Trio RNA sequencing in a cohort of medically complex children.

Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders. Although GS can enumerate most non-coding variation, determining which non-coding variants are disease-causing is challenging. RNA sequencing (RNA-seq) has emerged as an important tool to help address this issue, but its diagnostic utility remains understudied, and the added value of a trio design is unknown. We performed GS plus RNA-seq from blood using an automated clinical-grade high-throughput platform on 97 individuals from 39 families where the proband was a child with unexplained medical complexity. RNA-seq was an effective adjunct test when paired with GS. It enabled clarification of putative splice variants in three families, but it did not reveal variants not already identified by GS analysis. Trio RNA-seq decreased the number of candidates requiring manual review when filtering for de novo dominant disease-causing variants, allowing for the exclusion of 16% of gene-expression outliers and 27% of allele-specific-expression outliers. However, clear diagnostic benefit from the trio design was not observed. Blood-based RNA-seq can facilitate genome analysis in children with suspected undiagnosed genetic disease. In contrast to DNA sequencing, the clinical advantages of a trio RNA-seq design may be more limited.

Effects of sclerostin injection on soleus and extensor digitorum longus muscle tissue in male mice.

Sclerostin, a potent inhibitor of the Wnt signaling pathway, plays a critical role in bone homeostasis. Evidence suggests that sclerostin may also be involved in crosstalk between other tissues, including muscle. This pilot study attempted to examine the effects of sclerostin on soleus and extensor digitorum longus (EDL) muscle tissue from male mice that were given continuous recombinant sclerostin injections for 4 weeks. A total of 48 10-week-old male C57BL/6J mice were assigned to be sedentary or perform 1 h treadmill running per day for 4 weeks and administered subcutaneous injections of either saline or recombinant sclerostin 5 days/week. Sclerostin injection led to a reduction in the soleus myosin heavy chain (MHC) I, MHC I/IIA, MHC IIA/X, and MHC IIB cross-sectional area (p < 0.05) with no exercise effects on these reductions. In contrast, there were no effects of sclerostin injections or exercise on the fast-twitch EDL muscle in terms of size, MHC protein, or markers of Wnt signaling. These findings provide preliminary evidence of sclerostin's endocrine role in muscle via decreases in myofiber cross-sectional area, which seems to be independent of fiber type but muscle type-specific. More studies, however, are needed to confirm these preliminary results.

Motor unit firing rates during slow and fast contractions in boys and men.

BACKGROUND: Motor unit (MU) activation during maximal contractions is lower in children compared with adults. Among adults, discrete MU activation differs, depending on the rate of contraction. We investigated the effect of contraction rate on discrete MU activation in boys and men. METHODS: Following a habituation session, 14 boys and 20 men completed two experimental sessions for knee extension and wrist flexion, in random order. Maximal voluntary isometric torque (MVIC) was determined before completing trapezoidal isometric contractions (70%MVIC) at low (10%MVIC/s) and high (35%MVIC/s) contraction rates. Surface electromyography was captured from the vastus lateralis (VL) and flexor carpi radialis (FCR) and decomposed into individual MU action potential (MUAP) trains. RESULTS: In both groups and muscles, the initial MU firing rate (MUFR) was greater (p < 0.05) at high compared with low contraction rates. The increase in initial MUFR at the fast contraction in the VL was greater in men than boys (p < 0.05). Mean MUFR was significantly lower during fast contractions only in the FCR (p < 0.05). In both groups and muscles, the rate of decay of MUFR with increasing MUAP amplitude was less steep (p < 0.05) during fast compared with slow contractions. CONCLUSION: In both groups and muscles, initial MUFRs, as well as MUFRs of large MUs were higher during fast compared with slow contractions. However, in the VL, the increase in initial MUFR was greater in men compared with boys. This suggests that in large muscles, men may rely more on increasing MUFR to generate torque at faster rates compared with boys.

Different discrete motor-unit activation patterns in the flexor carpi radialis in boys and men.

BACKGROUND: Lower activation of higher threshold (type-II) motor units (MUs) has been suggested in children compared with adults. We examined child-adult differences in discrete MU activation of the flexor carpi radialis (FCR). METHODS: Fifteen boys (10.2 ± 1.4 years), and 17 men (25.0 ± 2.7 years) completed 2 laboratory sessions. Following a habituation session, maximal voluntary isometric wrist flexion torque (MVIC) was determined before completing trapezoidal isometric contractions at 70%MVIC. Surface electromyography was captured by Delsys Trigno Galileo sensors and decomposed into individual MU action potential trains. Recruitment threshold (RT), and MU firing rates (MUFR) were calculated. RESULTS: MVIC was significantly greater in men (10.19 ± 1.92 Nm) than in boys (4.33 ± 1.47 Nm) (p < 0.05), but not statistically different after accounting for differences in body size. Mean MUFR was not different between boys (17.41 ± 7.83 pps) and men (17.47 ± 7.64 pps). However, the MUFR-RT slope was significantly (p < 0.05) steeper (more negative) in boys, reflecting a progressively greater decrease in MUFR with increasing RT. Additionally, boys recruited more of their MUs early in the ramped contraction. CONCLUSION: Compared with men, boys tended to recruit their MUs earlier and at a lower percentage of MVIC. This difference in MU recruitment may explain the greater decrease in MUFR with increasing RT in boys compared with men. Overall, these findings suggest an age-related difference in the neural strategy used to develop moderate-high torque in wrist flexors, where boys recruit more of their MUs earlier in the force gradation process, possibly resulting in a narrower recruitment range.

Bone Turnover Markers and Osteokines in Adolescent Female Athletes of High- and Low-Impact Sports Compared With Nonathletic Controls.

This study examined differences in resting concentrations of markers of bone formation and resorption, and osteokines between female adolescent (12-16 y) swimmers, soccer players, and nonathletic controls. Resting, morning blood samples were obtained after an overnight fast from 20 swimmers, 20 soccer players, and 20 nonathletic controls, matched for age. carboxyl-terminal cross-linking telopeptide of type I collagen (CTX), amino-terminal propeptide of type I collagen (P1NP), total osteocalcin (OC), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa B ligand (RANKL) were analyzed in serum. After controlling for percent body fat, there were no significant differences between swimmers and nonathletic controls in any of the measured markers. In contrast, soccer players had significantly higher P1NP (89.5 [25.6] ng·mL-1), OC (57.6 [22.9] ng·mL-1), and OPG (1052.5 [612.6] pg·mL-1) compared with both swimmers (P1NP: 66.5 [20.9] ng·mL-1; OC: 24.9 [12.5] ng·mL-1; OPG: 275.2 [83.8] pg·mL-1) and controls (P1NP: 58.5 [16.2] ng·mL-1; OC: 23.2 [11.9] ng·mL-1; OPG: 265.4 [97.6] pg·mL-1), with no differences in CTX, sclerostin, and RANKL. These results suggest that bone formation is higher in adolescent females engaged in high-impact sports like soccer compared with swimmers and controls.

Ursolic Acid against Prostate and Urogenital Cancers: A Review of In Vitro and In Vivo Studies.

Prostate cancer is the second most diagnosed form of cancer in men worldwide and accounted for roughly 1.3 million cases and 359,000 deaths globally in 2018, despite all the available treatment strategies including surgery, radiotherapy, and chemotherapy. Finding novel approaches to prevent and treat prostate and other urogenital cancers effectively is of major importance. Chemicals derived from plants, such as docetaxel and paclitaxel, have been used in cancer treatment, and in recent years, research interest has focused on finding other plant-derived chemicals that can be used in the fight against cancer. Ursolic acid, found in high concentrations in cranberries, is a pentacyclic triterpenoid compound demonstrated to have anti-inflammatory, antioxidant, and anticancer properties. In the present review, we summarize the research studies examining the effects of ursolic acid and its derivatives against prostate and other urogenital cancers. Collectively, the existing data indicate that ursolic acid inhibits human prostate, renal, bladder, and testicular cancer cell proliferation and induces apoptosis. A limited number of studies have shown significant reduction in tumor volume in animals xenografted with human prostate cancer cells and treated with ursolic acid. More animal studies and human clinical studies are required to examine the potential of ursolic acid to inhibit prostate and other urogenital cancers in vivo.

Postexercise serum from humans influences the biological tug of war of APP processing in human neuronal cells.

