The protein gap-increasing protein intake in the diet of community-dwelling older adults: a simulation study.

OBJECTIVE: Approximately 50 % of Dutch community-dwelling older adults does not meet protein recommendations. This study assesses the effect of replacing low protein foods with protein-rich alternatives on the protein intake of Dutch community-dwelling older adults. DESIGN: The Dutch National Food Consumption Survey-Older Adults 2010-2012 (DNFCS-OA) was used for scenario modelling. Dietary intake was estimated based on two 24-h recalls. Commonly consumed products were replaced by comparable products rich in protein (scenario 1), foods enriched in protein (scenario 2) and a combination of both (scenario 3). Replacement scenarios were confined to participants whose dietary protein intake was < 1·0 g/kg BW/d (n 391). Habitual protein intake of all older adults was estimated, adjusting for effects of within-person variation in the 2-d intake data. SETTING: A simulation study based on the DNFCS-OA. PARTICIPANTS: 727 Dutch community-dwelling older adults aged 70+. RESULTS: Mean protein intake of the total population increased from 1·0 to 1·2 g/kg BW/d (scenarios 1 and 2) and to 1·3 g/kg BW/d (scenario 3). The percentage of participants with intakes of ≥ 1·0 g/kg BW/d increased from 47·1 % to 91·4 %, 90·2 % and 94·6 %, respectively, in scenarios 1, 2 and 3. The largest increases in protein intake were due to replacements in food groups: yoghurt, cream desserts and pudding, potatoes, vegetables and legumes and non-alcoholic beverages and milk in scenario 1 and bread; yoghurt, cream desserts and pudding and soups in scenario 2. CONCLUSIONS: This simulation model shows that replacing low protein foods with comparable alternatives rich in protein can increase the protein intake of Dutch community-dwelling older adults considerably. Results can be used as a basis for nutritional counselling.

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling.

Exhaustion of the bone marrow progenitor cell reserve is associated with major events in severe limb ischemia.

Lower numbers of progenitor cells (PCs) in peripheral blood (PB) have been associated with cardiovascular events in high-risk populations. Therapies aiming to increase the numbers of PCs in circulation have been developed, but clinical trials did not result in better outcomes. It is currently unknown what causes the reduction in PB PC numbers: whether it is primary depletion of the progenitor cell reserve, or a reduced mobilization of PCs from the bone marrow (BM). In this study, we examine if PB and BM PC numbers predict Amputation-Free Survival (AFS) in patients with Severe Limb Ischemia (SLI). We obtained PB and BM from 160 patients enrolled in a clinical trial investigating BM cell therapy for SLI. Samples were incubated with antibodies against CD34, KDR, CD133, CD184, CD14, CD105, CD140b, and CD31; PC populations were enumerated by flow cytometry. Higher PB CD34+ and CD133+ PC numbers were related to AFS (Both Hazard Ratio [HRevent] = 0.56, p = 0.003 and p = 0.0007, respectively). AFS was not associated with the other cell populations in PB. BM PC numbers correlated with PB PC numbers and showed similar HRs for AFS. A further subdivision based on relative BM and PB PC numbers showed that BM PC numbers, rather than mobilization, associated with AFS. Both PB and BM PC numbers are associated with AFS independently from traditional risk factor and show very similar risk profiles. Our data suggest that depletion of the progenitor cell reserve, rather than decreased PC mobilization, underlies the association between PB PC numbers and cardiovascular risk.

Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia.

RATIONALE: The impact of severe cardiovascular disease and critical limb ischemia (CLI) on the bone marrow (BM) is largely unknown. OBJECTIVE: To investigate microvascular and neuropathic changes in BM of patients with CLI. METHODS AND RESULTS: BM biopsies were obtained from patients with CLI (n=33) included in the Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial (NCT00371371) and controls (n=12). We performed immunohistochemistry and histomorphometry of the BM to assess microvascular density and to evaluate pan-neuronal and sympathetic innervation, which is involved in progenitor cell mobilization. Microvascular density was reduced significantly in CLI compared with controls (P=0.01), as was sympathetic (P=0.047) and pan-neuronal innervation (P=0.006). No differences in microvascular density and sympathetic or pan-neuronal innervation were observed between patients with CLI with and without diabetes mellitus. CONCLUSIONS: CLI is associated with BM microvascular and neuropathic changes, both in patients with and without diabetes mellitus.

Cellular Therapies in Systemic Sclerosis: Recent Progress.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with a high mortality and morbidity. While progress has been made in terms of identifying high-risk patients and implementing new treatment strategies, therapeutic options remain limited. In the past few decades, various cellular therapies have emerged, which have been studied in SSc and other conditions. Here, we provide a comprehensive review of currently available cellular therapies and critically assess their merit as disease-modifying treatment for SSc. Currently, hematopoietic stem cell transplantation is the only cellular therapy that has demonstrated clinical effects on the immune system, neoangiogenesis, and fibrosis. Robust mechanistic studies as well as clinical trials are essential to move the field forward.

Neovascularization capacity of mesenchymal stromal cells from critical limb ischemia patients is equivalent to healthy controls.

Critical limb ischemia (CLI) is often poorly treatable by conventional management and alternatives such as autologous cell therapy are increasingly investigated. Whereas previous studies showed a substantial impairment of neovascularization capacity in primary bone-marrow (BM) isolates from patients, little is known about dysfunction in patient-derived BM mesenchymal stromal cells (MSCs). In this study, we have compared CLI-MSCs to healthy controls using gene expression profiling and functional assays for differentiation, senescence and in vitro and in vivo pro-angiogenic ability. Whereas no differentially expressed genes were found and adipogenic and osteogenic differentiation did not significantly differ between groups, chondrogenic differentiation was impaired in CLI-MSCs, potentially as a consequence of increased senescence. Migration experiments showed no differences in growth factor sensitivity and secretion between CLI- and control MSCs. In a murine hind-limb ischemia model, recovery of perfusion was enhanced in MSC-treated mice compared to vehicle controls (71 ± 24% versus 44 ± 11%; P < 1 × 10(-6)). CLI-MSC- and control-MSC-treated animals showed nearly identical amounts of reperfusion (ratio CLI:Control = 0.98, 95% CI = 0.82-1.14), meeting our criteria for statistical equivalence. The neovascularization capacity of MSCs derived from CLI-patients is not compromised and equivalent to that of control MSCs, suggesting that autologous MSCs are suitable for cell therapy in CLI patients.

Paternal lifestyle as a potential source of germline mutations transmitted to offspring.

Paternal exposure to high levels of radioactivity causes heritable germline minisatellite mutations. However, the effect of more general paternal exposures, such as cigarette smoking, on germline mutations remains unexplored. We analyzed two of the most commonly used minisatellite loci (CEB1 and B6.7) to identify germline mutations in blood samples of complete mother-father-child triads from the Norwegian Mother and Child Cohort Study (MoBa). The presence of mutations was subsequently related to general lifestyle factors, including paternal smoking before the partner became pregnant. Paternally derived mutations at the B6.7 locus (mutation frequency 0.07) were not affected by lifestyle. In contrast, high gross yearly income as a general measure of a healthy lifestyle coincided with low-mutation frequencies at the CEB1 locus (P=0.047). Income was inversely related to smoking behavior, and paternally derived CEB1 mutations were dose dependently increased when the father smoked in the 6 mo before pregnancy, 0.21 vs. 0.05 in smoking and nonsmoking fathers, respectively (P=0.061). These results suggest that paternal lifestyle can affect the chance of heritable mutations in unstable repetitive DNA sequences. To our knowledge, this is the first study reporting an effect of lifestyle on germline minisatellite mutation frequencies in a human population with moderate paternal exposures.

Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis.

