Merging Orthovoltage X-Ray Minibeams spare the proximal tissues while producing a solid beam at the target

© 2019, The Author(s). Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method’s dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM’s low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries

Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery

Short-wavelength collective modes in a binary hard-sphere mixture

We use hard-sphere generalized hydrodynamic equations to discuss the extended hydrodynamic modes of a binary mixture. The theory presented here is analytic and it provides us with a simple description of the collective excitations of a dense binary mixture at molecular length scales. The behavior we predict is in qualitative agreement with molecular-dynamics results for soft-sphere mixtures. This study provides some insight into the role of compositional disorder in forming glassy configurations.Comment: Published; withdrawn since already published. Ordering in the archive gives misleading impression of new publicatio

Exogenous 17-β estradiol administration blunts progression of established angiotensin II-induced abdominal aortic aneurysms in female ovariectomized mice

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice. METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr(−/−) mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx with E2 administration for 2 months of continued AngII infusions. Aortic lumen diameters were quantified by ultrasound and analyzed by linear mixed model, and maximal AAA diameters were analyzed by one-way ANOVA. Atherosclerosis was quantified en face in the aortic arch. AAA tissue sections were analyzed for cellular composition. We quantified effects of E2 on abdominal aortic smooth muscle cell (SMC) growth, α-actin and transforming growth factor-beta (TGF-β) production, and wound healing. RESULTS: Serum E2 concentrations were increased significantly by E2. Aortic lumen diameters increased over time in sham-operated and Ovx (vehicle) females, but not in Ovx females administered E2. At day 70, E2 administration decreased significantly aortic lumen diameters compared to Ovx vehicle and sham-operated females. Compared to Ovx females (vehicle), maximal AAA diameters were reduced significantly by E2. AAA tissue sections from Ovx females administered E2 exhibited significant increases in α-actin and decreases in neutrophils compared to Ovx females administered vehicle. In abdominal aortic SMCs, E2 resulted in a concentration-dependent increase in α-actin, elevated TGF-β, and more rapid wound healing. E2 administration to Ovx females also significantly reduced atherosclerotic lesions compared to sham-operated females. This effect was accompanied by significant reductions in serum cholesterol concentrations. CONCLUSIONS: E2 administration to Ovx females abolished progressive growth and decreased severity of AngII-induced AAAs. These effects were accompanied by increased SMC α-actin, elevated TGF-β, and reduced neutrophils. Similarly, E2 administration reduced AngII-induced atherosclerosis. These results suggest that loss of E2 in post-menopausal females may contribute to progressive growth of AAAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13293-015-0030-1) contains supplementary material, which is available to authorized users

Towards modeling the retailer as a brand: A social construction of the grocery store from the customer standpoint

As a highly customer-sensitive business, retailing is one of the most socially active industries. Nevertheless, when addressing retailers as brands, the retailing literature has failed to account for their unique social orientation, exposing a gap in the literature. This paper utilizes the sociological view of brands to socially construct a conceptual retail brand model from the customer standpoint. An ethnographic study of grocery retailing revealed that the store has, metaphorically, a tree-shaped culture, which can organically model the interplay between building the retailer brand as a culture and the phases constituting the social-self concept

Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm

Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechanism involving ECM cleavage. The murine serine protease inhibitor, Serpina3n (SA3N), is an extracellular inhibitor of GZMB. In the present study, administration of SA3N was assessed using a mouse Angiotensin II-induced AAA model. Mice were injected with SA3N (0–120 μg/kg) before pump implantation. A significant dose-dependent reduction in the frequency of aortic rupture and death was observed in mice that received SA3N treatment compared with controls. Reduced degradation of the proteoglycan decorin was observed while collagen density was increased in the aortas of mice receiving SA3N treatment compared with controls. In vitro studies confirmed that decorin, which regulates collagen spacing and fibrillogenesis, is cleaved by GZMB and that its cleavage can be prevented by SA3N. In conclusion, SA3N inhibits GZMB-mediated decorin degradation leading to enhanced collagen remodelling and reinforcement of the adventitia, thereby reducing the overall rate of rupture and death in a mouse model of AAA

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

Quantitative Mass Spectrometry Analysis Using PAcIFIC for the Identification of Plasma Diagnostic Biomarkers for Abdominal Aortic Aneurysm

BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1-4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions. METHODOLOGY/PRINCIPAL FINDINGS: Pooled human plasma samples of 17 AAA and 17 control patients were depleted of the most abundant proteins and compared using a data-independent shotgun proteomic strategy, Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with spectral counting and isobaric tandem mass tags. Both quantitative methods collectively identified 80 proteins as statistically differentially abundant between AAA and control patients. Among differentially abundant proteins, a subgroup of 19 was selected according to Gene Ontology classification and implication in AAA for verification by Western blot (WB) in the same 34 individual plasma samples that comprised the pools. From the 19 proteins, 12 were detected by WB. Five of them were verified to be differentially up-regulated in individual plasma of AAA patients: adiponectin, extracellular superoxide dismutase, protein AMBP, kallistatin and carboxypeptidase B2. CONCLUSIONS/SIGNIFICANCE: Plasma depletion of high abundance proteins combined with quantitative PAcIFIC analysis offered an efficient and sensitive tool for the screening of new potential biomarkers of AAA. However, WB analysis to verify the 19 PAcIFIC identified proteins of interest proved inconclusive save for five proteins. We discuss these five in terms of their potential relevance as biological markers for use in AAA screening of population at risk