TaKeTiNa Music Therapy for Outpatient Treatment of Depression: Study Protocol for a Randomized Clinical Trial.

BACKGROUND/OBJECTIVES: Depression is a prevalent and debilitating illness that significantly affects psychological and physical well-being. Apart from conventional therapies such as psychotherapy and medication, individuals with depression often lack opportunities for activities that are generally perceived as enjoyable, such as music, meditation, and arts, which have demonstrated therapeutic effectiveness. TaKeTiNa music therapy has been employed as a therapeutic intervention for more than two decades. However, there is a notable absence of well-designed clinical trials investigating its antidepressant effects, a gap we aim to address in our current study. Furthermore, shifts in the progression of depression may manifest both psychologically, by influencing emotional states, and physiologically, by leading to alterations in lipid and sphingolipid metabolism, cortisol levels, and immune system function. Our study seeks to analyze the impact of TaKeTiNa music therapy on both levels. METHODS: This is a prospective monocentric randomized waitlist-controlled clinical trial. It investigates the influence of TaKeTiNa music therapy on patients with major depression in an outpatient setting. Therefore, interested persons are randomly assigned to two groups, an intervention group or a control group, after completing a screening procedure. The intervention group starts with an eight-week TaKeTiNa music therapy intervention. The waiting group receives the same therapy program after completing the follow-up period. Blood and saliva sampling as well as responses to questionnaires are obtained at specific time points. DISCUSSION: Our study investigates the effects of TaKeTiNa music therapy, a non-pharmacological antidepressant treatment option, on depressive symptoms. We also address functional and causal immunological changes; hormonal changes, such as changes in cortisol levels; and metabolic changes, such as changes in serum lipids and sphingolipids, during the course of depression. We expect that this study will provide evidence to expand the range of treatment options available for depression.

Cryo-electron structures of the extreme thermostable enzymes Sulfur Oxygenase Reductase and Lumazine Synthase.

Thermostable enzymes have the potential for use in a wide variety of biotechnological applications. Cryo-electron microscopy (cryo-EM) enables the imaging of biomolecules in their native aqueous environment. Here, we present high resolution cryo-EM structures of two thermostable enzymes that exhibit multimeric cage-like structures arranged into two different point-group symmetries. First, we determined the structure of the Sulfur Oxygenase Reductase (SOR) enzyme that catalyzes both the oxygenation and disproportionation of elemental sulfur in Archea and is composed of 24 homomeric units each of MW ≃ 35 kDa arranged in octahedral symmetry. The structure of SOR from Acidianus ambivalens (7X9W) was determined at 2.78 Å resolution. The active site of each subunit inside the central nanocompartment is composed of Fe3+ coordinated to two water molecules and the three amino acids (H86, H90 and E114). Second, we determined the structure of Lumazine Synthase (LS) from Aquifex aeolicus (7X7M) at 2.33 Å resolution. LS forms a cage-like structure consisting of 60 identical subunits each of MW ≃ 15 kDa arranged in a strict icosahedral symmetry. The LS subunits are interconnected by ion-pair network. Due to their thermostability and relatively easy purification scheme, both SOR and LS can serve as a model for the catalytic and structural characterization of biocatalysts as well as a benchmark for cryo-EM sample preparation, optimization of the acquisition parameters and 3D reconstruction.

Serial block-face scanning electron microscopy reveals neuronal-epithelial cell fusion in the mouse cornea.

The cornea is the most highly innervated tissue in the body. It is generally accepted that corneal stromal nerves penetrate the epithelial basal lamina giving rise to intra-epithelial nerves. During the course of a study wherein we imaged corneal nerves in mice, we observed a novel neuronal-epithelial cell interaction whereby nerves approaching the epithelium in the cornea fused with basal epithelial cells, such that their plasma membranes were continuous and the neuronal axoplasm freely abutted the epithelial cytoplasm. In this study we sought to determine the frequency, distribution, and morphological profile of neuronal-epithelial cell fusion events within the cornea. Serial electron microscopy images were obtained from the anterior stroma in the paralimbus and central cornea of 8-10 week old C57BL/6J mice. We found evidence of a novel alternative behavior involving a neuronal-epithelial interaction whereby 42.8% of central corneal nerve bundles approaching the epithelium contain axons that fuse with basal epithelial cells. The average surface-to-volume ratio of a penetrating nerve was 3.32, while the average fusing nerve was smaller at 1.39 (p ≤ 0.0001). Despite this, both neuronal-epithelial cell interactions involve similarly sized discontinuities in the basal lamina. In order to verify the plasma membrane continuity between fused neurons and epithelial cells we used the lipophilic membrane tracer DiI. The majority of corneal nerves were labeled with DiI after application to the trigeminal ganglion and, consistent with our ultrastructural observations, fusion sites recognized as DiI-labeled basal epithelial cells were located at points of stromal nerve termination. These studies provide evidence that neuronal-epithelial cell fusion is a cell-cell interaction that occurs primarily in the central cornea, and fusing nerve bundles are morphologically distinct from penetrating nerve bundles. This is, to our knowledge, the first description of neuronal-epithelial cell fusion in the literature adding a new level of complexity to the current understanding of corneal innervation.

