Discussion: “Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties” (Rowland, E. M., Mohamied, Y., Chooi, K. Y., Bailey, E. L., and Weinberg, P. D., 2015, ASME J. Biomech. Eng., 137(10), p. 101003): An Alternative Approach Using Segmentation Based on Local Hemodynamics

The biological response of living arteries to mechanical forces is an important component of the atherosclerotic process and is responsible, at least in part, for the well-recognized spatial variation in atherosusceptibility in man. Experiments to elucidate this response often generate maps of force and response variables over the arterial surface, from which the force–response relationship is sought. Rowland et al. discussed several statistical approaches to the spatial autocorrelation that confounds the analysis of such maps and applied them to maps of hemodynamic stress and vascular response obtained by averaging these variables in multiple animals. Here, we point out an alternative approach, in which discrete surface regions are defined by the hemodynamic stress levels they experience, and the stress and response in each animal are treated separately. This approach, applied properly, is insensitive to autocorrelation and less sensitive to the effect of confounding hemodynamic variables. The analysis suggests an inverse relation between permeability and shear that differs from that in Rowland et al. Possible sources of this difference are suggested

PTPσ inhibitors promote hematopoietic stem cell regeneration.

Receptor type protein tyrosine phosphatase-sigma (PTPσ) is primarily expressed by adult neurons and regulates neural regeneration. We recently discovered that PTPσ is also expressed by hematopoietic stem cells (HSCs). Here, we describe small molecule inhibitors of PTPσ that promote HSC regeneration in vivo. Systemic administration of the PTPσ inhibitor, DJ001, or its analog, to irradiated mice promotes HSC regeneration, accelerates hematologic recovery, and improves survival. Similarly, DJ001 administration accelerates hematologic recovery in mice treated with 5-fluorouracil chemotherapy. DJ001 displays high specificity for PTPσ and antagonizes PTPσ via unique non-competitive, allosteric binding. Mechanistically, DJ001 suppresses radiation-induced HSC apoptosis via activation of the RhoGTPase, RAC1, and induction of BCL-XL. Furthermore, treatment of irradiated human HSCs with DJ001 promotes the regeneration of human HSCs capable of multilineage in vivo repopulation. These studies demonstrate the therapeutic potential of selective, small-molecule PTPσ inhibitors for human hematopoietic regeneration

Uncertainty quantification of wall shear stress in intracranial aneurysms using a data-driven statistical model of systemic blood flow variability

Adverse wall shear stress (WSS) patterns are known to play a key role in the localisation, formation, and progression of intracranial aneurysms (IAs). Com- plex region-specific and time-varying aneurysmal WSS patterns depend both on vascular morphology as well as on variable systemic ow conditions. Com- putational uid dynamics (CFD) has been proposed for characterising WSS patterns in IAs; however, CFD simulations often rely on deterministic bound- ary conditions that are not representative of the actual variations in blood ow. We develop a data-driven statistical model of internal carotid artery (ICA) ow, which is used to generate a virtual population of waveforms used as inlet bound- ary conditions in CFD simulations. This allows the statistics of the resulting aneurysmal WSS distributions to be computed. It is observed that ICA wave- form variations have limited in uence on the time-averaged WSS (TAWSS) on the IA surface. In contrast, in regions where the ow is locally highly multidi- rectional, WSS directionality and harmonic content are strongly affected by the ICA ow waveform. As a consequence, we argue that the effect of blood ow variability should be explicitly considered in CFD-based IA rupture assessment to prevent confounding the conclusions

X-ray and MR contrast bearing nanoparticles enhance the therapeutic response of image-guided radiation therapy for oral cancer

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models. METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated. RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a dose-dependent manner. Magnetic resonance images depicted optimal tumor-to-background uptake at 4 h post injection. Theranostic nanoparticle + Radiation treated rats experienced reduced tumor growth compared to controls, and reduction in lung metastasis. CONCLUSIONS: Theranostic nanoparticles enable preprocedure radiotherapy planning, as well as enhance radiation treatment efficacy for head and neck tumors

