Neural control of blood pressure is altered following isolated leg heating in aged humans.

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. We tested the hypothesis that acute leg heating would decrease arterial blood pressure in aged adults secondary to sympathoinhibition. We exposed 13 young and 10 aged adults to 45 min of leg heating. Muscle sympathetic nerve activity (radial nerve) was measured before leg heating (preheat) and 30 min after (recovery) and is expressed as burst frequency. Neurovascular transduction was examined by assessing the slope of the relation between muscle sympathetic nerve activity and leg vascular conductance measured at rest and during isometric handgrip exercise performed to fatigue. Arterial blood pressure was well maintained in young adults (preheat, 86 ± 6 mmHg vs. recovery, 88 ± 7 mmHg; P = 0.4) due to increased sympathetic nerve activity (preheat, 16 ± 7 bursts/min vs. recovery, 22 ± 10 bursts/min; P < 0.01). However, in aged adults, sympathetic nerve activity did not differ from preheat (37 ± 5 bursts/min) to recovery (33 ± 6 bursts/min, P = 0.1), despite a marked reduction in arterial blood pressure (preheat, 101 ± 7 mmHg vs. recovery, 94 ± 6 mmHg; P < 0.01). Neurovascular transduction did not differ from preheat to recovery for either age group (P ≥ 0.1). The reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension.NEW & NOTEWORTHY There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular mechanisms mediating this response remain unknown. Our findings demonstrate for the first time that this reduction in arterial blood pressure is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension in aged adults.

MRI safety and imaging artifacts evaluated for a cannulated screw used for guided growth surgery.

OBJECTIVE: Percutaneously-placed cannulated screws are the implant of choice for treatment of skeletal deformity associated with growing children that have spastic cerebral palsy (CP). These patients often require MRI examinations throughout their childhood to evaluate associated comorbidities and frequently for research protocols. There are concerns related to the use of MRI when metallic implants are present. Therefore, this study characterized MRI safety and imaging artifacts for a cannulated screw commonly used for guided growth. METHODS: Standardized and well-accepted in vitro techniques were used to evaluate a cannulated screw (4.5 mm diameter x 50 mm length, 316 L stainless steel) for MRI issues. Static magnetic field interactions (i.e., translational attraction and torque) and artifacts were tested at 3-Tesla. Radiofrequency-related heating was assessed at 1.5-Tesla/64-MHz and 3-Tesla/128-MHz using relatively high levels of RF energy (whole-body averaged specific absorption rates of 2.7 W/kg and 2.9-W/kg, respectively). Artifacts were determined using T1-weighted, spin echo and gradient echo pulse sequences. RESULTS: The cannulated screw exhibited minor magnetic field interactions (14° deflection angle, no torque). The highest temperature changes at 1.5-Tesla/64-MHz and 3-Tesla/128-MHz MRI were 2.1 °C and 2.4 °C, respectively. The maximum artifact size on a gradient echo sequence extended 20 mm relative to the dimensions of the implant. CONCLUSIONS: The in vitro tests performed on the cannulated screw indicated that there were no substantial concerns with respect to the use of 1.5- and 3-Tesla MRI. Therefore, a patient with this cannulated screw can safely undergo MRI by following specific conditions to ensure safety.

Plasticity in the growth of body segments in relation to height-for-age and maternal education in Guatemala.

OBJECTIVES: Plasticity in the growth of body segments between populations has been researched in relation to migration, temporal change and high-altitude studies. We study the within population variation in body segments, thus controlling for some of the environmental and genetic differences that could be at play in between populations studies. We test a version of the thrifty phenotype hypothesis, where the growth of head-trunk and hand are prioritized due to their functional significance over height and leg growth. MATERIALS AND METHODS: A total of 3913 Guatemalan, rural, semi-urban and urban, Maya and Ladino children 6 to 15 years old were studied. Height, sitting height, leg length, and metacarpal length were studied in relation to three proxies for living conditions: height- and leg length-for-age, and maternal education. Estimation statistics and null hypothesis significance testing were used to analyze the data. RESULTS: Metatarsal length and sitting height values were higher than height and leg length respectively. Relative metacarpal length was conserved across height-for-age groups. Females were less affected than males for metacarpal length and sitting height, but more affected for leg length. CONCLUSION: Our results agree with the thrifty phenotype hypothesis, where metacarpal and sitting height growth would be prioritized over height and leg length due to greater functional significance.

Transphyseal anterior cruciate ligament reconstruction in adolescents with substantial remaining growth causes temporary growth arrest resulting in subclinical leg-length discrepancy.

The purpose of the present study was to investigate the characteristics of growth disturbances in patients with remaining growth after transphyseal anterior cruciate ligament (ACL) reconstruction who were confirmed to have no definite postoperative physeal abnormalities on magnetic resonance imaging (MRI).Forty adolescents (mean age 15.6 ±â€Š1.0 years [range 12.2-16.8], mean follow-up 2.7 ±â€Š0.7 years [range 2.0-5.5 years]), who underwent transphyseal ACL reconstruction and were confirmed to have no focal physeal disruptions on follow-up MRIs 6 to 12 months after the operation, were retrospectively evaluated. The patients were grouped according to the leg-length growth of the uninjured side, measured on scanograms, obtained before surgery, and at the final follow-up.Leg-length discrepancies (LLD) at the last follow-up were greater in patients with leg growth ≥4 cm than in those with leg growth <4 cm (5.3 ±â€Š9.0 mm vs -0.3 ±â€Š4.2 mm, P = .033); however, no significant difference was observed between subgroup patients with leg growth of 4 to 6 cm or ≥6 cm (5.6 ±â€Š10.4 mm vs 4.8 ±â€Š7.0 mm, P = .958). On multivariate analysis, leg growth was a significant predictive factor for the final LLD (P = .030).Adolescents with additional leg-length growth after transphyseal ACL reconstructions presented with greater LLDs (as shown in the <4 cm vs ≥4 cm groups), but they also presented a ceiling effect (as shown in the 4-6 cm vs ≥6 cm subgroups). Transphyseal ACL reconstructions appeared to cause temporary growth arrest/disturbances in patients with substantial remaining growth which then resumed resulting in clinically insignificant LLDs.

Body proportionality and adiposity are not related in 6- to 8-year-old Yucatec Maya children.

OBJECTIVE: The aim of this study was to analyze the association between relative leg length (RLL) (leg length × 100/height) and adiposity in a sample of 6- to 8-year-old children of Maya ancestry from Motul and Merida, Mexico. METHODS: This cross-sectional study included 260 children (128 girls) measured between 2011 and 2015. The RLL was used as a measure of body proportionality. Linear regression models were performed to examine the association between RLL (predictor) and three adiposity indicators (outcome variables): fat mass index (kg/m2 ), waist circumference (z-score), and sum of triceps and subscapular skinfolds (z-score). RESULTS: The prevalence of stunting was 12%, and a higher prevalence (19%) of short RLL (leg stunting) was found. The prevalence of overweight and obesity were 16% and 20%, respectively, but the highest prevalence was found for abdominal obesity (40%). None of the adiposity indicators were related to RLL (P > .05), even after adjusting for the influence of children's sex and age. CONCLUSIONS: Our results suggest that the coexistence of short RLL and high body adiposity is not observed in all populations. Our findings do not discount the possibility that a negative association between RLL and adiposity is expressed at older ages.

First use of anatomical networks to study modularity and integration of heads, forelimbs and hindlimbs in abnormal anencephalic and cyclopic vs normal human development.

The ill-named "logic of monsters" hypothesis of Pere Alberch - one of the founders of modern evo-devo - emphasized the importance of "internal rules" due to strong developmental constraints, linked teratologies to developmental processes and patterns, and contradicted hypotheses arguing that birth defects are related to a chaotic and random disarray of developmental mechanisms. We test these hypotheses using, for the first time, anatomical network analysis (AnNA) to study and compare the musculoskeletal modularity and integration of both the heads and the fore- and hindlimbs of abnormal cyclopic trisomy 18 and anencephalic human fetuses, and of normal fetal, newborn, and adult humans. Our previous works have shown that superficial gross anatomical analyses of these specimens strongly support the "logic of monsters" hypothesis, in the sense that there is an 'order' or 'logic' within the gross anatomical patterns observed in both the normal and abnormal individuals. Interestingly, the results of the AnNA done in the present work reveal a somewhat different pattern: at least concerning the musculoskeletal modules obtained in our AnNA, we observe a hybrid between the "logic of monsters" and the "lack of homeostasis" hypotheses. For instance, as predicted by the latter hypothesis, we found a high level of left-right asymmetry in the forelimbs and/or hindlimbs of the abnormal cyclopic trisomy 18 and anencephalic human fetuses. That is, a network analysis of the organization of/connection between the musculoskeletal structures of these fetuses reveals a more "chaotic" pattern than that detected by superficial gross anatomical comparisons. We discuss the broader developmental, evolutionary, and medical implications of these results.

