Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

PURPOSE: Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. METHODS: The present cross-sectional study included a cohort of 177 young adults aged 18-25 years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. RESULTS: Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). CONCLUSION: The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Grassland biodiversity bounces back from long-term nitrogen addition.

The negative effect of increasing atmospheric nitrogen (N) pollution on grassland biodiversity is now incontrovertible. However, the recent introduction of cleaner technologies in the UK has led to reductions in the emissions of nitrogen oxides, with concomitant decreases in N deposition. The degree to which grassland biodiversity can be expected to 'bounce back' in response to these improvements in air quality is uncertain, with a suggestion that long-term chronic N addition may lead to an alternative low biodiversity state. Here we present evidence from the 160-year-old Park Grass Experiment at Rothamsted Research, UK, that shows a positive response of biodiversity to reducing N addition from either atmospheric pollution or fertilizers. The proportion of legumes, species richness and diversity increased across the experiment between 1991 and 2012 as both wet and dry N deposition declined. Plots that stopped receiving inorganic N fertilizer in 1989 recovered much of the diversity that had been lost, especially if limed. There was no evidence that chronic N addition has resulted in an alternative low biodiversity state on the Park Grass plots, except where there has been extreme acidification, although it is likely that the recovery of plant communities has been facilitated by the twice-yearly mowing and removal of biomass. This may also explain why a comparable response of plant communities to reduced N inputs has yet to be observed in the wider landscape.

Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface.

Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.

Human interleukin-13 activates the interleukin-4-dependent transcription factor NF-IL4 sharing a DNA binding motif with an interferon-gamma-induced nuclear binding factor.

The effects of interleukin-13 (IL-13) and interleukin-4 (IL-4) on cellular functions were shown to be quite similar. We provide evidence that in monocytes as well as in T lymphocytes both IL-4 and IL-13 activate the same recently identified transcription factor NF-IL4 which binds to the specific responsive element IL-4RE. In addition, we show that a nuclear factor activated by interferon-gamma also interacts with the IL-4RE. It differs from NF-IL4 in the electrophoretic mobility of the complex with DNA, in its DNA-binding specificity and in the proteins interacting with the DNA sequence. Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines.

Utilization of prenatal diagnosis for cystic fibrosis over the past seven years.

OBJECTIVE: First trimester prenatal diagnosis (PD) by DNA analysis for cystic fibrosis (CF) has been available for parents of affected children since May 1986. METHODS: In a prospective study 37 couples with a single child affected by CF were investigated. Fathers and mothers were interviewed simultaneously, and their attitudes towards further childbearing and potential utilization of PD ascertained. Parental answers were treated as one. A 7-year follow-up allowed comparison between intended and actual behavior. RESULTS: At the time of the interview, 16 parents (43%) were determined to have further children. Nineteen parents (51%) said they would certainly or probably utilize PD in case of pregnancy. Their predominant reason for favoring PD was the strong desire to have a healthy child (47%). Among the 18 rejectors (49%) the fear of an unsolvable conflict in case of an affected fetus prevailed (39%). Twenty-four pregnancies actually occurred in 18 families. Utilization of PD was arranged in five (21%) and finally performed in four (17%) cases. CONCLUSION: Availability of PD does not substantially change the reproductive behavior of parents of children with CF. Reasons for this were multifactorial, with anticipated difficulty in deciding to continue or terminate pregnancy being predominant.

Parents' recollection of the initial communication of the diagnosis of cystic fibrosis.

