Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia.

Objective: Lung hypoplasia associated with congenital diaphragmatic hernia (CDH) results in respiratory insufficiency and pulmonary hypertension after birth. We have investigated whether aerating the lung before removing placental support (physiologically based cord clamping (PBCC)), improves the cardiopulmonary transition in lambs with a CDH.

Methods: At ≈138 days of gestational age, 17 lambs with surgically induced left-sided diaphragmatic hernia (≈d80) were delivered via caesarean section.

Effect of spontaneous breathing on umbilical venous blood flow and placental transfusion during delayed cord clamping in preterm lambs.

Introduction: During delayed umbilical cord clamping, the factors underpinning placental transfusion remain unknown. We hypothesised that reductions in thoracic pressure during inspiration would enhance placental transfusion in spontaneously breathing preterm lambs.

Objective: Investigate the effect of spontaneous breathing on umbilical venous flow and body weight in preterm lambs.

Complete genome sequence of Helicobacter pylori B128 7.13 and a single-step method for the generation of unmarked mutations.

Background: Helicobacter pylori represents an interesting model of bacterial pathogenesis given that most infections are asymptomatic, while a minority of infections cause severe gastric disease. H pylori strain B128 7.13 is used extensively to understand H pylori pathophysiology.

The Changing Landscape in Supporting Preterm Infants at Birth.

Noninvasive ventilation for preterm infants at birth has been recommended and universally adopted. The umbilical cord is often clamped immediately in order to provide the support the infant needs for stabilization. However, recent scientific data from experimental studies that involve animals in transition and human studies using physiological measurements at birth have increased awareness as to how little we know about how these interventions interact and integrate with the infant's changing physiology.

Sildenafil for Antenatal Treatment of Congenital Diaphragmatic Hernia: From Bench to Bedside.

Background: Persistent pulmonary hypertension (PPH) is one of the main causes of mortality and morbidity in infants affected by congenital diaphragmatic hernia (CDH). Since the structural changes that lead to PPH take place already in utero, a treatment starting in the prenatal phase may prevent the occurrence of this complication.

Objective: To summarize the development process of antenatal sildenafil for CDH.

Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls.

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone.

Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9.

Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans.

Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing.

Mammalian wounds typically heal by fibrotic repair without hair follicle (HF) regeneration. Fibrosis and regeneration are currently considered the opposite end of wound healing. This study sought to determine if scar could be remodeled to promote healing with HF regeneration.

A patient derived xenograft model of cervical cancer and cervical dysplasia.

Aim: To develop a patient derived xenograft (PDX) model of cervical cancer and cervical dysplasia using the subrenal capsule.

Methods: Cervical cancer (12 Squamous Cell Carcinoma, 1 Adenocarcinoma, 1 Adenosquamous Carcinoma), 7 cervical dysplasia biopsy and normal cervical tissues were transplanted beneath the renal capsule of immunocompromised NOD/SCID/gamma mice. Resulting tumours were harvested and portions serially transplanted into new recipient mice for up to three in vivo passages.

Bone health in chronic kidney disease-mineral and bone disorder: a clinical case seminar and update.

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation.

Partial amniotic carbon dioxide insufflation for fetal surgery.

Partial amniotic carbon dioxide insufflation (PACI) involves insufflating the amniotic sac with carbon dioxide (CO ) and, in some cases, draining some of the amniotic fluid. The creation of a gaseous intra-amniotic compartment improves visualization, even in the presence of limited bleeding, and creates the work space required for complex fetoscopic procedures. Clinically, PACI is mostly used to perform fetoscopic myelomeningocele (MMC) repair, enabling a minimally invasive alternative to open fetal surgery.

Supporting breathing of preterm infants at birth: a narrative review.

Most very preterm infants have difficulty aerating their lungs and require respiratory support at birth. Currently in clinical practice, non-invasive ventilation in the form of continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) is applied via facemask. As most very preterm infants breathe weakly and unnoticed at birth, PPV is often administered.

Animal models in neonatal resuscitation research: What can they teach us?

Animal models have made and continue to make important contributions to neonatal medicine. For example, studies in fetal sheep have taught us much about the physiology of the fetal-to-neonatal transition. However, whereas animal models allow multiple factors to be investigated in a logical and systematic manner, no animal model is perfect for humans and so we need to understand the fundamental differences in physiology between the species in question and humans.

Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8 T Cell-Lineage-Specific Function.

Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8 T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3) chromatin signature upon differentiation.

CT dose reduction factors in the thousands using X-ray phase contrast.

Phase-contrast X-ray imaging can improve the visibility of weakly absorbing objects (e.g. soft tissues) by an order of magnitude or more compared to conventional radiographs.

Altered downstream target gene expression of the placental Vitamin D receptor in human idiopathic fetal growth restriction.

Fetal growth restriction (FGR) affects up to 5% of pregnancies and is associated with significant perinatal complications. Maternal deficiency of vitamin D, a secosteroid hormone, is common in FGR-affected pregnancies. We recently demonstrated that decreased expression of the vitamin D receptor (VDR) in idiopathic FGR placentae could impair trophoblast growth.

Laryngeal closure impedes non-invasive ventilation at birth.

Background: Non-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction.

Combining hiPSCs and Human Genetics: Major Applications in Drug Development.

Merging iPSC models and human genetic research has opened up new avenues in understanding disease mechanisms and target biology, which facilitate exciting translation of this research to many areas of drug development. We highlight recent applications of these combined disciplines and discuss remaining challenges and potential solutions.

The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis.

Hip fractures in young adults: a retrospective cross-sectional study of characteristics, injury mechanism, risk factors, complications and follow-up.

Unlabelled: This study characterises risk factors, complications and follow-up of minimal trauma hip fractures in young adults, adding to limited information examining the management framework. This group have severe systemic disease and significant risk of post-operative complications and subsequent fractures. Improved medical referral pathways enable management of osteoporosis and comorbid diseases.

Serum phosphorus levels and fracture following renal transplantation.

Purpose: Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders. Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated.

Towards evidence-based resuscitation of the newborn infant.

Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic-ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials.