Theoretical study of the structural stability, electronic and magnetic properties of XVSb (X == Fe, Ni, and Co) half-Heusler compounds

The structural, electronic and magnetic properties of half-Heusler compounds XVSb (X $=$ Fe, Co and Ni) are investigated by using the density functional theory with generalized gradient approximation (GGA), and Tran-Blaha modified Becke-Johnson (TB-mBJ) exchange potential approximation. It is found that the half-metallic gaps are generally reasonably widened by mBJ as compared to the GGA approximation. The magnetic proprieties of XVSb (X $=$ Fe, Co and Ni) are well defined within mBJ with an exact integer value of magnetic moment. The band gaps given by TB-mBJ are in good agreement with the available theoretical data. The FeVSb exhibits a semiconductor nature. The CoVSb and NiVSb present half-metallic behaviour with total magnetic moment of $1\mu_\text{B}$ and $2\mu_\text{B}$ in good agreement with Slater-Pauling rule. These alloys seem to be a potential candidate of spintronic devices.Comment: 9 pages, 5 figure

Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors

Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

Purpose: 153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Methods: Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg 153Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before 153Sm-EDTMP treatment. Urine was collected 48 h after injection of 153Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of 153Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. Results: The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4±11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9±10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both perprotocol (n=13) and full-analysis sets (n=18). Toxicity was comparable to of monotherapy with 153Sm-EDTMP. Conclusion: Zoledronic acid treatment does not influence 153Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe

Prospective assessment of CYP2D6 by genotyping, phenotyping and measurement of tamoxifen, PD 05-09 4-hydroxy-tamoxifen and endoxifen in breast cancer patients treated with tamoxifen.

Tamoxifen (tam) is a widely used endocrine therapy in the treatment of early and advanced stage breast cancer in women and men. It is a pro-drug having weak affinity with the estrogen receptor and needs to be converted to its main metabolite, endoxifen (endox), to have full anticancer activity. Cytochrome 2D6 (CYP2D6) plays a major role in the metabolism of tamoxifen to endoxifen. It is genetically highly polymorphic and its activity influences profoundly the synthesis of endoxifen and potentially the efficacy of tamoxifen treatment. Genotyping is currently the most widely used approach in studies and also in clinical practice to categorize patients as poor- (PM), intermediate- (IM), extensive- (EM) and ultra rapid-metabolizers (UM). Some clinicians already use genotyping in order to tailor the endocrine therapy of their patients. Owing to the large inter-individual variations in concentrations of the active moitey due to genetic and non-genetic influences renders the predictive value of the test uncertain for an individual patient. A significant number of patients classified as EM or IM by genotyping have indeed relatively low endoxifen levels similar to PMs1. This suggests that genotyping is probably not the opti ma l meth o d f or predi cti ng end oxif en l evels

Plasma cholesterol levels and brain development in preterm newborns.

BackgroundTo assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.MethodsSixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.ResultsEarly plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.ConclusionsHigher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes

Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells

Ventralization, a major patterning process in the developing vertebrate neural tube (central nervous system, CNS), depends on Sonic hedgehog (SHH) as a main signaling morphogen. We studied the CNS of late larval and young adult zebrafish in a transgenic shh‐GFP line revealing increased neuroanatomical detail due to the progressed differentiation state compared to earlier stages. Some major findings emerge from the present study. (a) shh –GFP is still expressed along the adult zebrafish CNS neuraxis in most locations seen in larvae. (b) We newly identify a ventroposterior shh pallidal domain representing the basal telencephalic signaling center important for basal ganglia development known in other vertebrates (i.e., the anterior entopeduncular area—basal medial ganglionic eminence of mammals). (c) We further show late‐emerging shh‐GFP positive radial glia cells in the medial zone of the dorsal telencephalon (i.e., the teleostan pallial amygdala). (d) Immunostains for tyrosine hydroxylase demonstrate that there is selective colocalization in adult dopamine cells with shh‐GFP in the posterior tuberculum, including in projection cells to striatum, which represents a striking parallel to amniote mesodiencephalic dopamine cell origin from shh expressing floor plate cells. (e) There is no colocalization of shh and islet1 as shown by respective shh‐GFP and islet1‐GFP lines. (f) The only radially far migrated shh‐GFP cells are located in the preglomerular area. (g) There are no adult cerebellar and tectal shh‐GFP cells confirming their exclusive role during early development as previously reported by our laboratory

Paradoxical embolism following thromboaspiration of an arteriovenous fistula thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Paradoxical embolism is an increasingly reported cause of arterial embolism. Several embolic sources have been described, but thrombosis of an arteriovenous fistula as a paradoxical emboligenic source has not, to the best of our knowledge, been reported.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian woman received a renal graft for primary hyperoxaluria. After transplantation, she was maintained on daily hemodialysis. Thrombosis of her arteriovenous fistula occurred two weeks post-transplantation and was treated by thromboaspiration, which was partially successful. During a hemodialysis session immediately following thromboaspiration, she developed a coma with tetraplegia requiring intensive cardiorespiratory resuscitation. Brain magnetic resonance imaging revealed various hyperdense areas in the vertebrobasilar territory resulting from bilateral occlusion of posterior cerebral arteries. Transesophageal echocardiographic examination showed a patent foramen ovale, while pulse echography of the arteriovenous fistula revealed the persistence of extensive clots that were probably the embolic source. A paradoxical embolus through a patent foramen ovale was suggested because of the proximity of the neurological event to the thrombectomy procedure.</p> <p>Conclusions</p> <p>The risk of paradoxical embolism in a hemodialyzed patient with a patent foramen ovale deserves consideration and requires careful evaluation in situations of arteriovenous fistula thrombosis.</p