Fabrication of Lead Free Borate Glasses Modified by Bismuth Oxide for Gamma Ray Protection Applications

In the present work, bismuth borate glass samples with the composition of (99-x) B₂O₃ + 1Cr₂O₃ + (x) Bi₂O₃ (x = 0, 5, 10, 15, 20, and 25 wt %) were prepared using the melt quenching technique. The mass attenuation coefficient (MAC) of the prepared glass samples was measured through a narrow beam technique using a NaI(Tl) scintillation detector. Four point sources were used (²⁴¹Am, ¹³³Ba, ¹⁵²Eu, and ¹³⁷Cs) to measure the MAC for the prepared glasses. The experimental data were compared with the theoretical results obtained from the XCOM, and it was shown that for all samples at all tested energies, the relative deviation between the samples is less than 3%. This finding signifies that the experimental data can adequately be used to evaluate the shielding ability of the glasses. The MAC of the sample with x = 25 wt % was compared with different lead borate glasses and the results indicated that the present sample has high attenuation which is very close to commercial lead borate glasses. We determined the transmission factor (TF), and found that it is small at low energies and increases as the energy increases. The addition of Bi₂O₃ leads to reduction in the TF values, which improves the shielding performance of the glass system. The half value layer (HVL) of the BCrBi-10 sample was 0.400 cm at 0.595 MeV, 1.619 cm at 0.2447 MeV, and 4.946 cm at 1.4080 MeV. Meanwhile, the HVL of the BCrBi-20 sample is equal to 0.171 and 4.334 cm at 0.0595 and 1.4080 MeV, respectively. The HVL data emphasize that higher energy photons tend to penetrate through the glasses with greater ease than lower energy photons. Furthermore, the fast neutron removable cross section (FNRC) was determined for the present samples and compared with lead borate glass and concrete, and the results showed a remarkable superiority of the bismuth borate glass samples.     

Metastatic Disease to the Clivus Mimicking Clival Chordomas

Objectives/Hypothesis A comprehensive review of the literature of clival metastases and presentation of two additional cases.Study Design Literature review and report of two cases.Methods A literature review of the MEDLINE database (1950 to January 19, 2013) was performed to identify all cases of patients with metastatic disease to the clivus. Additionally, two novel cases are presented.Results In total, 47 cases were identified in the literature, including the two cases presented in this study. Metastatic disease to the clivus is the initial presenting symptom of the primary malignancy in 36% (13/36) of the cases. When there was a history of malignancy, the median interval of time to clival metastases was 24 months (range 1 to 172 months). Clinical symptoms manifested often as cranial neuropathies, with at least abducens palsies as the initial presenting symptom in 61.9% (26/42) of patients. Tumor pathology was diverse, but several pathologies were seen more commonly: prostate carcinoma (18.1%, 9/47), hepatocellular carcinoma (10.6%, 5/47), and thyroid follicular carcinoma (8.5%, 4/47).Conclusion Although clival metastases are extremely rare, they are an important part of the differential of clival masses as they can be the presenting symptom of distant malignancy.Level of Evidence 4.     

Cost analysis and risk factors for interval cholecystectomy after bariatric surgery: a national study

Background

Besides rate and extent of weight loss, little is known regarding demographic factors predicting interval cholecystectomy (IC) after bariatric surgery and its incremental costs.

Postoperative Care Fragmentation Is Associated with Increased 30-Day Mortality after Bariatric Surgery

Background

Compromised access following bariatric centers-or-excellence designations may have led to increased incidence of non-index readmissions and worsened care fragmentation. We seek to evaluate risk factors and impact of non-index readmissions on short-term mortality during readmission using a national bariatric registry data from 2015.

Methods

A retrospective cohort study was performed using a national clinical database. Multivariate logistic regression models were developed to quantify association between non-index readmissions and 30-day mortality among bariatric patients with 30-day readmissions.

Results

A total of 4704 patients were identified as undergoing bariatric surgery and readmitted within 30 days. Of these, 325 (6.9%) patients were readmitted to a non-index facility while the rest were hospitalized at the original hospital. Patient characteristics were largely similar between the two comparison groups, although patients with in-hospital complications and non-home disposition during the initial stay were more likely to experience non-index readmissions. Multivariate regression demonstrated that non-index readmission was associated with an adjusted odds ratio of 4.4 for 30-day mortality (95% confidence interval 2.6–9.2, p?<?0.01). The most common reason for mortality for both index and non-index readmissions was pulmonary embolism.

Conclusions

Care fragmentation may lead to increased 30-day mortality during readmissions following bariatric surgery. Heightened vigilance and longitudinal follow-up planning is recommended for patients with elevated risk for venous thromboembolism.

     

Fn14-TRAIL,a Chimeric Intercellular Signal Exchanger,Attenuates Experimental Autoimmune Encephalomyelitis

Hallmarks of the pathogenesis of autoimmune encephalomyelitis include perivascular infiltration of inflammatory cells into the central nervous system, multifocal demyelination in the brain and spinal cord, and focal neuronal degeneration. Optimal treatment of this complex disease will ultimately call for agents that target the spectrum of underlying pathogenic processes. In the present study, Fn14-TRAIL is introduced as a unique immunotherapeutic fusion protein that is designed to exchange and redirect intercellular signals within inflammatory cell networks, and, in so doing, to impact multiple pathogenic events and yield a net anti-inflammatory effect. In this soluble protein product, a Fn14 receptor component (capable of blocking the pro-inflammatory TWEAK ligand) is fused to a TRAIL ligand (capable of inhibiting activated, pathogenic T cells). Sustained Fn14-TRAIL expression was obtained in vivo using a transposon-based eukaryotic expression vector. Fn14-TRAIL expression effectively prevented chronic, nonremitting, paralytic disease in myelin oligodendrocyte glycoprotein-challenged C57BL/6 mice. Disease suppression in this model was reflected by decreases in the clinical score, disease incidence, nervous tissue inflammation, and Th1, Th2, and Th17 cytokine responses. Significantly, the therapeutic efficacy of Fn14-TRAIL could not be recapitulated simply by administering its component parts (Fn14 and TRAIL) as soluble agents, either alone or in combination. Its functional pleiotropism was manifest in its additional ability to attenuate the enhanced permeability of the blood-brain barrier that typically accompanies autoimmune encephalomyelitis.Despite a steadily expanding set of treatment options for multiple sclerosis (MS), there remains a pressing need for more effective therapeutic agents to address this debilitating autoimmune disorder of the central nervous system (CNS). Although the precise etiology of MS is unknown, key features of its pathogenesis and clinical evolution are emerging.^1,2,3 Among various immune cellular effectors that have been implicated, pathogenic T cells loom large as pivotal drivers of the disease. As a consequence, various therapeutic paths are converging on T effectors as targets, with complementary goals of blocking their activation and re-activation, eliminating them from the larger T-cell reservoir, and interfering with their transit to sites of pathogenesis within the CNS.A complex interplay of positive and negative intercellular signals regulates activation and maintenance of T-cell effector functions. Proteins of the tumor necrosis factor (TNF) superfamily figure prominently in this matrix of signals, bridging various cells of the immune system, as well as to cells of other organ systems. In so doing, TNF superfamily members contribute to both tissue homeostasis and pathogenesis via effects on cell survival and death, cellular differentiation, and inflammation.^4,5 From the standpoint of autoimmune pathogenesis, two especially interesting members of the TNF superfamily are the cell surface ligands TWEAK (TNF-related weak inducer of apoptosis)^6,7 and TRAIL (TNF-related apoptosis-inducing ligand).^8,9,10,11 TWEAK, a TNF superfamily ligand, and its counter-receptor Fn14 (fibroblast growth factor-inducible 14-kDa protein) are expressed in a range of immune and nonimmune cell types. TWEAK, which is expressed on cells such as macrophages, dendritic cells, NK cells, endothelial cells, microglial cells, and astrocytes,^6,12,13 stimulates proliferation of astrocytes and endothelial cells, as well as production of various inflammatory cytokines, chemokines, and adhesion molecules.^{14,15,16,17,18,19} Moreover, the TWEAK:Fn14 signaling axis has pro-inflammatory effects that go beyond promoting cell proliferation and cytokine production, some of which tie into autoimmune pathogenesis. TWEAK, whose endogenous expression is elevated in the CNS during experimental autoimmune encephalitis (EAE), a murine model for MS, increases the permeability of the neurovascular unit,²⁰ contributing in this way to perivascular inflammatory cell infiltration. Moreover, TWEAK has pro-angiogenic activity,²¹ which is of interest given the association between angiogenesis and autoimmune pathogenesis.²² TWEAK increases EAE severity and associated neurodegeneration,^14,23,24 and circulating TWEAK levels are significantly increased in patients with MS and other chronic inflammatory diseases.⁶ The induction of inhibitory anti-TWEAK or Fn14 antibody (Ab) in vivo, via vaccination with the extracellular domains of either TWEAK or Fn14, ameliorates EAE manifestations in rat and mouse models.²⁵TRAIL, a TNF superfamily ligand, binds to several different cognate TNF receptor superfamily receptors, some activating and others decoy. The activating receptors in humans are TRAIL-R1(DR4), TRAIL-R2 (DR5), and osteoprotegrin, whereas in mice, the sole activating receptor is DR5. Virtually all cells of the immune system (including T cells, B cells, natural killer cells, dendritic cells, monocytes, and granulocytes) up-regulate surface TRAIL ligand and/or release soluble TRAIL in response to interferon and other activation signals. TRAIL receptors are primarily expressed on immune cells, such as activated T cells.^8,26 Native TRAIL expression attenuates EAE, as is evident from experiments invoking genetic deletion of TRAIL (in TRAIL^−/− knockout mice) or administration of TRAIL blocking agents [soluble TRAIL receptor (sDR5) or neutralizing anti-TRAIL mAb].^27,28,29 Moreover, embryonic stem cell-derived dendritic cells with enforced co-expression of TRAIL and pathogenic myelin oligodendrocyte glycoprotein (MOG) protein suppress EAE induction.³⁰ Interestingly, soluble TRAIL has emerged as a response marker in MS patients undergoing interferon (IFN)-β therapy,³¹ with those most likely to respond to treatment showing early and sustained soluble TRAIL induction after therapeutic cytokine administration.Based on this intriguing constellation of activities associated with the TWEAK:Fn14 and TRAIL:TRAIL-R signaling axes, which impact immunological responses and inflammatory processes, we have now designed an Fn14-TRAIL fusion protein that bridges them. The Fn14 component of this fusion protein has the capacity to bind and block endogenous TWEAK, whereas the TRAIL ligand component, once anchored to TWEAK-bearing cells via the Fn14 bridge, can direct intercellular inhibitory signals to its cognate receptors on TRAIL receptor-bearing cells, such as activated T cells.Fn14-TRAIL is in essence exchanging TWEAK pro-inflammatory signals into immunoinhibitory TRAIL-driven ones. However, in contrast to another fusion protein that alters intercellular signals, the trans signal converter protein CTLA-4-FasL,^32,33,34,35 Fn14-TRAIL is designed to redirect an exchanged negative signal to third-party (TRAIL receptor-bearing) cells. Furthermore, by virtue of the highly pleiotropic functionality of the TRAIL:TRAIL-R and TWEAK:Fn14 signaling axes, Fn14-TRAIL has inherently greater potential for higher order functionality with a net anti-inflammatory output. The present study begins to explore this fusion protein’s functional repertoire by demonstrating Fn14-TRAIL’s capacity to ameliorate MOG-induced EAE.     

Mitochondrial effects of estrogen are mediated by estrogen receptor alpha in brain endothelial cells

Mitochondrial reactive oxygen species (ROS) and endothelial dysfunction are key contributors to cerebrovascular pathophysiology. We previously found that 17beta-estradiol profoundly affects mitochondrial function in cerebral blood vessels, enhancing efficiency of energy production and suppressing mitochondrial oxidative stress. To determine whether estrogen specifically affects endothelial mitochondria through receptor mechanisms, we used cultured human brain microvascular endothelial cells (HBMECs). 17beta-Estradiol treatment for 24 h increased mitochondrial cytochrome c protein and mRNA; use of silencing RNA for estrogen receptors (ERs) showed that this effect involved ERalpha, but not ERbeta. Mitochondrial ROS were determined by measuring the activity of aconitase, an enzyme with an iron-sulfur center inactivated by mitochondrial superoxide. 17beta-Estradiol increased mitochondrial aconitase activity in HBMECs, indicating a reduction in ROS. Direct measurement of mitochondrial superoxide with MitoSOX Red showed that 17beta-estradiol, but not 17alpha-estradiol, significantly decreased mitochondrial superoxide production, an effect blocked by the ER antagonist, ICI-182,780 (fulvestrant). Selective ER agonists demonstrated that the decrease in mitochondrial superoxide was mediated by ERalpha, not ERbeta. The selective estrogen receptor modulators, raloxifene and 4-hydroxy-tamoxifen, differentially affected mitochondrial superoxide production, with raloxifene acting as an agonist but 4-hydroxy-tamoxifen acting as an estrogen antagonist. Changes in superoxide by 17beta-estradiol could not be explained by changes in manganese superoxide dismutase. Instead, ERalpha-mediated decreases in mitochondrial ROS may depend on the concomitant increase in mitochondrial cytochrome c, previously shown to act as an antioxidant. Mitochondrial protective effects of estrogen in cerebral endothelium may contribute to sex differences in the occurrence of stroke and other age-related neurodegenerative diseases.     

Acoustic analysis for a split MRI system using FE method

In some MRI‐LINAC (Magnetic Resonance Imaging and Linear Accelerator) hybrid systems, the MRI scanner is split into two parts to form a central gap for the accommodation of the patient or a LINAC. Little is known about the acoustic characteristics of the split gradient coil structure needed for this system; however, it is believed to be very different from its typical configurations. It is important to develop dedicated numerical methods for the characterization of the unique acoustic properties, to provide engineering solutions for the noise attenuation for such a new system. In this article, we modeled the acoustic fields of a split MRI system and traditional gradient structures using the finite element method. The models were validated against acoustic experimental results obtained from a conventional MRI scanner. The acoustic field distribution analysis showed that the average sound pressure levels in the central gap were lower than those in the cylindrical tunnels of the split MRI system at most frequencies. This was also true when both the x coils or z coils were energized independently. Thus, if the patient bed is placed perpendicular to the axis of the main magnet of the split MRI system, the patient will be subjected to relatively lower acoustic intensities compared with that if the patient bed is placed parallel to the axis of the main magnet. Further work is planned to reduce the sound level in the central gap where the patient bed may be placed for this split system. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 85–96, 2015     

Frequency of Brugada-type ECG pattern (Brugada sign) in Southern Turkey

The frequency of Brugada sign was found to differ among ethnic groups. Yet, there is no data regarding the prevalence of Brugada syndrome and sign in our country. The aim of this study was to determine the frequency of a Brugada-type electrocardiogram (ECG) pattern in southern Turkey. A total of 1,238 subjects (males, 671, females, 567) were included in the study. The previously archived ECGs of 807 subjects without any evidence of structural heart disease were chosen randomly and evaluated. In addition, prospective analysis of the ECGs of 431 subjects (males, 293, females, 138) randomly chosen from healthy university students were also included. The mean age was 38.9 +/- 17.6 years. Six subjects (0.48%) had a Brugada-type ECG pattern. One (0.08%) of them had the coved-type and 5 (0.40%) had the saddleback-type. All subjects were asymptomatic. A Brugada-type ECG pattern was obtained in 1 (0.17%) female and in 5 (0.74%) males (OR: 4.2 CI: 0.5-36.4, P = 0.2). The Brugada-type ECG pattern frequency was 0.12% in subjects >or= 25 years old and 1.16% in subjects between 17-24 years old (OR: 9.4 CI: 1.1-81.2, P = 0.02). Young males between 17-24 years had the highest (1.70%) frequency. The results indicate that the frequency of the Brugada-type ECG pattern was 0.48% in the general population, being more prevalent in young males in our region. These results are similar to the findings of studies performed in other countries.