Search

Aim: We aimed to investigate the developmental outcome of children with Robin sequence (RS) for whom continuous positive airway pressure was the main strategy to release upper airway obstruction. Methods: We included children with isolated RS or RS associated with Stickler syndrome who were aged 15 months to 6 years. We used the French version of the Child Development Inventory and calculated the developmental quotient (DQ) for eight different domains and the global DQ (DQ‐global). We searched for determinants of risk of delay. Results: Of the 87 children, for 71%, the developmental evolution was within the norm (DQ‐global ≥86 or ≥−1 SD), 29% were at high risk of delay (DQ‐global <86 or <−1 SD), and only 3% were at very high risk of delay (DQ‐global <70 or <−2 SD). The DQs for expressive language and language comprehension were lower in our study population than the general population, but an improvement was noticed with the children's growth. Conclusion: Risk of a developmental delay was not greater for children with the most severe respiratory phenotype than the others. Children whose mothers had low education levels were more at risk than the others. [ABSTRACT FROM AUTHOR]

Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age‐related alterations and diseases. In this study, we investigated the role of the pro‐senescent phospholipase A2 receptor 1 (PLA2R1) in regulating some age‐related alterations in old mice and in mice subjected to a Western diet, whereas aged wild‐type mice displayed a decreased ability to regulate their glycemia during glucose and insulin tolerance tests, aged Pla2r1 knockout (KO) mice efficiently regulated their glycemia and displayed fewer signs of aging. Loss of Pla2r1 was also found protective against the deleterious effects of a Western diet. Moreover, these Pla2r1 KO mice were partially protected from diet‐induced senescent cell accumulation, steatosis, and fibrosis. Together these results support that Pla2r1 drives several age‐related alterations, especially in the liver, arising during aging or through a Western diet. [ABSTRACT FROM AUTHOR]

The article provides information on a study on the effect of SARS-CoV-2 on lung-cell senescence. Topics discussed include differential gene-expression analysis performed using model-based analysis of single-cell transcriptomics (MAST), expression of senescence markers, and histopathology and immunohistochemistry.

The article discusses a study on the effect of SARS-CoV-2 on lung cell senescence. Topics include older age as a major risk factor for severe coronavirus disease, role of cell senescence in age-associated lung diseases, and persistence of senescent cells in the lungs over time. A causal relationship between endothelial cell (EC) senescence and vascular thrombosis is also noted.

Rationale: Promoting endogenous pulmonary regeneration is crucial after damage to restore normal lungs and prevent the onset of chronic adult lung diseases.Objectives: To investigate whether the cell-cycle inhibitor p16INK4a limits lung regeneration after newborn bronchopulmonary dysplasia (BPD), a condition characterized by the arrest of alveolar development, leading to adult sequelae.Methods: We exposed p16INK4a-/- and p16INK4aATTAC (apoptosis through targeted activation of caspase 8) transgenic mice to postnatal hyperoxia, followed by pneumonectomy of the p16INK4a-/- mice. We measured p16INK4a in blood mononuclear cells of preterm newborns, 7- to 15-year-old survivors of BPD, and the lungs of patients with BPD.Measurements and Main Results: p16INK4a concentrations increased in lung fibroblasts after hyperoxia-induced BPD in mice and persisted into adulthood. p16INK4a deficiency did not protect against hyperoxic lesions in newborn pups but promoted restoration of the lung architecture by adulthood. Curative clearance of p16INK4a-positive cells once hyperoxic lung lesions were established restored normal lungs by adulthood. p16INK4a deficiency increased neutral lipid synthesis and promoted lipofibroblast and alveolar type 2 (AT2) cell development within the stem-cell niche. Besides, lipofibroblasts support self-renewal of AT2 cells into alveolospheres. Induction with a PPARγ (peroxisome proliferator-activated receptor γ) agonist after hyperoxia also increased lipofibroblast and AT2 cell numbers and restored alveolar architecture in hyperoxia-exposed mice. After pneumonectomy, p16INK4a deficiency again led to an increase in lipofibroblast and AT2 cell numbers in the contralateral lung. Finally, we observed p16INK4a mRNA overexpression in the blood and lungs of preterm newborns, which persisted in the blood of older survivors of BPD.Conclusions: These data demonstrate the potential of targeting p16INK4a and promoting lipofibroblast development to stimulate alveolar regeneration from childhood to adulthood. [ABSTRACT FROM AUTHOR]