BACKGROUND: The diagnosis of a chronic disease in children challenges parents' emotional coping abilities and cognitive capacities. OBJECTIVE: To study parents' emotional and cognitive reactions to the diagnosis of cystic fibrosis (CF) in their children. METHODS: Postal survey by means of a written questionnaire. PARTICIPANTS: Forty-six parents of 29 children with a median age of 2 months at diagnosis. RESULTS: Most parents initially lacked knowledge of CF (76%) and were provided only oral information (96%). Parental estimates of how much of the information given they had understood and retained were 77% and 76%, respectively, with 15 parents (33%) having understood and remembered less than 50% of what the physicians had told them. The most frequent stressing feelings were fear (83%) and despair (56%). Fifty-four percent of parents had initial shocklike reactions. In this group, a significant decrease in the understanding and recall of information was noted compared with parents who had less-emotional responses. CONCLUSIONS: Parents learning the diagnosis are, in effect, receiving a kind of lecture, which contains more information than they can possibly assimilate. Because of the incompatibility of emotional distress and optimum learning, impairment of early comprehension and retention of information about CF is unavoidable. Repeated interviews with both parents and the provision of written and audiovisual materials should be mandatory.

Erythema elevatum diutinum treated with niacinamide and tetracycline.

A 60-year-old woman with recurrent papular and vesiculobullous lesions of erythema elevatum diutinum responded to treatment with 100 mg of oral niacinamide three times a day and 250 mg of tetracycline hydrochloride four times a day. Prior therapy with 2.5 mg of dexamethasone daily and 1.0 g of erythromycin daily had been unsuccessful. After four weeks, tetracycline therapy was discontinued, and niacinamide alone sufficed to suppress the disorder. Recurrent lesions developed whenever niacinamide therapy was stopped.

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer.

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (greater than 3 ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6% of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA15-3 level and tumor stage in breast cancer. CA15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Further advances of chronic renal replacement therapy in eastern Germany, 1994 versus 1989.

Unlike the other former Soviet-block countries, Eastern Germany/the "GDR", had the opportunity to the re-unification with a highly developed western country, the Federal Republic of (West) Germany in 1990. In order to record the following rapid improvements in renal replacement therapy, we performed our own survey in Eastern Germany--excluding Eastern Berlin--by questionnaire, comparing the years 1989/December, and 1994/December. 112 of the 113 dialysis facilities for adult regular dialysis patients replied to our questionnaire (99%). From 1989 to 1994, the number of dialysis centers increased from 53 to 113 (-->213%), reaching 7.9 centres p.m.p. Of these facilities, 29% were hospital centers, 48% were private dialysis units, and 23% were run by nonprofit dialysis organizations. The number of dialysis stations increased from 602 to 1,719 (-->286%), i.e. 120 stations p.m.p. The number of patients in regular dialysis treatment rose from 2,127 to 5,335 (-->251%), that means a prevalence of 373 patients p.m.p. In 1989, 67 new patients (p.m.p.) had been accepted for maintenance treatment (incidence), in contrast to 130 new patients p.m.p. in 1994 (-->194%), now under the conditions of unlimited accessibility to dialysis treatment. Questions referring to this point--the incidence of new patients--were only asked in Thüringen (2.5 mio. inhabitants). Alternative treatment modalities became feasible under the new conditions in Eastern Germany. In contrast to 99% hemodialysis patients in December 1989, at the end of 1994 92.8% of the patients were treated by hemodialysis, 2.0% by hemofiltration, and 5.2% by peritoneal dialysis, predominantly CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals?

The anaesthetic effect of carbon dioxide (CO2) was investigated under predetermined exposure times in rats, mice and guinea pigs with admixture of 20% of oxygen (O2), and with 20% of ambient air in rats. In rats first symptoms (median) were detectable between 7 and 9.5 s, the induction time (median) varied between 16 and 20.5 s and the surgical tolerance (median) was 40 s (after 60 s of exposure) and 53.5 s (after 120 s of exposure) to 80% CO2/20% O2. When O2 was replaced by ambient air, a surgical tolerance of 53.5 s (after 60 s of exposure) and 77 s (after 120 s of exposure) was measured. In mice the induction time to 80% CO2/20% O2 was 10 s and the surgical tolerance 19.5 s (after 120 s of exposure). Guinea pigs showed an induction period of 20 s and a surgical tolerance of 50 s (after 30 s of exposure) to 80% CO2/O2. Recovery was short and smooth in all species. This method of general anaesthesia seems to be suitable for short and painful interventions, mainly in rats, but also in guinea pigs.

