Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis.

Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2-/- cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.

Limited plasticity of monocyte fate and function associated with epigenetic scripting at the level of progenitors.

Myeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress. Rather, their functional fate was constrained by chromatin accessibility established at or before the granulocyte-monocyte or monocyte-dendritic progenitor level. Subsets of primary monocytes had differential ability to control distinct infectious agents in vivo. Therefore, monocytes are a heterogeneous population of functionally restricted subtypes defined by the epigenome of their progenitors that are differentially selected by physiologic challenges with limited plasticity to transition from one subset to another.

Sleep modulates haematopoiesis and protects against atherosclerosis.

Sleep is integral to life1. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease2, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin-a stimulatory and wake-promoting neuropeptide-in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.

Psychotic-like experiences in non-clinical subgroups with and without specific beliefs.

BACKGROUND: Assuming a transdiagnostic and extended psychosis phenotype, psychotic-like experiences (PLEs) and psychotic symptoms are on a phenomenological and temporal continuum between clinical and non-clinical populations. Recent research points towards differences in PLE proneness in different subgroups and clinical impact of different PLE subtypes. This study examines the prevalence of PLEs in three groups of individuals with and without specific sets of beliefs aiming to elucidate the question whether proneness to PLEs varies according to traditional versus less traditional supernatural beliefs. METHODS: The anonymized 16-item version of the Prodromal Questionnaire (PQ-16) was used to assess PLEs in three groups including individuals with religious beliefs (RB), belief in esoterism and paranormal phenomena (EB), and those embedded in scientific evidence approach and scepticism towards para-scientific theories (non-believers, NB). Male and female participants between 18 and 90 years were eligible for participation. RESULTS: The sample comprised 159 individuals including 41 RB individuals, 43 EB individuals, and 75 NB individuals. The mean PQ-16 score of the EB individuals (6.86 ± 4.13) was significantly higher compared to NB individuals (3.43 ± 2.99) and to RB individuals (3.38 ± 3.23) with almost twice the score (both p-values < 0.001). There was no significant difference between the PQ-16 scores of the NB group and the RB group (p = 0.935). No significant impact of age (p = 0.330) and gender (p = 0.061) was found on the PQ16-Score. Group affiliation to esoterism was associated with a higher PQ-16 score compared to group affiliation to religious beliefs (p < 0.001) and group affiliation to scepticism (p = 0.011), while the latter two did not differ significantly (p = 0.735). No significant difference was found between the three groups in the degree of distress related to the affirmatively answered PQ-16 items (p = 0.74). CONCLUSION: Under the assumption of a transdiagnostic psychosis phenotype, our findings provide more insight which subgroups within non-clinical samples have a higher likelihood of reporting PLEs.

Health-related quality of life in multiple sclerosis: temperament outweighs EDSS.

BACKGROUND: The influence of personality on health-related quality of life in patients with multiple sclerosis has been the focus of previous studies showing that introversion and neuroticism were related with reduced health related quality of life. However, no data exist on the impact of temperament on quality of life in this patient group. METHODS: Between April 2014 and March 2016 139 multiple sclerosis patients were recruited from a specialized outpatient clinic of the general hospital of Vienna. Health-related quality of life was measured by "The Multiple Sclerosis International Quality of Life Questionnaire (MusiQol)", temperament by "Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Questionnaire - Münster version" (briefTEMPS-M), and disability by the "Expanded disability status scale". All patients underwent a diagnostic psychiatric semi-structured interview (MINI). RESULTS: Known predictors (like disease duration, EDSS, psychiatric co-morbidities, immunomodulatory treatments) explain the proportion of variation in the outcome of MusiQol global index score in 30.9% in multi-variable linear regression analysis. It increased respectively to 40.3, 42.5, and 45.8% if adding the depressive, cyclothymic, or hyperthymic temperament to the list of variables. An increase of depressive and cyclothymic temperament scores significantly reduced global index score of MusiQol (p = 0.005, p = 0.002, respectively), while the hyperthymic temperament significantly raised it (p < 0.001). CONCLUSION: In MS patients, the depressive and cyclothymic temperament predict a lower and hyperthymic temperament an increased health-related quality of life, independent of current disability status, immunomodulatory treatments, and affective co-morbidities.

Analysis on the Age Distribution of Sternum Fractures.

BACKGROUND: Sternum fractures (SFs) are described as a rare entity of bony fractures. Various accident mechanisms may cause SF such as the direct impact of traffic accidents and also by indirect mechanisms within the framework of falls. Osteoporotic fractures also play an increasing role in SF, but no reliable data on the age distribution of SF in a representative collective have been published so far. MATERIAL AND METHODS: The age distribution of all inpatients treated with SF (S22.2) in Germany from 2005 to 2012 using diagnosis-related group-based routine data was evaluated. Various accident statistics are included in the interpretation of age peaks. RESULTS: A total of 47,893 patients (24,960 as main diagnosis and 22,933 as secondary diagnosis) were included in the study. SF is a rarity in childhood, with a share of 1.83% before the age of 16 years, followed by a sudden increase in the frequency up to the age of 20 years. A decrease in the frequency is observed up to the age of 35 years before it increases again to the age of 75 years. Three age peaks can be observed at 18, 55, and 75 years. Those who are older than 65 years account for 43.3% of total SF. DISCUSSION AND CONCLUSION: The first age summit after the age of 16 years shows an identical course to the frequency of traffic accidents of this age group, as well as the decline to the fourth decade and the subsequent resurgence up to the fifth decade. After 65 years, the incidence of accidents increases, in particular, the risk of falling in elderly people. In the context of a weaker bone structure, low falls are a common course for fragility fractures. The present analysis of routines shows for the first time the age distribution of the SF taking into account all hospital cases of the observation period.

Concomitant Sternal Fracture in Flail Chest: An Analysis of 21,741 Polytrauma Patients from the TraumaRegister DGU®.

Background Isolated sternal fractures (SFs) rarely show complications, but their influence in a thorax trauma of the seriously injured still remains unclear. Methods A retrospective analysis of the TraumaRegister DGU® was performed involving the years 2009 to 2013 (Injury Severity Score [ISS] ≥ 16, primary admission to a trauma center). Cohort formation: Unilateral and bilateral flail chest (FC) injuries with and without a concomitant SF, respectively. Results In total, 21,741 patients (25% female) met the inclusion criteria, with 3,492 (16.1%) showing SF. Unilateral FC patients were on average 53.6 ± 18.4 years old, and bilateral FC patients were on average 55.2 ± 17.7 years old. The ISS in unilateral FC and bilateral FC amounted to 31.2 ± 13.0 and 43.4 ± 13.1 points, respectively. FC with an SF occurred more frequently as an injury to car occupants and less frequently as an injury to motorcyclists or in injuries due to falls. Conclusion Patients with an SF additional to an FC had longer hospital and intensive care unit stays and were longer artificially respirated than those patients without an SF. SF indicates possible cardiac and thoracic spine injuries.

The Operative Management of Flail Chest Injuries with Concomitant Sternal Fracture.

Background: Flail Chest Injuries (FCI) are one of the most severe thoracic injuries. Moreover, an additional sternal fracture (SF) even worsens the outcome, such as the duration of mechanical ventilation, therefore an surgical fixation of the fractures could be considered in certain cases to improve the weaning from the ventilator. This paper aims to emphasize on the management of different types of SF in FCI. Methods: All surgically treated cases (2012-2016) that showed the combination of FCI and SF have been evaluated for their clinical details, the morphology of the fractures and the technical aspects of the surgical procedure in a retrospective investigation. Results: All of the SF (n=15) had been fixed by locked plate osteosynthesis through a median approach in a supine position. Three main regions of the sternum showed the need for different fixation strategies: the upper manubrium, central and lower corpus sterni. Concomitant rib fractures were addressed either through the same approach or through additional limited incisions. Conclusions: Combinations of SF and FCI are high risc injuries with high demand on surgical skills. They can be properly fixed with a locking plate osteosynthesis through a combination of limited incisions employing different types of plates depending on the type of SF.

Surgical Stabilization of Costoclavicular Injuries - A Combination of Flail Chest Injuries and a Clavicula Fracture.

Background: Flail chest injuries (FCI) are associated with a high morbidity and mortality rate. As a concomitant clavicle fracture in FCI even worsens the outcome, the question is how can those costoclavicular injuries (CCI) be managed surgically. Methods: 11 patients with CCI were surgically treated by a locked plate osteosynthesis of the Clavicle and the underlying ribs through limited surgical approaches under general anesthesia. Patients were followed up after 2, 6, 12, 26 and 52 weeks. Results: All patients showed severe chest wall deformity due to severely displaced fractures of the ribs and the clavicle. They were suffering from pain and restriction of respiratory movements. The chest wall could be restored to normal shape in all cases with uneventful bone healing and a high patient convenience. Fractures of the clavicle and the second rib were managed through an innovative clavipectoral approach, the others through standard approaches to the anterolateral and the posterolateral chest wall. Two patients complained about numbness around the lateral approach and lasting periscapular pain. Conclusions: Surgical stabilization might be the appropriate therapy in CCI with dislocated fractures since they would cause severe deformity and loss of function of the chest wall and the shoulder.

Silicon micromachined ultrasonic scalpel for the dissection and coagulation of tissue.

This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young's modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost. Transverse displacement of the piezoelectric actuators is coupled into the planar silicon structure and amplified by its horn-like geometry. Using finite element modeling and experimental displacement and velocity data as well as cutting tests, key design parameters have been identified that directly influence the power efficiency and robustness of the device as well as its ease of controllability when driven in resonance. Designs in which the full- and half-wave transverse modes of the transducer are matched or not matched to the natural frequencies of the piezoelectric actuators have been evaluated. The performance of the Si micromachined scalpels has been found to be comparable to existing commercial titanium based ultrasonic scalpels used in surgical operations for efficient dissection of tissue as well as coaptation and coagulation of tissue for hemostasis. Tip displacements (peak-to-peak) of the scalpels in the range of 10-50 µm with velocities ranging from 4 to 11 m/s have been achieved. The frequency of operation is in the range of 50-100 kHz depending on the transverse operating mode and the length of the scalpel. The cutting ability of the micromachined scalpels has been successfully demonstrated on chicken tissue.

Psychosis in neurosyphilis -- clinical aspects and implications.

BACKGROUND: The World Health Organization estimates that 10-12 million new syphilis infections occur each year. Without treatment, years to decades after initial infection, 30% of affected individuals may develop tertiary syphilis, which can manifest as neurosyphilis. The aim of this review is to evaluate the research literature examining the psychopathological manifestations of psychosis in association with neurosyphilis. METHOD: The authors performed a systematic electronic search for published studies (1995-2012). The following databases were used: Medline, Embase and the Cochrane Library as well as the search engines Scopus and Google Scholar. RESULTS: 61 articles were used for detailed analysis. Psychotic symptoms due to neurosyphilis are numerous and can inform differential diagnosis for many psychotic manifestations according to ICD-10 or DSM-IV. CONCLUSION: Due to our results, current epidemiological data, and the difficulties in differential diagnosis of neurosyphilis, routine screening tests are still recommended in the psychiatric field. Long-term psychiatric input, with periodic syphilis titre controls, seems indicated in individuals affected by neurosyphilis with psychiatric symptoms. Furthermore, individuals with mental health problems may be at higher risk of acquiring syphilis.

Surgical fixation of sternal fractures: locked plate fixation by low-profile titanium plates--surgical safety through depth limited drilling.

PURPOSE: Operative treatment of sternal fractures has become a matter of increasing interest. Anterior plating seems to be the most appropriate method for fixing sternal fractures. However, there are several concerns in relation to the operative procedure such as severe injuries to mediastinal organs, patient comfort and proper stabilisation, for example. This paper describes a safe method of anterior sternal plating using locked plate fixation with limited depth drilling. METHODS: Ten patients with sternal fractures were included in this cohort study and were treated by anterior plating using one or two plates in parallel through a median approach to the sternum. Follow up was performed after six weeks, 12 weeks and six months. RESULTS: Follow up revealed no serious complications. One patient suffered from postoperative wound seroma. No problems were caused by the plates. CONCLUSIONS: Sternal plating using low profile locked titanium plates seems to be a safe and stable method with a high level of patient comfort.

Characterization of indoor dust from Brazil and evaluation of the cytotoxicity in A549 lung cells.

Over the past decade, ambient air particulate matter (PM) has been clearly associated with adverse health effects. In Brazil, small and poor communities are exposed to indoor dust derived from both natural sources, identified as blowing soil dust, and anthropogenic particles from mining activities. This study investigates the physicochemical and mineralogical composition of indoor PM10 dust samples collected in Minas Gerais, Brazil, and evaluates its cytotoxicity and inflammatory potential. The mean PM10 mass concentration was 206 µg/m(3). The high dust concentration in the interior of the residences is strongly related to blowing soil dust. The chemical and mineralogical compositions were determined by ICP-OES and XRD, and the most prominent minerals were clays, Fe-oxide, quartz, feldspars, Al(hydr)oxides, zeolites, and anatase, containing the transition metals Fe, Cr, V, Ni, Cu, Zn, Ti, and Mn as well as the metalloid As. The indoor dust samples presented a low water solubility of about 6 %. In vitro experiments were carried out with human lung alveolar carcinoma cells (A549) to study the toxicological effects. The influence of the PM10 dust samples on cell viability, intracellular formation of reactive oxygen species (ROS), and release of the pro-inflammatory cytokine IL-8 was analysed. The indoor dust showed little effects on alamarBlue reduction indicating unaltered mitochondrial activity. However, significant cell membrane damage, ROS production, and IL-8 release were detected in dependence of dose and time. This study will support the implementation of mitigation actions in the investigated area in Brazil.

Functional characteristics of an endophyte community colonizing rice roots as revealed by metagenomic analysis.

Roots are the primary site of interaction between plants and microorganisms. To meet food demands in changing climates, improved yields and stress resistance are increasingly important, stimulating efforts to identify factors that affect plant productivity. The role of bacterial endophytes that reside inside plants remains largely unexplored, because analysis of their specific functions is impeded by difficulties in cultivating most prokaryotes. Here, we present the first metagenomic approach to analyze an endophytic bacterial community resident inside roots of rice, one of the most important staple foods. Metagenome sequences were obtained from endophyte cells extracted from roots of field-grown plants. Putative functions were deduced from protein domains or similarity analyses of protein-encoding gene fragments, and allowed insights into the capacities of endophyte cells. This allowed us to predict traits and metabolic processes important for the endophytic lifestyle, suggesting that the endorhizosphere is an exclusive microhabitat requiring numerous adaptations. Prominent features included flagella, plant-polymer-degrading enzymes, protein secretion systems, iron acquisition and storage, quorum sensing, and detoxification of reactive oxygen species. Surprisingly, endophytes might be involved in the entire nitrogen cycle, as protein domains involved in N(2)-fixation, denitrification, and nitrification were detected and selected genes expressed. Our data suggest a high potential of the endophyte community for plant-growth promotion, improvement of plant stress resistance, biocontrol against pathogens, and bioremediation, regardless of their culturability.

Chondromodulin 1 stabilizes the chondrocyte phenotype and inhibits endochondral ossification of porcine cartilage repair tissue.

OBJECTIVE: To investigate the effect of chondromodulin 1 on the phenotype of osteochondral progenitor cells in cartilage repair tissue. METHODS: Self-complementary adeno-associated virus (AAV) vectors carrying chondromodulin 1 complementary DNA (AAV-Chm-1) were applied to cartilage lesions in the knee joints of miniature pigs that were treated by the microfracture technique. Alternatively, isolated porcine osteochondral progenitor cells were infected with AAV-Chm-1 or with AAV-GFP control vectors ex vivo prior to being transplanted into cartilage lesions in which the subchondral bone plate was left intact. The quality of the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods. The effects of chondromodulin 1 overexpression were also analyzed by angiogenesis assays and quantitative reverse transcriptase-polymerase chain reaction. RESULTS: AAV-Chm-1-infected cells efficiently produced chondromodulin 1, which had strong antiangiogenic effects, as verified by the inhibition of tube formation of endothelial cells. Gene expression analyses in vitro revealed the cell cycle inhibitor p21WAF1/Cip1 as one target up-regulated by AAV-Chm-1. Direct application of AAV-Chm-1 vectors into microfractured porcine cartilage lesions stimulated chondrogenic differentiation of ingrowing progenitor cells, but significantly inhibited terminal chondrocyte hypertrophy, the invasion of vessel structures, and excessive endochondral ossification, which were otherwise observed in untreated lesions. Indirect gene transfer, with infection of porcine osteochondral progenitor cells by AAV-Chm-1 ex vivo, also supported chondrogenic differentiation of these transplanted cells. AAV-Chm-1-infected cells maintained a chondrocyte-like phenotype and formed a hyaline-like matrix that was superior to that formed by uninfected or AAV-GFP-infected cells. CONCLUSION: Our findings indicate that the antiangiogenic factor chondromodulin 1 stabilizes the chondrocyte phenotype by supporting chondrogenesis but inhibiting chondrocyte hypertrophy and endochondral ossification.

Long-term effectiveness of Self-Help Plus in refugees and asylum seekers resettled in Western Europe: 12-month outcomes of a randomised controlled trial.

AIMS: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. METHODS: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. RESULTS: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). CONCLUSIONS: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

Protecting endangered megafauna through AI analysis of drone images in a low-connectivity setting: a case study from Namibia.

Assessing the numbers and distribution of at-risk megafauna such as the black rhino (Diceros bicornis) is key to effective conservation, yet such data are difficult to obtain. Many current monitoring technologies are invasive to the target animals and expensive. Satellite monitoring is emerging as a potential tool for very large animals (e.g., elephant) but detecting smaller species requires higher resolution imaging. Drones can deliver the required resolution and speed of monitoring, but challenges remain in delivering automated monitoring systems where internet connectivity is unreliable or absent. This study describes a model built to run on a drone to identify in situ images of megafauna. Compared with previously reported studies, this automated detection framework has a lower hardware cost and can function with a reduced internet bandwidth requirement for local network communication. It proposes the use of a Jetson Xavier NX, onboard a Parrot Anafi drone, connected to the internet throughout the flight to deliver a lightweight web-based notification system upon detection of the target species. The GPS location with the detected target species images is sent using MQ Telemetry Transport (MQTT), a lightweight messaging protocol using a publisher/subscriber architecture for IoT devices. It provides reliable message delivery when internet connection is sporadic. We used a YOLOv5l6 object detection architecture trained to identify a bounding box for one of five objects of interest in a frame of video. At an intersection over union (IoU) threshold of 0.5, our model achieved an average precision (AP) of 0.81 for black rhino (our primary target) and 0.83 for giraffe (Giraffa giraffa). The model was less successful at identifying the other smaller objects which were not our primary targets: 0.34, 0.25, and 0.42 for ostrich (Struthio camelus australis), springbok (Antidorcas marsupialis) and human respectively. We used several techniques to optimize performance and overcome the inherent challenge of small objects (animals) in the data. Although our primary focus for the development of the model was rhino, we included other species classes to emulate field conditions where many animal species are encountered, and thus reduce the false positive occurrence rate for rhino detections. To constrain model overfitting, we trained the model on a dataset with varied terrain, angle and lighting conditions and used data augmentation techniques (i.e., GANs). We used image tiling and a relatively larger (i.e., higher resolution) image input size to compensate for the difficulty faced in detecting small objects when using YOLO. In this study, we demonstrated the potential of a drone-based AI pipeline model to automate the detection of free-ranging megafauna detection in a remote setting and create alerts to a wildlife manager in a relatively poorly connected field environment.

Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease.

Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ's microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis. Limiting angiogenesis with endothelial deletion of Vegfr2 (encoding vascular endothelial growth factor (VEGF) receptor 2) curbed emergency hematopoiesis after MI. We noted that bone marrow endothelial cells assumed inflammatory transcriptional phenotypes in all examined stages of cardiovascular disease. Endothelial deletion of Il6 or Vcan (encoding versican), genes shown to be highly expressed in mice with atherosclerosis or MI, reduced hematopoiesis and systemic myeloid cell numbers in these conditions. Our findings establish that cardiovascular disease remodels the vascular bone marrow niche, stimulating hematopoiesis and production of inflammatory leukocytes.