Interleukin-4 and interleukin-4 soluble receptor alpha levels in bronchoalveolar lavage from children with asthma.

BACKGROUND: In asthma there is increased expression of the Th2-type cytokine interleukin-4 (IL-4). IL-4 is important in immunoglobulin isotype switching to immunoglobulin E and adhesion of eosinophils to endothelium. OBJECTIVE: We hypothesized that levels of IL-4 in bronchoalveolar lavage (BAL) fluid would be increased in stable, atopic asthmatic children compared with controls and that levels of its physiologic inhibitor IL-4 soluble receptor alpha (IL-4sR alpha) would be correspondingly decreased. METHODS: One hundred sixteen children attending a children's hospital for elective surgery were recruited. A nonbronchoscopic BAL was performed, and IL-4 and IL-4sR alpha were measured in the BAL supernatants. RESULTS: There was no significant difference in IL-4 concentrations between atopic asthmatic children, atopic normal controls, and nonatopic normal controls [0.13 pg/mL (0.13 to 0.87) vs 0.13 pg/mL (0.13 to 0.41) vs 0.13 pg/mL (0.13 to 0.5), P = 0.65]. IL-4sR alpha levels were significantly increased in asthmatic patients compared with atopic controls [6.4 pg/mL (5.0 to 25.5) vs 5.0 pg/mL (5.0 to 9.9), P = 0.018], but not when compared with the nonatopic controls [5.2 pg/mL (5.0 to 10.6), P = 0.19]. CONCLUSIONS: Contrary to expectation, IL-4sR alpha levels are increased in BAL from stable asthmatic children compared with nonatopic controls, and we speculate that IL-4sR alpha is released by inflammatory cells in the airways to limit the proinflammatory effects of IL-4.     

Morphological observations and morphometric analysis in three human fetuses with bilateral cervical cystic hygroma

Three human fetuses (crown-rump length, CRL, ranging from 71 to 77 mm), presenting bilateral cervical cystic hygroma were examined. The specimens were cleared and double-stained with alcian blue and alizarin red S for detecting the ossification growth patterns in the vertebral column, ribs, ischium, limbs, and face. Longitudinal measurements of some long bones in the upper (humerus, ulna, radius) and lower (femur, tibia, fibula) limb were taken. The values of both the total length (TL) and the ossified part (OL) of each long bone, as well as the OL/TL per cent ratio were considered. Reference points were located on the mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN), gonion (GO), inferior interdental point (IDI) for measuring linear dimensions. All values obtained were related with those relative to a group of fetuses, without any detectable malformation and chromosomal abnormalities, with CRL mean value 75 mm, in order to assess the presence of further anomalies, besides the cystic hygroma, in the three fetuses considered.     

Identification of a family with nonspecific mental retardation (MRX79) with the A140V mutation in the MECP2 gene: Is there a need for routine screening?

Mutations in the methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome, a severe neurodevelopmental disorder occurring predominantly in females. Male patients with Rett syndrome are extremely rare, as the Rett-causing mutations in the MECP2 gene are usually lethal in hemizygous males. However, different mutations in the same gene were reported to cause mental retardation, both in sporadic non-syndromic males as well as in syndromic families with disease manifestation in carrier females. The majority of the reported MECP2 mutations in mentally retarded patients cause amino acid substitutions and, especially in isolated cases, discrimination between a disease-causing mutation and a rare polymorphism is not obvious and the significance of each individual variation should be verified. We mapped a new non-syndromic X-linked family (MRX79) to the chromosomal region Xq27.3-Xq28 and identified an A140V mutation in the MEPC2 gene in all patients with the disease haplotype. In addition to data published by others, this suggests that A140V is a recurrent mutation (and not a polymorphism) found in patients with X-linked mental retardation.     

Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice

We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.     

Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation

The negative role exerted by cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the regulation of T-cell activity, as induced by T-cell receptor (TCR)/CD3 and CD28 costimulation, has been widely described. In the present work we investigated the role of CTLA-4 in the control of cell activation, as induced by costimulation of the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) in murine CD4+ T cells. Results show that CTLA-4 engagement inhibits interleukin-2 (IL-2) production, not only when induced by CD3/CD28 costimulation, but also when CD4+ T cells are costimulated by anti-CD3 and anti-LFA-1 monoclonal antibodies (mAbs). LFA-1 has been described to induce Ca2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA-4 engagement negatively affects Ca2+ mobilization and NF-AT activation, as induced by LFA-1 engagement alone. PLCgamma1 phosphorylation was also dampened within minutes after CTLA-4 engagement. Altogether these data indicate that through the control of signals induced by different receptors, CTLA-4 could be a global attenuator of T-cell activation.     

Detection of West Nile virus in the tissues of specific pathogen free chickens and serological response to laboratory infection: a comparative study.

Using an isolate of West Nile virus (WNV) from lineage 1 (Goose/Israel 1998), groups of specific pathogen free chickens were experimentally infected via the subcutaneous or intravenous routes. To evaluate the relative efficiency of detecting the virus in the infected chickens, samples from a range of tissues and organs were examined by virus isolation tests in tissue culture, including Vero, primary chicken embryo liver and fibroblast cells, and polymerase chain reaction (PCR) analyses. Additionally, in order to investigate the serological response of the chickens and produce WNV monospecific antibodies, serum samples were collected from the birds during the trial and analysed for antibodies by virus neutralization (VN) and the plaque-reduction neutralization test (PRNT). No clinical signs or gross pathological changes were seen in any of the inoculated chickens throughout the study. The nested PCR used in the study appeared to be significantly more sensitive at detecting the presence of the virus in both the tissues and the inoculated Vero cell cultures compared with the detection of gross cytopathic changes as observed in infected Vero cell culture. No cytopathic changes were seen in the inoculated avian cell cultures. Following primary inoculation of the chickens there was a weak antibody response 15 days post-inoculation. However, following re-inoculation with inactivated WNV and adjuvant there was a substantial increase in the neutralizing antibody titres when tested 2 weeks later. The results obtained suggested that the PRNT was more sensitive than the conventional VN test. Based on detection of virus and serology there was no evidence of viral transmission to the close contact controls. It can be concluded that the PCR used in this study was more sensitive than virus isolation for the detection of WNV while the PRNT also appeared more sensitive than the conventional VN test.     

Association of First-Week Nutrient Intake and Extrauterine Growth Restriction in Moderately Preterm Infants: A Regional Population-Based Study

The purpose of this study was to determine the influence of first-week nutrition intake on neonatal growth in moderate preterm (MP) infants. Data on neonatal morbidity and nutrition intake on day of life 7 (DoL7) were prospectively collected from 735 MP infants (32^0/7–34^6/7 weeks gestational age (GA)). Multivariable regression was used to assess the factors associated with extrauterine growth restriction (EUGR) defined as a decrease of more than 1 standard deviation (SD) in the weight z-score during hospitalization. Mean (SD) gestational age and birth weight were 33.2 (0.8) weeks and 2005 (369) g. The mean change in the weight z-score during hospitalization was −0.64 SD. A total of 138 infants (18.8%) had EUGR. Compared to adequate growth infants, EUGR infants received 15% and 35% lower total energy and protein intake respectively (p < 0.001) at DoL7. At DoL7, each increase of 10 kcal/kg/d and 1 g/kg/d of protein was associated with reduced odds of EUGR with an odds ratio of 0.73 (95% CI, 0.66–0.82; p < 0.001) and 0.54 (0.44–0.67; p < 0.001), respectively. Insufficient energy and protein intakes on DoL7 negatively affected neonatal growth of MP infants. Nutritional support should be optimized from birth onwards to improve neonatal weight growth.     

Wellbeing of Breastfeeding Women in Australia and New Zealand during the COVID-19 Pandemic: A Cross-Sectional Study

During the COVID-19 pandemic, breastfeeding women have experienced restricted access to support, placing them at increased risk of mental health concerns and limited breastfeeding assistance. This study investigated the effect of the pandemic on feeding choices and maternal wellbeing amongst breastfeeding mothers living in Australian and New Zealand. We conducted a cross-sectional online survey that examined feeding methods, maternal mental wellbeing, worries, challenges, and positive experiences during the pandemic. Most women were exclusively breastfeeding (82%). Partial breastfeeding was associated with perceived low milk supply and longer pregnancy duration during the pandemic. Reduced mental health and wellbeing was associated with lower levels of family functioning, increased perceived stress, and perinatal anxiety. Longer pregnancy duration during the pandemic was associated with lower mental health wellbeing scores, while higher perceived stress scores were reported for regions with higher COVID-19 infection rates and women with perceived low milk supply. Women reported that the pandemic resulted in less pressure and more time for family bonding, while worries about the pandemic, family health, and parenting challenges were also cited. Mental health concerns of breastfeeding women appear to be exacerbated by COVID-19, highlighting a critical need for access to mental health and broader family support during the pandemic.     

Household Food Insecurity,Lung Function,and COPD in US Adults

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.     

Diet Quality Indices and Physical Activity Levels Associated with Adequacy of Gestational Weight Gain in Pregnant Women with Gestational Diabetes Mellitus

The aim of this study was to evaluate the Diet Quality Index (DQI) and the Physical Activity (PA) levels associated with adequacy of gestational weight gain in pregnant women with gestational diabetes mellitus (GDM). A total of 172 pregnant women with a single fetus and a diagnosis of GDM participated. Food intake was self-reported on the food frequency questionnaire and DQI was quantified using the index validated and revised for Brazil (DQI-R). To assess PA, the Pregnancy Physical Activity Questionnaire was administered. Gestational weight gain was classified, following the criteria of the Institute of Medicine, into adequate (AWG), insufficient (IWG), or excessive (EWG) weight gain. A multinomial logistic regression analysis was performed, with level of significance <0.05. The participants were divided into 3 groups: AWG (33.1%), IWG (27.3%), and EWG (39.5%). The analysis indicated that if the pregnant women PA fell into tertile 1 or 2, then they had a greater chance of having IWG, whereas those with the lowest scores on the DQI-R, whose PA fell into tertile 2, and pregestational obesity women had the greatest chance of having EWG. This study has shown that low PA levels may contribute towards IWG. On the other hand, a low final DQI-R score, representing inadequate food habits, low PA levels, and pregestational obesity may increase the chance of EWG in patients with GDM.