A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

BACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. RESULTS: At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. CONCLUSION: These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study

<p>Abstract</p> <p>Background</p> <p>Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.</p> <p>Methods/Design</p> <p>In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.</p> <p>Discussion</p> <p>Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN16211826.</p

Resonant two-site tunnelling dynamics of bosons in a tilted optical superlattice

We study the non-equilibrium dynamics of a 1D Bose-Hubbard model in a gradient potential and a superlattice, beginning from a deep Mott insulator regime with an average filling of one particle per site. Studying a quench that is near resonance to tunnelling of the particles over two lattice sites, we show how a spin model emerges consisting of two coupled Ising chains that are coupled by interaction terms in a staggered geometry. We compare and contrast the behavior in this case with that in a previously studied case where the resonant tunnelling was over a single site. Using optimized tensor network techniques to calculate finite temperature behavior of the model, as well as finite size scaling for the ground state, we conclude that the universality class of the phase transition for the coupled chains is that of a tricritical Ising point. We also investigate the out-of-equilibrium dynamics after the quench in the vicinity of the resonance and compare dynamics with recent experiments realized without the superlattice geometry. This model is directly realizable in current experiments, and reflects a new general way to realize spin models with ultracold atoms in optical lattices.Comment: 12 pages, 6 figure

IGF-I, Growth, and Body Composition in Preterm Infants up to Term Equivalent Age

Context: There are concerns that a higher fat mass in the early life of preterm infants is associated with adverse cardiometabolic outcomes in young adulthood. Objective: To investigate the role of IGF-I and growth in determining body composition of preterm infants at term equivalent age. Methods: An observational study was conducted from August 2015 to August 2018. From birth to term equivalent age, IGF-I levels were measured bi-weekly and growth was assessed weekly. At term equivalent age, body composition was assessed through air displacement plethysmography; 65 infants with a gestational age of 24 to 32 weeks were assessed at term equivalent age, of whom 58 completed body composition measurement. The main outcome measures were fat (free) mass (g) and fat (free) mass percentage at term equivalent age. Results: In the first month of life, each 0.1 nmol/L per week increase in IGF-I was associated with a 465 g (SE 125 g) increase in fat free mass. A greater increase in weight SDS in the first month of life was associated with a higher fat free mass percentage (B 200.9; 95% CI, 12.1-389.6). A higher head circumference SDS was associated with more fat free mass (r = 0.46; 95% CI, 0.21-0.65). However, a greater increase in weight SDS up to term equivalent age was associated with a lower fat free mass percentage (B -55.7, SE 9.4). Conclusion: These findings suggest that impaired growth in the first month of life is associated with a less favorable body composition at term equivalent age

Follow-up of a randomized trial on postdischarge nutrition in preterm-born children at age 8 y

Background: Early nutritional interventions may modulate health risks in preterm-born infants. Previously, we showed that pretermborn infants fed an isocaloric protein- and mineral-enriched postdischarge formula (PDF) from term age to 6-mo corrected age (CA) gained more lean mass than did those fed term formula (TF). Longterm follow-up of randomized nutritional trials is important to test the hypothesis that short-term positive effects on health are sustainable. Objective: The aim of this follow-up study was to compare body size, body composition, and metabolic health at age 8 y in pretermborn children who were randomly assigned to receive either PDF or TF from term age until 6-mo CA. Design: A total of 79 of 152 children (52%) from the original randomized controlled trial were enrolled for follow-up at age 8 y. Weight, height, and head circumference were measured by using standard methods. Body composition, including fat mass, lean mass, bone mineral content, and bone mineral density, was determined by dual-energy X-ray absorptiometry. Blood pressure was measured in the supine position by using an automatic device. Metabolic variables, including glucose, insulin, insulin-like growth factor I, triglycerides, cholesterol, cortisol, and leptin, were measured after an overnight fast. Nutritional habits at age 8 y were assessed by using a 3-d nutritional diary. Results: At age 8 y, no differences were found in body size, body composition, bone variables, and metabolic health variables when comparing children fed PDF with those fed TF. Adjustment for known and possible confounders did not change these results. Conclusions: In this follow-up study in preterm-born children, we showed that the favorable effects of PDF at 6-mo CA either were not maintained or could not be confirmed because of attrition at the age of 8 y. We suggest that future research should focus on nutritional interventions in the pre- and postdischarge period as a continuum rather than as separate entities

Reference curves of birth weight, length, and head circumference for gestational ages in Yogyakarta, Indonesia

Background: The birth weight reference curve to estimate the newborns at risk in need of assessment and monitoring has been established. The previous reference curves from Indonesia, approximately 8 years ago, were based on the data collected from teaching hospitals only with limited gestational ages. The aims of the study were to update the reference curves for birth weight, supine length and head circumference for Indonesia, and to compare birth weight curves of boys and girls, first child and later children, and the ones in the previous studies. Methods: Data were extracted from the Maternal-Perinatal database between 1998-2007. Only live singletons with recorded gestational ages of 26 to 42 weeks and the exact time of admission to the neonatal facilities delivered or referred within 24 h of age to Sardjito Hospital, five district hospitals and five health centers in Yogyakarta Special Territory were included. Newborns with severely ill conditions, congenital anomaly and chromosomal abnormality were excluded. Smoothening of the curves was accomplished using a third-order polynomial equation. Results: Our study included 54,599 singleton live births. Growth curves were constructed for boys (53.3%) and girls (46.7%) for birth weight, supine length, and head circumference. At term, mean birth weight for each gestational age of boys was significantly higher than that of girls. While mean birth weight for each gestational age of first-born-children, on the other hand was significantly lower than that of later-born-children. The mean birth weight was lower than that of Lubchenco's study. Compared with the previous Indonesian study by Alisyahbana, no differences were observed for the aterm infants, but lower mean birth weight was observed in preterm infants. Conclusions: Updated neonatal reference curves for birth weight, supine length and head circumference are important to classify high risk newborns in specific area and to identify newborns requiring attention

Sensory modulation in preterm children: Theoretical perspective and systematic review

Background Neurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children. Aim This review aims to integrate available evidence on sensory modulation problems in preterm infants and children ( <37 weeks of gestation) and their association with neurocognitive and behavioral problems. Method Relevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children ( <37 weeks of gestation) or with prematurity as a risk factor. Results Eighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies. Conclusions Sensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problem

A comparative study using dual-energy X-ray absorptiometry, air displacement plethysmography, and skinfolds to assess fat mass in preterms at term equivalent age

The aim of this study was to compare whole body composition, generated by air displacement plethysmography (ADP) and dual-energy X-ray absorptiometry (DXA), and to evaluate the potential predictive value of the sum of skinfolds (∑SFT) for whole body composition, in preterm infants at term equivalent age. A convenience sample of sixty-five preterm infants with a mean (SD) gestational age of 29 (1.6) weeks was studied at term equivalent age. Fat mass measured by DXA and ADP were compared and the ability of the ∑SFT to predict whole body fat mass was investigated. There was poor agreement between fat mass percentage measured with ADP compared with DXA (limits of agreement: − 4.8% and 13.7%). A previously modeled predictive equation with the ∑SFT as a predictor for absolute fat mass could not be validated. Corrected for confounders, the ∑SFT explained 42% (ADP, p = 0.001) and 75% (DXA, p = 0.001) of the variance in fat mass percentage. Conclusions: The ∑SFT was not able to accurately predict fat mass and ADP and DXA did not show comparable results. It remains to be elucidated whether or not DXA provides more accurate assessment of whole body fat mass than ADP in preterm infants. Trial registration: NTR5311What is Known:• Diverse methods are used to assess fat mass in preterm infants.What is New:• This study showed that there is poor agreement between dual-energy X-ray absorptiometry, air displacement plethysmography, and skinfold thickness measurements.• Our results affirm the need for consensus guidelines on how to measure fat mass in preterm infants, to improve the assimilation of data from different studies and the implementation of the findings from those studies

Sensory processing difficulties in school-age children born very preterm: An exploratory study

Background Very preterm birth has a detrimental impact on the developing brain, including widespread white matter brain abnormalities that threaten efficient sensory processing. Yet, sensory processing difficulties in very preterm children are scarcely studied, especially at school age. Aims To investigate somatosensory registration, multisensory integration and sensory modulation. Participants 57 very preterm school-age children (mean age = 9.2 years) were compared to 56 gender and age matched full-term children. Methods Group differences on somatosensory registration tasks (Registration of Light Touch, Sensory Discrimination of Touch, Position Sense, Graphestesia), a computerized multisensory integration task, and the parent-reported Sensory Profile were investigated using t-tests and Mann-Whitney U tests. Results In comparison to full-term children, very preterm children are less accurate on somatosensory registration tasks, including Registration of Light Touch (d = 0.34), Position Sense (d = 0.31) and Graphestesia (d = 0.42) and show more sensory modulation difficulties (d = 0.41), including both behavioral hyporesponsivity (d = 0.52) and hyperresponsivity (d = 0.56) to sensory stimuli. Tactile discrimination and multisensory integration efficiency were not affected in very preterm children. Aspects of sensory processing were only modestly related. Conclusion Very preterm children show sensory processing difficulties regarding somatosensory registration and sensory modulation, and preserved multisensory (audio-visual) integration. Follow-up care for very preterm children should involve screening of sensory processing difficulties at least up to school age