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Scientific reports 7(1), 11670 (2017). doi:10.1038/s41598-017-10549-x, Published by Nature Publishing Group, London

Background— Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte-derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated. Methods and Results— Hematopoietic Hck/Fgr-deficient, LDLr −/− chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as the most prominent features. Despite a Ly6C high -skewed proinflammatory monocyte phenotype, Hck/Fgr deficiency led to disrupted adhesion of myeloid cells to and transmigration across endothelial monolayers in vitro and atherosclerotic plaques in vivo, as assessed by intravital microscopy, flow cytometry, and histological examination of atherosclerotic arteries. Moreover, Hck/Fgr-deficient macrophages showed blunted podosome formation and mesenchymal migration capacity. In consequence, transmigrated double-knockout macrophages were seen to accumulate in the fibrous cap, potentially promoting its focal erosion, as observed for double-knockout chimeras. Conclusions— The hematopoietic deficiency of Hck and Fgr led to attenuated atherosclerotic plaque formation by abrogating endothelial adhesion and transmigration; paradoxically, it also promoted plaque instability by causing monocyte subset imbalance and subendothelial accumulation, raising a note of caution regarding src kinase–targeted intervention in plaque inflammation.

microRNA-155 (miR155) is a central regulator of immune responses that is induced by inflammatory mediators. Although miR155 is considered to be a pro-inflammatory microRNA, in vitro reports show anti-inflammatory effects in lipid-loaded cells. In this study we examined the role of miR155 in atherosclerosis in vivo using bone marrow transplantation from miR155 deficient or wildtype mice to hyperlipidemic mice. Hematopoietic deficiency of miR155 enhanced atherosclerotic plaque development and decreased plaque stability, as evidenced by increased myeloid inflammatory cell recruitment to the plaque. The increased inflammatory state was mirrored by a decrease in circulating CD4(+)CD25(+)FoxP3(+) regulatory T cells, and an increase in granulocytes (CD11b(+)Ly6G(+)) in blood of miR155(-/-) transplanted mice. Moreover, we show for the first time a crucial role of miR155 in monocyte subset differentiation, since hematopoietic deficiency of miR155 increases the 'inflammatory' monocyte subset (CD11b(+)Ly6G(-)Ly6C(hi)) and reduces 'resident' monocytes (CD11b(+)Ly6G(-)Ly6C(low)) in the circulation. Furthermore, cytokine production by resident peritoneal macrophages of miR155(-/-) transplanted hyperlipidemic mice was skewed towards a more pro-inflammatory state since anti-inflammatory IL-10 production was reduced. In conclusion, in this hyperlipidemic mouse model miR155 acts as an anti-inflammatory, atheroprotective microRNA. Additionally, besides a known role in lymphoid cell development, we show a crucial role of miR155 in myeloid lineage differentiation.

Attention and expectancy have, in previous research, been demonstrated to influence symptom reporting and these findings can be relevant for understanding hypochondriasis. Earlier attention/expectancy effects on symptom reporting were studied when subjects were physically stimulated by the experimenter. If attention or expectancy produced symptom reporting, which plays a role in hypochondriasis, one expects that attention/expectancy will also produce symptoms in the absence of any deliberate physical stimulation. Eighty healthy volunteers were allocated to one of four groups: attention, expectancy, attention plus expectancy or a control condition. Compared to the control condition there was much higher symptom reporting in the 3 experimental groups. The experimental groups did not differ. It is argued that the effects of expectancy are obtained via increased attention. The relevance of the findings for understanding hypochondriasis is discussed.

Background: Studies on effectiveness of phytosterol/-stanol-enriched margarines in the community have received low priority. For postlaunch monitoring purposes including risk-benefit analyses, it is needed to investigate both exposure and effectiveness of these margarines. Objective: To study the use and effectiveness of phytosterol/-stanol-enriched margarine. Design, setting and subjects: The study population consisted of 2379 subjects that participated in a community intervention study ('Hartslag Limburg') aged 28-76 years. In 1998 and 2003, blood samples for total and high- density lipoprotein (HDL) cholesterol were obtained. A general questionnaire and food frequency questionnaire (FFQ) were administered. From 1999 onwards, phytosterol/-stanol-enriched margarines were introduced on the Dutch market. On the basis of 2003 data, subjects were classified in users of (a) phytosterol/-stanol-enriched margarine, (b) cholesterol-lowering drugs, (c) the combination (both enriched margarine and drugs) and (d) neither enriched margarines nor cholesterol-lowering drugs. Results: Mean (+/- s.d.) daily intake of phytosterol-enriched margarine (n=99) and phytostanol-enriched margarine (n=16) was 14 +/- 9 g. From 1998 to 2003, total serum cholesterol concentration changed significantly different among the four groups: in the combination users -2.04 +/- 1.50 mmol/l (-29%), in cholesterol-lowering drug users -1.09 +/- 1.17 mmol/l (-17%), in the enriched margarine users -0.24 +/- 0.75 mmol/l (-4%) and in non-users +0.10 +/- 0.72 mmol/l (+2%)(P

We report on the mechanisms, the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens, taking into account both allergen contamination and the developmental success of pyroglyphid Acari. Twenty patients with persisting rhinitic complaints were selected and matched. Although the patients had performed some conventional dust and mite avoidance measures (patient compliance was 90%), the dwellings proved to be a stimulus for mite development. Moisture problems due to faulty construction and excessive moisture production were common. Since humidity conditions could not be changed at short notice, the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without (control) and with an acaricide incorporated (acaricidal cleaner [Acarosan]). After the carrying out of conventional avoidance measures, these patients still had allergic symptoms, and dust from only 23 to 52% of their textile objects was under the proposed guanine (mite faeces indicator) risk level. Only the acaricidal cleaner was able to decrease the allergenic mite load (and the burden of the patients) significantly in this 12 month period. With respect to mite-extermination, acaricidal cleaning was 88% better than intensive cleaning. Reduction of guanine was 38% better in the Acarosan treatment group. Clinical results have been reported elsewhere. A significant difference in favour of the acaricidal cleaning was seen in both subjective (as regards symptoms) and in objective data (total IgE). Another 50 patients were questioned. About 90% were willing to spend two weekends (70%), or at the most one weekend (20%) per year sanitizing the dwelling by cleaning it with the whole family. The authors of this report consider acaricidal cleaning to be a significant improvement in the management of mite-allergic diseases, such as rhinitis. Compared with the replacement of home textiles, this treatment is less expensive and more effective. Patient compliance is acceptable, but depends on acceptance by physicians and the initial motivation and consequent burden on the patient.