Sex-dependent effect of post-migration adaptation on height and relative lower leg length in Polish youth.

BACKGROUND: Growth in tibia length is considered to be particularly sensitive to environmental stress. AIM: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children. SUBJECTS AND METHODS: Data included a nationwide random sample of 17,155 schoolchildren, 7-18 years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio. RESULTS: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio. CONCLUSION: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children.

Extreme Premature Small for Gestational Age Infants Have Appropriate Catch-up Growth at Term Equivalence Compared with Extreme Premature Appropriate for Gestational Age Infants

Recent studies have shown that small for gestational age (SGA) term infants undergo catch-up growth during infancy but there is limited studies on early growth outcomes of extreme premature SGA infants. The aim of this study was to compare factors associated during birth in extremely premature infants less than 28 weeks' gestation who were born SGA (<10th percentile for gestational age) with those who were born appropriate-for-gestational age (AGA) (10th-89th percentile) and to determine whether there was catch-up growth at term equivalence. One hundred fifty-three extreme premature infants (89 males) born below 28 weeks' gestation were prospectively recruited. All infants had auxological measurements undertaken and prospective data on pregnancy, maternal factors, perinatal and postnatal data obtained. SGA infants at birth had significantly higher Clinical Risk Index for Babies scores and mortality, lower birth weight, smaller head circumference, smaller mid arm circumference and shorter leg length at time of birth compared with AGA infants. However, at term equivalence, weight and leg length of were not significant between AGA and SGA infants born at extreme prematurity. Our study shows that extreme premature SGA infants have appropriate catch-up growth by the time they reach term equivalence suggesting that postnatal nutrition and care are important determinants of catch-up growth in SGA infants.

The motor repertoire of older adult fallers may constrain their response to balance perturbations.

Older adults are at a high risk of falls, and most falls occur during locomotor activities like walking. This study aimed to improve our understanding of changes in neuromuscular control associated with increased risk of falls in older adults in the presence of dynamic balance challenges during walking. Motor module (also known as muscle synergy) analyses identified changes in the neuromuscular recruitment of leg muscles during walking with and without perturbations designed to elicit the visual perception of lateral instability. During normal walking we found that a history of falls (but not age) was associated with reduced motor module complexity and that age (but not a history of falls) was associated with increased step-to-step variability of module recruitment timing. Furthermore, motor module complexity was unaltered in the presence of optical flow perturbations. The specific effects of a history of falls on leg muscle recruitment included an absence and/or inability to independently recruit motor modules normally recruited to perform biomechanical functions important for walking balance control. These results suggest that fallers do not recruit the appropriate motor modules necessary for well-coordinated walking balance control even in the presence of perturbations. The identified changes in the modular control of walking balance in older fallers may either represent a neural deficit that leads to poor balance control or a prior history of falls that results in a compensatory motor adaptation. In either case, our study provides initial evidence that a reduced motor repertoire in older adult fallers may be a constraint on their ability to appropriately respond to balance challenges during walking. NEW & NOTEWORTHY This is the first study to demonstrate a reduced motor repertoire during walking in older adults with a history of falls but without any overt neurological deficits. Furthermore, using virtual reality during walking to elicit the visual perception of lateral instability, we provide initial evidence that a reduced motor repertoire in older adult fallers may be a constraint on their ability to appropriately respond to balance challenges during walking.

Intergenerational changes in limb circumferences in children and adolescents aged 3-18 from Kraków (Poland) from 1983 to 2010.

OBJECTIVES: Measurements of body circumferences are often used in anthropology. The research on this topic, however, rarely concerns limb girths or secular trends. The main aim of this study was to investigate the occurrence of secular trends in selected limb circumferences among children and adolescents. METHODS: The research was based on measurements from two cross-sectional studies carried out in 1983 and 2010 with children and adolescents aged 3-18 from Krakow, Poland. The circumferences of the arm, forearm, thigh and calf, as well as the sum of circumferences and selected indicators, were analyzed. The series were compared using the two-way anova test. RESULTS: In most age groups of both sexes, a positive secular trend was observed for the majority of studied traits. The exception was the thigh circumference, for which, among girls, measurements in both series were similar, and negative intergenerational changes were recorded in the youngest age groups of both sexes as well as among the oldest girls. Most observed discrepancies were statistically significant in pre-school children and adolescents. CONCLUSIONS: The presence of positive secular trends shows that limb circumferences were increasing in subsequent generations, especially in boys. Contemporary girls, particularly in the older age groups, were more determined to have a slim figure and practiced conscious weight control. Summarizing, observed tendencies resulted from the improvement of socio-economic conditions, but were also related to the low level of physical activity.

Motor unit activity, force steadiness, and perceived fatigability are correlated with mobility in older adults.

The purpose of our study was to examine the associations between the performance of older adults on four tests of mobility and the physical capabilities of the lower leg muscles. The assessments included measures of muscle strength, muscle activation, and perceived fatigability. Muscle activation was quantified as the force fluctuations-a measure of force steadiness-and motor unit discharge characteristics of lower leg muscles during submaximal isometric contractions. Perceived fatigability was measured as the rating of perceived exertion achieved during a test of walking endurance. Twenty participants (73 ± 4 yr) completed one to four evaluation sessions that were separated by at least 3 wk. The protocol included a 400-m walk, a 10-m walk at maximal and preferred speeds, a chair-rise test, and the strength, force steadiness, and discharge characteristics of motor units detected by high-density electromyography of lower leg muscles. Multiple-regression analyses yielded statistically significant models that explained modest amounts of the variance in the four mobility tests. The variance explained by the regression models was 39% for 400-m walk time, 33% for maximal walk time, 42% for preferred walk time, and 27% for chair-rise time. The findings indicate that differences in mobility among healthy older adults were partially associated with the level of perceived fatigability (willingness of individuals to exert themselves) achieved during the test of walking endurance and the discharge characteristics of soleus, medial gastrocnemius, and tibialis anterior motor units during steady submaximal contractions with the plantar flexor and dorsiflexor muscles. NEW & NOTEWORTHY Differences among healthy older adults in walking endurance, walking speed, and ability to rise from a chair can be partially explained by the performance capabilities of lower leg muscles. Assessments comprised the willingness to exert effort (perceived fatigability) and the discharge times of action potentials by motor units in calf muscles during submaximal isometric contractions. These findings indicate that the nervous system contributes significantly to differences in mobility among healthy older adults.

Lack of age-specific influence on leg blood flow during incremental calf plantar-flexion exercise in men and women.

PURPOSE: Age-related exercising leg blood flow (LBF) responses during dynamic knee-extension exercise and forearm blood flow responses during handgrip exercise are preserved in normally active men but attenuated in activity-matched women. We explored whether these age- and sex-specific effects are also apparent during isometric calf plantar-flexion incremental exercise. METHODS: Normally active young men (YM, n = 15, 24 ± 2 years), young women (YW, n = 8, 22 ± 1 years), older men (OM, n = 13, 70 ± 7 years) and older women (OW, n = 10, 64 ± 7 years) were tested. LBF was measured between contractions using venous occlusion plethysmography. RESULTS: Peak force obtained was higher (P < 0.05) in men compared with women and in young compared with older individuals. However, peak LBF (YM; 971 ± 328 ml min-1, OM; 985 ± 504 ml min-1, YW; 844 ± 366 ml min-1, OW; 960 ± 244 ml min-1) and peak leg vascular conductance [LVC = LBF/(MAP + hydrostatic pressure)] responses (YM; 6.0 ± 1.8 ml min-1 mmHg-1, OM; 5.5 ± 2.8 ml min-1 mmHg-1, YW; 5.3 ± 2.1 ml min-1 mmHg-1, OW; 5.5 ± 1.6 ml min-1 mmHg-1) were similar among the four groups. Furthermore, the hyperaemic (YM; 8.8 ± 3.7 ml min-1 %Fpeak-1 OM; 8.3 ± 5.4 ml min-1 %Fpeak-1, YW; 8.2 ± 3.5 ml min-1 %Fpeak-1, OW; 9.6 ± 2.2 ml min-1 %Fpeak-1) and vasodilatory responses (YM; 0.053 ± 0.020 ml min-1 mmHg-1 %Fpeak-1, OM; 0.048 ± 0.028 ml min-1 mmHg-1 %Fpeak-1, YW; 0.051 ± 0.019 ml min-1 mmHg-1 %Fpeak-1, OW; 0.055 ± 0.014 ml min-1 mmHg-1 %Fpeak-1) were not different among the four groups. These results were accompanied by similar resting LBF responses among groups and were not affected when data were normalised to estimated leg muscle mass. CONCLUSIONS: Our results demonstrate that exercising LBF responses during isometric incremental calf muscle exercise are preserved in older men and women, suggesting that the previously observed age-related attenuations in leg and forearm hyperaemia among women may be muscle-group specific.