Background & Aim: The canalicular bile salt export pump (BSEP/ABCB11) of hepatocytes is the main adenosine triphosphate (ATP)‐binding cassette (ABC) transporter responsible for bile acid secretion. Mutations in ABCB11 cause several cholestatic diseases, including progressive familial intrahepatic cholestasis type 2 (PFIC2) often lethal in absence of liver transplantation. We investigated in vitro the effect and potential rescue of a BSEP mutation by ivacaftor, a clinically approved cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7) potentiator. Methods: The p.T463I mutation, identified in a PFIC2 patient and located in a highly conserved ABC transporter motif, was studied by 3D structure modelling. The mutation was reproduced in a plasmid encoding a rat Bsep‐green fluorescent protein. After transfection, mutant expression was studied in Can 10 cells. Taurocholate transport activity and ivacaftor effect were studied in Madin‐Darby canine kidney (MDCK) clones co‐expressing the rat sodium‐taurocholate co‐transporting polypeptide (Ntcp/Slc10A1). Results: As the wild‐type protein, BsepT463I was normally targeted to the canalicular membrane of Can 10 cells. As predicted by 3D structure modelling, taurocholate transport activity was dramatically low in MDCK clones expressing BsepT463I. Ivacaftor treatment increased by 1.7‐fold taurocholate transport activity of BsepT463I (P <.0001), reaching 95% of Bsepwt activity. These data suggest that the p.T463I mutation impairs ATP‐binding, resulting in Bsep dysfunction that can be rescued by ivacaftor. Conclusion: These results provide experimental evidence of ivacaftor therapeutic potential for selected patients with PFIC2 caused by ABCB11 missense mutations affecting BSEP function. This could represent a significant step forward for the care of patients with BSEP deficiency. [ABSTRACT FROM AUTHOR]

Aims Increase of cardiac cAMP bioavailability and PKA activity through adenylyl-cyclase 8 (AC8) overexpression enhances contractile function in young transgenic mice (AC8TG). Ageing is associated with decline of cardiac contraction partly by the desensitization of β-adrenergic/cAMP signalling. Our objective was to evaluate cardiac cAMP signalling as age increases between 2 months and 12 months and to explore whether increasing the bioavailability of cAMP by overexpression of AC8 could prevent cardiac dysfunction related to age. Methods and results Cardiac cAMP pathway and contractile function were evaluated in AC8TG and their non-transgenic littermates (NTG) at 2- and 12 months old. AC8TG demonstrated increased AC8, PDE1, 3B and 4D expression at both ages, resulting in increased phosphodiesterase and PKA activity, and increased phosphorylation of several PKA targets including sarco(endo)plasmic-reticulum-calcium-ATPase (SERCA2a) cofactor phospholamban (PLN) and GSK3α/β a main regulator of hypertrophic growth and ageing. Confocal immunofluorescence revealed that the major phospho-PKA substrates were co-localized with Z-line in 2-month-old NTG but with Z-line interspace in AC8TG, confirming the increase of PKA activity in the compartment of PLN/SERCA2a. In both 12-month-old NTG and AC8TG, PLN and GSK3α/β phosphorylation was increased together with main localization of phospho-PKA substrates in Z-line interspaces. Haemodynamics demonstrated an increased contractile function in 2- and 12-month-old AC8TG, but not in NTG. In contrast, echocardiography and tissue Doppler imaging (TDI) performed in conscious mice unmasked myocardial dysfunction with a decrease of systolic strain rate in both old AC8TG and NTG. In AC8TG TDI showed a reduced strain rate even in 2-month-old animals. Development of age-related cardiac dysfunction was accelerated in AC8TG, leading to heart failure (HF) and premature death. Histological analysis confirmed early cardiomyocyte hypertrophy and interstitial fibrosis in AC8TG when compared with NTG. Conclusion Our data demonstrated an early and accelerated cardiac remodelling in AC8TG mice, leading to the development of HF and reduced lifespan. Age-related reorganization of cAMP/PKA signalling can accelerate cardiac ageing, partly through GSK3α/β phosphorylation. [ABSTRACT FROM AUTHOR]

Copyright of Orthodontie Française is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: A preliminary study of the surface reactivity of 2D‐α‐Mo2C crystallites grown on a copper foil was performed using x‐ray photoelectron spectroscopy. Different sample preparation protocols for the as‐received materials were explored in order to remove hydrocarbon surface contamination. Annealing in vacuum and in argon led to the formation of graphitic layers, while annealing in O2 lead to almost the complete disappearance of the Mo signal. Gentle argon ion sputtering proved effective at removing the hydrocarbon contamination to reveal pristine molybdenum carbide. XPS spectra were recorded following the exposure of the prepared sample at 297 K to furfural. The results are commented on in relation to deoxygenation and olefin metathesis surface chemistry. [ABSTRACT FROM AUTHOR]

Abstract: The effect of silver minerals on the dissolution behaviour of gold particles embedded within multi‐sulphidic minerals was investigated. A multi‐layer packed‐bed reactor approach was used to study the leaching behaviour of free gold (within silica) and gold associated with a series of synthetic multi‐mineral systems consisting of pyrite, silica, and successively, X = chalcopyrite, sphalerite, and stibnite. The reactor was filled with sieved powders of sulphidic minerals (pyrite, X), gold and silica and arranged as electrically‐isolated three‐layer //Pyrite//X//Silica// and two‐layer //Pyrite + X//Silica// systems. Gold powder was introduced successively in each layer of the three‐ and two‐layer mineral systems and the gold leaching behaviour was studied. The highest gold recovery was achieved for the gold particles within the pyrite layer while the lowest was within the silica layer. In case of the //Pyrite//Stibnite//Silica// system, the surface passivation inhibited gold leaching strongly. Gold cyanidation experiments were also performed with the addition of silver minerals, with both Au and Ag minerals dispersed in a three‐layer //Pyrite//X//Silica// and two‐layer //Pyrite + X//Silica// systems. Silver minerals addition proved beneficial for the pyrite‐sphalerite‐silica system. Gold leaching was severely retarded for the pyrite‐chalcopyrite‐silica and pyrite‐stibnite‐silica systems. Passivating films were observed at the surface of gold particles in case of gold cyanidation with pyrite‐chalcopyrite‐silica and pyrite‐stibnite‐silica systems. [ABSTRACT FROM AUTHOR]

Purpose: Microsurgical reconstruction in a vessel-depleted neck is a challenge due to the lack of reliable vessels in or nearby the host site. The use of the internal thoracic pedicle (ITP) by rib section or sparring is a limited option due to the small length of the pedicle of some flaps. However, in cardiac surgery, the internal thoracic artery (ITA) is widely used for myocardial revascularization, providing a long and versatile pedicle. We aimed at determining precise anatomical bases for the use of the ITP, approached by sternotomy and rerouted in the neck, as recipient vessels for free-flap facial reconstructions.Methods: We performed a descriptive single centre anatomical study on 20 formalin-embalmed cadavers. The ITP was harvested on both sides from the emergence of the artery under the brachiocephalic vein to its terminal division. The level reached by the ITP in the cervicofacial area was described. Distal arterial and venous diameters, pedicle length and other parameters were measured.Results: In at least 85% of the cases, the ITP reached the mandibular angle. The mean diameter at the distal extremity for the ITA was 2.36 ± 0.15, and 2.48 ± 0.19 mm for the committing vein. The mean length of the ITP was 177.3 mm.Conclusion: Rerouting the ITP towards the cervicofacial area could provide a reliable pedicle for free-flap reconstructions in patients with a vessel-depleted neck but it should be limited to selected patients. This novel solution for situations where current techniques are unfeasible warrants further clinical research. [ABSTRACT FROM AUTHOR]

Abstract: Lead salt stimulated the dissolution of gold when gold associated with silver minerals was interspersed in the silica or in the pyrite‐silica layer. Gold dissolution was likewise promoted through lead addition for chalcopyrite‐silica and the sphalerite‐silica systems. Lead addition did not boost gold dissolution and a recovery of 6.9 % was achieved for gold and silver minerals dispersed in stibnite. Lead pretreatment also enhanced gold recovery except for the stibnite‐silica system. Gold surface‐passivating films were observed for gold associated with silver minerals and stibnite. [ABSTRACT FROM AUTHOR]

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking. [ABSTRACT FROM AUTHOR]

Aim Long-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice. Methods and results Thirty-three WT mice were subjected to HFD (60% fat, n = 16) and chow diet (CD, 13% fat, n = 17). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks. Invasive haemodynamic data and myocardial samples were collected at 5 and 20 weeks. Echocardiographic data included left ventricular (LV) diameters and thickness, and systolic function using radial strain rate (SR). Histological assessment of cardiomyocyte and adipocyte sizes, interstitial fibrosis, and apoptosis index were performed. During follow-up, body weight, and glycaemia levels were higher in HFD than in CD mice, in association with an early adipose tissue remodelling. Despite no difference between both groups in blood pressure and LV mass at 5 weeks, an early LV dysfunction was observed in HFD mice as assessed by radial SR (21 ± 0.8 vs. 27 ± 0.8 unit/s, P <0.001) and haemodynamic assessment. During follow-up, both groups demonstrated a progressive systolic and diastolic LV dysfunction and remodelling including dilatation and hypertrophy, which were more severe in HFD mice. Compared with CD mice, the early LV impairment in HFD mice was coupled with a higher cardiomyocyte apoptosis level (0.95 vs. 0.02%, P <0.05) associated with an interstitial fibrosis process (2.3 vs. 0.2%, P <0.05), which worsen during follow- up. Conclusion The HFD promoted early metabolic and cardiac dysfunctions, and adipose and myocardial tissues remodelling. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this anatomic study was to compare the retraction force necessary to expose the mandibular neck in the Risdon and the high cervical anteroparotid transmasseteric (HAT) approaches. Methods: An anatomic study was performed on 18 formalin-embalmed cadavers. We performed a Risdon approach on the left side, and an HAT approach on the right side in all the cases. The subjects were placed in a normative frame and the force necessary to maintain a satisfactory exposure of the condyle was measured with a system of cables, pulleys, and mechanical dynamometer. The statistical comparison between the two sides was carried out using the Wilcoxon signed-rank test for paired series. Results: In all the cases, the region of interest was exposed as in the operating room. In the Risdon approach, the mean force was 32 Newtons (4-47). In the HAT approach, the mean force was 19 Newtons (4-33). The difference was statistically significant ( p < 0.001). The age, gender, and duration of conservation had no influence on the retraction force. Conclusion: In the HAT approach, the retraction of the soft tissues was significantly lower than in the Risdon approach. This study gave an additional explanation to the remarkable safety of the HAT approach. Our results were in favor of the generalization of this technique. [ABSTRACT FROM AUTHOR]

Gold is mostly found in metallic form, while silver exists in various mineral forms. Pyrite, chalcopyrite, sphalerite, and stibnite were the sulphidic minerals investigated for the effect of silver sulphide on gold cyanidation. Four sets of mineral systems, pyrite-silica, chalcopyrite-silica, sphalerite-silica, and stibnite-silica, were established to investigate the effect of silver sulphide. Silver sulphide addition promoted gold dissolution for the pyrite-silica and sphalerite-silica systems. The gold dissolution was retarded with the chalcopyrite-silica and stibnite-silica systems, irrespective of the dispersion of gold and silver sulphide in the mineral as well as in the quartz layer. The surface characterization of the gold particles was attempted by using X-ray photoelectron spectroscopy (XPS) in order to identify the surface obstructing species. XPS analysis showed that the passivation layers of silver sulphide (Ag2S), Cu2O/Cu(OH)2, and antimony oxide (Sb2O5) might form on the surface of goldparticles by the simultaneous dissolution of silver sulphide as well as sulphide minerals, resulting in the retardation of gold dissolution. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Patients with empty nose syndrome (ENS) following turbinate surgery often complain about breathing difficulties. We set out to determine if dyspnea in patients with ENS was associated with hyperventilation syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be explained by HVS.Study Design: Observational prospective study.Methods: All consecutive patients referred to our center for ENS over 1 year were invited to participate. Patients completed the Nijmegen score and underwent a hyperventilation provocation test (HVPT) and arterial blood gas and cardiopulmonary tests. HVS was defined by a delayed return of the end-tidal partial pressure of carbon dioxide in the expired gas to baseline during HVPT. Patients with HVS were asked to complete the Sinonasal Outcome Test (SNOT)-16 questionnaire before and after a specific eight-session respiratory rehabilitation program.Results: Twenty-two of the 29 patients referred for ENS during the study period were eligible for inclusion and underwent a complete workup. HVS was diagnosed in 17 of these patients (77.3%). In the five patients who completed the SNOT-16, the score was significantly lower after rehabilitation.Conclusions: This study suggests that HVS is frequent in patients with ENS, and that symptoms can be improved by respiratory rehabilitation. Pathophysiological links between ENS and HVS deserve to be further explored.Level Of Evidence: 2b Laryngoscope, 127:1983-1988, 2017. [ABSTRACT FROM AUTHOR]

