Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden.

Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients' already high economic and mental burden.

Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary.

What Is This Plain Language Summary About?: This summary explains the results of a long-term extension study on the effects of a specific medicine. A long-term extension study allows people who have already completed a research study to continue taking treatment. Researchers can then look at how a treatment works over a long period of time.

Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty gene.

What Is This Plain Language Summary About?: This plain language summary describes the results of a study looking at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty gene. This condition is called LMNA-related DCM. DCM happens when the heart becomes bigger and weaker than normal, impacting functional capacity and leading to symptoms of heart failure.

Long-Term Efficacy and Safety of ARRY-371797 (PF-07265803) in Patients With Lamin A/C-Related Dilated Cardiomyopathy.

Dilated cardiomyopathy associated with lamin A/C (LMNA) gene variants (LMNA-related dilated cardiomyopathy [DCM]) is a life-threatening condition with a high unmet need, accounting for approximately 6% of idiopathic DCM cases. Currently, no disease-specific treatments target the underlying disease mechanism. ARRY-371797 (PF-07265803), a potent, selective, oral, small-molecule inhibitor of the p38α mitogen-activated protein kinase pathway, improved 6-minute walk test (6MWT) distance in 12 patients with symptomatic LMNA-related DCM in a 48-week, open-label, phase 2 study.

Variation in Neonatal Nutrition Practice and Implications: A Survey of Australia and New Zealand Neonatal Units.

Significant global variation exists in neonatal nutrition practice, including in assigned milk composition values, donor milk usage, fortification regimens, probiotic choice and in methods used to calculate and report nutrition and growth outcomes, making it difficult to synthesize data to inform evidence-based, standardized nutritional care that has potential to improve neonatal outcomes. The Australasian Neonatal Dietitians' Network (ANDiN) conducted a survey to determine the degree to which neonatal nutritional care varies across Australia and New Zealand (A&NZ) and to highlight potential implications. A two-part electronic neonatal nutritional survey was emailed to each ANDiN member ( = 50).

AAV6 as an effective gene delivery vector for prolonged transgene expression in intervertebral disc cells .

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno-associated virus (AAV) have emerged as powerful transgene delivery vehicles yet a systematic investigation into their respective tropism, transduction efficiency, and relative toxicity have not yet been performed in the disc .

Do preterm girls need different nutrition to preterm boys? Sex-specific nutrition for the preterm infant.

Boys born preterm are recognised to be at higher risk of adverse outcomes than girls born preterm. Despite advances in neonatal intensive care and overall improvements in neonatal morbidity and mortality, boys born preterm continue to show worse short- and long-term outcomes than girls. Preterm birth presents a nutritional crisis during a critical developmental period, with postnatal undernutrition and growth-faltering common complications of neonatal intensive care.

Vitamin and Mineral Supplementation Practices in Preterm Infants: A Survey of Australian and New Zealand Neonatal Intensive and Special Care Units.

Preterm infants are at increased risk of micronutrient deficiencies as a result of low body stores, maternal deficiencies, and inadequate supplementations. The aim of this survey was to investigate current vitamin and mineral supplementation practices and compare these with published recommendations and available evidence on dosages and long-term outcomes of supplementations in preterm infants. In 2018, a two-part electronic survey was emailed to 50 Australasian Neonatal Dietitians Network (ANDiN) member and nonmember dietitians working in neonatal units in Australia and New Zealand.

Neonatal dietitian resourcing and roles in New Zealand and Australia: A survey of current practice.

Aim: Dietitian-led implementation of evidence-based nutrition support practices improves nutrient intakes, clinical outcomes and growth, decreases length of stay and related costs, and reduces intravenous nutrition costs and prescription errors. We aimed to investigate current neonatal dietitian resourcing and roles in New Zealand and Australian neonatal units, and to compare this with dietitian workforce recommendations and previously reported survey data.

Methods: A two-part electronic survey was emailed to 50 Australasian Neonatal Dietitians Network members and other dietitians working in neonatal intensive care or special care baby units in New Zealand and Australia.

Omega-3 fatty acids for cystic fibrosis.

Background: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review.

Objectives: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.

Omega-3 fatty acids for cystic fibrosis.

Background: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis.

Objectives: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

A novel low-molecular-weight compound enhances ectopic bone formation and fracture repair.

Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model.

Omega-3 fatty acids for cystic fibrosis.

Background: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis.

Objectives: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.

Search Strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Recombinant soluble human FcgammaR1A (CD64A) reduces inflammation in murine collagen-induced arthritis.

Binding of immune complexes to cellular FcgammaRs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble FcgammaR, rh-FcgammaRIA (CD64A), was shown to block inflammation in passive transfer models of immune complex-mediated disease. To assess whether rh-FcgammaRIA could block inflammation in a T cell- and B cell-dependent model of immune complex-mediated disease, the efficacy of rh-FcgammaRIA in collagen-induced arthritis was evaluated.

Effect on bone induction of using contrast media to reconstitute recombinant human bone morphogenetic protein-2 in an ectopic model in rats.

Object: In this study the authors tested the osteoinductive potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) when combined with each of three commercially available contrast media (Conray, Omniscan, and Optiray).

Methods: Initial in vitro and cadaver tests verified the feasibility of using contrast media to visualize absorbable collagen sponge implants containing rhBMP-2 on fluoroscopic radiographic images. For the feasibility studies, lyophilized rhBMP-2 was prepared for injection by reconstitution with contrast media instead of sterile water.

Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination.

The developmental neurotoxicity of chlorpyrifos (CPF) involves mechanisms other than inhibition of cholinesterase. In the current study, we examined the ability of CPF to evoke lipid peroxidation in the developing brain of fetal and neonatal rats. CPF given to pregnant rats on gestational days 17-20 or to neonatal rats on postnatal days 1-4, failed to elicit increases in thiobarbituric acid-reactive species (TBARS) in brain regions even when the dose was raised above the threshold for systemic toxicity and hepatic damage.

Lasting effects of developmental dexamethasone treatment on neural cell number and size, synaptic activity, and cell signaling: critical periods of vulnerability, dose-effect relationships, regional targets, and sex selectivity.

Glucocorticoids administered to prevent respiratory distress in preterm infants are associated with neurodevelopmental disorders. To evaluate the long-term effects on forebrain development, we treated developing rats with dexamethasone (Dex) at 0.05, 0.

Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses.

Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC).

Mechanism of bone formation with gene transfer of the cDNA encoding for the intracellular protein LMP-1.

Background: LIM mineralization protein-1 (LMP-1), an intracellular protein, is thought to induce secretion of soluble factors that convey its osteoinductive activity. Although evidence suggests that LMP-1 may be a critical regulator of osteoblast differentiation in vitro and in vivo, little is known about its mechanism of action. The purpose of the present study was to identify candidates for the induced secreted factors and to describe the time sequence of histological changes during bone formation induced by LMP-1.