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Purpose Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia. Materials and Methods Baseline data were used from a multicenter prospective cohort study of 221 unselected children with sickle cell anemia. A questionnaire was used to evaluate, by parental report during the previous month, the presence of enuresis and its severity. Overnight polysomnography was used to determine the presence of sleep disordered breathing by the number of obstructive apneas and/or hypopneas per hour of sleep. Logistic and ordinal regression models were used to evaluate the association of sleep disordered breathing and enuresis. Results The mean age of participants was 10.1 years (median 10.0, range 4 to 19). Enuresis occurred in 38.9% of participants and was significantly associated with an obstructive apnea-hypopnea index of 2 or more per hour after adjusting for age and gender (OR 2.19; 95% CI 1.09, 4.40; p = 0.03). Enuresis severity was associated with obstructive apneas and hypopneas with 3% or more desaturation 2 or more times per hour with and without habitual snoring (OR 3.23; 95% CI 1.53, 6.81; p = 0.001 and OR 2.07; 95% CI 1.09, 3.92; p = 0.03, respectively). Conclusions In this unselected group of children with sickle cell anemia, sleep disordered breathing was associated with enuresis. Results of this study support that children with sickle cell anemia who present with enuresis should be evaluated by a pulmonologist for sleep disordered breathing.

In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. When the redox-sensitive oligomerization state of PTX3 was further investigated, PTX3 accumulated as an octamer as a result of disulfide-bond formation in heart, kidney, and lung—common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in circulation. The oligomerization state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the oligomerization state of PTX3 between survivors and non-survivors. From day 2 onward, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post-admission, octameric PTX3 was barely detectable in survivors, but it still constituted more than half of the total PTX3 in non-survivors (p < 0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP and high-sensitivity troponin I and T. Relative to the conventional measurements of total PTX3 or NT-proBNP, the oligomerization of PTX3 was a superior predictor of disease outcome.

AimsSepsis-associated cardiac dysfunction represents an intrinsic impairment of cardiomyocyte function due in part to a decrease in myofilament Ca2+ sensitivity associated with a sustained increase in cardiac troponin I (cTnI) phosphorylation at Ser23/24. Dephosphorylation of cTnI is under regulatory control. Thus, muscarinic and adenosine A1-receptor agonists antagonize β-adrenergic stimulation via activation of protein phosphatase 2A (PP2A). The aim of this study was to determine whether modulation of PP2A and thus cTnI phosphorylation could improve sepsis-induced contractile dysfunction.Methods and resultsCardiomyocytes were isolated from control or septic mice 16–18 h after an injection of vehicle or lipopolysaccharide (LPS; 9 mg/kg ip) respectively. Protein expression and phosphatase activity were determined in homogenates of control and septic hearts. Our data showed that LPS significantly increased cTnI phosphorylation at Ser23/24 in cardiomyocytes and reduced contraction amplitude without affecting Ca2+-transients. Treatment of cardiomyocytes with the A1 agonist cyclopentyladenosine (CPA) or the protein kinase A inhibitor H89 significantly attenuated the LPS-induced contractile dysfunction without effect on Ca2+-transients. Co-treatment with CPA and H89 completely reversed the contractile dysfunction. Increased cTnI phosphorylation in septic hearts was associated with a significant reduction in the protein expression of both the catalytic and regulatory subunits (B56α) of PP2A and a decrease in PP2A activity. CPA treatment of septic hearts increased PP2A activity. An increase in the protein expression of demethylated PP2A and a decrease in the PP2A-methyltransferase (PPMT; the methyltransferase that catalyses this reaction) were also observed.ConclusionThese data support the hypothesis that sustained cTnI phosphorylation underlies the contractile dysfunction seen in sepsis.