CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

[Figure: see text].

Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.

BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models. First, atherosclerotic lesion development in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was assessed in a model of shear stress-modulated vulnerable plaque formation. RESULTS: Both lesion and necrotic core size were significantly reduced in ApoE-/-Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was also reduced in the model of shear stress-modulated vulnerable plaque formation. A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5, CD11c- macrophages displayed a significant increase in expression of the efferocytosis-regulating integrin-ß3 and its ligand milk fat globule-epidermal growth factor 8 protein and enhanced efferocytosis in vitro and in situ. CONCLUSIONS: IRF5 is detrimental in atherosclerosis by promoting the maintenance of proinflammatory CD11c+ macrophages within lesions and controlling the expansion of the necrotic core by impairing efferocytosis.

Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques.

Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE(-/-)) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE(-/-) mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming.

A Successful Gap-Year Clinical Research Technician (CRT) Program at an Academic Anesthesiology Department.

BACKGROUND: Many students elect to take gap years in between graduating college and matriculating into medical school. At an academic institution, investigators can be limited in conducting research due to clinical endeavors. Utilizing a structured, clinical research, gap-year program with students called clinical research technicians (CRTs) can aid both investigators conducting research and students applying to graduate health programs. In this original article, we sought to understand CRT and investigator perceptions of and experiences in the program. METHODS: We distributed a survey to past and present CRTs and the investigators with whom they worked at Atrium Health Wake Forest Baptist Medical Center. We conducted thematic and sentiment analyses of the survey results. We also collected data on grant approvals, research funding awards, and CRT, clinical research nurse, and clinical research coordinator salaries. RESULTS: We received responses from 20/29 investigators and 21/22 CRTs. We identified five themes for the investigator survey, including research accuracy and precision; research output; alleviating responsibilities; cost; and likelihood of referral. We identified five themes for the CRT survey, including future career assistance; physician career insights; mentorship; likelihood of referral; and other. The majority of respondents strongly agreed or agreed with the survey statements. The majority of comments were coded as positive. All of CRTs were accepted into a graduate health profession program. CONCLUSIONS:  Our program's success demonstrates how a structured, clinical research, gap-year program for premedical students can serve as a new educational tool and important research infrastructure resource for hospitals.

The role of peripheral nerve stimulation in refractory non-operative chronic knee osteoarthritis.

Aim: This case series aimed to analyze the efficacy of a temporary peripheral nerve stimulation (PNS) device implanted for 60 days at 60 days post-explant for patients with non-surgical osteoarthritic knee pain. Patients & methods: 19 patients were selected for treatment with temporary PNS at an outpatient pain management clinic. Results: Patients demonstrated improvement in their knee pain from baseline post-temporary PNS explant (p = 0.973). Conclusion: Temporary PNS serves as a promising therapy for patients with limited options for therapy, necessitating further high-quality studies.

Temporary peripheral nerve stimulation (PNS) is a treatment for patients with knee swelling and pain who can't get surgery. The authors studied temporary PNS to see if the patient's knee pain improved. 19 patients were treated with temporary PNS. The study found the patients' knee pain improved after completing the treatment. More research is needed in the future to temporary PNS in knee pain patients.

Role of inflammatory cells and toll-like receptors in atherosclerosis.

The primary cause of cerebrovascular disease is atherosclerosis, to which many factors contribute. At first many saw atherosclerosis as a lipid-driven disease. Recently inflammation has appeared as a significant factor in the disease. Innate immune cells, for example monocytes and macrophages, are important in atherosclerosis. Toll-like receptors (TLRs) are the best-studied family of receptor in the immune system. TLR engagement with their ligands stimulates pro-inflammatory cytokine production and foam cell generation. Recently certain TLRs have shown a protective role in atherosclerosis. In this review, we analyse innate immunity, focusing on TLR signalling and macrophages, in atherosclerosis and acute cerebrovascular complications, and thereby discuss their potential as therapeutic targets.