3D time-varying simulations of Ca2+ dynamics in arterial coupled cells: A massively parallel implementation

Preferential locations of atherosclerotic plaque are strongly associated with the areas of low wall shear stress and disturbed haemodynamic characteristics such as flow detachment, flow recirculation and oscillatory flow. The areas of low wall shear stress are also associated with the reduced production of adenosine triphosphate in the endothelial layer, as well as the resulting reduced production of inositol trisphosphate (IP3). The subsequent variation in Ca2+ signalling and nitric oxide synthesis could lead to the impairment of the atheroprotective function played by nitric oxide. In previous studies, it has been suggested that the reduced IP3 and Ca2+ signalling can explain the correlation of atherosclerosis with induced low WSS and disturbed flow characteristics. The massively parallel implementation described in this article provides insight into the dynamics of coupled smooth muscle cells and endothelial cells mapped onto the surface of an idealised arterial bifurcation. We show that variations in coupling parameters, which model normal and pathological conditions, provide vastly different smooth muscle cell Ca2+ dynamics and wave propagation profiles. The extensibility of the coupled cells model and scalability of the implementation provide a solid framework for in silico investigations of the interaction between complex cellular chemistry and the macro-scale processes determined by fluid dynamics

Obesity Indicators and C - reactive Protein in African and Haitian Americans with and without Type 2 Diabetes

Purpose: High sensitivity C-reactive protein (CRP) is a risk factor for cardiovascular disease based on finding in primarily non-Hispanic White populations. Obesity, another risk factor for cardiovascular disease, is higher in Blacks as compared to non-Hispanic Whites. The objective of this study was to assess the relationship between CRP, a marker of systemic inflammation, and obesity indicators by ethnicity, diabetes status and gender for two Black ethnicities. Methods: Anthropometrics and venous blood were collected for African and Haitian Americans with and without type 2 diabetes in a cross-sectional study. A total of 434 participants; 190 African Americans, 244 Haitian Americans, met the inclusion criteria of CRP ≤10 mg/L. Main effects and interactions of ethnicity, diabetes status, gender, and each obesity indicator (waist circumference, waist-to-height ratio, and body mass index) were performed using General Linear Models. Results: African Americans were more likely to be obese, have higher CRP, and smoke as compared to Haitian Americans. Haitian Americans has a lower rate of health care coverage than African American. Having a higher education level than Haitian Americans was a protective health factor for African Americans; whereas, Haitian Americans were protected by a higher percent married as compared to African Americans. All obesity indicators were associated with CRP. All differences in CRP by ethnicity and diabetes status were negated by obesity indicators. Being female was associated with higher CRP for waist circumference and BMI models. Adjusting for health insurance, smoking, marital status and education negated the relationship of gender and CRP for waist-to- height ratio. Conclusion: Being African American as opposed to Haitian American was a greater risk factor for obesity and inflammation. Obesity was associated with elevated CRP levels in African and Haitian Americans regardless of diabetes status. Inflammation constitutes a serious health problem for minorities with high rates of obesity

Contexto bioético de la venta de misoprostol en las farmacias y boticas del Perú

La presente es una investigación bibliográfica y tuvo como objetivos describir, comprender y analizar el contexto bioético de la venta del misoprostol en las farmacias y boticas del Perú. Se analizó la documentación científica así como oficial de instituciones públicas y privadas, nacionales e internacionales, como los riesgos para la salud y vida de la mujer del uso del misoprostol de manera clandestina, la vigencia de este medicamento en las terapias como protector de la mucosa gástrica, su venta en las farmacias y boticas de manera oficial y clandestina. Los resultados indicaron que sí existen por la venta del misoprostol al público transgresiones contra principios bioéticos y regulatorios que ponen en riesgo la vida y la salud de la mujer y del concebido. Las conclusiones proponen alternativas a los problemas bioéticos que plantea este medicamento en su venta en farmacias y boticas del Perú.Tesi

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool