Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

Objective: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic.

Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.

Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which delays mitotic onset. Under-replication of common fragile sites (CFSs), however, escapes surveillance, resulting in mitotic chromosome breaks.

Epidemiology of Musculoskeletal Manifestations in Pediatric Inflammatory Bowel Disease: A Systematic Review.

Objective: Pediatric inflammatory bowel disease (p-IBD) is a chronic relapsing gastrointestinal disorder of childhood with long-term morbidity. Several extraintestinal manifestations are described, the most common being joint pain and/or inflammation. However, patient and disease characteristics, treatments, and outcomes of p-IBD-associated musculoskeletal disease are not well established.

Selective Adhesion and Switchable Release of Breast Cancer Cells via Hyaluronic Acid Functionalized Dual Stimuli-Responsive Microgel Films.

The detection of tumor cells from liquid biopsy samples is of critical importance for early cancer diagnosis, malignancy assessment, and treatment. In this work, coatings of hyaluronic acid (HA)-functionalized dual-stimuli responsive poly(-isopropylacrylamide) (PNIPAM) microgels are used to study the specificity of breast cancer cell binding and to assess cell friendly release mechanisms for further diagnostic procedures. The microgels are established by straightforward precipitation polymerization with amine bearing comonomers and postfunctionalization with a UV-labile linker that covalently binds HA to the microgel network.

Take your Positions and Shine: Effects of Positioning Aggregation-Induced Emission Luminophores within Sequence-Defined Macromolecules.

A luminophore with aggregation-induced emission (AIE) is employed for the conjugation onto supramolecular ligands to allow for detection of ligand binding. Supramolecular ligands are based on the combination of sequence-defined oligo(amidoamine) scaffolds and guanidiniocarbonyl-pyrrole (GCP) as binding motif. We hypothesize that AIE properties are strongly affected by positioning of the luminophore within the ligand scaffold.

Secondary Anticoagulation Prophylaxis for Catheter-Related Thrombosis in Pediatric Intestinal Failure: Comparison of Short- Vs Long-Term Treatment Protocols.

Introduction: Catheter-related thrombosis (CRT) is a devastating complication of central venous catheters in children with intestinal failure (IF), but the optimal preventive therapy of CRT is unknown. This study assessed the efficacy and safety of 2 protocols of secondary anticoagulation prophylaxis with low-molecular-weight heparin (LMWH).

Methods: This is a comparative cohort study of children from 2 IF programs who received secondary anticoagulation prophylaxis with LMWH for CRT.

Implementation of a Postpartum Hemorrhage Safety Bundle at an Urban Safety-Net Hospital.

 Postpartum hemorrhage (PPH) is a leading cause of preventable maternal morbidity and mortality. Standardized response to obstetric hemorrhage is associated with significant improvement in maternal outcomes, yet implementation can be challenging.  The primary objective is to describe the methodology for program implementation of the Alliance for Innovation on Maternal Health Safety Bundle on PPH at an urban safety-net hospital.

Transcription-mediated organization of the replication initiation program across large genes sets common fragile sites genome-wide.

Common fragile sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription could elicit their instability; however, the underlying mechanisms remain elusive. Genome-wide replication timing analyses here show that stress-induced delayed/under-replication is the hallmark of CFSs.

An in vitro model of hemogenic endothelium commitment and hematopoietic production.

Adult-type hematopoietic stem and progenitor cells are formed during ontogeny from a specialized subset of endothelium, termed the hemogenic endothelium, via an endothelial-to-hematopoietic transition (EHT) that occurs in the embryonic aorta and the associated arteries. Despite efforts to generate models, little is known about the mechanisms that drive endothelial cells to the hemogenic fate and about the subsequent molecular control of the EHT. Here, we have designed a stromal line-free controlled culture system utilizing the embryonic pre-somitic mesoderm to obtain large numbers of endothelial cells that subsequently commit into hemogenic endothelium before undergoing EHT.

Health governance by collaboration: a case study on an area-based programme to tackle health inequalities in the Dutch city of the Hague.

Background: Area-based programmes are seen as a promising strategy for tackling health inequalities. In these programmes, local authorities and other local actors collaborate to employ health promoting interventions and policies. Little is known about the underlying processes of collaborative governance.

Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial.

Background: Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients' situation.

The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer.

Background: Cancer cell growth has been described to depend on glucose utilization. Activation of Akt and up-regulation of pyruvate kinase M2 (M2-PK) are attributes of tumour glycolysis.

Patients And Methods: In order to evaluate the prognostic relevance of glycolytic markers in breast cancer, the expression of pAkt and M2PK was analysed in 160 tissue samples.

Induction of programmed cell death by inhibition of AKT with the alkylphosphocholine perifosine in in vitro models of platinum sensitive and resistant ovarian cancers.

Purpose: We analyzed the anti-tumor effect and the mechanism of action of perifosine, an orally active alkylphospholipid AKT inhibitor using in vitro models of human ovarian cancer.

Methods: Ovarian cancer cells OAW42, PA-1, SKOV3, and A2780 as well as platinum resistant A2780cis cells were incubated with increasing concentrations of perifosine, with and without multi-caspase inhibitor zVAD-FMK. The effect of a combined treatment with cisplatin and perifosine was investigated in OAW42, SKOV3, A2780 and A2780cis cells.

Generating political priority to tackle health disparities: a case study in the Dutch city of The Hague.

Objectives: We sought to study the factors that determined the success of a recent initiative to generate political priority for the problem of health disparities in the city of The Hague, the Netherlands.

Methods: Our study had a prospective design. The qualitative data collection included interviews, document analyses, and observations.

Glycolytic phenotype in breast cancer: activation of Akt, up-regulation of GLUT1, TKTL1 and down-regulation of M2PK.

Purpose: Metabolic dependence on glucose utilisation has been described for different tumours characterised by activation of Akt, upregulation of GLUT1, M2PK and TKTL1. To date, however, little is known about glucose metabolism in breast cancer tissue.

Methods: We analysed 55 breast cancer specimens, 26 adjacent ductal carcinomas in situ (DCIS) and 23 adjacent normal breast tissues for expression of glycolytic markers by immunohistochemistry.

Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma.

Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status. Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value. Therefore, we investigated the role of these factors in ACC.

Which factors engage women in deprived neighbourhoods to participate in exercise referral schemes?

Background: Exercise referral schemes (ERS) have become a popular way of promoting physical activity. The aim of these schemes is to encourage high risk patients to exercise. In evaluating these schemes, little attention has been paid to lower socio-economic groups in a multi-ethnic urban setting.

Expression of transketolase-like 1 (TKTL1) and p-Akt correlates with the progression of cervical neoplasia.

Aim: It is supposed that increased glycolysis is crucial for the energy supply during tumor progression. Unfortunately, the relevance of glycolysis in cervical neoplasia is unknown, but what is certain is the fact that cervical cancer shows a high expression of glucose membrane transporters, which are necessary for glucose uptake as an energy source. Transketolase-like enzyme 1 (TKTL1) and the oncogene p-Akt have been described to play an important role in glycolysis during tumorigenesis.

Expression of VEGFR-1 (Flt-1) in breast cancer is associated with VEGF expression and with node-negative tumour stage.

Background: Vascular endothelial growth factor (VEGF) promotes breast cancer progression by inducing angiogenesis via VEGF receptors on endothelial cells but also signals directly through receptors such as VEGFR-1 (Flt-1) expressed on tumour cells. The impact of autocrine signalling loops on treatment with VEGF inhibitors is still unclear.

Materials And Methods: Six breast cancer cell lines were tested for expression of VEGFR-1 by RT-PCR and Western blot.

Expression of CD56 isoforms in primary and relapsed adult granulosa cell tumors of the ovary.

Background: Adult granulosa cell tumors of the ovary (GCTs) are sex cord stromal tumors of unpredictable behaviour. Up to now, the prediction of the relapsing/malignant potential remains difficult. CD56 (NCAM) in GCTs was previously described in only two studies.

Glucose metabolism and angiogenesis in granulosa cell tumors of the ovary: activation of Akt, expression of M2PK, TKTL1 and VEGF.

Objectives: Very little is known about the biology of granulosa cell tumors of the ovary. A hallmark of granulosa cell tumors of the ovary is extensive growth, distant metastases however, are rarely found. We hypothesise that granulosa cell tumors of the ovary on the one hand need to stimulate vascularisation; on the other hand glucose metabolism has to be altered to ensure the supply of nutrients and metabolites.

Inhibition of cytosolic and mitochondrial creatine kinase by siRNA in HaCaT- and HeLaS3-cells affects cell viability and mitochondrial morphology.

The creatine kinase (CK) system is essential for cellular energetics in tissues or cells with high and fluctuating energy requirements. Creatine itself is known to protect cells from stress-induced injury. By using an siRNA approach to silence the CK isoenzymes in human keratinocyte HaCaT cells, expressing low levels of cytoplasmic CK and high levels of mitochondrial CK, as well as HeLa cancer cells, expressing high levels of cytoplasmic CK and low levels of mitochondrial CK, we successfully lowered the respective CK expression levels and studied the effects of either abolishing cytosolic brain-type BB-CK or ubiquitous mitochondrial uMi-CK in these cells.