Profiling of epigenetic marker regions in murine ILCs under homeostatic and inflammatory conditions.

Epigenetic modifications such as DNA methylation play an essential role in imprinting specific transcriptional patterns in cells. We performed genome-wide DNA methylation profiling of murine lymph node-derived ILCs, which led to the identification of differentially methylated regions (DMRs) and the definition of epigenetic marker regions in ILCs. Marker regions were located in genes with a described function for ILCs, such as Tbx21, Gata3, or Il23r, but also in genes that have not been related to ILC biology.

Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5 intestinal stem cell function.

Basic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5 intestinal epithelial stem cells (ISC).

In vitro profiling of volatile organic compounds released by Simpson-Golabi-Behmel syndrome adipocytes.

Breath analysis offers a non-invasive and rapid diagnostic method for detecting various volatile organic compounds that could be indicators for different diseases, particularly metabolic disorders including type 2 diabetes mellitus. The development of type 2 diabetes mellitus is closely linked to metabolic dysfunction of adipose tissue and adipocytes. However, the VOC profile of human adipocytes has not yet been investigated.

Non-return valves do not prevent backflow and bacterial contamination of intravenous infusions.

Non-return valves (NRVs) are designed to avoid backflow of infusion fluid against the designated direction of flow (DDF) when more than one infusion is delivered via one venous access. We tested in vitro whether NRVs reliably prevent flow against the DDF at clinically relevant low flow rates. Since catheter-related infections caused by the infusion of contaminated fluids represent a relevant problem in patient care, we tested whether NRVs preclude bacterial contamination of infusions proximal to the NRVs and thus might play a role in preventing healthcare-associated infections.

Development and testing of tools to evaluate public health nursing clinical education at the baccalaureate level.

Tools to evaluate clinical coursework with community groups for basic baccalaureate students are limited and often have not been sufficiently validated. This study developed and tested 2 tools. The initial phase of development involved identifying expected outcomes for clinical course work and specific tool items from 2 sources of information: (a) U.

Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients.

Aims: Sentinel lymph node (SLN) -positive melanoma patients are usually recommended completion lymph node dissection (CLND) with the aim to provide regional disease control and improve survival. Nevertheless, only 20% these patients have additional metastases in non-sentinel lymph nodes (NSLN), indicating that CLND may be unnecessary in the majority of patients. In this retrospective study, we (i) sought to identify clinico-pathological features predicting NSLN status, as well as disease-free (DFS) and -specific (DSS) survival and (ii) evaluated the applicability of previously published algorithms, which were able to define a group of patients at zero-risk for NSLN-metastasis.

Complexity and team dynamics in multiple intervention programmes: challenges and insights for public health psychology.

Psychologists engaged in public health research and intervention will become more involved in multiple intervention programming approaches. Managing innovation and complexity is a challenge when the team members come from different disciplines, organizational cultures and research perspectives. This report captures some of those challenges with a participatory, capacity-building, community-based intervention over research stages.

Integrating clinical guidelines into nursing education.

A project planning group consisting of college and university representatives from a collaborative undergraduate nursing program developed an inclusive, process-oriented faculty development initiative to enhance the integration of clinical guidelines in clinical courses. In the first phase, results of a needs assessment were used to inform the development of a six-hour workshop for the third year clinical faculty in acute care, mental health, and community health. Pre-post surveys were conducted with students and clinical faculty during the first phase.

Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours.

Background: In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol-binding protein.

Objectives: To evaluate protein and mRNA expression of RPE65 in actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) compared with normal skin.

Cell type-specific genotoxic effects of intermittent extremely low-frequency electromagnetic fields.

The issue of adverse health effects of extremely low-frequency electromagnetic fields (ELF-EMFs) is highly controversial. Contradictory results regarding the genotoxic potential of ELF-EMF have been reported in the literature. To test whether this controversy might reflect differences between the cellular targets examined we exposed cultured cells derived from different tissues to an intermittent ELF-EMF (50 Hz sinusoidal, 1 mT) for 1-24h.

Non-thermal DNA breakage by mobile-phone radiation (1800 MHz) in human fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro.

Cultured human diploid fibroblasts and cultured rat granulosa cells were exposed to intermittent and continuous radiofrequency electromagnetic fields (RF-EMF) used in mobile phones, with different specific absorption rates (SAR) and different mobile-phone modulations. DNA strand breaks were determined by means of the alkaline and neutral comet assay. RF-EMF exposure (1800 MHz; SAR 1.

Sentinel node status in melanoma patients is not predictive for overall survival upon multivariate analysis.

Sentinel lymph node biopsy (SLNB) has become a widely accepted standard procedure in the staging of patients with cutaneous melanoma and absence of clinical lymph node metastases, although there is no final proof that SLNB influences overall survival in these patients. This study investigated the accuracy of SLNB and the clinical outcome of patients after a mean follow-up of 22 months. Between 1998 and 2003, SLNB was performed in 309 consecutive patients.

No effects of intermittent 50 Hz EMF on cytoplasmic free calcium and on the mitochondrial membrane potential in human diploid fibroblasts.

The recently described increase in DNA strand breaks of cultured human diploid fibroblasts after intermittent exposure to extremely-low-frequency electromagnetic fields (ELF-EMF) of more than about 70 microT ELF-EMF is difficult to explain by a direct induction of covalent bond disruption. Therefore the hypothesis has been tested that ELF-EMF-induced DNA strand breaks might be mediated by cellular processes that cause alteration of the intracellular concentration of free calcium ([Ca2+]i) and/or the membrane potential (DeltaPsi(m)). [Ca2+]i was determined by the ratiometric fura-2 technique.

Age-related effects on induction of DNA strand breaks by intermittent exposure to electromagnetic fields.

Several studies indicating a decline of DNA repair efficiency with age raise the question, if senescence per se leads to a higher susceptibility to DNA damage upon environmental exposures. Cultured fibroblasts of six healthy donors of different age exposed to intermittent ELF-EMF (50 Hz sinus, 1 mT) for 1-24 h exhibited different basal DNA strand break levels correlating with age. The cells revealed a maximum response at 15-19 h of exposure.

Intermittent extremely low frequency electromagnetic fields cause DNA damage in a dose-dependent way.

Objectives: Epidemiological studies have reported an association between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and increased risk of cancerous diseases, albeit without dose-effect relationships. The validity of such findings can be corroborated only by demonstration of dose-dependent DNA-damaging effects of ELF-EMFs in cells of human origin in vitro.

Methods: Cultured human diploid fibroblasts were exposed to intermittent ELF electromagnetic fields.

Organotypic keratinocyte coculture using normal human serum: an immunomorphological study at light and electron microscopic levels.

Organotypic human skin equivalents of keratinocytes and fibroblasts embedded in collagen matrix have been the subject of studies dealing with various culture conditions. Development of standardized living skin equivalents using defined culture media containing respective supplements can provide important instruments of investigation in skin biology. In addition, tissue engineering has created human skin substitutes for treatment of acute and chronic wounds.

Home care or long-term care facility: factors that influence the decision.

In order to answer the research question--What factors determine if a long-term care client will be cared for at home or in a long-term care facility?--data were collected in five provinces in Canada in urban and rural sites, through focus groups with community care coordinators. A questionnaire provided information about the 89 participants and their workload. Factors are grouped under organizational, system, client, informal provider, formal provider, and case manager factors.

Vanadate induces DNA strand breaks in cultured human fibroblasts at doses relevant to occupational exposure.

To study possible genotoxic effects of occupational exposure to vanadium pentoxide, we determined DNA strand breaks (with alkaline comet assay), 8-hydroxy-2'deoxyguanosine (8-OHdG) and the frequency of sister chromatid exchange (SCE) in whole blood leukocytes or lymphocytes of 49 male workers employed in a vanadium factory in comparison to 12 non-exposed controls. In addition, vanadate has been tested in vitro to induce DNA strand breaks in whole blood cells, isolated lymphocytes and cultured human fibroblasts of healthy donors at concentrations comparable to the observed levels of vanadium in vivo. To investigate the impact of vanadate on the repair of damaged DNA, co-exposure to UV or bleomycin was used in fibroblasts, and DNA migration in the alkaline and neutral comet assay was determined.

Induction of DNA strand breaks by intermittent exposure to extremely-low-frequency electromagnetic fields in human diploid fibroblasts.

Results of epidemiological research show low association of electromagnetic field (EMF) with increased risk of cancerous diseases and missing dose-effect relations. An important component in assessing potential cancer risk is knowledge concerning any genotoxic effects of extremely-low-frequency-EMF (ELF-EMF). Human diploid fibroblasts were exposed to continuous or intermittent ELF-EMF (50Hz, sinusoidal, 24h, 1000microT).

Induction of 8-hydroxy-2'-deoxyguanosine by cobalt(II) and hydrogen peroxide in vitro.

In order to test the effects of cobalt on oxidative DNA damage, we measured the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the presence of cobalt in calf thymus DNA and in DNA of human diploid fibroblasts. Treatment of calf thymus DNA with Co(II) at 500 microM hydrogen peroxide resulted in a dose-dependent increase in 8-OHdG, which culminated at 25 microM Co(II) (62.6 modified/10(5) dG) and declined at higher Co(II) concentrations [9.

Basal levels of DNA strand breaks in human leukocytes determined by comet assay.

In order to determine background levels of DNA strand breaks, we examined 80 healthy individuals by comet assay considering age, sex, and smoking as confounding factors. Only age was found to have a significant effect on basal levels. One thousand cells of each donor were graded by eye into 5 categories according to the amount of DNA in the tail: classification group A (no damage) <5%, B (low damage) 5-20%, C (medium damage) 20-40%, D (high damage) 40-95%, and group E (total damage) >95%.

Looking beyond caseload numbers for long-term home-care case managers.

Determining the best use of case managers' time is difficult both because of the great variability in the factors and the lack of outcome studies. In place of the outcome studies, the responses to focus group questions of 89 experienced case managers from across Canada were used to indicate a value for case management functions in the areas of direct care, indirect care management, and program management. The case managers identified greater value for direct care with clients and families who are new to home care or who have complex problems in comparison to clients in more stable or manageable situations.

Ethical dilemmas in home care case management.

The role of case manager is fraught with challenges in a healthcare environment characterized by rapid aging of the population, a move against institutionalization of seniors, and the need to contain healthcare costs. This study examined experiences of 89 case managers through focus groups in five urban and five rural regions of Canada to identify ethical dilemmas and issues encountered in their role. Overall, the case managers expressed frustration for the lack of support for their work as evidenced by inadequate resources and few agency policies.

Balancing relationship and discipline: the pressing concern of mothers of early-adolescent girls.

Mothers of early-adolescent girls (10-14 years) often experience difficulties in dealing with their daughters. This study explored the mother-daughter relationship from the perspective of the mothers, to identify their most pressing concern and the strategies that might help them address this concern. A qualitative design employing a feminist participatory approach was used with 2 groups of mothers living in low socioeconomic status (SES) areas of a small city in Ontario, Canada, over a 10-week period.

Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs.

Objectives: Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination.

Methods: Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics.