Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling.

Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease.

Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis.

Necrotizing enterocolitis remains one of the most vexing problems in the neonatal intensive care unit. Risk factors for NEC include prematurity, formula feeding, and inappropriate microbial colonization of the GI tract. The pathogenesis of NEC is believed to involve weakening of the intestinal barrier by perinatal insults, translocation of luminal bacteria across the weakened barrier, an exuberant inflammatory response, and exacerbation of the barrier damage by inflammatory factors, leading to a vicious cycle of inflammation-inflicted epithelial damage.

Nitrogen and phosphorus co-limitation and grazing moderate nitrogen impacts on plant growth and nutrient cycling in sand dune grassland.

Unlabelled: Atmospheric nitrogen (N) deposition alters plant biodiversity and ecosystem function in grasslands worldwide. This study examines the impact of 6 years of nutrient addition and grazing management on a sand dune grassland. Results indicate that co-limitation of N and phosphorus (P) moderates the impact of realistic rates of N addition (7.

Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.

Background: Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the feasibility and utility of additional endoscopy and biopsy for assessment of resistance mechanisms ex vivo and in vivo.

Methods: Patients with HER2 overexpressing OGA were treated for 10 days with Lapatinib monotherapy, and then in combination with three cycles of Oxaliplatin and Capecitabine before surgery.

The Cost Effectiveness of Docetaxel and Active Symptom Control versus Active Symptom Control Alone for Refractory Oesophagogastric Adenocarcinoma: Economic Analysis of the COUGAR-02 Trial.

Background: The COUGAR-02 trial recently showed survival and quality-of-life benefits of docetaxel and active symptom control (DXL + ASC) over active symptom control (ASC) alone in patients with refractory oesophagogastric adenocarcinoma.

Aim: The aim of this study was to conduct an economic evaluation conforming to National Institute for Health and Care Excellence (NICE) technology appraisal guidance to evaluate the cost effectiveness of DXL + ASC versus ASC from the perspective of the English National Health Service (NHS).

Methods: Cost-utility analyses were conducted using trial data.

A rehabilitation training partnership in Madagascar.

We describe here the development of a mid-level training programme for doctors in Madagascar to direct regional and national rehabilitation services. Eight doctors enrolled and all gained their diplomas and have gone on to form the Association of Physical and Rehabilitation Medicine of Madagascar, which is leading further training and service developments. The course was specific to Madagascar's needs, and was devised according to the vision of the senior rehabilitation specialist in the Ministry of Health in Madagascar with support from the University of Antananarivo.

Docetaxel and its potential in the treatment of refractory esophagogastric adenocarcinoma.

Adenocarcinomas of the esophagus and stomach are a major cause of cancer-related morbidity and mortality worldwide. For patients with advanced disease, first-line chemotherapy with platinum-fluoropyrimidine combinations prolongs survival, but inevitably the disease progresses with a median progression-free survival of approximately 6 months. At the time of progression, approximately 40-50% of patients remain fit and eligible for second-line treatment.

Pathogenesis of neonatal necrotizing enterocolitis.

Although necrotizing enterocolitis (NEC) is the most lethal gastrointestinal disease in the neonatal population, its pathogenesis is poorly understood. Risk factors include prematurity, bacterial colonization, and formula feeding. This review examines how mucosal injury permits opportunistic pathogens to breach the gut barrier and incite an inflammatory response that leads to sustained overproduction of mediators such as nitric oxide and its potent adduct, peroxynitrite.

Risky Sexual Behavior and Substance Use among Adolescents: A Meta-analysis.

This study presents the results of a meta-analysis of the association between substance use and risky sexual behavior among adolescents. 87 studies fit the inclusion criteria, containing a total of 104 independent effect sizes that incorporated more than 120,000 participants. The overall effect size for the relationship between substance use and risky sexual behavior was in the small to moderate range (r = .

Fibroblast growth factor 10 alters the balance between goblet and Paneth cells in the adult mouse small intestine.

Intestinal epithelial cell renewal relies on the right balance of epithelial cell migration, proliferation, differentiation, and apoptosis. Intestinal epithelial cells consist of absorptive and secretory lineage. The latter is comprised of goblet, Paneth, and enteroendocrine cells.

TWIST1-Induced miR-424 Reversibly Drives Mesenchymal Programming while Inhibiting Tumor Initiation.

Epithelial-to-mesenchymal transition (EMT) is a dynamic process that relies on cellular plasticity. Recently, the process of an oncogenic EMT, followed by a reverse mesenchymal-to-epithelial transition (MET), has been implicated as critical in the metastatic colonization of carcinomas. Unlike governance of epithelial programming, regulation of mesenchymal programming is not well understood in EMT.

