Update on calcium and phosphorus requirements of preterm infants and recommendations for enteral mineral intake

Background: With current Ca and P recommendations for enteral nutrition, preterm infants, especially VLBW, fail to achieve a bone mineral content (BMC) equivalent to term infants. During the first 3 years, most notably in light at term equivalent age (<−2 Z score) VLBW infants’ BMC does not catch up. In adults born preterm with VLBW or SGA, lower adult bone mass, lower peak bone mass, and higher frequency of osteopenia/osteoporosis have been found, implying an increased risk for future bone fractures. The aim of the present narrative review was to provide recommendation for enteral mineral intake for improving bone mineral accretion. Methods: Current preterm infant mineral recommendations together with fetal and preterm infant physiology of mineral accretion were reviewed to provide recommendations for improving bone mineral accretion. Results: Current Ca and P recommendations systematically underestimate the needs, especially for Ca. Conclusion: Higher enteral fortifier/formula mineral content or individual supplementation is required. Higher general mineral intake (especially Ca) will most likely improve bone mineralization in preterm infants and possibly the long-term bone health. However, the nephrocalcinosis risk may increase in infants with high Ca absorption. Therefore, individual additional enteral Ca and/or P supplementations are recommended to improve current fortifier/formula mineral intake

Light or Deep Pressure: Medical Staff Members Differ Extensively in Their Tactile Stimulation During Preterm Apnea

Background: Even though tactile stimulation is common practice to terminate preterm apnea, the style and intensity of these interventions is not specified during theoretical or practical training and has never been clinically evaluated. Objective: The present study was designed to analyze the various modes of tactile stimulation used to terminate preterm apnea and measure the pressure intensity and frequency of these stimulations. Methods: A model with the size and weight of an actual preterm infant was equipped with sensor technology to measure stimulation pressure and frequency of tactile stimulation. Additionally a camera system was used to record hand positions and stimulation modes. Seventy medical staff members took part in the experiment. Results: We found extreme between subjects differences in stimulation pressure that could not be explained by professional experience but, to a degree, depended on apnea intensity. Pressures ranged from 11.11 to 226.87 mbar during low intensity apnea and from 9.89 to 428.15 mbar during high intensity apnea. The majority of participants used rhythmic stimulation movements with a mean frequency of ∼1 Hz. Different modes (rubbing, squeezing, tickling, and tapping) and finger positions were used. Conclusion: Medical staff members intuitively adjust their tactile stimulation pressure depending on the premature infants’ apnea intensity. However, mean pressure values varied greatly between subjects, with similar pressure ranges for low and high intensity apnea. The question remains which pressure intensities are necessary or sufficient for the task. It is reasonable to assume that some stimulation types may be more effective in rapidly terminating an apneic event

Signaling Cascade Involved in Rapid Stimulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Dexamethasone

Impairment of mucociliary clearance with reduced airway fluid secretion leads to chronically inflamed airways. Cystic fibrosis transmembrane conductance regulator (CFTR) is crucially involved in airway fluid secretion and dexamethasone (dexa) has previously been shown to elevate CFTR activity in airway epithelial cells. However, the pathway by which dexa increases CFTR activity is largely unknown. We aimed to determine whether the increase of CFTR activity by dexa is achieved by non-genomic signaling and hypothesized that the phosphoinositide 3-kinase (PI3K) pathway is involved in CFTR stimulation. Primary rat airway epithelial cells and human bronchial submucosal gland-derived Calu-3 cells were analyzed in Ussing chambers and kinase activation was determined byWestern blots. Results demonstrated a critical involvement of PI3K and protein kinase B (AKT) signaling in the dexa-induced increase of CFTR activity, while serum and glucocorticoid dependent kinase 1 (SGK1) activity was not essential. We further demonstrated a reduced neural precursor cell expressed, developmentally downregulated 4-like (NEDD4L) ubiquitin E3 ligase activity induced by dexa, possibly responsible for the elevated CFTR activity. Finally, increases of CFTR activity by dexa were demonstrated within 30 min accompanied by rapid activation of AKT. In conclusion, dexa induces a rapid stimulation of CFTR activity which depends on PI3K/AKT signaling in airway epithelial cells. Glucocorticoids might thus represent, in addition to their immunomodulatory actions, a therapeutic strategy to rapidly increase airway fluid secretion

Development and Functional Characterization of Fetal Lung Organoids

Preterminfants frequently suffer frompulmonary complications due to a physiological and structural lung immaturity resulting in significant morbidity and mortality. Novel in vitro and in vivo models are required to study the underlying mechanisms of late lung maturation and to facilitate the development of new therapeutic strategies. Organoids recapitulate essential aspects of structural organization and possibly organ function, and can be used to model developmental and disease processes. We aimed at generating fetal lung organoids (LOs) and to functionally characterize this in vitro model in comparison to primary lung epithelial cells and lung explants ex vivo. LOs were generated with alveolar and endothelial cells from fetal rat lung tissue, using a Matrigel-gradient and air-liquid-interface culture conditions. Immunocytochemical analysis showed that the LOs consisted of polarized epithelial cell adhesion molecule (EpCAM)-positive cells with the apical membrane compartment facing the organoid lumen. Expression of the alveolar type 2 cell marker, RT2-70, and the Club cell marker, CC-10, were observed. Na+ transporter and surfactant protein mRNA expression were detected in the LOs. First time patch clamp analyses demonstrated the presence of several ion channels with specific electrophysiological properties, comparable to vital lung slices. Furthermore, the responsiveness of LOs to glucocorticoids was demonstrated. Finally, maturation of LOs induced by mesenchymal stem cells confirmed the convenience of the model to test and establish novel therapeutic strategies. The results showed that fetal LOs replicate key biological lung functions essential for lung maturation and therefore constitute a suitable in vitro model system to study lung development and related diseases

Glucocorticoids Equally Stimulate Epithelial Na+ Transport in Male and Female Fetal Alveolar Cells

Preterm infants frequently suffer from respiratory distress syndrome (RDS), possibly due to lower expression of epithelial Na+ channels (ENaC). RDS incidence is sex-specific, affecting males almost twice as often. Despite the use of antenatal glucocorticoids (GCs), the sex difference persists. It is still controversial whether both sexes benefit equally from GCs. We previously showed that Na+ transport is higher in female compared with male fetal distal lung epithelial (FDLE) cells. Since GCs increase Na+ transport, we hypothesized that their stimulating effect might be sex-specific. We analyzed FDLE cells with Ussing chambers and RT-qPCR in the presence or absence of fetal serum. In serum-free medium, GCs increased the ENaC activity and mRNA expression, independent of sex. In contrast, GCs did not increase the Na+ transport in serum-supplemented media and abolished the otherwise observed sex difference. Inhibition of the GC receptor in the presence of serum did not equalize Na+ transport between male and female cells. The GC-induced surfactant protein mRNA expression was concentration and sex-specific. In conclusion, female and male FDLE cells exhibit no sex difference in response to GCs with regard to Na+ transport, and GR activity does not contribute to the higher Na+ transport in females

The identification and management of ADHD offenders within the criminal justice system: a consensus statement from the UK Adult ADHD Network and criminal justice agencies.

The UK Adult ADHD Network (UKAAN) was founded by a group of mental health specialists who have experience delivering clinical services for adults with Attention Deficit Hyperactivity Disorder (ADHD) within the National Health Service (NHS). UKAAN aims to support mental health professionals in the development of services for adults with ADHD by the promotion of assessment and treatment protocols. One method of achieving these aims has been to sponsor conferences and workshops on adult ADHD.This consensus statement is the result of a Forensic Meeting held in November 2009, attended by senior representatives of the Department of Health (DoH), Forensic Mental Health, Prison, Probation, Courts and Metropolitan Police services. The objectives of the meeting were to discuss ways of raising awareness about adult ADHD, and its recognition, assessment, treatment and management within these respective services. Whilst the document draws on the UK experience, with some adaptations it can be used as a template for similar local actions in other countries. It was concluded that bringing together experts in adult ADHD and the Criminal Justice System (CJS) will be vital to raising awareness of the needs of ADHD offenders at every stage of the offender pathway. Joint working and commissioning within the CJS is needed to improve awareness and understanding of ADHD offenders to ensure that individuals are directed to appropriate care and rehabilitation. General Practitioners (GPs), whilst ideally placed for early intervention, should not be relied upon to provide this service as vulnerable offenders often have difficulty accessing primary care services. Moreover once this hurdle has been overcome and ADHD in offenders has been identified, a second challenge will be to provide treatment and ensure continuity of care. Future research must focus on proof of principle studies to demonstrate that identification and treatment confers health gain, safeguards individual's rights, improves engagement in offender rehabilitation programmes, reduces institutional behavioural disturbance and, ultimately, leads to crime reduction. In time this will provide better justice for both offenders and society.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Numerical Relativity in D dimensional space-times: Collisions of unequal mass black holes

We present unequal mass head-on collisions of black holes in D = 5 dimensional space-times. We have simulated BH systems with mass ratios q = 1,1/2,1/3,1/4. We extract the total energy radiated throughout the collision and compute the linear momentum flux and the recoil velocity of the final black hole. The numerical results show very good agreement with point particle calculations when extrapolated to this limit

Numerical Relativity in D dimensional space-times: Collisions of unequal mass black holes

We present unequal mass head-on collisions of black holes in D = 5 dimensional space-times. We have simulated BH systems with mass ratios q = 1,1/2,1/3,1/4. We extract the total energy radiated throughout the collision and compute the linear momentum flux and the recoil velocity of the final black hole. The numerical results show very good agreement with point particle calculations when extrapolated to this limit

Numerical Relativity in D dimensional space-times: Collisions of unequal mass black holes

We present unequal mass head-on collisions of black holes in D = 5 dimensional space-times. We have simulated BH systems with mass ratios q = 1,1/2,1/3,1/4. We extract the total energy radiated throughout the collision and compute the linear momentum flux and the recoil velocity of the final black hole. The numerical results show very good agreement with point particle calculations when extrapolated to this limit

Prospective Multicenter Trial of Cervical Arthroplasty with the ROTAIO® Cervical Disc Prosthesis.

STUDY DESIGN Clinical observational study. OBJECTIVE The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years. MATERIAL AND METHODS 120 patients (72 females and 48 males with median age of 43.0 years [23-60 yrs] underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n = 104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months in 100%, 96% and 77% of the cohort by VAS, NDI, WL-26, Patient`s Satisfaction Index (PSI), SF-36, Nurick Score, mJOA, Composite Success Rate, complications, patient`s overall satisfaction and analgesics use. RESULTS Highly significant clinical improvements were observed according to NDI and VAS (P < .0001 (arm); P < .001 (neck); P = .002 (head)) at all time points. Analgetic use could be reduced in 87.1 to 95.2%. Doctor`s visits have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high with 78.4 to 83.5% of patients. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed resulting in a revision rate of 1.7% in 2 years. CONCLUSION The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating highly significant clinical improvement and high patient`s overall satisfaction with very low revision rates at 2 years