Aesthetic Improvement of Undeveloped Calves After Treatment of Congenital Clubfoot Deformity.

BACKGROUND: Even when clubfoot deformity is treated in a timely manner, the consequences observed in adulthood include hypoplasia of the calf muscles, gait impairment, decreases in foot size, and it can also affect the tibial length. These consequences may have negative impacts on the patient's subjective appraisal of long-term outcomes, and can influence the patient's self-esteem in both male and female patients. OBJECTIVES: We present our experience in the treatment of undeveloped calves after surgical treatment of congenital clubfoot. METHODS: In total, 72 patients underwent corrective surgery in order to improve undeveloped calves resulting from a congenital clubfoot deformity. We used calf silicone implants in combination with fat grafting in multistaged procedures, in order to decrease complication rates and improve aesthetic outcome. RESULTS: Amongst our patients there were 54 (75%) females and 18 (25%) males. All of the patients, except one, had unilateral calf hypoplasia. The procedures were divided into several groups: (1) medial calf augmentation with silicone implants; (2) medial calf augmentation with silicone implants and fat grafting; and (3) medial and lateral calf augmentation with silicone implants and fat grafting. We had one case of a hyperpigmented scar and one case of partial scar dehiscence. There were no cases of compartment syndrome. The average follow-up period was 9.8 months. CONCLUSIONS: Calf enhancement surgery in patients with congenital clubfoot deformity is very gratifying. When combining calf implants with fat grafting in multistaged procedures, we can achieve excellent results with low complication rates.

Survey of musculoskeletal abnormalities in school-going children of hilly and foothill regions of Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine screening method.

OBJECTIVE: To study the prevalence and pattern of musculosketetal abnormalities in school-going children living in the hilly and foothill regions of the Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine (pGALS) screening tool. METHODS: Total of 3608 children, aged 3-12 years were enrolled from 16 schools (5 in the hills) in the eastern Himalayan region. After the three screening questions, the pGALS maneuvers were administered. Subjects were shown a video on pGALS before the actual testing. Those detected to have abnormality were probed in greater detail and referred for treatment as necessary. RESULTS: The pGALS examination was completed in 3463 children with a median time of 3 min (range 1.9-5.4 min). The abnormality pattern was in the order: growing pains (38.86%), hypermobility (25.54%), mechanical pains (24.46%) and others (11.14%). Among mechanical pain, back and neck problems occurred with a similar overall frequency of 7.61%. Similar order was observed considering only children from the pains. However, in hill children, the proportion of mechanical problems (32.28%) exceeded proportion of hypermobility (23.62%). Asymptomatic hypermobility was more common than symptomatic hypermobility. Maximum prevalence of hypermobility was in 6-9 year age group. Of the 94 children with hypermobility, 55.32% had some kind of joint pain. CONCLUSIONS: Pediatric Gait, Arms, Legs, Spine is an acceptable screening tool for musculoskeletal abnormalities in apparently healthy children. Growing pain is the commonest musculoskeletal complaint while hypermobility is the commonest physical abnormality in school-going children in the Eastern Himalayas. Asymptomatic hypermobility is more common than symptomatic hypermobility.

Relationship of medial gastrocnemius relative fascicle excursion and ankle joint power and work performance during gait in typically developing children: A cross-sectional study.

Muscle fascicles lengthen in response to chronic passive stretch through in-series sarcomere addition in order to maintain an optimum sarcomere length. In turn, the muscles' force generating capacity, maximum excursion, and contraction velocity is enhanced. Thus, longer fascicles suggest a greater capacity to develop joint power and work. However, static fascicle length measurements may not be taking sarcomere length differences into account. Thus, we considered relative fascicle excursions through passive ankle dorsiflexion may better correlate with the capacity to generate joint power and work than fascicle length. Therefore, the aim of the present study was to determine if medial gastrocnemius relative fascicle excursions correlate with ankle joint power and work generation during gait in typically developing children. A sample of typically developing children (n = 10) were recruited for this study and data analysis was carried out on 20 legs. Medial gastrocnemius relative fascicle excursion from resting joint angle to maximum dorsiflexion was estimated from trigonometric relations of medial gastrocnemius pennation angle and thickness obtained from B-mode real-time ultrasonography. Furthermore, a three-dimensional motion capture system was used to obtain ankle joint work and power during the stance phase of gait. Significant correlations were found between relative fascicle excursion and peak power absorption (-) r(14) = -0.61, P = .012 accounting for 31% variability, positive work r(18) = 0.56, P = .021 accounting for 31% variability, and late stance positive work r(15) = 0.51, P = .037 accounting for 26% variability. The large unexplained variance may be attributed to mechanics of neighboring structures (e.g., soleus or Achilles tendon mechanics) and proximal joint kinetics which may also contribute to ankle joint power and work performance, and were not taken into account. Further studies are encouraged to provide greater insight on the relationship between relative fascicle excursions and joint function.

Knemometry Assessment of Short-term Growth in Children With Asthma Receiving Fluticasone Furoate for 2 Weeks: A Randomized, Placebo-controlled, Crossover Trial.

PURPOSE: A dry powder inhaler formulation of the inhaled corticosteroid fluticasone furoate (FF) is being evaluated for use in children. An important potential risk associated with the use of inhaled corticosteroids in children is growth suppression. Therefore, the aim of this study was to assess the short-term lower leg growth in children with asthma treated for 2 weeks with inhaled FF versus placebo from the ELLIPTA inhaler. METHODS: Prepubertal children with persistent asthma (n = 60; aged 5 to <12 years) were recruited into a randomized, double-blind, placebo-controlled, 2-way crossover, noninferiority study. The study consisted of four 2-week periods: run-in, 2 treatment periods, 1 washout period, and a 1-week follow-up period. Interventions were FF 50 µg and placebo once daily in the evening. Lower leg length was measured by using knemometry. FINDINGS: The randomized ITT population comprised 36 boys and 24 girls with a mean age of 8.7 (standard deviation, 1.5; range, 5-11) years; 58% had a duration of asthma ≥5 years. Fifty-eight subjects completed both treatment periods. The least squares mean growth rate was 0.31 mm/week during treatment with FF and 0.36 mm/week during the placebo period. The difference in adjusted least squares mean growth rates between FF and placebo was -0.052 mm/week with a 95% CI of -0.122 to 0.018. This finding was greater than the prespecified noninferiority margin of -0.20 mm/week. The overall incidence of adverse events was 35% with placebo and 22% with FF. IMPLICATIONS: Inhaled FF 50 µg provided once daily for 2 weeks was noninferior to placebo in terms of effects on short-term lower leg growth in children with asthma. To further quantify the risk of growth suppression in children, intermediate-term growth studies should be conducted. Inhaled FF 50 µg was well tolerated in this study population. ClinicalTrials.gov identifier: NCT02502734.

Leg Length Versus Torso Length in Pedophilia: Further Evidence of Atypical Physical Development Early in Life.

Adult men's height results from an interaction among positive and negative influences, including genetic predisposition, conditions in utero, and influences during early development such as nutritional quality, pathogen exposure, and socioeconomic status. Decreased height, reflected specifically as a decreased leg length, is strongly associated with increased risk of poorer health outcomes. Although prior research has repeatedly shown that pedophiles are shorter than nonpedophiles, the largest study to date relied on self-reported height. In the present study, pedophiles demonstrated reduced measured height and reduced leg length as compared with teleiophiles. Given the prenatal and early childhood origins of height, these findings contribute additional evidence to a biological, developmental origin of pedophilia. In addition, the magnitude of this height difference was substantially larger than that found in children exposed to a variety of early environmental stressors, but similar to that seen in other biologically based neurodevelopmental disorders.

