Detailing radio frequency heating induced by coronary stents: a 7.0 tesla magnetic resonance study

The sensitivity gain of ultrahigh field Magnetic Resonance (UHF-MR) holds the promise to enhance spatial and temporal resolution. Such improvements could be beneficial for cardiovascular MR. However, intracoronary stents used for treatment of coronary artery disease are currently considered to be contra-indications for UHF-MR. The antenna effect induced by a stent together with RF wavelength shortening could increase local radiofrequency (RF) power deposition at 7.0 T and bears the potential to induce local heating, which might cause tissue damage. Realizing these constraints, this work examines RF heating effects of stents using electro-magnetic field (EMF) simulations and phantoms with properties that mimic myocardium. For this purpose, RF power deposition that exceeds the clinical limits was induced by a dedicated birdcage coil. Fiber optic probes and MR thermometry were applied for temperature monitoring using agarose phantoms containing copper tubes or coronary stents. The results demonstrate an agreement between RF heating induced temperature changes derived from EMF simulations versus MR thermometry. The birdcage coil tailored for RF heating was capable of irradiating power exceeding the specific-absorption rate (SAR) limits defined by the IEC guidelines by a factor of three. This setup afforded RF induced temperature changes up to +27 K in a reference phantom. The maximum extra temperature increase, induced by a copper tube or a coronary stent was less than 3 K. The coronary stents examined showed an RF heating behavior similar to a copper tube. Our results suggest that, if IEC guidelines for local/global SAR are followed, the extra RF heating induced in myocardial tissue by stents may not be significant versus the baseline heating induced by the energy deposited by a tailored cardiac transmit RF coil at 7.0 T, and may be smaller if not insignificant than the extra RF heating observed under the circumstances used in this study

Illness trajectory from prodromal symptoms to incident bipolar disorder and schizophrenia

Background: The concept of prodrome is highly variable but, when applied retrospectively in cohorts who progress to meet diagnostic criteria for bipolar disorder (BD) and schizophrenia (SZ), it can contribute to clarify early origins and trajectory of the illness. In the context of race and ethnicity, studies with population-based and registry-based cohorts, such as the Rochester Epidemiology Project (REP), can potentially identify, through retrospective assessment of the prodromes of BD and SZ, differences while addressing the heterogeneous nature of the illness. Objective: We aim to describe and compare the illness trajectories of individuals with BD or SZ prior to the incident case. Additionally, we assessed for differences in access to healthcare in racially diverse patients and within those with schizophrenia, we sought to analyze differences in prodrome duration based on place of birth (U.S. born vs. foreign born). Methods: Using a records-linkage system from Minnesota, we searched for subjects born after 1985 that had been diagnosed with BD or SZ. Cases were ascertained for diagnosis and identification of the first episode of mania or psychosis. Using the medical records we extracted data from their medical history prior to their first episode. Results: We identified 205 cases with the first episode of psychosis or mania (SZ = 131; BD = 74). The mean age of onset for BD was 21.34 years and 20.45 years for SZ. We did not find a difference between the mean duration of the trajectory of mental health problems to a first episode. Both disorders were preceded by high healthcare utilization and had similar rates of psychiatric diagnoses, substance use, and prescriptions of psychiatric medications. SZ was more common in Non-white patients and in immigrants and BD had a higher rate of depressive disorder and adjustment disorders. Conclusions: Results from this study provide critical information on social and clinical features that precede a first manic or psychotic episode that may help early illness detection, identification of individuals at high risk of BD and SZ and address health disparities

The Italian Response to the COVID-19 Crisis: Lessons Learned and Future Direction in Social Development:

Against the backdrop of a continuously changing situation, the aim of this paper is to discuss the impact of COVID-19 crisis in Italy, the government response to cope with the crisis and the major lessons learned during its management. The analysis shows how Italy's response has been characterised by some rapid measures to tackle the health crisis, but few plans in the mitigation stage and a lack of community involvement. This contribution stress the importance of a cultural shift, through the effort to apply in practice the principles already indicated in the main global policy frameworks to guide disaster management. A community social development approach can help to build concrete actions in this direction

Ablation of NG2 Proteoglycan Leads to Deficits in Brown Fat Function and to Adult Onset Obesity

Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O2 consumption and CO2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator (PGC)1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes

Connective tissue growth factor is induced in bleomycin-induced skin scleroderma

The origin of fibrotic cells within connective tissue is unclear. For example, the extent to which microvascular pericytes contribute to the number of myofibroblasts present in dermal fibrosis in uncertain. Connective tissue growth factor (CTGF/CCN2) is a marker and mediator of fibrosis. In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, α-smooth muscle actin (α-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were α−SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma

Biomaterials Approaches to Combating Oral Biofilms and Dental Disease

Background: Possibilities for biomaterials to impact the dental caries epidemic are reviewed with emphasis placed on novel delivery biomaterials and new therapeutic targets

In Situ Dividing and Phagocytosing Retinal Microglia Express Nestin, Vimentin, and NG2 In Vivo

BACKGROUND: Following injury, microglia become activated with subsets expressing nestin as well as other neural markers. Moreover, cerebral microglia can give rise to neurons in vitro. In a previous study, we analysed the proliferation potential and nestin re-expression of retinal macroglial cells such as astrocytes and Müller cells after optic nerve (ON) lesion. However, we were unable to identify the majority of proliferative nestin(+) cells. Thus, the present study evaluates expression of nestin and other neural markers in quiescent and proliferating microglia in naïve retina and following ON transection in adult rats in vivo. METHODOLOGY/PRINCIPAL FINDINGS: For analysis of cell proliferation and cells fates, rats received BrdU injections. Microglia in retinal sections or isolated cells were characterized using immunofluorescence labeling with markers for microglia (e.g., Iba1, CD11b), cell proliferation, and neural cells (e.g., nestin, vimentin, NG2, GFAP, Doublecortin etc.). Cellular analyses were performed using confocal laser scanning microscopy. In the naïve adult rat retina, about 60% of resting ramified microglia expressed nestin. After ON transection, numbers of nestin(+) microglia peaked to a maximum at 7 days, primarily due to in situ cell proliferation of exclusively nestin(+) microglia. After 8 weeks, microglia numbers re-attained control levels, but 20% were still BrdU(+) and nestin(+), although no further local cell proliferation occurred. In addition, nestin(+) microglia co-expressed vimentin and NG2, but not GFAP or neuronal markers. Fourteen days after injury and following retrograde labeling of retinal ganglion cells (RGCs) with Fluorogold (FG), nestin(+)NG2(+) microglia were positive for the dye indicating an active involvement of a proliferating cell population in phagocytosing apoptotic retinal neurons. CONCLUSIONS/SIGNIFICANCE: The current study provides evidence that in adult rat retina, a specific resident population of microglia expresses proteins of immature neural cells that are involved in injury-induced cell proliferation and phagocytosis while transdifferentiation was not observed

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

Here, we identify CD44(+)CD90(+)CD73(+)CD34(−)CD45(−) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes

The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells

Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain

In Vitro Model of Vascularized Bone: Synergizing Vascular Development and Osteogenesis

Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1∶1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1∶1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell – osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis