditure, although length was unaffected. High-fat diet feeding failed to improve growth in CF mice. Morbid db/db-like obesity was reduced in CF double-mutant mice by reduced CFTR activity.

Achieving a new balance: women's transition to second-time parenthood.

OBJECTIVE: To describe the experience of transition to second-time parenthood from the mother's perspective. DESIGN: Descriptive phenomenology using Colaizzi's approach. SETTING: Participants were interviewed in their homes. PARTICIPANTS: Ten second-time mothers with a second child between the ages of 6 months and 24 months. RESULTS: The birth of the second child motivated these women to seek and achieve a new balance to integrate a second child into the existing family. Seven themes emerged as common elements in all of the women's lives: (a) balancing the positive and negative elements of the early weeks, (b) knowing what to expect, (c) establishing a new routine, (d) maintaining the marital relationship, (e) taking a break, (f) seeking out support, and (g) nurturing relationships among family members. CONCLUSIONS: Mothers overwhelmingly found the addition of a second child to the family to be a positive experience regardless of the effort it took to accommodate their lives to the needs of two children. Although second-time mothers approach the experience with a wealth of knowledge, this research highlights that these women may have concerns that are not addressed. The nurse can focus assessments and offer interventions to meet the needs of these women as they become mothers for the second time.

The lived experience of adolescent females with type 1 diabetes.

PURPOSE: The purpose of this study was to gain a better understanding of what it means for adolescent females to live with type 1 diabetes. METHODS: Van Manen's phenomenological framework was used to guide the project of inquiry. Adolescents were recruited from a diabetes camp. A purposive sample of 10 adolescent females, aged 16 and 17 years, volunteered to participate in the study. Unstructured, one-on-one interviews were conducted and participants' accounts were transcribed and analyzed for themes. RESULTS: Five themes were identified: (1) blending in with the adolescent culture, (2) standing out and being watched, (3) weighing the options and making choices, (4) being tethered to the system and to diabetes, and (5) struggling with conflicts. These adolescent females struggled with several conflicts and choices they were forced to make on a daily basis. They felt tethered to a disease that would never go away and to the healthcare system. Yet, they adopted ways to handle their disease so that it was manageable within the context of their lives. Fitting in with their peers was often more important than diabetes management. CONCLUSIONS: Making visible the experience of adolescent females living with type 1 diabetes has implications for practice, education, and research in diabetes education.