Muscle development in healthy children evaluated by bioelectrical impedance analysis.

OBJECTIVES: This study aimed to use bioelectrical impedance analysis (BIA) to generate a new muscle density index (MDI), the MDI_BIA, to evaluate muscle development, and to demonstrate the changes that occur in the BIA-based muscle cross-sectional area index (MCAI_BIA) that accompany growth. We also sought to determine the traceability of chronological changes in the MDI_BIA and MCAI_BIA. METHODS: Healthy children (n=112) aged 8.68±3.16years (0.33-14.00years) underwent bioelectrical impedance (BI) measurements of their upper arms, thighs, and lower legs. The MDI_BIA and MCAI_BIA were calculated, and cross-sectional investigations were conducted into the changes in these indices that accompanied growth. Data collected after 1.10±0.08years from 45 participants determined the traceability of the chronological changes in the MDI_BIA and MCAI_BIA. RESULTS: The MDI_BIA and MCAI_BIA were significantly positively correlated with age and height at all locations (P<0.01). The relationships between the locations and the MDI_BIA and MCAI_BIA differed, indicating that these indices evaluated the muscles from different perspectives. Except for the upper arm MDI_BIA, both indices at all locations regardless of age, showed significant chronological increases after an average period of 1.10years. CONCLUSIONS: The MDI_BIA and MCAI_BIA were significantly correlated with age and height in healthy children, and they showed significant chronological increases. Hence, these indices could be used to represent muscle development and muscle mass increases. BIA is non-invasive, convenient, and economical and it may be useful in evaluating muscle development and muscle cross-sectional areas in children.

Kidney transplantation fails to provide adequate growth in children with chronic kidney disease born small for gestational age.

BACKGROUND: Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). METHODS: Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. RESULTS: Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. CONCLUSIONS: In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

Knemometry is more sensitive to systemic effects of inhaled corticosteroids in children with asthma than 24-hour urine cortisol excretion.

BACKGROUND: Pharmacodynamic assessment of the systemic effect of inhaled corticosteroids (ICSs) is often done by measuring 24-hour urine free cortisol (UFC) excretion. Knemometry assessing short-term lower-leg growth rate (LLGR) is a more rarely used alternative. OBJECTIVE: The primary aim of this study was to compare the sensitivity of LLGR and 24-hour UFC excretion for evaluating systemic exposure to ICSs in prepubertal children with asthma. The secondary aim was to evaluate factors influencing the precision of LLGR calculated by the traditional 1 leg nonparametric method versus a new 2 leg parametric method. METHODS: The study evaluated 60 children with mild asthma aged 5 to 12 years participating in a randomized controlled trial of ICSs with longitudinal concomitant assessments of LLGR and 24-hour UFC excretion. The sensitivity of the safety assessments was analyzed by comparing LLGR and 24-hour UFC in the placebo run-in period with values in the ICS treatment period by using paired t tests. Factors with a potential influence on LLGR were analyzed by means of ANOVA and the Levene test of homogeneity. RESULTS: The mean LLGR was significantly reduced during the ICS versus placebo run-in periods: 0.18 mm/wk (SD, 0.55 mm/wk) versus 0.45 mm/wk (SD, 0.39 mm/wk), with a mean difference of 0.27 mm/wk (95% CI, 0.05-0.48 mm/wk; P = .02). In contrast, there was no difference in 24-hour UFC excretion: 6.91 nmol/mmol (SD, 4.67 nmol/mmol) versus 7.58 nmol/mmol (SD, 6.17 nmol/mmol), with a mean difference of 0.67 nmol/mmol (95% CI, -1.13 to 2.48 nmol/mmol; P = .46). We observed no significant difference in parametric determined LLGR caused by the child's age or sex, investigator, or season of measurement, whereas some differences were observed for the nonparametric LLGR. CONCLUSION: These findings suggest that knemometry is a more sensitive pharmacodynamic measure of systemic effects of ICSs than 24-hour UFC excretion and that a parametric determination of LLGR increases the sensitivity of the method. These findings should be considered by legislative authorities in the future.