Neurodegenerative diseases such as Alzheimer's disease (AD) are becoming more prevalent in our aging society. One specific neuropathological hallmark of this disease is the accumulation of amyloid-ß (Aß) peptides, which aggregate to form extraneuronal plaques. Increased Aß peptides are often observed well before symptoms of AD develop, highlighting the importance of targeting Aß-producing pathways early on in disease progression. Evidence indicates that exercise has the capacity to reduce Aß peptide production in the brain; however, the mechanisms remain unknown. Exercise-induced signaling mediators could be the driving force behind some of the beneficial effects observed in the brain with exercise. The purpose of this study was to examine if postexercise serum and the factors it contains can alter neuronal amyloid precursor protein (APP) processing. Human SH-SY5Y neuronal cells were differentiated with retinoic acid for 5 days and treated with 10% pre- or postexercise serum from humans for 30 min. Cells were collected for analysis of acute (30 min; n = 6) or adaptive (24 h posttreatment; n = 6) responses. There were no statistical differences in a disintegrin and metalloproteinase 10 (ADAM10) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) mRNA or protein expression with postexercise serum treatment at either time point. However, there was an increase in the ratio of soluble amyloid precursor protein α (sAPPα) to soluble amyloid precursor protein ß (sAPPß) protein content (P = 0.05) after 30 min of postexercise serum treatment. In addition, 30 min of postexercise serum treatment increased ADAM10 (P = 0.01) and BACE1 (P = 0.02) activity. These findings suggest that postexercise serum modulates important enzymes involved in APP processing, potentially pushing the cascade toward the nonamyloidogenic arm.

Menstrual Cycle Related Fluctuations in Circulating Markers of Bone Metabolism at Rest and in Response to Running in Eumenorrheic Females.

This study examined potential fluctuations in bone metabolic markers across the menstrual cycle both at rest and after a 30-min bout of continuous running at 80% of V̇O2max. Resting and post-exercise (0, 30, 90 min) sclerostin, parathyroid hormone (PTH), carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTXI), and procollagen type 1 N propeptide (PINP) were assessed in 10 eumenorrheic women (age: 21 ± 3 y, BMI: 23.2 ± 3.0 kg.m2) during the mid- to late-follicular (FP: day 8.0 ± 1.4) and mid-luteal (LP: day 22.0 ± 2.5) phases of the menstrual cycle. Ovulation was determined using ovulation kits and daily measurement of oral body temperature upon awakening. Menstrual cycle phase was subsequently confirmed by measurement of plasma estradiol and progesterone. On average, resting estradiol concentrations increased from 46.3 ± 8.9 pg·mL-1 in the FP to 67.3 ± 23.4 pg·mL-1 in the LP (p = 0.015), and resting progesterone increased from 4.12 ± 2.36 ng·mL-1 in the FP to 11.86 ± 4.49 ng·mL-1 in the LP (p < 0.001). At rest, there were no differences between menstrual cycle phases in sclerostin (FP: 260.1 ± 135.0 pg·mL-1; LP: 303.5 ± 99.9 pg·mL-1; p = 0.765), PTH (FP: 0.96 ± 0.64 pmol·L-1; LP: 0.79 ± 0.44 pmol·L-1; p = 0.568), ß-CTXI (FP: 243.1 ± 158.0 ng·L-1; LP: 202.4 ± 92.3 ng·L-1; p = 0.198), and PINP (FP: 53.6 ± 8.9 µg·L-1; LP: 66.2 ± 20.2 µg·L-1; p = 0.093). Main effects for time (p < 0.05) were shown in sclerostin, PTH, ß-CTXI and PINP, without phase or interaction effects. Sclerostin increased from pre- to immediately post-exercise (45%; p = 0.007), and so did PTH (43%; p = 0.011), both returning to resting concentrations 30 min post-exercise. ß-CTXI decreased from pre- to post-exercise (20%; p = 0.027) and was still below its pre-exercise concentrations at 90 min post-exercise (17%; p = 0.013). PINP increased immediately post-exercise (29%; p < 0.001), returning to resting concentrations at 30 min post-exercise. These results demonstrate no effect of menstrual cycle phase on resting bone marker concentrations or on the bone metabolic marker response to intense exercise.