3D Analysis of Ordered Porous Polymeric Particles using Complementary Electron Microscopy Methods.

Highly porous particles with internal triply periodic minimal surfaces were investigated for sorption of proteins. The visualization of the complex ordered morphology requires complementary advanced methods of electron microscopy for 3D imaging, instead of a simple 2D projection: transmission electron microscopy (TEM) tomography, slice-and-view focused ion beam (FIB) and serial block face (SBF) scanning electron microscopy (SEM). The capability of each method of 3D image reconstruction was demonstrated and their potential of application to other synthetic polymeric systems was discussed. TEM has high resolution for details even smaller than 1 nm, but the imaged volume is relatively restricted (2.5 µm)3. The samples are pre-sliced in an ultramicrotome. FIB and SBF are coupled to a SEM. The sample sectioning is done in situ, respectively by an ion beam or an ultramicrotome, SBF, a method so far mostly applied only to biological systems, was particularly highly informative to reproduce the ordered morphology of block copolymer particles with 32-54 nm nanopores and sampling volume (20 µm)3.

Rapid Size-Based Protein Discrimination inside Hybrid Isoporous Membranes.

Owing to their unique morphology, isoporous membranes derived from block copolymers (BCPs) have rapidly advanced the process of macromolecular separation. In such separations, fouling is the most daunting challenge, affecting both the permeability and selectivity of high-performance isoporous membranes. To overcome this, we increase the hydrophilicity of nanostructured BCP isoporous membranes by incorporating hydrophilic polymer-grafted graphene oxide nanosheets into them. Due to the synergy of these two highly functional components, the hybrid isoporous membranes show pH-responsive and alcohol-gating behaviors, along with improved bactericidal capabilities. Leveraging the high permeability and selectivity behavior of BCP isoporous membranes together with the antifouling capabilities imparted by the polymer-grafted graphene oxide nanosheets, we achieved the highest separation factor (33) ever obtained during the ultrafiltration of the common blood proteins bovine serum albumin and immunoglobulin. This was accompanied by a 60% enhanced flux compared to that of the pristine BCP membranes during this challenging size-based separation of a protein mixture. We surmise that such fouling-resistant hybrid isoporous membranes with rationally functionalized filler materials can be used to replace existing membranes for specific energy-efficient bioseparation applications with improved performance.

Artificial 3D hierarchical and isotropic porous polymeric materials.

Hierarchical porous materials that replicate complex living structures are attractive for a wide variety of applications, ranging from storage and catalysis to biological and artificial systems. However, the preparation of structures with a high level of complexity and long-range order at the mesoscale and microscale is challenging. We report a simple, nonextractive, and nonreactive method used to prepare three-dimensional porous materials that mimic biological systems such as marine skeletons and honeycombs. This method exploits the concurrent occurrence of the self-assembly of block copolymers in solution and macrophase separation by nucleation and growth. We obtained a long-range order of micrometer-sized compartments. These compartments are interconnected by ordered cylindrical nanochannels. The new approach is demonstrated using polystyrene-b-poly(t-butyl acrylate), which can be further explored for a broad range of applications, such as air purification filters for viruses and pollution particle removal or growth of bioinspired materials for bone regeneration.

Integrated approach to characterize fouling on a flat sheet membrane gravity driven submerged membrane bioreactor.

Fouling in membrane bioreactors (MBR) is acknowledged to be complex and unclear. An integrated characterization methodology was employed in this study to understand the fouling on a gravity-driven submerged MBR (GD-SMBR). It involved the use of different analytical tools, including optical coherence tomography (OCT), liquid chromatography with organic carbon detection (LC-OCD), total organic carbon (TOC), flow cytometer (FCM), adenosine triphosphate analysis (ATP) and scanning electron microscopy (SEM). The three-dimensional (3D) biomass morphology was acquired in a real-time through non-destructive and in situ OCT scanning of 75% of the total membrane surface directly in the tank. Results showed that the biomass layer was homogeneously distributed on the membrane surface. The amount of biomass was selectively linked with final destructive autopsy techniques. The LC-OCD analysis indicated the abundance of low molecular weight (LMW) organics in the fouling composition. Three different SEM techniques were applied to investigate the detailed fouling morphology on the membrane.

Corneal stroma microfibrils.

Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-ß. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10 nm diameter). Immunogold evidence clearly identified these fibrils as fibrillin EFMBs and EFMBs were also observed with TEM (without immunogold) in adult mammals of several species. Evidence of the presence of EFMBs in adult corneas will hopefully pique an interest in further studies that will ultimately improve our understanding of the cornea's biomechanical properties and its capacity to repair.

Microbial community composition and ultrastructure of granules from a full-scale anammox reactor.

Granules in anammox reactors contain besides anammox bacteria other microbial communities whose identity and relationship with the anammox bacteria are not well understood. High calcium concentrations are often supplied to anammox reactors to obtain sufficient bacterial aggregation and biomass retention. The aim of this study was to provide the first characterization of bacterial and archaeal communities in anammox granules from a full-scale anammox reactor and to explore on the possible role of calcium in such aggregates. High magnification imaging using backscattered electrons revealed that anammox bacteria may be embedded in calcium phosphate precipitates. Pyrosequencing of 16S rRNA gene fragments showed, besides anammox bacteria (Brocadiacea, 32%), substantial numbers of heterotrophic bacteria Ignavibacteriacea (18%) and Anaerolinea (7%) along with heterotrophic denitrifiers Rhodocyclacea (9%), Comamonadacea (3%), and Shewanellacea (3%) in the granules. It is hypothesized that these bacteria may form a network in which heterotrophic denitrifiers cooperate to achieve a well-functioning denitrification system as they can utilize the nitrate intrinsically produced by the anammox reaction. This network may provide a niche for the proliferation of archaea. Hydrogenotrophic methananogens, which scavenge the key fermentation product H2, were the most abundant archaea detected. Cells resembling the polygon-shaped denitrifying methanotroph Candidatus Methylomirabilis oxyfera were observed by electron microscopy. It is hypothesized that the anammox process in a full-scale reactor triggers various reactions overall leading to efficient denitrification and a sink of carbon as biomass in anammox granules.

Synthesis and properties of the metallo-supramolecular polymer hydrogel poly[methyl vinyl ether-alt-mono-sodium maleate]·AgNO3: Ag+/Cu2+ ion exchange and effective antibacterial activity.

The commercial polymeric anhydride poly(methyl vinyl ether-alt-maleic anhydride) (PVM/MA) is converted by reaction with NaOH to give poly(methyl vinyl ether-alt-mono-sodium maleate) (PVM/Na-MA). By addition of AgNO3-solution, the formation of the silver(i) supramolecular polymer hydrogel poly[methyl vinyl ether-alt-mono-sodium maleate]·AgNO3 is reported. Freeze-dried samples of the hydrogel show a mesoporous network of polycarboxylate ligands that are crosslinked by silver(i) cations. In the intact hydrogel, ion-exchange studies are reported and it is shown that Ag+ ions can be exchanged by copper(ii) cations without disintegration of the hydrogel. The silver(i) hydrogel shows effective antibacterial activity and potential application as burn wound dressing.

Risk Factors of Congenital Heart Diseases: A Case-Control Study inNorthwest Iran.

INTRODUCTION: Congenital heart diseases are of immense importance and also a high prevalence. Contributing factors to developing these defects have not been abundantly studied. Therefore, the current study was conducted aiming at determining the effective factors on Congenital Heart Disease (CHD) in newborn infants of Northwest Iran. METHODS: A case-control study was carried out in North-West of Iran from 2002 to 2012 and a total of 473 infants entered the study. Required data were obtained through check lists completed by the information of hospital records and interview with mothers of 267 newborn infants with CHD together with medical records of mothers as the case group, and 206 medical records of healthy infants at the same period all together with those of their mothers as the control group. The obtained data were statistically analyzed using descriptive statistical methods, T-test, Spearman's correlation coefficient, and Multi-variable Logistic Regression Model (OR with 95% CI), using SPSS.19. In the present study, P value less than 0.05 was considered statistically significant. RESULTS: Based on the results of univariable analyses, the number of previous cesarean sections, past medical history of diseases, gestational age (GA), fetal weight at birth, diastolic blood pressure, fetal heart rate, pulse rate, fetal hemoglobin and hematocrit levels, and fetal head circumference at birth have significant relationship with incidence of congenital abnormalities (P<0.05). Family history, past cesarean sections history, past medical history and GA had significant relationship with CHD incidence. CONCLUSION: Based on the results of present study, in order to control and reduce the cases of CHD, it is crucial to make proper decisions and implement policies for reducing cesarean cases, lowering consanguineous marriages, providing proper pre-marriage counseling, prompt treatment of mothers' illnesses, improving pregnancy health care and mothers' health status for the purpose of better well-being of newborn infants.

Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy.

The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart.

Block copolymer hollow fiber membranes with catalytic activity and pH-response.

We fabricated block copolymer hollow fiber membranes with self-assembled, shell-side, uniform pore structures. The fibers in these membranes combined pores able to respond to pH and acting as chemical gates that opened above pH 4, and catalytic activity, achieved by the incorporation of gold nanoparticles. We used a dry/wet spinning process to produce the asymmetric hollow fibers and determined the conditions under which the hollow fibers were optimized to create the desired pore morphology and the necessary mechanical stability. To induce ordered micelle assembly in the doped solution, we identified an ideal solvent mixture as confirmed by small-angle X-ray scattering. We then reduced p-nitrophenol with a gold-loaded fiber to confirm the catalytic performance of the membranes.

Characterization of internal structure of hydrated agar and gelatin matrices by cryo-SEM.

There has been a considerable interest in recent years in developing polymer gel matrices for many important applications such as 2DE for quantization and separation of a variety of proteins and drug delivery system to control the release of active agents. However, a well-defined knowledge of the ultrastructures of the gels has been elusive. In this study, we report the characterization of two different polymers used in 2DE: Gelatin, a naturally occurring polymer derived from collagen (protein) and agar, a polymer of polysaccharide (sugar) origin. Low-temperature SEM is used to examine the internal structure of these gels in their frozen natural hydrated states. Results of this study show that both polymers have an array of hollow cells that resembles honeycomb structures. While agar pores are almost circular, the corresponding Gaussian curve is very broad exhibiting a range of radii from nearly 370 to 700 nm. Gelatin pores are smaller and more homogeneous reflecting a narrower distribution from nearly 320 to 650 nm. Overall, these ultrastructural findings could be used to correlate with functions of the polymers.

From micelle supramolecular assemblies in selective solvents to isoporous membranes.

The supramolecular assembly of PS-b-P4VP copolymer micelles induced by selective solvent mixtures was used to manufacture isoporous membranes. Micelle order in solution was confirmed by cryo-scanning electron microscopy in casting solutions, leading to ordered pore morphology. When dioxane, a solvent that interacts poorly with the micelle corona, was added to the solution, polymer-polymer segment contact was preferential, increasing the intermicelle contact. Immersion in water gave rise to asymmetric porous membranes with exceptional pore uniformity and high porosity. The introduction of a small number of carbon nanotubes to the casting solution improved the membrane stability and the reversibility of the gate response in the presence of different pH values.

Switchable pH-responsive polymeric membranes prepared via block copolymer micelle assembly.

A process is described to manufacture monodisperse asymmetric pH-responsive nanochannels with very high densities (pore density >2 × 10(14) pores per m(2)), reproducible in m(2) scale. Cylindric pores with diameters in the sub-10 nm range and lengths in the 400 nm range were formed by self-assembly of metal-block copolymer complexes and nonsolvent-induced phase separation. The film morphology was tailored by taking into account the stability constants for a series of metal-polymer complexes and confirmed by AFM. The distribution of metal-copolymer micelles was imaged by transmission electron microscopy tomography. The pH response of the polymer nanochannels is the strongest reported with synthetic pores in the nm range (reversible flux increase of more than 2 orders of magnitude when switching the pH from 2 to 8) and could be demonstrated by cryo-field emission scanning electron microscopy, SAXS, and ultra/nanofiltration experiments.

[Inflammatory myofibroblastic tumor of the lymph node with paraneoplastic thrombosis and eosinophilia]. / Inflammatorischer myofibroblastärer Tumor des Lymphknotens mit paraneoplastischer Thrombose und Eosinophilie.