AIMS: In patients with obstructive coronary artery disease (CAD), the growth of collateral arteries, i.e. arteriogenesis, can preserve myocardial tissue perfusion and function. Monocytes modulate this process, supplying locally the necessary growth factors and degrading enzymes. Knowledge on factors involved in human arteriogenesis is scarce. Thus, the aim of the present study is to identify targets in monocytes that are critical for arteriogenesis in patients with CAD. METHODS AND RESULTS: A total of 50 patients with a chronic total coronary occlusion were dichotomized according to their collateral flow index. From each patient, RNA was isolated from unstimulated peripheral blood monocytes, monocytes stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4, and from macrophages. Increased mRNA expression of galectin-2 was found in three out of four monocytic cell types of patients with a low capacity of the collateral circulation (P= 0.03 for unstimulated monocytes; P= 0.02 for LPS-stimulated monocytes; P= 0.20 for IL-4-stimulated monocytes; P= 0.02 for macrophages). Additionally, galectin-2 mRNA expression was significantly associated with the rs7291467 polymorphism in LGALS2 encoding galectin-2 in all four monocytic cell types. Patient with the rs7291467 CC genotype displayed highest galectin-2 expression, and also tended to have a lower arteriogenic response. To evaluate the effect of galectin-2 on arteriogenesis in vivo, we used a murine hindlimb model. Treatment with galectin-2 markedly impaired the perfusion restoration at Day 7. CONCLUSION: Collectively, these results identify galectin-2 as a novel inhibitor of arteriogenesis. Modulation of galectin-2 may constitute a new therapeutic strategy for the stimulation of arteriogenesis in patients with CAD.

The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts.

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red+, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis.

KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium.

The shear stress-induced transcription factor Krüppel-like factor 2 (KLF2) confers antiinflammatory properties to endothelial cells through the inhibition of activator protein 1, presumably by interfering with mitogen-activated protein kinase (MAPK) cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA microarray analysis. No gross changes in MAPKs were detected; rather, phosphorylation of actin cytoskeleton-associated proteins, including focal adhesion kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH(2)-terminal kinase (JNK) and its downstream targets ATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, termed shear fibers by us, which are distinct from thrombin- or tumor necrosis factor-alpha-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly, and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers.

Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-ß.

AIMS: Activin A and transforming growth factor-ß1 (TGF-ß1) belong to the same family of growth and differentiation factors that modulate vascular lesion formation in distinct ways, which we wish to understand mechanistically. METHODS AND RESULTS: We investigated the expression of cell-surface receptors and activation of Smads in human vascular smooth muscle cells (SMCs) and demonstrated that activin receptor-like kinase-1 (ALK-1), ALK-4, ALK-5 and endoglin are expressed in human SMCs. As expected, TGF-ß1 activates Smad1 and Smad2 in these cells. Interestingly, activin A also induces phosphorylation of both Smads, which has not been reported for Smad1 before. Transcriptome analyses of activin A and TGF-ß1 treated SMCs with subsequent Gene-Set Enrichment Analyses revealed that many downstream gene networks are induced by both factors. However, the effect of activin A on expression kinetics of individual genes is less pronounced than for TGF-ß1, which is explained by a more rapid dephosphorylation of Smads and p38-MAPK in response to activin A. Substantial differences in expression of fibronectin, alpha-V integrin and total extracellular collagen synthesis were observed. CONCLUSIONS: Genome-wide mRNA expression analyses clarify the distinct modulation of vascular lesion formation by activin A and TGF-ß1, most significantly because activin A is non-fibrotic.

Protein Intake among Community-Dwelling Older Adults: The Influence of (Pre-) Motivational Determinants.

An adequate protein intake is important for healthy ageing, yet nearly 50% of Dutch community-dwelling older adults do not meet protein recommendations. This study explores protein intake in relation to eight behavioral determinants (I-Change model) among Dutch community-dwelling older adults. Data were collected through an online questionnaire from October 2019-October 2020. Protein intake was assessed by the Protein Screener 55+, indicating a high/low chance of a low protein intake (<1.0 g/kg body weight/day). The behavioral determinants of cognizance, knowledge, risk perception, perceived cues, attitude, social support, self-efficacy and intention were assessed by evaluating statements on a 7-point Likert scale. A total of 824 Dutch community-dwelling older adults were included, recruited via online newsletters, newspapers and by personal approach. Poisson regression was performed to calculate quartile-based prevalence ratios (PRs). Almost 40% of 824 respondents had a high chance of a low protein intake. Univariate analyses indicated that lower scores for all different behavioral determinants were associated with a higher chance of a low protein intake. Independent associations were observed for knowledge (Q4 OR = 0.71) and social support (Q4 OR = 0.71). Results of this study can be used in future interventions aiming to increase protein intake in which focus should lie on increasing knowledge and social support.

Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis.

Increased interferon (IFN)-ß signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNß on collateral artery growth in mice have been reported. The mechanisms of IFNß-induced inhibition of arteriogenesis are unknown. In stimulated monocytes from patients with chronic total coronary artery occlusion and decreased arteriogenic response, whole genome expression analysis showed increased expression of IFNß-regulated genes. Immunohistochemically, the IFNß receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFNß resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFNß was attenuated by inhibition of p21 by RNA interference. IFNß-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFNß-signaling. RNA interference of the IFNß receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFNß signaling and FAS and TRAIL expression were attenuated in monocytes from IFNAR1(-/-) mice, indicating reduced monocyte apoptosis. Hindlimb perfusion restoration 1 week after femoral artery ligation was improved in IFNAR1(-/-) mice compared with wild-type mice as assessed by infusion of fluorescent microspheres. These results demonstrate that IFNß inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFNß stimulates VSMC proliferation and collateral artery growth.

Low awareness of community-dwelling older adults on the importance of dietary protein: new insights from four qualitative studies.

Meeting the recommended daily protein intake can be a challenge for community-dwelling older adults (CDOA). In order to understand why, we studied attitudes towards protein-rich products and healthy eating in general; identified needs and preferences, barriers and promotors and knowledge regarding dietary behaviour and implementation of high protein products. Attitudes towards protein-rich products and healthy eating were evaluated in focus groups (study 1, n 17). To gain insights in the needs and preferences of older adults with regard to meals and meal products (study 2, n 30), visual information on eating behaviour was assessed using photovoicing and verified in post-photovoice interviews. In studies 3 and 4, semi-structured interviews were conducted to identify protein consumption-related barriers, opportunities (n 20) and knowledge and communication channels (n 40), respectively. Risk of low protein intake was assessed using ProteinScreener55+ (Pro55+) in studies 2-4 (n 90). Focus groups showed that participants were unaware of potential inadequate dietary protein. Photovoicing showed that sixteen of thirty participants mainly consumed traditional Dutch products. In post-photovoice interviews, participants indicated that they were satisfied with their current eating behaviour. Barriers for adequate use of protein-rich products were 'lack of knowledge', 'resistance to change habits' and 'no urge to receive dietary advice'. Promotors were 'trust in professionals' and 'product offers'. Sixty-two percent had a low risk of low protein intake. CDOA feel low urgency to increase protein intake, possibly linked to low knowledge levels. A challenge for professionals would be to motivate older adults to change their eating pattern, to optimise protein intake.

What Is on the Menu?-A Quantitative Analysis on Label Format among (Potential) Restaurant Guests and Restaurant Owners.

About 20% of energy intake in the Netherlands is consumed out-of-home. Eating out-of-home is associated with higher energy intake and poorer nutrition. Menu labeling can be considered a promising instrument to improve dietary choices in the out-of-home sector. Effectiveness depends on the presentation format of the label and its attractiveness and usability to restaurant guests and restaurant owners. This exploratory study investigated which menu labeling format would be mostly appreciated by (a) (potential) restaurant guests (n386) and (b) the uninvestigated group of restaurant owners (n41) if menu labeling would be implemented in Dutch full-service restaurants. A cross-sectional survey design was used to investigate three distinct menu labeling formats: a simple health logo; (star) ranking and calorie information. Questionnaires were used as study tool. Ranking has been shown to be the most appreciated menu labeling format by both (potential) restaurant guests and owners. Statistical analysis showed that label preference of potential restaurant guests was significantly associated with age, possibly associated with level of education, and not associated with health consciousness. In summary, we found that ranking is the most appreciated menu label format according to both (potential) restaurant guests and restaurant owners, suggesting it to be a promising way to improve healthy eating out-of-home.

Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients.

BACKGROUND: Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD) patients. RESULTS: We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12. CONCLUSIONS: The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.

Interferon-beta signaling is enhanced in patients with insufficient coronary collateral artery development and inhibits arteriogenesis in mice.

Stimulation of collateral artery growth in patients has been hitherto unsuccessful, despite promising experimental approaches. Circulating monocytes are involved in the growth of collateral arteries, a process also referred to as arteriogenesis. Patients show a large heterogeneity in their natural arteriogenic response on arterial obstruction. We hypothesized that circulating cell transcriptomes would provide mechanistic insights and new therapeutic strategies to stimulate arteriogenesis. Collateral flow index was measured in 45 patients with single-vessel coronary artery disease, separating collateral responders (collateral flow index, >0.21) and nonresponders (collateral flow index, < or 1). Isolated monocytes were stimulated with lipopolysaccharide or taken into macrophage culture for 20 hours to mimic their phenotype during arteriogenesis. Genome-wide mRNA expression analysis revealed 244 differentially expressed genes (adjusted P, <0.05) in stimulated monocytes. Interferon (IFN)-beta and several IFN-related genes showed increased mRNA levels in 3 of 4 cellular phenotypes from nonresponders. Macrophage gene expression correlated with stimulated monocytes, whereas resting monocytes and progenitor cells did not display differential gene regulation. In vitro, IFN-beta dose-dependently inhibited smooth muscle cell proliferation. In a murine hindlimb model, perfusion measured 7 days after femoral artery ligation showed attenuated arteriogenesis in IFN-beta-treated mice compared with controls (treatment versus control: 31.5+/-1.2% versus 41.9+/-1.9% perfusion restoration, P<0.01). In conclusion, patients with differing arteriogenic response as measured with collateral flow index display differential transcriptomes of stimulated monocytes. Nonresponders show increased expression of IFN-beta and its downstream targets, and IFN-beta attenuates proliferation of smooth muscle cells in vitro and hampers arteriogenesis in mice. Inhibition of IFN-beta signaling may serve as a novel approach for the stimulation of collateral artery growth.

What do screening tools measure? Lessons learned from SCREEN II and SNAQ65.

BACKGROUND: Over the last decade, different screening tools for malnutrition have been developed. Within these tools, a distinction can be made between tools that assess nutritional risk and tools that assess protein energy malnutrition. Insights in differences in characteristics of participants at risk and in differences in prevalence rates will aid in deciding which tool(s) to use in daily practice. METHODS: Dutch community-dwelling older adults (n = 200, 78.2 ± 6.9 years), not known to have specific nutrition problems, were recruited to participate in this cross-sectional study. SNAQ65+ (low risk vs moderate/high risk) was used to assess risk of protein energy malnutrition and SCREEN II was used to assess nutrition risk (score <54 out of 64). Chi-square tests were used to test associations between demographic, health, physical and social factors and outcome of SNAQ65+ and SCREEN II. RESULTS: Of all participants 69.0% were at nutrition risk (SCREEN II), while 13.5% were at risk of protein energy malnutrition (SNAQ65+). Agreement between the two tools was poor (kappa < 0.20). Gender, BMI, living status, income, activity level and protein/energy intake were associated with SCREEN II; age, BMI, comorbidities, medication use, help at home, activity level and low basic mobility were associated with SNAQ65+. CONCLUSION: SCREEN II and SNAQ65+ measure different concepts of malnutrition and therefore identify different persons at risk. SCREEN II is more inclusive and comprises both undernutrition and overnutrition as well as different determinants that can impact on food intake, while SNAQ65+ is solely focused on protein-energy malnutrition.