Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients.

In the majority of colorectal cancers (CRCs) under clinical suspicion for a hereditary cause, the disease-causing genetic factors are still to be discovered. To identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite-stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history.

Integrated use of minimal residual disease classification and IKZF1 alteration status accurately predicts 79% of relapses in pediatric acute lymphoblastic leukemia.

Response to therapy as determined by minimal residual disease (MRD) is currently used for stratification in treatment protocols for pediatric acute lymphoblastic leukemia (ALL). However, the large MRD-based medium risk group (MRD-M; 50-60% of the patients) harbors many relapses. We analyzed MRD in 131 uniformly treated precursor-B-ALL patients and evaluated whether combined MRD and IKZF1 (Ikaros zinc finger-1) alteration status can improve risk stratification.

Finding maximal transcriptome differences between reprotoxic and non-reprotoxic phthalate responses in rat testis.

The chemical legislation of the EU, Registration, Evaluation, and Authorization of Chemicals (REACH), stipulates that about 30 000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. In particular, the assessment of reproductive toxicity is a very complicated, time-consuming and animal-demanding process.

The epigenetics of (hereditary) colorectal cancer.

In the last decade, it has become apparent that not only DNA sequence variations but also epigenetic modifications may contribute to disease, including cancer. These epigenetic modifications involve histone modification including acetylation and methylation, DNA methylation, and chromatin remodeling. One of the best-characterized epigenetic changes is aberrant methylation of cytosines that occur in so-called CpG islands.

Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial.

Background: Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity in patients with multiple myeloma, often requiring adjustment of treatment and affecting quality of life. We investigated the molecular profiles of early-onset (within one treatment cycle) versus late-onset (after two or three treatment cycles) bortezomib-induced peripheral neuropathy and compared them with those of vincristine-induced peripheral neuropathy during the induction phase of a prospective phase 3 trial.

Methods: In the induction phase of the HOVON-65/GMMG-HD4 trial, patients (aged 18-65 years) with newly diagnosed Salmon and Durie stage 2 or 3 multiple myeloma were randomly assigned to three cycles of bortezomib-based or vincristine-based induction treatment.

Influence of left ventricular dysfunction (diastolic versus systolic) on long-term prognosis in patients with versus without diabetes mellitus having elective peripheral arterial surgery.

Diabetes mellitus (DM) and left ventricular dysfunction (LVD) are often coexistent and invariably associated with increased mortality. Data on long-term prognosis of "isolated" diastolic LVD in diabetics are lacking; therefore, we evaluated these prognostic implications in patients with peripheral arterial disease (PAD) and DM. Using echocardiography, 1321 patients were screened for diastolic, systolic (ejection fraction <50%) or combined LVD.

Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.

In myelodysplastic syndromes (MDS), deletions of chromosome 7 or 7q are common and correlate with a poor prognosis. The relevant genes on chromosome 7 are unknown. We report here that EZH2, located at 7q36.

Mouse models for the p53 R72P polymorphism mimic human phenotypes.

The p53 tumor suppressor gene contains a common single nucleotide polymorphism (SNP) that results in either an arginine or proline at position 72 of the p53 protein. This polymorphism affects the apoptotic activity of p53 but the mechanistic basis and physiologic relevance of this phenotypic difference remain unclear. Here, we describe the development of mouse models for the p53 R72P SNP using two different approaches.

Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery.

Background: The prognostic value of heart failure symptoms on postoperative outcome is well acknowledged in perioperative guidelines. The prognostic value of asymptomatic left ventricular (LV) dysfunction remains unknown. This study evaluated the prognostic implications of asymptomatic LV dysfunction in vascular surgery patients assessed with routine echocardiography.

Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma.

Noonan Syndrome (NS) is an autosomal dominant condition characterized by short stature, facial dysmorphisms, and congenital heart defects, and is caused by mutations in either PTPN11, KRAS, NRAS, SHOC2, RAF1, or SOS1. Furthermore, NS is known for its predisposition to develop cancer, particularly hematological malignancies and specific solid tumors, mainly neuroblastoma and embryonal rhabdomyosacroma (ERMS). Until recently, however, cancer predisposition in NS patients with SOS1 mutations was not reported.

IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL.

Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis and relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell.

Thinking strategies of baccalaureate nursing students prompted by self-regulated learning strategies.

The standard in nursing education today is to prepare nurses for future practice through generic programs with a culminating practicum experience. The clinical faculty in this program was interested in evaluating differences in student thinking strategies that occurred as a result of an increase from 60 to 120 clinical hours, coupled with reflective journaling. The Self-Regulated Learning model was used as a conceptual support for the journaling prompts, as well as a structure for narrative analysis.