Reduced El Niño-Southern Oscillation during the Last Glacial Maximum.

El Niño-Southern Oscillation (ENSO) is a major source of global interannual variability, but its response to climate change is uncertain. Paleoclimate records from the Last Glacial Maximum (LGM) provide insight into ENSO behavior when global boundary conditions (ice sheet extent, atmospheric partial pressure of CO2) were different from those today. In this work, we reconstruct LGM temperature variability at equatorial Pacific sites using measurements of individual planktonic foraminifera shells.

The SIX1-EYA transcriptional complex as a therapeutic target in cancer.

Introduction: The SIX homeodomain proteins and the eyes absent (EYA) family of co-activators form a bipartite transcription factor complex that promotes the proliferation and survival of progenitor cells during organogenesis and is down-regulated in most adult tissues. Abnormal over-expression of SIX1 and EYA in adult tissue is associated with the initiation and progression of diverse tumor types. Importantly, SIX1 and EYA are often co-overexpressed in tumors, and the SIX1-EYA2 interaction has been shown to be critical for metastasis in a breast cancer model.

Comment on "A 12-million-year temperature history of the tropical Pacific Ocean".

Zhang et al. (Reports, 4 April 2014, p. 84) interpret TEX86 and U(37)(K') paleotemperature data as providing a fundamentally new view of tropical Pacific climate during the warm Pliocene period.

Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis.

Although phenotypic intratumoral heterogeneity was first described many decades ago, the advent of next-generation sequencing has provided conclusive evidence that in addition to phenotypic diversity, significant genotypic diversity exists within tumors. Tumor heterogeneity likely arises both from clonal expansions, as well as from differentiation hierarchies existent in the tumor, such as that established by cancer stem cells (CSCs) and non-CSCs. These differentiation hierarchies may arise due to genetic mutations, epigenetic alterations, or microenvironmental influences.

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Purpose: This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated.

Patients And Methods: Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines.

Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3.

Introduction: Triple-negative breast cancers, particularly the claudin-low subtype, are highly aggressive and exhibit increased tumor-initiating cell (TIC) characteristics. In this study, we demonstrate that vascular endothelial growth factor C (VEGF-C) is highly expressed in the claudin-low breast cancer subtype and also that it mediates tumor progression, not only through its role in lymphangiogenesis but also through regulating TIC characteristics and the response to reactive oxygen species (ROS).

Methods: VEGF C expression was examined in breast cancer subtypes, and a VEGF C expression signature was derived.

Homeoprotein Six2 promotes breast cancer metastasis via transcriptional and epigenetic control of E-cadherin expression.

Misexpression of developmental transcription factors occurs often in human cancers, where embryonic programs may be reinstated in a context that promotes or sustains malignant development. In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer. We found that Six2 promoted breast cancer metastasis by a novel mechanism involving both transcriptional and epigenetic regulation of E-cadherin.

The ErbB4 ligand neuregulin-4 protects against experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) affects up to 10% of premature infants, has a mortality of 30%, and can leave surviving patients with significant morbidity. Neuregulin-4 (NRG4) is an ErbB4-specific ligand that promotes epithelial cell survival. Thus, this pathway could be protective in diseases such as NEC, in which epithelial cell death is a major pathologic feature.

Survival of pediatric blunt trauma patients presenting with no signs of life in the field.

Background: Prehospital traumatic cardiopulmonary arrest is associated with dismal prognosis, and patients rarely survive to hospital discharge. Recently established guidelines do not apply to the pediatric population because of paucity of data. The study objective was to determine the survival of pediatric patients presenting in the field with no signs of life after blunt trauma.

Nitric oxide in human gingival crevicular fluid after orthodontic force application.

Nitric oxide (NO) is involved in bone remodelling and has been shown to play a role in regulating the rate of orthodontic tooth movement (OTM) in rat models. In humans, however, the role of NO in OTM remains less clear. In this study, NO concentration in gingival crevicular fluid (GCF) was measured in patients undergoing orthodontic treatment.

Late onset of necrotizing enterocolitis in the full-term infant is associated with increased mortality: results from a two-center analysis.

Purpose: The effect of timing of onset of necrotizing enterocolitis (NEC) on outcomes has not been determined for the full-term infant. In this study we aimed to characterize the full-term NEC population and to evaluate onset of NEC.

Methods: We performed a two-center retrospective review of all full-term infants (≥ 37weeks) with a diagnosis of NEC between 1990 and 2012.