Cytokine concentrations in saliva vs. plasma at rest and in response to intense exercise in adolescent athletes.

BACKGROUND: Salivary measures are advantageous in conducting large paediatric studies involving repeated measures. However, research measuring salivary cytokines in youth is limited. AIM: Compare salivary with plasma concentrations of inflammatory cytokines at rest and following exercise in adolescent swimmers (21 male, 22 female). METHODS: Following collection of resting saliva and blood samples, participants performed a bout of high-intensity interval swimming, with samples taken again ∼15 min post-swimming and analysed for interleukin-6 (IL-6), interleukin 10 (IL-10), and tumour necrosis factor-alpha (TNF-α). RESULTS: Resting IL-10 was significantly lower, while IL-6 and TNF-α were significantly higher in saliva compared with plasma. IL-10 increased from pre- to post-swimming in plasma, but less so in saliva (51% vs. 29%; p = 0.02). TNF-α decreased post-swimming in saliva, but not in plasma (-27% vs -1%; p = 0.01). IL-6 decreased post-swimming in saliva compared with plasma (-21% vs. -3%; p = 0.06). Intraclass correlation coefficients (ICC) revealed no association between salivary and plasma IL-6 and TNF-α, while IL-10 showed a weak correlation only at rest (ICC = 0.39; p = 0.05). CONCLUSIONS: Differences in concentrations and exercise responses, along with weak correlations, suggest that salivary cytokine levels are not an accurate representation of blood cytokine levels, and should not be used as a surrogate measure in paediatric studies.

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence.

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.

Comparison of laser speckle contrast imaging and laser-Doppler fluxmetry in boys and men.

OBJECTIVE: We compare microvascular reactivity assessed by laser-Doppler fluxmetry (LDF) and laser speckle contrast imaging (LSCI) of boys and men during rest, post-occlusive reactive hyperaemia (PORH), and cycling exercise. METHODS: 19 boys (9 ±â€¯1 y) and 18 men (22 ±â€¯2 y) participated. LDF and LSCI measures were taken of the forearm during rest, PORH, and exercise. RESULTS: For all 3 assessments, the LSCI presented with higher flux values than the LDF for both boys and men (p < 0.001). Bland-Altman analyses indicated that there was a positive linear bias between LSCI and LDF measurements in both boys and men. Regression analyses showed that the responses for the two methods were variable, depending on the particular assessment. For instance, at rest in boys there was no relationship between LDF and LSCI (r2 = 0.002), while in men there was a strong relationship (r2 = 0.86). CONCLUSIONS: LSCI presented with higher values than LDF during rest, PORH, and exercise; the disparity between the two measures was larger as blood flow increased. The assessments were generally consistent, both methods appear to provide usable data for the assessment of microvascular reactivity in both boys and men. There are biases to each method and the data are not interchangeable between LDF and LSCI.

Dairy product intake decreases bone resorption following a 12-week diet and exercise intervention in overweight and obese adolescent girls.

BACKGROUND: We examined whether increased dairy intake was associated with changes in the levels of bone-related biochemical markers in overweight/obese adolescent girls undergoing a 12-week diet and exercise intervention. METHODS: Thirty-five girls were assigned to a low dairy group (LDa; 0-2 servings/day; n = 16) or a higher dairy group (RDa; 4 servings/day; n = 19). Morning, fasted/resting blood samples were collected before and after the intervention and serum concentrations of procollagen-type-1-N-terminal-propeptide (P1NP), ß-isomerized-C-terminal-cross-linking-telopeptides (ß-CTX), osteocalcin (OC), 25-hydroxyvitamin-D, sclerostin and parathyroid hormone were measured. RESULTS: At baseline, there were no significant differences between groups in any bone variable. Changes (∆) over time in ß-CTΧ (p = 0.035; interaction) and OC (p = 0.015; interaction) were significantly different between groups characterized by decreases in RDa and increases in LDa. P1NP and P1NP:ß-CTX ratio decreased in both groups (main time effects: p = 0.003, p = 0.041, respectively). ∆ß-CTX (r = -0.37; p = 0.028) and ∆OC (r = -0.39; p = 0.021) were correlated with average number of dairy servings consumed during the study and with each other (r = 0.45; p = 0.006). ∆OC was not correlated with ∆P1NP (r = 0.19; p = 0.27). CONCLUSIONS: Our results suggest that the osteogenic response to a diet and exercise program in this population can be improved with increased dairy intake via a decrease in bone resorption. IMPACT: We demonstrated that bone resorption significantly decreased over the intervention period in the group consuming adequate levels of dairy products compared to the group consuming little to no dairy products. Change in bone resorption was negatively correlated with average number of dairy servings consumed during the study. Our results suggest that the osteogenic response to a diet and exercise program in this population can be improved with increased dairy intake via a decrease in bone resorption. This is the first study to date to assess changes in bone marker status following a lifestyle intervention with exercise and different intakes of dairy products in a sample of OW/OB adolescent girls. We provide evidence that increased dairy product intake is associated with beneficial changes in circulating levels of bone-related biochemical markers in these girls undergoing a 12-week lifestyle (nutrition counseling and exercise training) intervention program. The main impact of our work relates particularly to the recent changes to Canada's food guide. Using the old recommendations, we demonstrated that the inclusion of 3-4 servings of mixed dairy foods per day improved bone health (primarily as a decrease in resorption) in OW/OB adolescent girls and that this level of dairy product intake appears appropriate and should still be encouraged for this age group. We also demonstrated that adolescent girls, a group that usually does not sufficiently consume dairy products, also improved their BMI percentile and nutrient intake with the inclusion of dairy products in their diets.

The skin blood flow response to exercise in boys and men and the role of nitric oxide.

PURPOSE: Children thermoregulate effectively during exercise despite sweating rate being consistently lower when compared with adults. The skin blood flow (SkBF) response of children to exercise is inconsistent, when compared with adults. We examined the SkBF response to exercise in children and adults, along with the potential contribution of nitric oxide to the SkBF response. METHODS: Forearm SkBF during cycling (30 min at 60% [Formula: see text]O2max) was investigated in 12 boys (10 ± 1 years) and 12 men (22 ± 2 years) using laser-Doppler flowmetry and Nω-nitro-L-arginine methyl ester (L-NAME) iontophoresis to inhibit nitric oxide synthase. RESULTS: The exercise-induced SkBF increase was similar in boys and men (mean ± SD, 540 ± 127 vs. 536 ± 103% baseline, respectively, p = 0.43, d = 0.01 [- 0.8 to 0.8]). However, the total hyperaemic response to exercise (area-under-the-curve, AUC) indicated that boys had a greater vasodilatory response (cutaneous vascular resistance, CVC) (p < 0.01, d = 0.6 [- 1.2 to 2.8] than the men (134,215 ± 29,207 vs. 107,257 ± 20,320 CVC·s-1). L-NAME blunted the SkBF response more in boys than in men (group-by-treatment interaction, p < 0.001) and resulted in smaller AUC in boys (56,411 ± 23,033 CVC·s-1; p < 0.001, d = 1.4 [- 0.4 to 3.2] compared with men (80,556 ± 28,443 CVC·s-1; p = 0.08, d = 0.8 [0.0-1.6]). Boys had a shorter delay from the onset of exercise to onset of SkBF response compared with men (205 ± 48 and 309 ± 71 s, respectively; p < 0.01, d = 1.7 [0.9-2.8]). L-NAME increased the delay in boys and men (to 268 ± 90 and 376 ± 116 s, respectively; p = 0.01, d = 1.0 [0.4-2.1]) but this delay was not significantly different between the groups (p = 0.85). CONCLUSIONS: These findings suggest that boys experience greater vasodilation and faster increases in SkBF during exercise compared with men. The contribution of nitric oxide to the SkBF response to exercise appears to be greater in boys than in men.

Correction to: The skin blood flow response to exercise in boys and men and the role of nitric oxide.

One of the co-authors, Raffy Dotan, wishes to remove his name from the original version of this article. The corrected author group should be.

Salivary and Serum Concentrations of Cortisol and Testosterone at Rest and in Response to Intense Exercise in Boys Versus Men.

This study compared salivary and serum concentrations of testosterone and cortisol at rest and in response to intense multitask exercise in boys and men. Early morning saliva and venous blood samples were obtained before and 15 minutes after exercise from 30 competitive swimmers (15 boys, age 14.3 [1.9] y; 15 men, age 21.7 [3.1] y). Exercise included a swim-bench maximal strength task and an all-out 200-m swim, followed by a high-intensity interval swimming protocol (5 × 100 m, 5 × 50 m, and 5 × 25 m). At baseline, fasting testosterone (but not cortisol) concentration was higher in men than boys in serum and saliva (P < .05). Salivary and serum cortisol increased postexercise, with a greater increase in men compared with boys (men: 226% and 242%; boys: 78% and 64%, respectively; group by time interaction, P < .05). Testosterone was reduced postexercise in serum but not in saliva (men: -14.7% and 0.1%; boys: -33.9% and -4.5%, respectively, fluid by time interaction, P < .01). Serum and salivary cortisol (but not testosterone), preexercise and postexercise values were strongly correlated in both men and boys (r = .79 and .82, respectively; P < .01). In summary, early morning high-intensity exercise results in a decrease in testosterone in serum, but not saliva, and an increase in cortisol irrespective of the fluid used, in both boys and men. When examining immediate postexercise changes, the lack of correlation in testosterone between saliva and serum suggests that saliva may not be an appropriate fluid to examine changes in testosterone. The high correlation observed between serum and saliva for cortisol indicates that, in both boys and men, saliva may be used to monitor the immediate cortisol response to exercise.

Low dose lithium supplementation activates Wnt/ß-catenin signalling and increases bone OPG/RANKL ratio in mice.

Lithium, a well-known inhibitor of glycogen synthase kinase-3ß (GSK3ß), can improve bone formation by activating the Wnt/ß-catenin signalling pathway. However, most studies have used higher doses of lithium, which potentially have adverse effects. Herein, we report that low dose lithium supplementation (10 mg/kg/d for 6 weeks) in mice results in a serum lithium concentration of 0.02 mM significantly inhibiting GSK3ß while activating Wnt/ß-catenin in bone. In turn, we observed a significant increase in the expression of osteoprotegerin (OPG), with unaltered expression of nuclear-factor kß ligand (RANKL), ultimately leading to a significant increase in the OPG/RANKL ratio. Altogether, our findings provide initial evidence that low dose lithium supplementation can promote the signalling pathways associated with bone formation.

Comparison of different wheelchair seating on thermoregulation and perceptual responses in thermoneutral and hot conditions in children.

We examined the effects of 4 different wheelchair seatings on physiological and perceptual measures in 21 healthy, pre-pubertal children (9 ±â€¯2 years). Participants were able-bodied and did not regularly use a wheelchair. Participants sat for 2 h in Neutral (∼22.5 °C, ∼40%RH) and Hot (∼35 °C, ∼37%RH) conditions. Four seating technologies were: standard incontinent cover and cushion (SEAT1); standard incontinent cover with new cushion (SEAT2) were tested in Neutral and Hot; new non-incontinent cover with new cushion (SEAT3); new incontinent cover and new cushion (SEAT4) were tested in Neutral only. Measurements included skin blood flow (SkBF), sweating rate (SR) and leg skin temperature (TlegB) on the bottom of the leg (i.e. skin-seat interface), heart rate (HR), mean skin temperature, tympanic temperature, thermal comfort, and thermal sensation. During Neutral, SkBF and TlegB were lower (∼50% and ∼1 °C, respectively) and SR higher (∼0.5 mg cm-2·min-1) (p < 0.05) with SEAT3 compared to all other seats. SkBF was ∼30% lower (p < 0.05) for SEAT2 and SEAT4 compared to SEAT1. No other differences were observed between SEATs (all p > 0.05). During Hot, HR and temperatures were higher than in Neutral but there were no differences (p > 0.05) between SEATs. New cover and cushion improved thermoregulatory responses during Neutral but not Hot. An impermeable incontinent cover negated improvements from cushion design. Seat cover appears more important than seat cushion during typical room conditions.

Effect of passive heat exposure on cardiac autonomic function in healthy children.

PURPOSE: The aim of this study was to examine the effect of passive heat stress on heart rate variability parameters in healthy children. METHOD: Fifteen children (9.3 ± 1.6 years) of both sexes (eight male) participated in two randomized experimental conditions separated by 5-12 days. Children were seated for 2 h in an environmental chamber for two sessions: neutral (22.4 ± 0.1 °C, 40.4 ± 6.5% RH) and hot (34.9 ± 0.3 °C, 36.6 ± 6.2% RH) conditions. Electrocardiogram, mean skin temperature, tympanic temperature, and blood pressure were recorded. Five min epochs were averaged for analysis of cardiac autonomic function over the 2-h protocol. RESULT: Mean skin and tympanic temperatures and heart rate increased during the hot condition (all p < 0.01) while mean arterial pressure decreased (p < 0.01). During the hot condition, root-mean-square difference of successive normal RR intervals (45 ± 9 to 38 ± 7 ms), and low- (LF, 1536 ± 464 vs. 935 ± 154 ms2) and high-frequency power (HF, 1544 ± 693 vs. 866 ± 355 ms2) decreased, whereas LF/HF ratio increased (1.64 ± 0.24 vs. 2.40 ± 0.23 au); all indices were different from neutral (all p < 0.05). These were all unchanged throughout the neutral condition (all p > 0.05), except for LF/HF ratio which decreased during the neutral condition (p < 0.05). CONCLUSION: Mild hyperthermia elicited marked changes in cardiac autonomic control in young children. These data suggest that, in healthy children, vagal withdrawal is responsible for the cardiac autonomic response to hyperthermia.

Wnt Signaling-Related Osteokines at Rest and Following Plyometric Exercise in Prepubertal and Early Pubertal Boys and Girls.

PURPOSE: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. METHODS: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-ß ligand (RANKL). RESULTS: Girls had higher resting sclerostin than boys [187.1 (40.1) vs 150.4 (36.4) pg·mL-1, respectively; P = .02]. However, boys had higher DKK-1 [427.7 (142.3) vs 292.8 (48.0) pg·mL-1, respectively; P = .02] and RANKL [3.9 (3.8) vs 1.0 (0.4) pg·mL-1, respectively; P < .01] than girls. In girls, sclerostin significantly decreased 5-minute and 1-hour postexercise (χ2 = 12.7, P = .01), and RANKL significantly decreased 5-minute postexercise (χ2 = 19.1, P < .01) and continued to decrease up to 24-hour postexercise, with large effect sizes. In boys, DKK-1 significantly decreased 1-hour postexercise and remained lower than preexercise 24-hour postexercise (χ2 = 13.0, P = .01). OPG increased in both boys (χ2 = 13.7, P < .01) and girls (χ2 = 11.4, P = .01), with boys having significantly higher OPG at 5-minute and 1-hour postexercise, whereas in girls, this increase was only seen 24-hour postexercise. CONCLUSION: Plyometric exercise induces an overall anabolic osteokine response favoring osteoblastogenesis over osteoclastogenesis in both boys and girls although the timeline and mechanism(s) may be different.

Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: the PRO-BONE study.

PURPOSE: Soft tissues, such as fat mass (FM) and lean mass (LM), play an important role in bone development but this is poorly understood in highly active youths. The objective of this study was to determine whether FM or LM is a stronger predictor of areal bone mineral density (aBMD) and hip geometry estimates in a group of physically active boys after adjusting for height, chronological age, moderate-to-vigorous physical activity (MVPA), FM, and LM. METHODS: Participants included 121 boys (13.1 ± 1.0 years) from the PRO-BONE study. Bone mineral content (BMC) and aBMD were measured at total body, femoral neck and lumbar spine using dual-energy X-ray absorptiometry (DXA), and hip structural analysis was used to estimate bone geometry at the femoral neck. Body composition was assessed using DXA. The relationships of FM and LM with bone outcomes were analysed using simple and multiple linear regression analyses. RESULTS: Pearson correlation coefficients showed that total body (less head) aBMD was significantly correlated with LM but not FM. Multiple linear regression analyses showed that FM, after accounting for height, age, MVPA and LM had no significant relationship with aBMD or hip geometry estimates, except for arms aBMD. By contrast, there were positive associations between LM and most aBMD and hip geometry estimates, after accounting height, age, MVPA and FM. CONCLUSIONS: The results of this study suggest that LM, and not FM, is the stronger predictor of aBMD and hip geometry estimates in physically active boys. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN17982776.