Incidence of venous thromboembolism and adequacy of thromboprophylaxis in 2380 acutely-ill hospitalized patients: Results from the PROFMiG cohort study.

Introduction: Hospital-acquired venous thromboembolism (VTE) is a major cause of preventable deaths. Incidence of VTE and adequacy of thromboprophylaxis have rarely been reported in low-resourced countries. The aim of this study was to estimate the incidence of VTE and to evaluate the adequacy of thromboprophylaxis in acutely-ill medical hospitalized patients.

BMI1 is required for melanocyte stem cell maintenance and hair pigmentation.

The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16 and p19 . However, in cutaneous melanoma, BMI1 drives epithelial-mesenchymal transition programs, and thus metastasis, while having little impact on proliferation or primary tumor growth. This raised questions about the requirement and role for BMI1 in melanocyte stem cell (McSC) biology.

E2F4's cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6.

Multiciliated cells play critical roles in the airway, reproductive organs, and brain. Generation of multiple cilia requires both activation of a specialized transcriptional program and subsequent massive amplification of centrioles within the cytoplasm. The E2F4 transcription factor is required for both roles and consequently for multiciliogenesis.

Inherited susceptibility to miscarriage: a nested case-control study of 31,565 women from an intergenerational cohort.

Background: Miscarriage can be a devastating outcome for couples, and most miscarriages are unexplained. Many adverse obstetric outcomes (such as preeclampsia, preterm birth, and growth restriction) are thought to be inherited. It is possible that these conditions could share similar pathophysiologic mechanisms (such as endothelial dysfunction) with miscarriage.

Author Correction: Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis.

This corrects the article DOI: 10.1038/ncomms15857.

Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis.

Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors.

Development and piloting of a food-based intervention to increase vitamin E intake in pregnant women in a randomized controlled trial.

Low maternal vitamin E intake during pregnancy is associated with childhood asthma and a trial is required to test whether increasing maternal vitamin E intake reduces childhood asthma. This study investigated whether such a trial is possible using food to increase vitamin E intake. Three soup varieties with enhanced vitamin E content (16-19 mg/can) from food ingredients were developed.

E2f4 and E2f5 are essential for the development of the male reproductive system.

The E2F transcription factors are primarily implicated in the regulation of entry and exit from the cell cycle. However, in vivo studies have established additional roles for E2Fs during organ development and homeostasis. With the goal of addressing the intestinal requirements of E2f4 and E2f5, we crossed mice carrying Vil-cre, E2f4 conditional and E2f5 germline alleles.

Influence of reverse Trendelenburg position on aortocaval compression in obese pregnant women.

Introduction: Obese pregnant women are at risk of aortocaval compression and associated hypotension with neuraxial anaesthesia. We hypothesised that addition of reverse Trendelenburg tilt to the standard practice of pelvic tilt may attenuate aortocaval compression.

Methods: After ethical approval and consent, six women with a singleton pregnancy and booking body mass index of 30-35kg/m(2) underwent magnetic resonance imaging scanning in six different positions: right lateral decubitus; left lateral decubitus; supine with pelvic tilt; and reverse Trendelenburg positions of 5°, 10° and 15°.

Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation.

The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and proteomic changes in the colon and lungs, where Rb(KO) was sufficient or insufficient to induce ectopic proliferation, respectively.

Maternal vitamin D and E intakes during early pregnancy are associated with airway epithelial cell responses in neonates.

Background: Antenatal factors including maternal diet may predispose to airway disease, possibly by impacting on fetal airway development.

Objective: This cohort study tested the hypothesis that maternal vitamin D and E status in early pregnancy is associated with airway epithelial cell (AEC) responses in new born infants and examined constitutive and TNFα/IL-1β, house dust mite (HDM) extract or lipopolysaccharide (LPS)-stimulated neonatal AEC responses in vitro.

Methods: Maternal dietary vitamin D and E intakes (plasma 25[OH]D3 or α-tocopherol) were characterized at 10-12 weeks gestation.

Measurement of aortic augmentation index in pregnant women with raised blood pressure and subsequent outcomes: a preliminary prospective cohort study.

Objective: Preeclampsia is associated with arterial dysfunction and augmentation index (AIX%) is an established indicator of arterial dysfunction. Our aim was to investigate the relationship of AIX% with time-to-delivery and other outcomes in women admitted to an antenatal triage unit.

Methods: We recruited 28 women with singleton pregnancies attending antenatal triage ward for assessment of hypertension.

Culture of airway epithelial cells from neonates sampled within 48-hours of birth.

Introduction: Little is known about how neonatal airway epithelial cell phenotype impacts on respiratory disease in later life. This study aimed to establish a methodology to culture and characterise neonatal nasal epithelial cells sampled from healthy, non-sedated infants within 48 hours of delivery.

Methods: Nasal epithelial cells were sampled by brushing both nostrils with an interdental brush, grown to confluence and sub-cultured.

Instrumental vaginal deliveries; are midwives safer practitioners? A retrospective cohort study.

Objective: To compare obstetric morbidity of midwife-performed instrumental vaginal deliveries with those performed by doctors.

Design: Retrospective cohort study.

Setting: University Hospital, UK.

Protease concentration in amniotic fluid at term and early childhood respiratory symptoms.

Objective: Asthma is a common chronic disease associated with altered proteolytic activity. The present study tested the hypothesis that altered protease concentration in amniotic fluid (AF), an index of airway fluid at birth, precedes early cough and wheeze.

Methods: AF was collected and analysed for the following: matrix metalloproteinases (MMP) -2, -8 and -9, tissue inhibitor of metalloproteinases (TIMP) -1 and 2, plasminogen activator inhibitor (PAI)-1.

Outcomes of pregnancy following postpartum haemorrhage.

Objective: To assess the outcomes of pregnancy following postpartum haemorrhage (PPH) in the first pregnancy.

Design: Cohort study.

Setting: Aberdeen Maternity Hospital, Scotland, UK.

Loss of pRB and p107 disrupts cartilage development and promotes enchondroma formation.

The pocket proteins pRB, p107 and p130 have established roles in regulating the cell cycle through the control of E2F activity. The pocket proteins regulate differentiation of a number of tissues in both cell cycle-dependent and -independent manners. Prior studies showed that mutation of p107 and p130 in the mouse leads to defects in cartilage development during endochondral ossification, the process by which long bones form.

Rb regulates fate choice and lineage commitment in vivo.

Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma. Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb). The best known is pRb's ability to promote cell-cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell-cycle regulators.

A vertebrate gene, ticrr, is an essential checkpoint and replication regulator.

Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression.

Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects.

The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects.

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

Background: Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.

E2F4 cooperates with pRB in the development of extra-embryonic tissues.

The retinoblastoma gene, RB-1, was the first identified tumor suppressor. Rb(-/-) mice die in mid-gestation with defects in proliferation, differentiation and apoptosis. The activating E2F transcription factors, E2F1-3, contribute to these embryonic defects, indicating that they are key downstream targets of the retinoblastoma protein, pRB.

Smoking cessation in pregnancy.

Background: Pregnant women who continue to smoke expose their developing fetus to a wide range of risks. Assisting these patients to stop smoking can be an important intervention for the health of the baby and the mother. The management of pregnant smokers can be challenging, due to the potential risks of pharmacotherapy.

Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage.

Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance.