Changes in the use of anti-asthmatic medication in an international cohort

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4-3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5-4.5%). In the sample with asthma in both surveys (n=423), the use of inhaled corticosteroids increased by 12.2% (6.6-17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma

Increased prevalence of abnormal vertebral patterning in fetuses and neonates with trisomy 21

Purpose: To assess the prevalence of an abnormal number of ribs in a cohort of fetuses and neonates with trisomy 21 and compare this with a subgroup of fetuses without anomalies. Materials and methods: Radiographs of 67 deceased fetuses, neonates, and infants that were diagnosed with trisomy 21 were reviewed. Terminations of pregnancy were included. The control group was composed of 107 deceased fetuses, neonates, and infants without known chromosomal abnormalities, structural malformations, infections or placental pathology. Cases in which the number of thoracic ribs or presence of cervical ribs could not be reliably assessed were excluded. The literature concerning vertebral patterning in trisomy 21 cases and healthy subjects was reviewed. Results: Absent or rudimentary 12th thoracic ribs were found in 26/54 (48.1%) cases with trisomy 21 and cervical ribs were present in 27/47 (57.4%) cases. This prevalence was significantly higher compared to controls (28/100, 28.0%, Χ2(1) = 6.252, p = .012 and 28/97, 28.9%, Χ2(1) = 10.955, p < .001, respectively). Conclusions: Rudimentary or absent 12th thoracic ribs and cervical ribs are significantly more prevalent in deceased fetuses and infants with trisomy 21

Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy

To accomplish a diagnosis in patients with a rare unclassified disorder is difficult. In this study, we used magnetic resonance imaging pattern recognition analysis to identify patients with the same novel heritable disorder. Whole-exome sequencing was performed to discover the mutated gene. We identified seven patients sharing a previously undescribed magnetic resonance imaging pattern, characterized by initial swelling with T2 hyperintensity of the basal nuclei, thalami, cerebral white matter and cortex, pons and midbrain, followed by rarefaction or cystic degeneration of the white matter and, eventually, by progressive cerebral, cerebellar and brainstem atrophy. All patients developed a severe encephalopathy with rapid deterioration of neurological functions a few weeks after birth, followed by respiratory failure and death. Lactate was elevated in body fluids and on magnetic resonance spectroscopy in most patients. Whole-exome sequencing in a single patient revealed two predicted pathogenic, heterozygous missense mutations in the SLC19A3 gene, encoding the second thiamine transporter. Additional predicted pathogenic mutations and deletions were detected by Sanger sequencing in all six other patients. Pathology of brain tissue of two patients demonstrated severe cerebral atrophy and microscopic brain lesions similar to Leigh's syndrome. Although the localization of SLC19A3 expression in brain was similar in the two investigated patients compared to age-matched control subjects, the intensity of the immunoreactivity was increased. Previously published patients with SLC19A3 mutations have a milder clinical phenotype, no laboratory evidence of mitochondrial dysfunction and more limited lesions on magnetic resonance imaging. In some, cerebral atrophy has been reported. The identification of this new, severe, lethal phenotype characterized by subtotal brain degeneration broadens the phenotypic spectrum of SLC19A3 mutations. Recognition of the associated magnetic resonance imaging pattern allows a fast diagnosis in affected infant

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

Changing prevalence of asthma in Turin school children between 1994 and 1999

Beckground: Asthma is a widespread chronic disorder in children and its prevalence has been on the increase in Europe. Only few studies have described the prevalence variation in respiratory symptoms in Italian regions. The aim of this study, conducted in Turin during the 1998/1999 school year, is to investigate the distribution of respiratory symptoms in a sample of Turin school children and to compare the obtained results with the findings of the SIDRIA study performed in 1994-95. Methods: the sample in study is composed of all the children attending to three elementary schools in Turin. All of the selected schools had already participated in the 94-95 ISAAC-SIDRIA study. A total of 448 pupils aged 6- 10 years received a standardised questionnaire to be filled by parents. Results: response rate is higher than 97% in all the studies. In 1999 we found that the prevalence of wheezing in the past 12 months was 7.3%. The 13.3% of children had asthma at least once in life and the 5.3% reported an attack in the last year. The comparison of our study results with the ISAACSIDRIA (1994-95) shows that the prevalence of asthma and asthma-like symptoms is rather stable among children, while the prevalence of bronchitis reveals a reduction of about 5.5%, but not statistically significant (p=0.094; 95%CI:-11.9;0.9). A considerable reduction in exposure to parents' passive smoke is shown: ΔP%=-4.7 (95%CI: -9.4;-0.1) for maternal smoking in pregnancy, ΔP%=-8.2 and -15.2, respectively for maternal and paternal smoking in the first two years of life. Conclusions: The results indicate a stable prevalence rate in asthma symptoms in children. A possible explanation of slight variation in asthma prevalence may be due to a reduced exposure to outdoor and indoor risk factors as reported in the questionnaires

Star Formation Shut Down by Multiphase Gas Outflow in a Galaxy at a Redshift of 2.45

Large-scale outflows driven by supermassive black holes are thought to play a fundamental role in suppressing star formation in massive galaxies. However, direct observational evidence for this hypothesis is still lacking, particularly in the young universe where star formation quenching is remarkably rapid, thus requiring effective removal of gas as opposed to slow gas heating. While outflows of ionized gas are commonly detected in massive distant galaxies, the amount of ejected mass is too small to be able to suppress star formation. Gas ejection is expected to be more efficient in the neutral and molecular phases, but at high redshift these have only been observed in starbursts and quasars. Here we report JWST spectroscopy of a massive galaxy experiencing rapid quenching at redshift z=2.445. We detect a weak outflow of ionized gas and a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to quench the star formation. Neither X-ray or radio activity are detected; however, the presence of a supermassive black hole is suggested by the properties of the ionized gas emission lines. We thus conclude that supermassive black holes are able to rapidly suppress star formation in massive galaxies by efficiently ejecting neutral gas.Comment: 21 pages, 9 figures. Published in Natur

JWST Reveals Widespread AGN-Driven Neutral Gas Outflows in Massive z ~ 2 Galaxies

We use deep JWST/NIRSpec R~1000 slit spectra of 113 galaxies at 1.7 < z < 3.5, selected from the mass-complete Blue Jay survey, to investigate the prevalence and typical properties of neutral gas outflows at cosmic noon. We detect excess Na I D absorption (beyond the stellar contribution) in 46% of massive galaxies ($\log$ M$_*$/M$_\odot >$ 10), with similar incidence rates in star-forming and quenching systems. Half of the absorption profiles are blueshifted by at least 100 km/s, providing unambiguous evidence for neutral gas outflows. Galaxies with strong Na I D absorption are distinguished by enhanced emission line ratios consistent with AGN ionization. We conservatively measure mass outflow rates of 3 - 100 $M_\odot$ yr$^{-1}$; comparable to or exceeding ionized gas outflow rates measured for galaxies at similar stellar mass and redshift. The outflows from the quenching systems (log(sSFR)[yr$^{-1}$] $\lesssim$ -10) have mass loading factors of 4 - 360, and the energy and momentum outflow rates exceed the expected injection rates from supernova explosions, suggesting that these galaxies could possibly be caught in a rapid blowout phase powered by the AGN. Our findings suggest that AGN-driven ejection of cold gas may be a dominant mechanism for fast quenching of star formation at z~2.Comment: 16 pages, 8 figures, submitted to MNRA