Frailty modelling for adult and old age mortality: the application of a modified DeMoivre hazard function to sex differentials in mortality.

Unobserved differences in individual's susceptibility to death are an important aspect in the analysis of contemporary mortality patterns. However, observed mortality rates at adult ages, which are usually well described by a Gompertz curve, are often perceived inconsistent with frailty models of mortality. The authors therefore propose a modified DeMoivre hazard function that is suitable for the application of frailty models to adult and old ages. The proposed hazard increases faster than exponential, and when combined with unobserved frailty it can capture a broad range of patterns encountered in the analysis of adult mortality. The authors' application to Bulgaria during 1992-93 suggests that the stronger selection process in the male population, caused by an overall higher level of mortality, may constitute a primary mechanism leading to the convergence of male and female mortality at higher ages. Hence, the convergence between male and female mortality is not necessarily caused by differential process of aging across sexes, but is merely a consequence of the different levels of mortality at adult ages.

Interventional assessment of physical and mental health in children and adolescents with cystic fibrosis.

In spite of being an integral part of health care the subjective estimation of health status in patients with cystic fibrosis is frequently neglected. In a prospective study in 65 patients maternal, paternal, and patients' ratings were determined and correlated with objective data such as Shwachman scores and lung function tests. No statistically relevant correlations were obtained for parental physical assessment versus Shwachman and lung function data. The adolescents' own assessment of health had a significant relationship to clinical evaluation (r = 0, 42; p less than 0.05). Misjudgements, mainly in the form of overestimations, occurred with a frequency of 28.6% to 53.8%, reflecting inadequate understanding of the disease and its psychological consequences.

STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett's adenocarcinomas.

Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC, n=49) and Barrett's adenocarcinomas (BAC, n=61) revealed similar STAT3 expression in ESCCs and BACs (P=0.109), but preferentially activated P-STAT3 in ESCCs (P=0.013). In vitro, strong STAT3 activation was seen by epidermal growth factor (EGF) stimulation in OE21 (ESCC) cells, whereas OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 (P=0.0148) and OE33 (P=0.0243) cells. Importantly, STAT3 knockdown reduced cell migration of OE33 cells by 2.5-fold in two types of migration assays (P=0.073, P=0.015), but not in OE21 cells (P=0.1079, P=0.386). Investigation of transcriptome analysis of STAT3 knockdown revealed a reduced STAT3 level associated with significant downregulation of cell cycle genes in both OE21 (P<0.0001) and OE33 (P=0.01) cells. In contrast, genes promoting cell migration (CTHRC1) were markedly upregulated in OE21 cells, whereas a gene linked to tight-junction stabilization and restricted cell motility (SHROOM2) was downregulated in OE21 but upregulated in OE33 cells. This study shows frequent, but distinct, patterns of STAT3 expression and activation in ESCCs and BACs. STAT3 knockdown reduces cell proliferation in ESCC and BAC cells, inhibits migration of BAC cells and may support cell migration of ESCC cells. Thereby, novel STAT3-regulated genes involved in ESCC and BAC cell proliferation and cell migration were identified. Thus, STAT3 may be further exploited as a potential novel therapeutic target, however, by careful distinction between the two histotypes of esophageal cancers.

First commissioning results with the Grenoble test electron cyclotron resonance ion source at iThemba LABS.

iThemba Laboratory for Accelerator Based Science (iThemba LABS) is a multi-disciplinary accelerator facility. One of its main activities is the operation of a separated-sector cyclotron with a K-value of 200, which provides beams of various ion species. These beams are used for fundamental nuclear physics research in the intermediate energy region, radioisotope production, and medical physics applications. Due to the requirements of nuclear physics for new ion species and higher energies, the decision was made to install a copy of the so-called Grenoble test source (GTS) at iThemba LABS. In this paper, we will report on the experimental setup and the first results obtained with the GTS2 at iThemba LABS.