Biallelic TLR4 deficiency in humans.

Background: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins.

Objective: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency.

Human AGR2 Deficiency Causes Mucus Barrier Dysfunction and Infantile Inflammatory Bowel Disease.

Background & Aims: The gastrointestinal epithelium plays a crucial role in maintaining homeostasis with the gut microbiome. Mucins are essential for intestinal barrier function and serve as a scaffold for antimicrobial factors. Mucin 2 (MUC2) is the major intestinal gel-forming mucin produced predominantly by goblet cells.

Pediatric Cervicofacial Actinomycosis: Lessons From a Craniofacial Unit.

Actinomycosis is a rare disease that remains difficult to diagnose and manage. Prompted by 2 recent cases the authors sought evidence-based conclusions about best practice. A systematic review was conducted using standard PRISMA methodology.

The Possible Role of Placental Morphometry in the Detection of Fetal Growth Restriction.

Fetal growth restriction (FGR) is often the result of placental insufficiency and is characterized by insufficient transplacental transport of nutrients and oxygen. The main underlying entities of placental insufficiency, the pathophysiologic mechanism, can broadly be divided into impairments in blood flow and exchange capacity over the syncytiovascular membranes of the fetal placenta villi. Fetal growth restriction is not synonymous with small for gestational age and techniques to distinguish between both are needed.

Methods to decrease variability in histological scoring in placentas from a cohort of preterm infants.

Objective: Reliable semiquantitative assessment of histological placental acute inflammation is problematic, even among experts. Tissue samples in histology slides often show variability in the extent and location of neutrophil infiltrates. We sought to determine whether the variability in pathologists' scoring of neutrophil infiltrates in the placenta could be reduced by the use of 'regions of interest' (ROIs) that break the sample into smaller components.

Preclinical evaluation of drugs to block inflammation-driven preterm birth.

Intrauterine inflammation, the major cause of early preterm birth, can have microbial and sterile aetiologies. We assessed in a Transwell model the anti-inflammatory efficacies of five drugs on human extraplacental membranes delivered after preterm spontaneous labour (30-34 wk). Drugs [TPCA1 (IKKβ inhibitor), 5 z-7-oxozeaenol (OxZ, TAK1 inhibitor), inhibitor of NF-κB essential modulator binding domain (iNBD), SB239063 (p38 MAPK inhibitor) and N-acetyl cysteine (free radical scavenger free radicals)] were added after 12 h equilibration to the amniotic compartment.

Haemophilus influenzae: a potent perinatal pathogen disproportionately isolated from Indigenous women and their neonates.

Background: Nontypeable Haemophilus influenzae (NTHi) bacteraemia in pregnant women is strongly associated with pregnancy loss and preterm delivery. However, the clinical significance of isolation of NTHi from nonsterile sites is unknown.

Aims: To examine the hypothesis that isolation of NTHi from any specimen is associated with adverse perinatal outcomes and to investigate the impression that NTHi is disproportionately isolated from indigenous women and their neonates.

Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia.

Preeclampsia is a systemic vascular disorder of pregnancy and is associated with increased sensitivity to angiotensin II (AngII) and hypertension. The cause of preeclampsia remains unknown. We identified the role of regulator of G protein (heterotrimeric guanine nucleotide-binding protein) signaling 5 (RGS5) in blood pressure regulation during pregnancy and preeclampsia.

Risk of cancer among children with birth defects: a novel approach.

Background: Associations between birth defects (BDs) and childhood cancers have been studied previously and have identified several specific birth defect-cancer associations. No studies have examined the risk after exclusion of known associations.

Methods: We analyzed data from high-quality population-based registers of BDs and cancers for Western Australian births 1982 to 2007.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells.

Overexpression of aromatase associated with loss of heterozygosity of the STK11 gene accounts for prepubertal gynecomastia in boys with Peutz-Jeghers syndrome.

Context: Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder that arises as a consequence of mutations in the STK11 gene that encodes LKB1. PJS males often have estrogen excess manifesting as gynecomastia and advanced bone age. We and others have previously described an increase in testicular aromatase expression in PJS patients.

Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy.

Nemaline myopathy (NEM) is a common congenital myopathy. At the very severe end of the NEM clinical spectrum are genetically unresolved cases of autosomal-recessive fetal akinesia sequence. We studied a multinational cohort of 143 severe-NEM-affected families lacking genetic diagnosis.

Inflammatory and haematological markers in the maternal, umbilical cord and infant circulation in histological chorioamnionitis.

Background: The relationship between histological chorioamnionitis and haematological and biochemical markers in mothers and infants at delivery, and in infants postnatally, is incompletely characterised. These markers are widely used in the diagnosis of maternal and neonatal infection. Our objective was to investigate the effects of histological chorioamnionitis (HCA) on haematological and biochemical inflammatory markers in mothers and infants at delivery, and in infants post-delivery.

Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases.

Aims:   To report a large series of solitary and multiple myofibromas with systematic clinicopathological correlations.

Methods And Results:   We report on 114 patients with myofibromas, 97 of which were solitary and 17 multifocal. The age at presentation ranged from newborn to 70 years.

Fetal akinesia: review of the genetics of the neuromuscular causes.

Fetal akinesia refers to a broad spectrum of disorders in which the unifying feature is a reduction or lack of fetal movement. Fetal akinesias may be caused by defects at any point along the motor system pathway including the central and peripheral nervous system, the neuromuscular junction and the muscle, as well as by restrictive dermopathy or external restriction of the fetus in utero. The fetal akinesias are clinically and genetically heterogeneous, with causative mutations identified to date in a large number of genes encoding disparate parts of the motor system.

Fetal oromandibular limb hypogenesis syndrome following uterine curettage in early pregnancy.

Background: Fetal structural abnormalities, particularly limb reduction defects, have been reported after early hypoxic injury, such as chorionic villus sampling (CVS) before 66 day's gestation.

Case: We present a case of uterine curettage in early pregnancy associated with the subsequent prenatal diagnosis of fetal oromandibular limb hypogenesis syndrome.

Conclusions: This case is consistent with previous hypotheses concerning the role of hypoxic trauma in inducing fetal structural defects in early pregnancy.

Caudal dysgenesis and sirenomelia-single centre experience suggests common pathogenic basis.

Abnormally formed lower limbs with varying degrees of fusion are the major feature of sirenomelia whereas maldeveloped lower limbs without fusion are found in association with caudal dysgenesis (CD). The relationship between these two entities has been a topic of debate for many years. The presence of a single umbilical artery originating from the abdominal aorta was considered a major feature distinguishing sirenomelia from CD.

Infection and fetal loss in the mid-second trimester of pregnancy.

Introduction: Chorioamnionitis is a common cause of second trimester pregnancy loss, usually due to ascending infection. This study investigates the prevalence and bacteriology of chorioamnionitis in cases of spontaneous pregnancy loss in previable gestations (16-22 weeks).

Methods: Fetal losses between 16- and 22-week gestation were identified from the institutional database over a three-year period.

Function of caspase-14 in trophoblast differentiation.

Background: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues.

Gross placental structure in a low-risk population of singleton, term, first-born infants.

Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be exacerbated by an increased placental weight-to-fetal weight ratio. Placental weight is a summary measure of placental growth and development throughout pregnancy. However, measures of placental structure, including the chorionic disk surface area and thickness and eccentricity of the umbilical cord insertion, have been shown to account for additional variance in birth weight beyond that explained by placental weight.

Frequency and timing of loss of imprinting at 11p13 and 11p15 in Wilms' tumor development.

Epigenetic changes occur frequently in Wilms' tumor (WT), especially loss of imprinting (LOI) of IGF2/H19 at 11p15. Our previous results have identified imprinted transcripts (WT1-AS and AWT1) from the WT1 locus at 11p13 and showed LOI of these in some WTs. In this article, we set out to test the relationship between LOI at 11p13 and 11p15 and their timing in WT progression relative to other genetic changes.

Placental characteristics and birthweight.

Standard gross placental measures capture dimensions relevant to specific placental functions. Our objective was to determine their accountability independent of placental weight for variance in birthweight, an important proxy for intrauterine 'adequacy' in fetal origins studies. The sample consisted of 24 152 singleton liveborn children of the Collaborative Perinatal Project delivered from 34 to 42 completed weeks gestation, with complete data for six placental measures (placental disc shape, umbilical cord length, distance from cord insertion to nearest margin, large diameter, small diameter, placental thickness) and placental weight.

Fetal growth and the risk of childhood CNS tumors and lymphomas in Western Australia.

The etiology of childhood cancers is largely unknown, although the early age at diagnosis has led to particular interest in in utero and perinatal factors. Birth weight is the most frequently studied perinatal factor in relation to risk of childhood cancers, and results have been inconsistent. We investigated whether the risk of CNS tumors and lymphomas in children was associated with three measures of the appropriateness of intra-uterine growth: proportion of optimal birth weight (POBW), birth length (POBL) and weight for length (POWFL).

Renal tumours of childhood: an update.

The role of the pathologist has been fundamental in the progress of the treatment of paediatric renal tumours. There are different philosophies in the treatment of these tumours, and there have been many recent advances in the areas of chemotherapy, identification of new entities, prognostic histological criteria following treatment and molecular prognostic and diagnostic features. This review discusses the different approaches of the different treatment protocols from Europe and North America, and reviews staging criteria, prognostic criteria and also the different tumour entities.