Implications of maternal obesity on fetal growth and the role of ultrasound.

Over fifty percent of women entering pregnancy are overweight or obese. This has a significant impact on short and long term maternal and infant health outcomes, and the intergenerational effects of obesity are now a major public health problem globally. Areas covered: There are two major pathways contributing to fetal growth.

Caspase-2-mediated cell death is required for deleting aneuploid cells.

Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2 mice were exposed to anti-mitotic drugs and followed up by live cell imaging.

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.

Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.

Background: Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes.

Thermoregulation, scratch, itch and sleep deficits in children with eczema.

Successful sleep onset and maintenance is associated with a reduction in core temperature, facilitated by heat loss at the distal periphery. Problems with initiating and maintaining sleep in children with eczema may relate to impaired thermoregulatory mechanisms, which also contribute to itching and scratching. Our hypothesis was that nocturnal distal skin temperature in eczematous children would be lower than controls, and would also be related to poor sleep quality.

Is FGF13 a major contributor to genetic epilepsy with febrile seizures plus?

Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+) in a single family segregating a balanced translocation with a breakpoint in this X chromosome gene, predicting a partial knockout involving 3 of 5 known FGF13 isoforms. Investigation of a mouse model of complete Fgf13 knock-out revealed increased susceptibility to hyperthermia-induced seizures and epilepsy. Here we investigated whether mutation of FGF13 would explain other cases of GEFS+ compatible with X-linked inheritance.

Meningococcal serogroup B-specific responses after vaccination with bivalent rLP2086: 4 year follow-up of a randomised, single-blind, placebo-controlled, phase 2 trial.

Background: Bivalent rLP2086 is a recombinant factor H binding protein-based vaccine approved in the USA for prevention of meningococcal serogroup B disease in 10-25-year-olds. We aimed to assess the persistence of bactericidal antibodies up to 4 years after a three-dose schedule of bivalent rLP2086.

Methods: We did this randomised, single-blind, placebo-controlled, phase 2 trial at 25 sites in Australia, Poland, and Spain.

Interventions to prevent maternal obesity before conception, during pregnancy, and post partum.

Prevention of obesity in women of reproductive age is widely recognised to be important both for their health and for that of their offspring. Weight-control interventions, including drug treatment, in pregnant women who are obese or overweight have not had sufficient impact on pregnancy and birth outcomes, which suggests that the focus for intervention should include preconception or post-partum periods. Further research is needed into the long-term effects of nutritional and lifestyle interventions before conception.

Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

Objective: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations.

Methods: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE).

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals.

Safety and immunogenicity of a booster dose of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults: A randomized phase 1 study.

Objective: A 2-stage, phase 1, randomized, placebo-controlled study in healthy adults to assess immunogenicity and safety of a booster dose at three dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) containing recombinant clumping factor A (ClfA) and capsular polysaccharides 5 and 8 (CP5 and CP8) conjugated to a diphtheria toxoid.

Methods: Six months after initial single vaccination, in Stage 2, SA3Ag recipients were randomized (1:1) to booster vaccination or placebo, while Stage 1 placebo recipients received placebo again. Pre- and post-vaccination blood samples were analyzed.

Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children.

Aim: The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children.

Methods: A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included.

Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B.

First trimester trophoblasts forming endothelial-like tubes in vitro emulate a 'blood vessel development' gene expression profile.

Extravillous cytotrophoblasts isolated from first trimester placenta, and immortalised cell lines derived from them, have the intrinsic ability to form endothelial-like tubes when cultured on Matrigel™ extracellular matrix. This in vitro tube formation may model placental angiogenesis and/or endovascular differentiation by trophoblasts. To interpret the relevance of this phenomenon to placental development, we used a gene expression microarray approach to identify which genes and pathways are associated with the tube-forming phenotype of HTR8/SVneo first trimester trophoblasts (HTR8-M), compared with HTR8/SVneo not forming tubes on plastic culture surface (HTR8-P).

Delivery of Dietary and Lifestyle Interventions in Pregnancy: is it Time to Promote the Use of Electronic and Mobile Health Technologies?

Fifty percent of women who enter pregnancy are overweight or obese, increasing complications for both the mother and the infant, along with significant burden on individuals and the health care system. Pregnancy represents a "teachable moment" in a woman's life, however, antenatal interventions focusing on improving dietary and physical activity patterns have been associated with modest behavior change. There are many barriers that need to be overcome, including lack of knowledge, access and time pressures.

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

This study was undertaken to determine whether perinatal maternal resveratrol (Resv)--a phytoalexin known to confer cardiovascular protection--could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21.

Vaccines in pregnancy: The dual benefit for pregnant women and infants.

Maternal immunization has the potential to reduce the burden of infectious diseases in the pregnant woman and her infant. Many countries now recommend immunization against influenza at any stage of pregnancy and against pertussis in the third trimester. Despite evidence of the safety and effectiveness of these vaccines when administered during pregnancy, uptake generally remains low for influenza and moderate for pertussis vaccine.

Genomic dissection of Australian Bordetella pertussis isolates from the 2008-2012 epidemic.

Objectives: Despite high pertussis vaccination coverage, Australia experienced a prolonged epidemic in 2008-2012. The predominant Bordetella pertussis genotype harboured pertussis toxin promoter allele, ptxP3, and pertactin gene allele, prn2. The emergence and expansion of prn non-expressing isolates (Prn negative), were also observed.

Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents.

Background: In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9-12 years through the existing school-based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents' knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent.

Systematic review of antenatal dietary and lifestyle interventions in women with a normal body mass index.

Introduction: Women who commence pregnancy with a normal body mass index (BMI) are at the greatest risk of excessive gestational weight gain, impacting on infant birthweight, pregnancy-related complications and postpartum weight retention. Our aim was to review systematically the effect of antenatal dietary and lifestyle interventions in pregnant women with a normal BMI on maternal and infant outcomes.

Material And Methods: We searched the Cochrane Controlled Trials Register, PubMed, Medline, and the Australian and International Clinical Trials Registry with the date of the last search in July 2015.

Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.

Reduced or absent cytotrophoblast invasion of the maternal uterine spiral arterioles is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms mediating invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour.

Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.

Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent.

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills.