Mature locomotion involves modular spinal drives generating a set of fundamental patterns of motoneuron activation, each timed at a specific phase of locomotor cycles and associated with a stable muscle synergy. How locomotor modules develop and to what extent they depend on prior experience or intrinsic programs remains unclear. To address these issues, we herein leverage the presence at birth of two types of locomotor-like movements, spontaneous kicking and weight-bearing stepping. The former is expressed thousands of times in utero and postnatally, whereas the latter is elicited de novo by placing the newborn on the ground for the first time. We found that the neuromuscular modules of stepping and kicking differ substantially. Neonates kicked with an adult-like number of temporal activation patterns, which lacked a stable association with systematic muscle synergies across movements. However, on the ground neonates stepped with fewer temporal patterns but all structured in stable synergies. Since kicking and ground-stepping coexist at birth, switching between the two behaviors may depend on a dynamic reconfiguration of the underlying neural circuits as a function of sensory feedback from surface contact. We tracked the development of ground-stepping in 4- to 48-mo-old infants and found that, after the age of 6 mo, the number of temporal patterns increased progressively, reaching adult-like conformation only after independent walking was established. We surmise that mature locomotor modules may derive by combining the multiple patterns of repeated kicking, on the one hand, with synergies resulting from fractionation of those revealed by sporadic weight-bearing stepping, on the other hand.
Background: Neonatal onset hypopituitarism is a life-threatening, potentially treatable endocrine disease. A possible cause is congenital absence of the anterior pituitary gland, a condition very rarely reported in the literature. Methods: A series of 5 cases of children with pituitary aplasia referred to the Centre of Paediatric Endocrinology ‘Rina Balducci’, Tor Vergata University, Rome, is presented. Results: Major clinical features in our patients were respiratory distress on the first day of life, in spite of uneventful pregnancy, labour and delivery, metabolic acidosis, non-cholestatic jaundice, hypotonia, severe hypoglycaemia, hypogenitalism, and midline defects. Diagnosis was established by endocrine tests during hypoglycaemia and hypothalamic-pituitary MRI scan. Symptoms disappeared soon after replacement therapy was started. Conclusion: We stress the importance of performing baseline endocrine tests as soon as possible during hypoglycaemia and MRI of the brain aimed at visualizing the hypothalamic-pituitary area in neonates with hypogenitalism and severe unexplained hypoglycaemia, so that the irreversible neurological and developmental consequences of panhypopituitarism can be prevented by adequate replacement therapy.
The efficacy of caffeine in an episode of Apnoea of Prematurity (AOP) has been known for over thirty years. Its use over long periods of time has not only found it to be manageable within the field of neonatology, but it has also been found to have other favourable actions, such as reducing the incidence of extubation failure, preventing Bronchopulmonary Dysplasia (BPD), reducing the need for Patent Ductus Arteriosus treatment and the beneficial effect it has on Retinopathy of Prematurity. Recent in vitro trials have highlighted the neuroprotective role that caffeine plays, which has already partly been observed from in vivo trials. Just recently, caffeine citrate has become a "label" drug and it would be beneficial if more studies could confirm the more significant effects it has on the more severe conditions of prematurity.
Stepping on ground can be evoked in human neonates, though it is rather irregular and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can provide insights into the role of contact- or load-related proprioceptive feedback during early development of locomotion. However, the detailed characteristics of foot placements and their association with motor patterns are still incompletely documented. We elicited stepping in 33 neonates supported on a table. Unilateral limb kinematics, bilateral plantar pressure distribution and EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement characteristics in neonates showed a wide variation. In ~25% of steps, the swinging foot stepped onto the contralateral foot due to generally small step width. In the remaining steps with separate foot placements, the stance phase could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite forefoot or heel initial contacts, the kinematic and loading patterns markedly differed relatively to toe-walking or adult-like two-peaked vertical force profile. Furthermore, while the general stepping parameters (cycle duration, step length, range of motion of proximal joints) were similar, the initial foot contact was consistently associated with specific center-of-pressure excursion, range of motion in the ankle joint, and the center-of-activity of extensor muscles (being shifted by ~5% of cycle toward the end of stance in the “heel” relative to “forefoot” condition). In sum, we found a variety of footfall patterns in conjunction with associated changes in motor patterns. These findings suggest the potential contribution of load-related proprioceptive feedback and/or the expression of variations in the locomotor program already during early manifestations of stepping on ground in human babies.
It has been shown that growth hormone (GH) and insulin-like growth factor-1 (IGF1) enhance steroidogenesis responsiveness to ACTH in cultured adrenal cells. To investigate the GH effect on adrenal steroidogenesis in non-GH-deficient subjects, we studied 9 girls with Turner syndrome (chronological age 5.5–7.2 years; bone age 5–7 years). In all subjects an ACTH test (Synacthen depot, 0.25 mg i.v. with blood samples at 0 and 60 min) was performed basally at 8–9 a.m. and 6 months after GH therapy (1 IU/kg/week). 17-Hydroxypregnenolone (17PGN), 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHA), its sulfate (DHA-S), androstenedione and cortisol were evaluated by radioimmunoassay. Two groups of normal girls were selected as controls: group A age-matched the patients at the start of the study, and group B age-matched the patients at the end of the study. The responsiveness of each hormone to ACTH was expressed as the difference between stimulated and basal values. A p value of < 0.01 was considered to indicate significance. There were no significant differences between pre- and posttreatment basal values of 17PGN, 17OHP, DHA, androstenedione and cortisol in the Turner syndrome patients, whereas a significant increase was observed for basal DHA-S (1.57 ± 0.31; 1.89 ± 0.43 µmol/l, p < 0.01). Comparison of increments before and after GH treatment showed a significant increase in responsiveness to ACTH after GH therapy DHA (p < 0.01). The increase in 17PGN was evident (p < 0.02), but the established significant p value was not reached. No differences for 17OHP, androstenedione and cortisol were found. The stimulated 17PGN/17OHP ratio was significantly higher (p < 0.01) after GH, whereas the 17OHP/androstenedione ratio was considerably lower, but the p value was < 0.02. No differences between pretreatment values with the control group androstenedione was found, whereas basal and stimulated posttreatment values of DHA and stimulated values of 17PGN were higher in patients after GH therapy than in control group B. No differences between the 2 control groups were found. In conclusion our study showed that adrenal steroid responsiveness to ACTH increases in Turner syndrome after long-term treatment with high GH doses. An increase in the number of ACTH adrenal receptors and/or a modulation of enzyme activities may be suggested. The positive or negative pharmacological implications of these data remain to be determined especially when taking into consideration the wide use of GH therapy in non-GH-deficient subjects.
The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.
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