Background: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS.Methods: We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h. Before sacrifice, right ventricular systolic pressure and cardiac output were measured and total pulmonary resistance was calculated. After sacrifice, lung inflammation, edema and injury were assessed with bronchoalveolar lavage (BAL) and histology. In other experiments, right ventricular systolic pressure was recorded during hypoxic challenges in uninjured WT mice pretreated with rHuIL-6 or rHuIL-6 + non-selective nitric oxide synthase inhibitor L-NAME or vehicle.Results: IL-6KO(LPS+MV) mice showed a faster deterioration of lung elastic properties and more severe bronchoalveolar cellular inflammation as compared to WT(LPS+MV). Treatment with rHuIL-6 partially prevented this lung deterioration. Total pulmonary resistance was higher in IL-6KO(LPS+MV) mice and this increase was abolished in rHuIL-6-treated IL-6KO mice. Finally, rHuIL-6 reduced hypoxic pulmonary vasoconstriction in uninjured WT mice, an effect that was abolished by co-treatment with L-NAME.Conclusions: In a double-hit murine model of ARDS, IL-6 deficient mice experienced more severe bronchoalveolar cellular inflammation as compared to wild-type littermates. Furthermore, IL-6 deficiency caused marked acute pulmonary hypertension, which may be, at least partially, due to vasoactive mechanisms. A dysregulation of nitric oxide synthase may account for this observation, a hypothesis that will need to be investigated in future studies. [ABSTRACT FROM AUTHOR]

In practice, teacher turnover appears to have negative effects on school quality as measured by student performance. However, some simulations suggest that turnover can instead have large positive effects under a policy regime in which low-performing teachers can be accurately identified and replaced with more effective teachers. This study examines this question by evaluating the effects of teacher turnover on student achievement under IMPACT, the unique performance-assessment and incentive system in the District of Columbia Public Schools (DCPS). Employing a quasi-experimental design based on data from the first years of IMPACT, we find that, on average, DCPS replaced teachers who left with teachers who increased student achievement by 0.08 standard deviation (SD) in math. When we isolate the effects of lower-performing teachers who were induced to leave DCPS for poor performance, we find that student achievement improves by larger and statistically significant amounts (i.e., 0.14 SD in reading and 0.21 SD in math). In contrast, the effect of exits by teachers not sanctioned under IMPACT is typically negative but not statistically significant. [ABSTRACT FROM AUTHOR]

Rationale: Angiopoietins are involved in blood vessel maturation and remodeling. Objectives: One consequence of endothelium-specific tyrosine kinase-2 (Tie2) receptor activation by angiopoietin-1 (Ang1) is the release of endothelium-derived growth factors that recruit vascular wall cells. We investigated this process in idiopathic pulmonary arterial hypertension (iPAH). Methods: Ang1, Ang2, and total and phosphorylated Tie2 expression (mRNA and protein) was evaluated in human lung specimens and in cultured pulmonary artery smooth muscle cells (PA-SMCs) and pulmonary endothelial cells (P-ECs) isolated from patients with iPAH and control subjects. Media collected from Ang1-treated P-ECs were assessed for their PA-SMC growth-promoting effect. Measurements and Main Results: Tie2 receptor was fourfold higher in lungs and P-ECs from patients with iPAH than in those from control subjects, with a parallel increase in phosphorylated lung Tie2 receptor. In contrast, Ang1 and Ang2 expression in lungs, P-ECs, and PA-SMCs did not differ. Incubation of PA-SMCs with medium collected from P-EC cultures induced marked proliferation, and this effect was stronger when using P-ECs from patients with iPAH than from control subjects. Ang1 pretreatment of P-ECs from either patients or control subjects induced a further increase in PA-SMC proliferation. Fluoxetine, an inhibitor of the mitogenic action of serotonin, reduced the growth-promoting effect of P-EC media. Ang1 added to P-ECs from patients with iPAH increased the production of endothelin-1 (ET-1) and serotonin, but not of platelet-derived growth factor-BB or epidermal growth factor, and increased the amount of mRNA encoding tryptophan hydroxylase-1 (the rate-limiting enzyme of serotonin synthesis), preproET-1, and ET-1-converting enzyme. Conclusions: The Ang1/Tie2 pathway is potentiated in iPAH, contributing to PA-SMC hyperplasia via increased stimulation of endothelium-derived growth factors synthesis by P-ECs. [ABSTRACT FROM AUTHOR]

Regional energy efficiency programmes are of particular interest as they tackle local constraints which are not always targeted by national energy policy. Within this framework, an energy efficiency programme for existing dwellings has been implemented in a southern European region, providing financial incentives for a combination of energy efficiency actions (heat pump combined with insulation and/or solar water heater). Ex-post evaluation results of this pilot programme are reported in this study. More than 200 households were surveyed regarding their individual energy consumption as well as house and household characteristics. Likewise, the survey highlights household behaviours concerning both space heating and air conditioning, before and after refurbishment. A 3-year billing analysis is used to calculate the energy savings attributed to the operation. Evaluations are carried out taking into account critical parameters like climate differences between years or direct (enhanced space heating comfort) and indirect (use of air conditioning) rebound effects via a statistical model. Moreover, an uncertainty assessment of energy savings was realized on the basis of three scenarios (low, median and high). This study is particularly focused on the use of air conditioning by households, data rarely found in the literature, whereas the consumption linked to air conditioning should increase in the residential sector especially in southern regions. These results help in answering questions about the installation of heat pumps in existing single-family houses with respect to energy savings as well as direct and indirect rebound effects. [ABSTRACT FROM AUTHOR]

Rationale: Sleep disorders may lead to stress-induced premature aging and telomere shortening.Objectives: To determine whether obstructive sleep apnea syndrome causing intermittent hypoxemic episodes was associated with telomere shortening independently from the comorbidities associated with this syndrome.Methods: We conducted a cross-sectional study in 161prospectivelly enrolled, untreated, middle-aged men free of known comorbidities related or unrelated to sleep apnea. Each participant underwent full standard overnight polysomnography. Patients with apnea sleep syndrome were naive to treatment.Measurements and Main Results: In univariate analysis, we found that telomere shortening was associated with older age, apnea-hypopnea index, oxygen desaturation index, waist circumference, and fat mass. After adjustment for age, only apnea-hypopnea index and oxygen desaturation index were significantly related to telomere shortening. The mean telomere length ratio was 0.70 ± 0.37 in the participants without sleep apnea, compared with 0.61 ± 0.22 and 0.53 ± 0.16 in those with mild to moderate and severe sleep apnea, respectively (P = 0.01). In multivariate analysis, we found that oxygen desaturation index was the only factor independently associated with telomere length. Arterial stiffness assessed by carotid-femoral pulse wave velocity correlated negatively with telomere length.Conclusions: Intermittent hypoxemia due to obstructive sleep apnea syndrome is a major contributor to telomere shortening in middle-aged men. Oxidative stress may explain this finding. [ABSTRACT FROM AUTHOR]