Germline copy number variation and cancer risk.

The human genome is subject to substantial structural variation, including copy number variation (CNV). Constitutional CNVs may either represent benign polymorphic variants or be associated with disease, including cancer predisposition. Rare nonpolymorphic CNVs, that is DNA lesions that result in gene deletions, inversions, and/or fusions, may be responsible for a high cancer risk.

BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia.

Resistance to glucocorticoids (GCs) is a major clinical problem in the treatment of acute lymphoblastic leukemia (ALL), but the underlying mechanisms are not well understood. Although mutations in the glucocorticoid receptor (GR) gene can give rise to therapy resistance in vitro, acquired somatic mutations in the GR are rarely encountered in patients. Here we report that the protein encoded by the BTG1 gene, which is frequently deleted in (pediatric) ALL, is a key determinant of GC responsiveness.

Comparisons of means using exploratory and confirmatory approaches.

This article discusses comparisons of means using exploratory and confirmatory approaches. Three methods are discussed: hypothesis testing, model selection based on information criteria, and Bayesian model selection. Throughout the article, an example is used to illustrate and evaluate the two approaches and the three methods.

Metacognitive factors that impact student nurse use of point of care technology in clinical settings.

The utility of personal digital assistants (PDA) as a point of care resource in health care practice and education presents new challenges for nursing faculty. While there is a plethora of PDA resources available, little is known about the variables that effect student learning and technology adoption. In this study nursing students used PDA software programs which included a drug guide, medical dictionary, laboratory manual and nursing diagnosis manual during acute care clinical experiences.

Case report: epitheliotropic lymphoma in a zebrafish (Danio rerio).

A proliferative disorder of lymphocytes was observed in a macroscopically normal young adult wild-type zebrafish (Danio rerio) during routine histological screening in a two-generation toxicity study. Proliferating lymphocytes were observed to invade the gill arches, infiltrate the cranial skeletal muscle and inner ear, and accumulate at distant sites in the frontal epidermis. The test compound, tetrabromobisphenol A (TBBPA, a flame retardant), is not known as a carcinogen and no tumours were detected in any of the 53 other fish in the study, including tank mates.

Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging.

Defects in the DNA repair mechanism nucleotide excision repair (NER) may lead to tumors in xeroderma pigmentosum (XP) or to premature aging with loss of subcutaneous fat in Cockayne syndrome (CS). Mutations of mitochondrial (mt)DNA play a role in aging, but a link between the NER-associated CS proteins and base excision repair (BER)-associated proteins in mitochondrial aging remains enigmatic. We show functional increase of CSA and CSB inside mt and complex formation with mtDNA, mt human 8-oxoguanine glycosylase (mtOGG)-1, and mt single-stranded DNA binding protein (mtSSBP)-1 upon oxidative stress.

Prevalence and pharmacological treatment of left-ventricular dysfunction in patients undergoing vascular surgery.

Aims: This study evaluated the prevalence of left-ventricular (LV) dysfunction in vascular surgery patients and pharmacological treatment, according ESC guidelines.

Methods And Results: Echocardiography was performed pre-operatively in 1,005 consecutive patients. Left ventricular ejection fraction (LVEF) View Article and Find Full Text PDF

Co-existence of COPD and left ventricular dysfunction in vascular surgery patients.

Background: The co-existence between chronic obstructive pulmonary disease (COPD) and heart failure has been previously described. However, the co-existence between COPD and subclinical left ventricular (LV) dysfunction, without the presence of heart failure symptoms, is less well understood. This study determined the relationship and clinical relevance of COPD and subclinical LV dysfunction in vascular surgery patients.

The tumor suppressor gene FBXW7 is disrupted by a constitutional t(3;4)(q21;q31) in a patient with renal cell cancer.

FBXW7 (alias CDC4) is a p53-dependent tumor suppressor gene that exhibits mutations or deletions in a variety of human tumors. Mutation or deletion of the FBXW7 gene has been associated with an increase in chromosomal instability and cell cycle progression. In addition, the FBXW7 protein has been found to act as a component of the ubiquitin proteasome system and to degrade several oncogenic proteins that function in cellular growth regulatory pathways.

Camp BONES: a partnership initiative to engage underrepresented adolescents in a career in nursing at the baccalaureate level.

The nursing profession is confronted with significant challenges related to the ever-increasing shortage and lack of diversity in the workforce. To address these challenges, a program for underrepresented middle school students was developed collaboratively between local school districts, academia, and health care partners. The program, Camp BONES, included a 2-week summer camp and follow-up weekend and summer camp experiences for students.