Sleep-Disordered Breathing in Children with Prader-Willi Syndrome in Relation to Growth Hormone Therapy Onset.

OBJECTIVE: The aim of this study was to consider sleep apnea in Prader-Willi syndrome (PWS) children depending on age at growth hormone (GH) therapy onset. STUDY DESIGN: We analyzed longitudinally cardiorespiratory polygraphy of 62 PWS children (aged 0-2.5 years at baseline). Twenty-one children (Group A) started GH-therapy during and 41 children (Group B) after their first year of life. Data were acquired before, at 3 and 6 months, then 1.2, 2.2, and 3.2 years after GH onset. Outcomes were determined with the obstructive apnea hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), and by measuring obstructive sleep apnea (OSA) and peripheral blood oxygen saturation (SpO2). RESULTS: We observed no significant differences in OAHI, CAI, ODI, and SpO2 depending on treatment onset. At baseline, 5/21 patients (23.8%) in Group A versus 15/41 patients (36.6%) in Group B showed pathological sleep apnea (OAHI ≥1.5). Pathological OSA increased significantly in Group A during the first 3 months of therapy but dropped below baseline after 1 year in both groups. ODI changed during GH therapy in both groups (from 4.0 to 2.6 in Group A, and 3.6 to 1.6 in Group B; baseline to 3.2 years; p < 0.05). CONCLUSIONS: OSA in PWS children appears to develop independently of treatment onset. Treatment may therefore safely be initiated early but should be accompanied by regular sleep analysis.

Invader presence disrupts the stabilizing effect of species richness in plant community recovery after drought.

Higher biodiversity can stabilize the productivity and functioning of grassland communities when subjected to extreme climatic events. The positive biodiversity-stability relationship emerges via increased resistance and/or recovery to these events. However, invader presence might disrupt this diversity-stability relationship by altering biotic interactions. Investigating such disruptions is important given that invasion by non-native species and extreme climatic events are expected to increase in the future due to anthropogenic pressure. Here we present one of the first multisite invader × biodiversity × drought manipulation experiment to examine combined effects of biodiversity and invasion on drought resistance and recovery at three semi-natural grassland sites across Europe. The stability of biomass production to an extreme drought manipulation (100% rainfall reduction; BE: 88 days, BG: 85 days, DE: 76 days) was quantified in field mesocosms with a richness gradient of 1, 3, and 6 species and three invasion treatments (no invader, Lupinus polyphyllus, Senecio inaequidens). Our results suggest that biodiversity stabilized community productivity by increasing the ability of native species to recover from extreme drought events. However, invader presence turned the positive and stabilizing effects of diversity on native species recovery into a neutral relationship. This effect was independent of the two invader's own capacity to recover from an extreme drought event. In summary, we found that invader presence may disrupt how native community interactions lead to stability of ecosystems in response to extreme climatic events. Consequently, the interaction of three global change drivers, climate extremes, diversity decline, and invasive species, may exacerbate their effects on ecosystem functioning.

Increased CTLA-4+ T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease.

Impaired T helper type 1 (Th1) function is implicated in the susceptibility of patients with chronic obstructive pulmonary disease (COPD) to respiratory infections, which are common causes of acute exacerbations of COPD (AECOPD). To understand the underlying mechanisms, we assessed regulatory T (Treg) cells and the expression of an inhibitory T-cell receptor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Cryopreserved peripheral blood mononuclear cells (PBMC) from patients with AECOPD (n = 17), patients with stable COPD (sCOPD; n = 24) and age-matched healthy non-smoking controls (n = 26) were cultured for 24 hr with brefeldin-A or monensin to detect intracellular or surface CTLA-4 (respectively) by flow cytometry. T cells in PBMC from AECOPD (n = 9), sCOPD (n = 14) and controls (n = 12) were stimulated with anti-CD3 with and without anti-CTLA-4 blocking antibodies and cytokines were quantified by ELISA. Frequencies of circulating T cells expressing intracellular CTLA-4 were higher in sCOPD (P = 0·01), whereas patients with AECOPD had more T cells expressing surface CTLA-4 than healthy controls (P = 0·03). Increased frequencies of surface CTLA-4+ CD4+ T cells and CTLA-4+ Treg cells paralleled increases in plasma soluble tumour necrosis factor receptor-1 levels (r = 0·32, P = 0·01 and r = 0·29, P = 0·02, respectively) in all subjects. Interferon-γ responses to anti-CD3 stimulation were inversely proportional to frequencies of CD4+ T cells expressing intracellular CTLA-4 (r = -0·43, P = 0·01). Moreover, CTLA-4 blockade increased the induction of interferon-γ, tumour necrosis factor-α and interleukin-6 in PBMC stimulated with anti-CD3. Overall, chronic inflammation may expand sub-populations of T cells expressing CTLA-4 in COPD patients and therefore impair T-cell function. CTLA-4 blockade may restore Th1 function in patients with COPD and so aid the clearance of bacterial pathogens responsible for AECOPD.

An evaluation of CD39 as a novel immunoregulatory mechanism invoked by COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are characterized by increased pulmonary and systemic inflammation and commonly caused by bacterial and/or viral infection. Little is known about the T-cell dysregulation in AECOPD that promotes these outcomes. CD39 is an ectonucleotidase able to hydrolyse adenosine triphosphate to create adenosine that may inhibit T-cell responses in patients with AECOPD. Here T-cell expression of CD39 measured by flow cytometry was higher in AECOPD patients than stable COPD patients or healthy controls. Higher expression of CD39 was associated with higher levels of plasma soluble tumor necrosis factor receptor but lower interferon-γ (IFNγ) levels in supernatants from staphylococcal enterotoxin-B stimulated peripheral blood mononuclear cells. This links increased expression of CD39 with systemic inflammation and impaired T-cell responses (e.g. IFNγ). The blockade of CD39 pathways may be a novel approach to the control of AECOPD, reducing the dependency on antibiotics.

Evaluation of the perforators of the anterior communicating artery (AComA) using routine cerebral 3D rotational angiography.

BACKGROUND: Damage to perforating branches of the anterior communicating artery (AComA) is a known complication of surgical or interventional treatment procedures for AComA aneurysm leading to neurologic deficits. In spite of the clinical relevance of these AComA branches, they have not been systematically analyzed using imaging techniques and most of our knowledge is based on post-mortem injection studies or neurosurgical reports. We therefore analyzed three-dimensional rotational angiography (3DRA) images of the AComA, and propose a first imaging definition of the microvascular structures surrounding the AComA. METHODS: Reconstructed 3D data derived from standard-of-care rotational angiography acquisitions (5 s DSA) were retrospectively analyzed. 20 patients undergoing selective cerebral angiography and 3DRA for therapy assessment were included in our study. 3DRA datasets were reconstructed and displayed using the volume rendering technique (VRT). Additionally, multiplanar reformatted CT-like cross-sectional images (MPR) were used to evaluate the number, size, and origin of the perforators of the AComA. RESULTS: Perforating branches of the AComA could be demonstrated in all cases with large interindividual variations in vessel visibility. MPRs appeared to be superior to total VRT volumes in the visualization of the perforating branches of the AComA. CONCLUSIONS: 3DRA can be used to visualize perforating branches of the AComA in vivo. Since damage to these perforators may result in neurologic deficits, visualization of these vessels prior to surgery or endovascular aneurysm treatment could help in the planning of therapeutic interventions. Further refinement of current imaging techniques will be necessary, however, to increase the reliability of small vessel angiography.