Relating cardiorespiratory responses to work rate during incremental ramp exercise on treadmill in children and adolescents: sex and age differences

PURPOSE: Evaluation of cardiopulmonary exercise testing (CPET) slopes such as [Formula: see text] (cardiac/skeletal muscle function) and [Formula: see text] (O2 delivery/utilization), using treadmill protocols is limited because the difficulties in measuring the total work rate ([Formula: see text]). To overcome this limitation, we proposed a new method in quantifying [Formula: see text] to determine CPET slopes.METHODS: CPET's were performed by healthy patients, (n=674, 9-18year) 300 female (F) and 374 male (M), using an incremental ramp protocol on a treadmill. For this protocol, a quantitative relationship based on biomechanical principles of human locomotion, was used to quantify the [Formula: see text] of the subject. CPET slopes were determined by linear regression of the data recorded until the gas exchange threshold occurred.RESULTS: The method to estimate [Formula: see text] was substantiated by verifying that: [Formula: see text] for treadmill exercise corresponded to an efficiency of muscular work similar to that of cycle ergometer; [Formula: see text] (mL min-1W-1) was invariant with age and greater in M than F older than 12 years old (13-14years: 9.6±1.5(F) vs. 10.5±1.8(M); 15-16years: 9.7±1.7(F) vs. 10.6±2.2(M); 17-18years: 9.6±1.7(F) vs. 11.0±2.3(M), p<0.05); similar to cycle ergometer exercise, [Formula: see text] was inversely related to body weight (BW) (r=0.71) or [Formula: see text] (r=0.66) and [Formula: see text] was not related to BW (r=- 0.01), but had a weak relationship with [Formula: see text] (r=0.28).CONCLUSION: The proposed approach can be used to estimate [Formula: see text] and quantify CPET slopes derived from incremental ramp protocols at submaximal exercise intensities using the treadmill, like the cycle ergometer, to infer cardiovascular and metabolic function in both healthy and diseased states

Gender differences in V˙O2 and HR kinetics at the onset of moderate and heavy exercise intensity in adolescents

The majority of the studies on (V)over dotO(2) kinetics in pediatric populations investigated gender differences in prepubertal children during submaximal intensity exercise, but studies are lacking in adolescents. The purpose of this study was to test the hypothesis that gender differences exist in the (V)over dotO(2) and heart rate (HR) kinetic responses to moderate (M) and heavy (H) intensity exercise in adolescents. Twenty-one healthy African-American adolescents (9 males, 15.8 +/- 1.1 year; 12 females, 15.7 +/- 1 year) performed constant work load exercise on a cycle ergometer at M and H. The (V)over dotO(2) kinetics of the male group was previously analyzed (Lai et al., Appl. Physiol. Nutr. Metab. 33:107-117, 2008b). For both genders, (V)over dotO(2) and HR kinetics were described with a single exponential at M and a double exponential at H. The fundamental time constant (tau(1)) of (V)over dotO(2) was significantly higher in female than male at M (45 +/- 7 vs. 36 +/- 11 sec, P < 0.01) and H (41 +/- 8 vs. 29 +/- 9 sec, P < 0.01), respectively. The functional gain (G(1)) was not statistically different between gender at M and statistically higher in females than males at H: 9.7 +/- 1.2 versus 10.9 +/- 1.3 mL min(-1) W-1, respectively. The amplitude of the slow component was not significantly different between genders. The HR kinetics were significantly (tau(1), P < 0.01) slower in females than males at M (61 +/- 16 sec vs. 45 +/- 20 sec, P < 0.01) and H (42 +/- 10 sec vs. 30 +/- 8 sec, P = 0.03). The G(1) of HR was higher in females than males at M: 0.53 +/- 0.11 versus 0.98 +/- 0.2 bpm W-1 and H: 0.40 +/- 0.11 versus 0.73 +/- 0.23 bpm W-1, respectively. Gender differences in the (V)over dotO(2) and HR kinetics suggest that oxygen delivery and utilization kinetics of female adolescents differ from those in male adolescents

Intrinsic NLRP3 inflammasome activity is critical for normal adaptive immunity via regulation of IFN-γ in CD4+ T cells

The NLRP3 inflammasome controls interleukin-1b maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described.We found that the NLRP3 inflammasome assembles in human CD4+ Tcells and initiates caspase-1–dependent interleukin-1b secretion, thereby promoting interferon-g production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in Tcells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses

A Novel Role for CD55 in Granulocyte Homeostasis and Anti-Bacterial Host Defense

Background: In addition to its complement-regulating activity, CD55 is a ligand of the adhesion class G protein-coupled receptor CD97; however, the relevance of this interaction has remained elusive. We previously showed that mice lacking a functional CD97 gene have increased numbers of granulocytes. Methodology/Results: Here,wedemonstratethatCD55-deficientmicedisplay a comparable phenotype with about two-fold more circulating granulocytes in the blood stream, the marginated pool, and the spleen. This granulocytosis was independent of increased complement activity. Augmented numbers of Gr-1-positive cells in cell cycle in the bone marrow indicated a higher granulopoietic activity in mice lacking either CD55 or CD97. Concomitant with the increase in blood granulocyte numbers, Cd55-/mice challenged with the respiratory pathogen Streptococcus pneumoniae developed less bacteremia and died later after infection. Conclusions: Collectively, these data suggest that complement-independent interaction of CD55 with CD97 is functionall

Fetal cardiac intervention for pulmonary atresia with intact ventricular septum: international fetal cardiac intervention registry

Introduction:Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience.Objectives:Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR).Methods:We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics.Results:Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9-31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (+/- 0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%).Conclusions:Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients

The complement cascade as a mediator of tissue growth and regeneration

Recent evidence has demonstrated that the complement cascade is involved in a variety of physiologic and pathophysiologic processes in addition to its role as an immune effector. Research in a variety of organ systems has shown that complement proteins are direct participants in maintenance of cellular turnover, healing, proliferation and regeneration. As a physiologic housekeeper, complement proteins maintain tissue integrity in the absence of inflammation by disposing of cellular debris and waste, a process critical to the prevention of autoimmune disease. Developmentally, complement proteins influence pathways including hematopoietic stem cell engraftment, bone growth, and angiogenesis. They also provide a potent stimulus for cellular proliferation including regeneration of the limb and eye in animal models, and liver proliferation following injury. Here, we describe the complement cascade as a mediator of tissue growth and regeneration

Sleep and immune function

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations

CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis

The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6 -/- mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6 -/- mice and C1qtnf6 -/- embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H 2 O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases