Family- and neighborhood-level environmental associations with physical health conditions in 9- and 10-year-olds.

OBJECTIVE: To determine how environmental factors are associated with physical health conditions in 9- to 10-year-old participants in the Adolescent Brain Cognitive Development (ABCD) Study, and how they are moderated by family-level socioeconomic status (SES). METHOD: We performed cross-sectional analyses of 8,429 youth participants in the ABCD Study, in which nine physical health conditions (having underweight or overweight/obesity, not participating in sports activities, short sleep duration, high sleep disturbances, lack of vigorous and strengthening-related physical activity, miscellaneous medical problems, and traumatic brain injury) were regressed on three environmental factors [neighborhood disadvantage (area deprivation index [ADI]), risk of lead exposure, and concentrations of particulate matter 2.5 (PM2.5)] and their interaction with family-level SES (i.e., parent-reported annual household income). Environmental data were geocoded to participants' primary residential addresses at 9- to 10-year-olds. RESULTS: Risk of lead exposure and ADI were positively associated with the odds of having overweight/obesity, not participating in sports activity, and short sleep durations. ADI was also positively associated with high sleep disturbances. PM2.5 was positively associated with the odds of having overweight/obesity and reduced vigorous physical activity. Family-level SES moderated relationships between ADI and both underweight and overweight/obesity, with high SES being associated with more pronounced changes given increased ADI. CONCLUSIONS: Policymakers and public health officials must implement policies and remediation strategies to ensure children are free from exposure to neurotoxicant and environmental factors. Physical health conditions may be less of a product of an individual's choices and more related to environmental influences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Long-term comparative trial of two different physiotherapy techniques; postural drainage with percussion and autogenic drainage, in the treatment of cystic fibrosis.

UNLABELLED: In N. America, over the past decade, various airway clearance techniques (ACT) have been introduced for the treatment of cystic fibrosis (CF). We hypothesized that autogenic drainage (AD), an ACT developed in Belgium would be as effective as postural drainage with percussion (PD) in treating patients with CF. METHODS: Thirty-six CF patients, aged 12-18 years, with Shwachman score 65-98, were enrolled in a 2-year cross-over trial. Patients were matched as pairs and members of each pair were randomly assigned to two groups. For the first study year, Group A performed PD while Group B performed AD. At the end of 1 year Groups A and B crossed over physiotherapy techniques. Clinical status and pulmonary function (FVC, FEV(1), FEF(25-75)) were measured at 3 monthly intervals. Only results from the first year of the study are reported, as 10 out of 17 patients who had completed performing AD for the first year refused to change back to PD for the second year. RESULTS: During the first year of the study, both the AD and PD groups demonstrated improved pulmonary function with no significant difference between the two groups. Change in FVC and FEV(1) percent predicted for Groups A and B was 0.47 ± 1.65(se) versus 2.35 ± 1.51(se) and 2.09 ± 2.2(se) versus 0.92 ± 2.25(se). However, CF patients exhibited a marked preference for the AD technique. Results suggest that both AD and PD are effective methods of performing physiotherapy for CF patients and that the benefits of either technique are enhanced by measures which encourage adherence.

Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease.

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) genotype does not explain the heterogeneity observed in CF pulmonary disease severity. Modifier genes are implicated for this heterogeneity. alpha1-antitrypsin (alpha1-AT) is one of the few antiproteases capable of inactivating neutrophil elastase. We investigated whether alpha1-AT alleles (Z, S deficiency alleles and the 3' G1237-->A mutation) were associated with increased disease severity and the alpha1-AT acute phase response during pulmonary exacerbations. This was a multicenter Canadian study. Seven hundred sixteen patients with CF (age range, 5.0-63.6 yr) were genotyped for the Z, S, and G1237-->A polymorphisms of the alpha1-AT gene. Stable and acute levels of alpha1-AT were measured on 31 adult patients with CF and were correlated to clinical parameters. There were 69, 13, and 18 patients with CF who were MS, SS, and MZ, respectively. There were 95 and 7 patients with CF heterozygous or homozygous for the A1237 allele, respectively. alpha1-AT genotype did not predict pulmonary disease severity, and was not associated with more severe clinical outcome (death or lung transplantation) or age of onset of Pseudomonas aeruginosa infection. Body mass index was a significant predictor of alpha1-AT levels during exacerbations. alpha1-AT genotype is not a major contributor to the variability of pulmonary disease severity in CF.

A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency.

OBJECTIVE: Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10). Patients commonly present during early infancy with acute metabolic derangements and severe metabolic acidosis. Recently, a late onset form of HLCS deficiency was also described. The different phenotypes (early and late presenting) may be related to a spectrum of mutations in HLCS gene. Applications of mutation analysis in HLCS had been limited previously by the requirement of cDNA from living tissue for study. We described here a genomic approach for molecular diagnosis of HLCS deficiency which we have used to detect mutations in Chinese patients who had the late-onset form of HLCS deficiency. In addition, a fibroblast cell line with MCD from Coriell Cell repositories was also studied. DESIGN AND METHODS: Three Chinese patients with late onset HLCS deficiency were studied. The genomic sequence of HLCS was retrieved and newly designed primers were used to cover all coding sequences of the gene. PCR products were analyzed by direct sequencing. Population allelic frequencies of mutations detected were determined by genotyping of control samples by restriction fragment length polymorphism. RESULTS: We found a recurrent mutation, R508W, in the three unrelated Chinese patients. Two were homozygous for this mutation. The other patient was a compound heterozygote of R508W and a novel mutation, D634N. The results suggest that R508W may be an important and relatively prevalent disease-causing mutation in Chinese MCD patients. A fibroblast cell-line from an African patient revealed an additional novel mutation, R565X and a known mutation, V550M. CONCLUSION: R508W is a recurrent mutation in Chinese MCD patients which is associated with the late onset phenotype. This new genomic approach for mutation analysis of HLCS gene provides new opportunities in studies of MCD.

The intravascular persistence and methemoglobin formation of Hemolink (hemoglobin raffimer) in dogs.

Hemoglobin raffimer (HEMOLINK, Hemosol Inc, Mississauga, Canada) is an o-raffinose cross-linked, purified human hemoglobin-based oxygen therapeutic that is currently being evaluated in late stage clinical trials. It is composed of several molecular weight (MW) species, comprising principally of stabilized tetramers (34-42%) and oligomers (54-62%). The objective of this study was to determine the in vivo circulating half-life (T1/2) of hemoglobin raffimer (Hb raffimer) and of its individual MW components in dogs subjected to a topload infusion of 25% of the estimated blood volume (18 mL/kg). Sampling was done over a 64-hour period that was expected to be equivalent to approximately two-and-half to three half-lives. Methemoglobin (MetHb) levels were also measured at intervals over the same period. The mean circulating half-life of Hb raffimer was 25.4 +/- 3.9 hours. The T1/2 for the individual MW components (determined by size exclusion chromatography) of Hb raffimer was 11 +/- 2 hours for the cross-linked tetramer and 35 +/- 7 hours for the fraction of oligomers. The apparent volume of distribution for Hb raffimer was estimated at 78 mL/kg. There was no difference in the apparent volumes of distribution of the tetrameric and oligomeric components of Hb raffimer. Throughout the course of the experiment (in which MetHb could be measured), plasma MetHb concentration, expressed as a percentage of the total plasma hemoglobin concentration, remained at 10% or less, and the mass concentration of MetHb in plasma remained at about 1 g/L. Thus, in the dog subjected to an estimated 25% topload infusion, the T1/2 of the infused Hb raffimer is approximately one day with the intravascular retention of the individual Hb raffimer components being dependent on the MW. Furthermore, oxidation of Hb raffimer to MetHb is limited under these conditions.

Epidemiology of Pseudomonas aeruginosa in cystic fibrosis in British Columbia, Canada.

Pseudomonas aeruginosa is the most common respiratory pathogen in patients with cystic fibrosis (CF), but the predominant mechanism by which it is acquired is controversial. To determine the frequency of patient-to-patient spread, we evaluated P. aeruginosa isolates from 174 patients treated at the CF clinics in Vancouver, BC, Canada, since 1981. Multiple isolates were obtained from each patient and genetically typed by random amplified polymorphic DNA and pulsed field gel electrophoresis analyses. A total of 157 genetic types of P. aeruginosa was identified, 123 of which were unique to individual patients. A total of 34 types was shared by more than one patient; epidemiologic evidence linked these individuals only in the cases of 10 sibships and 1 pair of unrelated patients. We conclude that there is an extremely low risk in Vancouver for patients with CF to acquire P. aeruginosa from other patients. It appears that prolonged close contact, such as occurs between siblings, is necessary for patient-to-patient spread. The major source of acquisition of P. aeruginosa in CF appears to be from the environment. Considering these observations, we do not recommend segregation of patients with CF on the basis of their colonization status with P. aeruginosa.