Aims Cardiac involvement is common in sickle cell disease (SCD). Studies are needed to establish haematological determinants of this involvement and prognostic markers. The aim of the study was to identify haematological factors associated with cardiac involvement in SCD and their impact on prognosis. Methods and results This longitudinal observational study was performed on 1780 SCD patients with SS or S-β0-thalassemia referred to our centre. Six hundred fifty-six met our inclusion criteria (availability of a blood-workup and echocardiogram obtained <1 year apart, no heart valve surgery and no current pregnancy). Median age was 31 (interquartile range, 25-40) years, and median haemoglobin (Hb) was 87 (80-95)g/L. Left ventricular (LV) dilation, left atrial dilation, cardiac index (CI) >4 L/min/m², LV ejection fraction <55%, and tricuspid regurgitant velocity (TRV) ≥2.5 m/s were found in 35, 78, 23, 8.5, and 17% of patients, respectively. Compared with other patients, those in the fourth quartiles (Q4) of LV end-diastolic dimension index (LVEDDind) and left atrial dimension index (LADind) and those with high CI had significantly lower Hb, % foetal Hb (HbF), and red blood cell (RBC) counts; and significantly higher lactate dehydrogenase, bilirubin, and %dense RBCs. Independent haematologic determinants of Q4 LVEDDind and LADind were low RBC count and %HbF; high %dense RBCs were associated with LADind. Low %HbF and RBC count were associated with high CI. High %dense RBCs or no a-thalassemia gene deletion was associated with greater severity of anaemia and cardiac dilation and with higher CI. During the median follow-up of 48 (32-59) months, 50 (7.6%) patients died. Tricuspid regurgitant velocity ≥ 2.5 m/s was a predictor of mortality. The risk of death increased four-fold when left ventricular ejection fraction <55% was present also (P = 0.0001). Conclusion Cardiac dilation and CI elevation in patients with SCD are associated with haematologic variables reflecting haemolysis, RBC rigidity, and blood viscosity. Tricuspid regurgitant velocity ≥ 2.5 and LV dysfunction (even mild) predict mortality. [ABSTRACT FROM AUTHOR]

Age-associated decline in organ function governs life span. We determined the effect of aging on lung function and cellular/molecular changes of 8- to 32-month old mice. Proteomic analysis of lung matrix indicated significant compositional changes with advanced age consistent with a profibrotic environment that leads to a significant increase in dynamic compliance and airway resistance. The excess of matrix proteins deposition was associated modestly with the activation of myofibroblasts and transforming growth factor-beta signaling pathway. More importantly, detection of senescent cells in the lungs increased with age and these cells contributed toward the excess extracellular matrix deposition observed in our aged mouse model and in elderly human samples. Mechanistic target of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with those from younger mice associated with the increased expression of the histone variant protein, MH2A, a marker for aging and potentially for senescence. Introduction in the mouse diet of rapamycin, significantly blocked the mTOR activity and limited the activation of myofibroblasts but did not result in a reduction in lung collagen deposition unless it was associated with prevention of cellular senescence. Together these data indicate that cellular senescence significantly contributes to the extracellular matrix changes associated with aging in a mTOR 1-dependent mechanism. [ABSTRACT FROM AUTHOR]

The activation of the calpain system is involved in the repair process following myocardial infarction (MI). However, the impact of the inhibition of calpain by calpastatin, its natural inhibitor, on scar healing and left ventricular (LV) remodeling is elusive. Male mice ubiquitously overexpressing calpastatin (TG) and wild-type (WT) controls were subjected to an anterior coronary artery ligation. Mortality at 6 wk was higher in TG mice (24% in WT vs. 44% in TG, P < 0.05) driven by a significantly higher incidence of cardiac rupture during the first week post-MI, despite comparable infarct size and LV dysfunction and dilatation. Calpain activation post-MI was blunted in TG myocardium. In TG mice, inflammatory cell infiltration and activation were reduced in the infarct zone (IZ), particularly affecting M2 macrophages and CD4+ T cells, which are crucial for scar healing. To elucidate the role of calpastatin overexpression in macrophages, we stimulated peritoneal macrophages obtained from TG and WT mice in vitro with IL-4, yielding an abrogated M2 polarization in TG but not in WT cells. Lymphopenic Rag1-/- mice receiving TG splenocytes before MI demonstrated decreased T-cell recruitment and M2 macrophage activation in the IZ day 5 after MI compared with those receiving WT splenocytes. Calpastatin overexpression prevented the activation of the calpain system after MI. It also impaired scar healing, promoted LV rupture, and increased mortality. Defective scar formation was associated with blunted CD4+ T-cell and M2-macrophage recruitment. [ABSTRACT FROM AUTHOR]

Study Objectives: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle.Design: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied.Settings: Bench study.Results: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied.Conclusion: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Chemical Engineering is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)