Systemic oxidative stress and antioxidant capacity in cancer patients

Various factors impact the outcome of patients with the diagnosis of cancer. Common treatment modalities of cancer, including surgery, radiation therapy and cytostatic agents, all lead to a systemic inflammatory reaction. In particular, this reaction is of physiological importance as it is crucial for patient recovery. However, in some patients, a self-perpetuating inflammatory response develops due to the presence of unfavorable risk factors, several of which are still unknown, but might lead to a worse disease prognosis. Inflammation has been intimately associated with oxidative stress, that is characterized by an imbalance between pro-oxidants, also termed reactive species, and antioxidants. Systemically, oxidative stress can be quantified by measuring thiols (R-SH, sulfhydryl compounds), which are considered to be regulatory nodes within the extracellular antioxidant network. Most importantly, thiol measurements in serum or plasma form a robust and powerful read-out of the in vivo reduction-oxidation (redox) status as thiols are highly redox-active and thus readily oxidized by circulating reactive species. Therefore, systemic quantification of thiols might be a valuable addition to the clinically available diagnostic and prognostic armamentarium as it is able to reliably capture the overall balance between oxidants and the antioxidant capacity of patients. In this review, we summarized the currently available literature on thiol levels as amendable markers for oxidative stress in patients with lung, prostate and colorectal cancer. Total thiols, native (free) thiols and disulfide levels are significantly altered in these patients compared to healthy individuals. In general, these findings indicate that the extracellular antioxidant capacity is severely affected in patients with these types of cancer. Moreover, lower thiol levels are associated with a lowered overall survival. Future research should focus on exploration of the clinical significance of thiols in cancer

Professionals' perspectives on interventions to reduce problematic alcohol use in older adults:A realist evaluation of working elements

Objectives This study set out to understand how (which elements), in what context and why (which mechanisms) interventions are successful in reducing (problematic) alcohol use among older adults, from the perspective of professionals providing these interventions.Design Guided by a realist evaluation approach, an existing initial programme theory (IPT) on working elements in alcohol interventions was evaluated by conducting semistructured interviews with professionals.Setting and participants These professionals (N=20) provide interventions across several contexts: with or without practitioner involvement; in-person or not and in an individual or group setting. Data were coded and links between contexts, elements, mechanisms and outcomes were sought for to confirm, refute or refine the IPT.Results From the perspective of professionals, there are several general working elements in interventions for older adults: (1) pointing out risks and consequences of drinking behaviour; (2) paying attention to abstinence; (3) promoting contact with peers; (4) providing personalised content and (5) providing support. We also found context-specific working elements: (1) providing personalised conversations and motivational interviewing with practitioners; (2) ensuring safety, trust and a sense of connection and a location nearby home or a location that people are familiar with in person and (3) sharing experiences and tips in group interventions. Furthermore, the mechanisms awareness and accessible and low threshold participation were important contributors to positive intervention outcomes.Conclusion In addition to the IPT, our findings emphasise the need for social contact and support, personalised content, and strong relationships (both between client and practitioner, and client and peers) in interventions for older adults

Hypomagnesemia in persons with type 1 diabetes:associations with clinical parameters and oxidative stress

Background: Among persons with type 1 diabetes mellitus (T1DM) low concentrations of magnesium have been reported. Previous (small) studies also suggested a relation of hypomagnesemia with (poor) glycaemic control and complications. We aimed to investigate the magnitude of hypomagnesemia and the associations between magnesium with parameters of routine T1DM care in a population of unselected outpatients. Methods: As part of a prospective cohort study, initially designed to measure quality of life and oxidative stress, data from 207 patients with a mean age of 45 [standard deviation (SD) 12] years, 58% male, diabetes duration 22 [interquartile range (IQR) 16, 31] years and glycated haemoglobin (HbA1c) of 60 (SD 11) mmol/mol [7.6 (SD 1.0)%] were examined. Hypomagnesemia was defined as a concentration below Results: Mean magnesium concentration was 0.78 (SD 0.05) mmol/l. A deficiency was present in 4.3% of participants. Among these persons, mean concentration was 0.66 (SD 0.03) mmol/l. There was no correlation between magnesium and HbA1c at baseline (r = -0.014, p = 0.843). In multivariable analysis, free thiols (reflecting the degree of oxidative stress) were significantly and negatively associated with magnesium concentrations. Conclusion: In this cohort of T1DM outpatients, the presence of hypomagnesemia was infrequent and, if present, relative mild. Magnesium was not associated with glycaemic control nor with presence of micro- and macrovascular complications. Although these results need confirmation, in particular the negative association of magnesium with free thiols, this suggests that hypomagnesemia is not a relevant topic in routine care for people with T1DM

Integrating research evidence and physical activity policy making-REPOPA project

Evidence shows that regular physical activity is enhanced by supporting environment. Studies are needed to integrate research evidence into health enhancing, cross-sector physical activity (HEPA) policy making. This article presents the rationale, study design, measurement procedures and the initial results of the first phase of six European countries in a five-year research project (2011–2016), REsearch into POlicy to enhance Physical Activity (REPOPA). REPOPA is programmatic research; it consists of linked studies; the first phase studied the use of evidence in 21 policies in implementation to learn more in depth from the policy making process and carried out 86 qualitative stakeholder interviews. The second, ongoing phase builds on the central findings of the first phase in each country; it consists of two sets of interventions: game simulations to study cross-sector collaboration and organizational change processes in the use of evidence and locally tailored interventions to increase knowledge integration. The results of the first two study phases will be tested and validated among policy makers and other stakeholders in the third phase using a Delphi process. Initial results from the first project phase showed the lack of explicit evidence use in HEPA policy making. Facilitators and barriers of the evidence use were the availability of institutional resources and support but also networking between researchers and policy makers. REPOPA will increase understanding use of research evidence in different contexts; develop guidance and tools and establish sustainable structures such as networks and platforms between academics and policy makers across relevant sectors

Developing a policy game intervention to enhance collaboration in public health policymaking in three European countries

Background: One of the key elements to enhance the uptake of evidence in public health policies is stimulating cross-sector collaboration. An intervention stimulating collaboration is a policy game. The aim of this study was to describe the design and methods of the development process of the policy game 'In2Action' within a real-life setting of public health policymaking networks in the Netherlands, Denmark and Romania.Methods: The development of the policy game intervention consisted of three phases, pre intervention, designing the game intervention and tailoring the intervention.Results: In2Action was developed as a role-play game of one day, with main focus to develop in collaboration a cross-sector implementation plan based on the approved strategic local public health policy.Conclusions: This study introduced an innovative intervention for public health policymaking. It described the design and development of the generic frame of the In2Action game focusing on enhancing collaboration in local public health policymaking networks. By keeping the game generic, it became suitable for each of the three country cases with only minor changes. The generic frame of the game is expected to be generalizable for other European countries to stimulate interaction and collaboration in the policy process

Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7

Background: Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. Results: We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C> T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. Conclusions: We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of the gene. The mutated gene implicates the extracellular matrix in the regular organization of chrondrocyte columns of the growth plate. Conservation of individual amino acids may not be necessary at the protein level but instead may reflect underlying conservation of nucleotide sequence that are required for efficient splicing

The acceptance and use of the e-Health instrument 'The personal health check' in four Dutch municipalities:Lessons learned

This pilot study assessed the acceptance and use of the e-Health instrument “the Personal Health Check” (PHC) among clients and professionals in primary care settings. By filling in the online PHC instrument, participants were provided insights into their health and lifestyle. When results revealed an increased health risk, participants were advised to undertake additional lab tests measuring blood pressure and haemaglobin levels. Based on the online questionnaire and optional lab tests, participants then received a report that included individually-tailored feedback from the e-Health application about personal health risks and suggestions for health interventions. The PHC was implemented in 2016 in four Dutch municipalities that determined which neighbourhood(s) the PHC targeted and how participants were invited. The Unified Theory of Acceptance and Use of Technology was used as a theoretical framework to address our research questions. Methods used to assess acceptance were: PHC instrument data, data from additional questionnaires completed by PHC participants, focus groups with PHC participants and professionals in primary care, and telephone interviews with non-responders to the invitation to participate in the online PHC. Of the 21,735 invited, 12% participated. Our results showed that participants and professionals in this pilot were predominantly positive about the PHC. Participants reported that they made an effort to apply the PHC lifestyle advice they received. Almost all had the knowledge and resources needed to use the PHC online instrument. Invitations from general practitioners almost doubled participation relative to invitations from the sponsoring municipalities. The overall low response rate, however, suggests that the PHC is unsuitable as a foundation on which to develop local public health policy