Functional Analysis and Molecular Docking studies of Medicinal Compounds for AChE and BChE in Alzheimer's Disease and Type 2 Diabetes Mellitus.

Acetylcholinesterase and Butyrylcholinesterase share unravelling link with components of metabolic syndromes that's characterised by low levels of HDL cholesterol, obesity, high fast aldohexose levels, hyper-trigliceridaemia and high blood pressure, by regulation of cholinergic transmission and therefore the enzyme activity within a living system. The phosphomotifs associated with amino acid and tyrosine binding motifs in AChE and BChE were known to be common. Phylogenetic tree was constructed to these proteins usinf UPGMA and Maximum Likelihood methods in MEGA software has shown interaction of AChE and BChE with ageing diseases like Alzheimer's disease and Diabetes. AChE has shown closely related to BChE, retinol dehydrogenase and ß-polypeptide. The present studies is also accomplished that AChE, BChE, COLQ, HAND1, APP, NLGN2 and NGF proteins has interactions with diseases such as Alzheimer's and D2M using Pathwaylinker and STRING. Medicinal compounds like Ortho-7, Dibucaine and HI-6 are predicted as good targets for modeled AChE and BChE proteins based on docking studies. Hence perceptive studies of cholinesterase structure and the biological mechanisms of inhibition are necessary for effective drug development.

Serum GGT activity and hsCRP level in patients with type 2 diabetes mellitus with good and poor glycemic control: An evidence linking oxidative stress, inflammation and glycemic control.

BACKGROUND: Diabetes is undoubtedly one of the most challenging health problems in 21st century. Understanding the pathogenesis and preventing long term complications have been major goals of research in diabetes mellitus (DM). Research in the past few years has linked oxidative stress and inflammation to beta cell dysfunction. Aim of this study is to evaluate serum gamma-glutamyl transferase (GGT) activity (marker of oxidative stress) and high sensitivity C reactive protein (hsCRP) level (an inflammatory marker) in type 2 DM subjects with good and poor glycemic control. Further, we investigated correlation between serum GGT and hsCRP level with glycemic control (FBS, PP2BS, HbA1c) in subjects. METHODS: A cross sectional study consists of 150 patients out of them 50 patients having type 2 DM with good control (Group II), 50 patients with type 2 DM with poor control (Group III) and 50 normal healthy control (Group I) were selected. Serum GGT, serum hsCRP, FBS, PP2BS, HbA1c, and other biochemical investigations include serum liver enzymes and lipids were measured. RESULTS: Mean serum GGT and hsCRP concentration were statistically significantly higher in group III patients compared to group I and group II subjects as well as increased in group II compared to group I (p < 0.001). Further significant positive correlation was observed between GGT and hsCRP concentration as well as both with HbA1c, FBS, and PP2BS. CONCLUSIONS: Oxidative stress and inflammation appears to be a key component and also associated with poor glycemic control and further pathogenesis of diabetes and its complications. All our finding suggesting a link between oxidative stress, inflammation and glycemic control in patient with type 2 diabetes mellitus.

Toll-like receptors and macrophage activation in atherosclerosis.

Atherosclerosis is a multi-factorial inflammatory disease and is the primary initiator of coronary artery and cerebrovascular disease. Initially believed to be exclusively lipid-driven, recent evidence demonstrates that inflammation is a significant driving force of the disease. Cellular components of innate immunity, for example monocytes and macrophages, play a predominant role in atherosclerosis. Toll-like receptors (TLRs) are the most characterised innate immune receptors and recent evidence demonstrates an important role in atherogenesis. Engagement of TLRs results in the transcription of pro-inflammatory cytokines, foam cell formation and activation of adaptive immunity. Recently they have also been implicated in protection from vascular disease. In this review, we detail the role of the innate immune system, specifically macrophages and TLR signalling, in atherosclerosis and acute cardiovascular complications, and thereby identify the potential of TLRs to act as therapeutic targets.