Erythrocyte-bound apolipoprotein B in atherosclerosis and mortality.

BACKGROUND: The binding of apolipoprotein (apo) B-containing lipoproteins to circulating erythrocytes (ery-apoB) is associated with a decreased prevalence of atherosclerosis. In this study, we evaluated ery-apoB as a possible prognostic factor in cardiovascular events and all-cause mortality, in a prospective cohort study. MATERIALS AND METHODS: Ery-apoB was measured by flow cytometry in subjects with and without cardiovascular disease (CVD). The primary endpoint was the cardiovascular event rate. Secondary endpoints were all-cause mortality and the combined endpoint of all-cause mortality and cardiovascular events (any event rate). A Cox regression analysis with univariate and multivariate analyses and Kaplan-Meier survival analysis was performed. RESULTS: Follow-up data were available of 384 subjects. Subjects were divided according to high (> 2·0 au, n = 60), intermediate (0·2-2·0 au, n = 274) or low (< 0·2 au, n = 50) ery-apoB. Median follow-up was 1767 days (IQR 1564-2001). In univariate analysis, low ery-apoB was associated with increased all-cause mortality [HR 9·9 (1·2-79·0), P = 0·031] and any event rate [HR 3·4 (95% CI 1·3-8·7), P = 0·012]. In a Cox regression analysis, only a history of CVD was significantly associated with any event rate [HR 3·6 (1·6-8·0), P = 0·002], while low ery-apoB showed a trend [HR 2·4 (0·9-6·4), P = 0·07]. In a subgroup analysis, in subjects with a history of CVD, ery-apoB was significantly associated with all-cause mortality (log rank P = 0·021) and any event rate (log rank P = 0·009). CONCLUSIONS: Low ery-apoB is associated with increased mortality and cardiovascular risk, especially in patients with a prior history of CVD. These subjects may benefit from more aggressive secondary prevention treatment.

Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function.

Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aß)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aß plaques and associated iron. Cognitive tests and T2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (ß = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. Copyright © 2014 John Wiley & Sons, Ltd.

FoxP3(+) and IL-17(+) cells are correlated with improved prognosis in cervical adenocarcinoma.

Cervical adenocarcinoma comprises approximately 15 % of cervical cancer cases. This histological subtype has different characteristics than cervical squamous cell carcinoma, which may influence disease progression. To study whether the infiltration of T cell subpopulations was correlated with cervical adenocarcinoma patient survival, similar to squamous cell carcinoma, the tumor-infiltrating T cells, Tregs, Th17 cells and IL-17(+) cell frequencies were analyzed in a cohort of cervical adenocarcinoma patients (n = 67). Intraepithelial, stromal and total cell frequencies were scored using triple immunofluorescence. The majority of Tregs were present in the tumor stroma, while other T cells and IL-17(+) cells infiltrated the tumor epithelium three times more frequently. A high total number of Tregs were significantly correlated with improved disease-specific and disease-free survival (p = 0.010, p = 0.007). Within the tumor epithelium, a high T cell frequency was significantly correlated with improved disease-free survival (p = 0.034). In particular, a low number of both Tregs and IL-17(+) cells were correlated with poor disease-specific survival (p = 0.007). A low number of Tregs combined with Th17 cells present were also correlated with poor survival (p = 0.018). An increased number of IL-17(+) cells were significantly correlated with the absence of vaso-invasion (p = 0.001), smaller tumor size (p = 0.030) and less infiltration depth (p = 0.021). These results suggest that Tregs and IL-17(+) cells represent a beneficial immune response, whereas Th17 cells might represent a poor response in cervical adenocarcinoma. This contrasts with the correlations described in squamous cell carcinoma, suggesting that the local immune response in cervical adenocarcinoma contributes differently to tumor growth than in squamous cell carcinoma.

The one-carbon metabolism as an underlying pathway for placental DNA methylation - a systematic review.

Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B12 provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 (n = 15) and in vitro studies (n = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation (n = 9), (2) genome-wide analyses (n = 4), and (3) gene specific (n = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including LEP, NR3C1, CRH, and PlGF; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.

Identification of functionally distinct and interacting cancer cell subpopulations from glioblastoma with intratumoral genetic heterogeneity.

BACKGROUND: Glioblastomas display a high level of intratumoral heterogeneity with regard to both genetic and histological features. Within single tumors, subclones have been shown to communicate with each other to affect overall tumor growth. The aim of this study was to broaden the understanding of interclonal communication in glioblastoma. METHODS: We have used the U-343 model, consisting of U-343 MG, U-343 MGa, U-343 MGa 31L, and U-343 MGa Cl2:6, a set of distinct glioblastoma cell lines that have been derived from the same tumor. We characterized these with regard to temozolomide sensitivity, protein secretome, gene expression, DNA copy number, and cancer cell phenotypic traits. Furthermore, we performed coculture and conditioned media-based experiments to model cell-to-cell signaling in a setting of intratumoral heterogeneity. RESULTS: Temozolomide treatment of a coculture composed of all 4 U-343 cell lines presents a tumor relapse model where the least sensitive population, U-343 MGa 31L, outlives the others. Interestingly, the U-343 cell lines were shown to have distinct gene expression signatures and phenotypes although they were derived from a single tumor. The DNA copy number analysis revealed both common and unique alterations, indicating the evolutionary relationship between the cells. Moreover, these cells were found to communicate and affect each other's proliferation, both via contact-dependent and -independent interactions, where NOTCH1, TGFBI, and ADAMTS1 signaling effects were involved, respectively. CONCLUSIONS: These results provide insight into how complex the signaling events may prove to be in a setting of intratumoral heterogeneity in glioblastoma and provide a map for future studies.

Epidemiological impact and cost-effectiveness of providing long-acting pre-exposure prophylaxis to injectable contraceptive users for HIV prevention in South Africa: a modelling study.

INTRODUCTION: Although pre-exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub-Saharan Africa, likely due to non-adherence. Adherence may be improved with the use of injectable long-acting PrEP methods currently being developed. We hypothesize that providing long-acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy-to-reach target population. In this modelling study, we assessed the epidemiological impact and cost-effectiveness of providing long-acting PrEP to injectable contraceptive users in Limpopo, South Africa. METHODS: We developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long-acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled-up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long-acting PrEP for which this intervention would be cost-effective over a time horizon of 40 years, from a healthcare payer perspective. In the base-case scenario we assumed long-acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability-adjusted life-year (DALY) averted were considered potentially cost-effective, and <$519 as cost-effective. RESULTS: Without long-acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long-acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long-acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost-effective the annual long-acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030. CONCLUSIONS: Providing long-acting PrEP to injectable contraceptive users in Limpopo is only potentially cost-effective when long-acting PrEP drug prices are low. If low prices are not feasible, providing long-acting PrEP only to women at high risk of HIV infection will become important.

Preparing patients for gastrointestinal endoscopy: the influence of information in medical situations.

The effects of the provision of information were tested in a sample of patients who underwent a gastrointestinal endoscopy for the first time (N=260). On the basis of their Threatening Medical Situation Inventory (TMSI)-monitoring score these patients were divided in high monitors versus low monitors. On the basis of the existing literature each group received the type of information that was considered most beneficial with regard to their coping style, and each group was compared with a control group receiving standard care (the usual information plus coaching by a nurse). Dependent variables were anxiety at different points in time, heart rate and skin conductance, pain, experience of the procedure, course of the procedure, duration of gagging, and satisfaction with the information provided. Unexpectedly, it turned out that high monitors did not profit by extensive information when compared with high monitors receiving standard care. Also for low monitors their minimal informational intervention did not exceed the effects of standard care. In the discussion, four factors possibly responsible for these results were elaborated. It is concluded that reservedness is required in providing (too) extensive information to patients who ask for this. Furthermore, considering the rather unpredictable and uncontrollable course of a gastrointestinal endoscopy, coaching by a nurse remains a valuable type of support.

Promotion of evidence-based practice by professional nursing associations: literature review.

AIM: This paper reports a literature review examining the activities of professional nursing associations in the promotion of evidence-based practice. BACKGROUND: Professional nursing associations can play a role in the implementation and achievement of evidence-based practice as such associations aim to develop and further educate nurses professionally, build professional networks representing the interests of nurses and the nursing profession, influence the government and policymakers, and support and protect the basic values of nurses. The exact role of professional nursing associations in the promotion of evidence-based practice is as yet unclear, along with just how the role of such associations can be expanded and which strategies can be used to promote evidence-based practice among members. METHOD: A literature and Internet search was undertaken using the PUBMED, CINAHL, SCIRUS, INVERT, and the Cochrane databases using the terms evidence-based practice(s)* or EBP*, which were then combined with Nursing Society*, Nursing Organization*, Nursing Organisation*, Nursing Association* or Nursing Council*. Other sources included a Google search of the Internet, and the sites of various members of the International Council of Nurses. Publications in English, French or German from 1993 to 2004 were used, and the Internet search was conducted on 17 July 2003. RESULTS: Sixty nursing associations described the dissemination of evidence-based practice using one or more types of activities (179 activities in total). All of these activities were of a voluntary nature, with a predominant focus (132/179 activities) on intrinsic motivation of nurses. More specifically, most of the activities were aimed at nurses' competences and attitudes in relation to evidence-based practice. CONCLUSION: Professional nurses' associations are active in promoting evidence-based practice among their nurse members, but only those focusing on changing competences and attitude by addressing intrinsic motivation are well used. Other types of activities deserve to be explored, including behaviour-oriented approaches, approaches using structural, social or financial influence measures and perhaps methods based on 'involuntary involvement'.

Improper intake of medication by elders--insights on contributing factors: a review of the literature.

Elders represent 6.4% of the world's populations, and 60% of them take medication. In one of six hospital admissions of elders, failures in medication intake are involved. Most of these admissions (88%) could be prevented if elders at risk can be identified (Beijer & Blaey, 2002). This review was conducted to identify and gain insight into which factors influence medication intake in elders. The factors are grouped into six categories: physiological factors, cognitive factors, polypharmacy and medication frequency, patient consent to the treatment and motivation for taking the medication, demographic variables, and family caregivers and social support. In order to identify elders at risk in an early stage, it is recommended that a risk-assessment instrument be developed.

Promoting evidence-based practice: the roles and activities of professional nurses' associations.

AIM: This paper reports a study exploring the role perceptions and current activities in evidence-based practice promotion of professional nurses' associations in the Netherlands. BACKGROUND: The promotion of evidence-based practice contributes to professional standards in nursing and good quality care for patients. As professional nurses' associations can be key players in this process, the nature of their roles and current activities deserves to be explored. METHODS: Roles and activities were explored for 43 professional nurses' associations (83% of all national associations). Data were collected using interviews with the associations' board members. Findings from the interviews were validated with those from an analysis of the associations' policy reports and other publications in the previous 2 years. RESULTS: Board members primarily thought that they had roles in the selection and distribution of evidence. The roles of participant (n = 13) and performer (n = 13) in selecting evidence, and those of facilitator (n = 12), initiator (n = 15) and performer (n = 41) in the distribution of evidence were often addressed. A few respondents reflected on roles in generating evidence and implementing evidence-based practice in patient care. A majority of the associations was contemplating activities in the promotion of evidence-based practice. Specific activities for each of six relevant aspects in the promotion of evidence-based practice were found in fewer than five associations. CONCLUSION: Professional nurses' association roles in the promotion of evidence-based practice need to be viewed in relation to the tasks to be accomplished, especially those of selecting and distributing evidence. Although many organizations expressed motivation, professional nurses' associations have a long way to go in the promotion of evidence-based practice among their members.