CASE REPORT: A 52-year-old female patient was admitted to hospital because of progressive thrombosis despite therapeutic anticoagulation as well as leukocytosis with eosinophilia and thrombocytopenia. On examination, the patient presented with dyspnea and swelling oft her left leg and arm. The laboratory findings revealed leukocytosis (31,000/microl) with eosinophilia (54%), thrombocytopenia (58,000/microl), together with an increased C-reactive protein of 247 mg/dl (reference range < 5 mg/dl). Initial computed tomography scans showed pulmonary embolism and a slightly enlarged left inguinal lymph node. Histological examination of the lymph node biopsy revealed in part an epitheloid and spindle cell-like tumorous lesion with slightly increased tissue eosinophilia consistent with an inflammatory myofibroblastic tumor (IMT). Resection of the left inguinal lymph node resulted in an immediate regression of the paraneoplastic eosinophilia and thrombocytopenia. Anti-inflammatory medication with ibuprofen was subsequently initiated. Imaging and clinical examination at 3 months after discharge revealed no relapse and no signs of a paraneoplastic syndrome. CONCLUSION: The IMT is a rare soft-tissue tumor of intermediate dignity with a low tendency to metastasize. It is consistently accompanied by paraneoplastic syndromes. Therapy of choice is complete resection of the tumor. In nonresectable cases, corticosteroids and nonsteroidal antirheumatics have been shown to be effective. Because of the variable clinical course ranging from spontaneous regression to metastasis, IMTs might be separated into different entities (autoimmune, inflammatory, neoplastic subtype) which thus far cannot be classified on a histopathologic basis. A clinical assessment of the dignity is therefore important until further subclassifications of this rare disease become available.

Localization of DNA and RNA in eosinophil secretory granules.

BACKGROUND: Although the accepted paradigm is that the proteins stored in eosinophil crystalloid granules are translated from messenger RNA transcribed in the cell nucleus, recent ultrastructural evidence suggests that protein synthesis may also take place within eosinophilic granules. METHODS: We used 2 different methods to detect the presence of DNA and RNA in eosinophil secretory granules. Using bromodeoxyuridine, a thymidine analogue, and bromouridine, a uracil analogue, we labeled the DNA and RNA in eosinophils in vivo in rabbits. Immunoelectron microscopy to localize these molecules was performed on ultrathin sections of blood and bone marrow eosinophils using monoclonal anti-bromodeoxyuridine antibody with IgG as a control. The immunogold grain density was measured in each subcellular compartment within the eosinophils and analyzed using image analysis software. A combination of DNA/CD63 immunofluorescence staining and a fluorescently labeled molecular probe that stains RNA was used to examine the presence of DNA and RNA in the secretory granules of human blood eosinophils. RESULTS: The mean density of bromodeoxyuridine-labeled DNA and bromouridine-labeled RNA immunogold grains in the secretory granules of blood and bone marrow eosinophils were significantly higher (p < 0.0005) than cytoplasmic or background staining. We also demonstrated the existence of DNA and RNA in the CD63-positive secretory granules of human peripheral blood eosinophils by means of immunofluorescent staining and a fluorescently labeled molecular probe. CONCLUSIONS: These results provide evidence that eosinophil granules are the site of DNA and RNA synthesis and suggest the potential for a new role(s) for eosinophil-secretory granules.

The disruption of the epithelial mesenchymal trophic unit in COPD.

Progression of COPD is associated with a measurable increase in small airway wall thickness resulting from a repair and remodeling process that involves fibroblasts of the epithelial mesenchymal trophic unit (EMTU). The present study was designed to examine the organization of fibroblasts within the lamina propria of small airways with respect to their contacts with the epithelium and with each other in persons with COPD. Transmission electron microcopy (TEM) and three-dimensional (3D) reconstructions of serial TEM sections were used to estimate the frequency and determine the nature of the contacts between the epithelium and fibroblasts within the EMTU in small airways from 5 controls (smokers with normal lung function), from 6 persons with mild (GOLD-1) and 5 with moderate (GOLD-2) COPD. In airways from control lungs fibroblasts make frequent contact with cytoplasmic extensions of epithelial cells through apertures in the epithelial basal lamina, but the frequency of these fibroblast-epithelial contacts is reduced in both mild and moderate COPD compared to controls (p < 0.01). The 3D reconstructions showed that the cytoplasmic extensions of lamina propria fibroblasts form a reticulum with fibroblast-fibroblast contacts in an airway from a control subject but this reticulum may be reorganized in airways of COPD patients. Development of COPD is associated with significant disruption of the EMTU due to a reduction of contacts between fibroblasts and the epithelium.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.