Inflammatory Pseudotumor of the Liver Complicated by Lung Necrosis and Pleural Empyema: A Case Report

Inflammatory pseudotumor of the liver (IPTL) is a rare condition, but an important differential diagnosis of hepatic space-occupying lesions. It may regress spontaneously and mimic other liver tumors. Complications are usually intrahepatic. Herein, we present a case of IPTL which developed pleural empyema and lung necrosis as an uncommon complication

Living Donor Liver Transplantation for Caroli's Disease: A Report of Two Cases

Caroli's disease (CD) is a rare autosomal recessive disorder characterized by intrahepatic cystic dilatation of the bile ducts. Patients with bilobar or progressive disease may require orthotopic liver transplantation (OLT). In the MELD era, living donor liver transplantation (LDLT) raised as the ultimate treatment option for these patients, once their MELD score is usually low. Herein, we describe 2 cases of patients (a 2-year-old girl and a 19-year-old teenager) that successfully underwent LDLT as a treatment for diffuse CD. The good postoperative courses of the two cases indicate that LDLT is a feasible option in the treatment of this disorder, even in complicated or early age patients

Health economics: identifying leading producers, countries relative specialization and themes

El área de investigación en economía de la salud tuvo una gran evolución a partir de la década de 1960 y está en constante crecimiento. Actualmente, el gasto en salud es un tema clave en todo el mundo. La bibliometría proporciona varios métodos para explorar el impacto y la evolución de la investigación. Así pues, el principal objetivo del presente estudio es comprender la situación actual de la investigación en materia de economía de la salud para el período 2010-2019. Se analizaron tres aspectos diferentes: la producción de los países, el índice de prioridad relativa y los temas principales. El conjunto de datos se obtuvo a partir de los documentos indizados en la base de datos Web of Science de 2010 a 2019. Se utilizó el software SciMAT para obtener el análisis temático mediante el análisis de mapas de la ciencia. Las revistas Health economics, Value in Health, Journal of Health Economics y European Journal of Health Economics son los principales productoras. Estados Unidos, Inglaterra y Alemania son los que tienen una mayor producción; los Países Bajos, Inglaterra y Australia son los que tienen el índice de prioridad relativa más alto. Los años de vida ajustados en función de la calidad y la desigualdad en materia de salud son los temas con mayor número de documentos y medidas de impacto. Este estudio es un marco útil basado en ciencia que servirá de base para futuras acciones de investigación.Health economics research area was a high evolution from the 1960s and it is constantly growing. Currently, the health expenditure is a key issue worldwide. Bibliometrics provides several methods to explore the impact and evolution of the research. Thus, the main aim of the present study is to understand the current status of the research in health economics for the period 2010-2019. Three different aspects were analyzed: countries production, relative priority index and main themes. The dataset was obtained from the documents indexed in the Web of Science database from 2010 to 2019. SciMAT software was used to obtain the thematic analysis by means of science mapping analysis. The journals Health economics, Value in Health, Journal of Health Economics, and European Journal of Health Economics are the main producers. USA, England and Germany are those with highest production; Netherlands, England and Australia are those with the highest relative priority index. Quality adjusted life years and Health inequality are the themes with the highest number of documents and impact measures. This study is a useful evidence-based framework on which to base future research actions

Scalable Focused Ion Beam Creation of Nearly Lifetime-Limited Single Quantum Emitters in Diamond Nanostructures

The controlled creation of defect center---nanocavity systems is one of the outstanding challenges for efficiently interfacing spin quantum memories with photons for photon-based entanglement operations in a quantum network. Here, we demonstrate direct, maskless creation of atom-like single silicon-vacancy (SiV) centers in diamond nanostructures via focused ion beam implantation with $\sim 32$ nm lateral precision and $< 50$ nm positioning accuracy relative to a nanocavity. Moreover, we determine the Si+ ion to SiV center conversion yield to $\sim 2.5\%$ and observe a 10-fold conversion yield increase by additional electron irradiation. We extract inhomogeneously broadened ensemble emission linewidths of $\sim 51$ GHz, and close to lifetime-limited single-emitter transition linewidths down to $126 \pm13$ MHz corresponding to $\sim 1.4$-times the natural linewidth. This demonstration of deterministic creation of optically coherent solid-state single quantum systems is an important step towards development of scalable quantum optical devices

Binding of the anticancer drug BI-2536 to human serum albumin. A spectroscopic and theoretical study

BI-2536 is a potent Polo-like kinase inhibitor which induces apoptosis in diverse human cancer cell lines. The binding affinity of BI-2536 for human serum albumin (HSA) protein may define its pharmacokinetic and pharmacodynamic profile. We have studied the binding of BI-2536 to HSA by means of different spectroscopic techniques and docking calculations. We have experimentally observed that the affinity of BI-2536 for HSA is higher than that of other common HSA binding drugs. Therefore, it can be postulated that the drug dose should be increased to achieve a certain concentration of free drug in plasma, although BI-2536 could also reach tumour tissues by uptaking HSA/BI-2536 complex. Only a single binding site on HSA has been observed for BI-2536 which seems to correspond to the subdomain IIA pocket. The formation of the HSA/BI-2536 complex is a spontaneous and entropy-driven process that does not cause a significant change of the secondary structure of the protein. Its endothermic character could be related to proton release. Thermodynamic analysis showed that the main protein-drug interactions are of the van der Waals type although the presence of amide and ether groups in BI-2536 could also allow H-bonding with some residues in the subdomain IIA pocket

Shedding light on the binding mechanism of kinase inhibitors BI-2536, Volasetib and Ro-3280 with their pharmacological target PLK1

In the present work, the interactions of the novel kinase inhibitors BI-2536, Volasetib (BI-6727) and Ro-3280 with the pharmacological target PLK1 have been studied by fluorescence spectroscopy and molecular dynamics calculations. High Stern-Volmer constants were found in fluorescence experiments suggesting the formation of stable protein-ligand complexes. In addition, it was observed that the binding constant between BI-2536 and PLK1 increases about 100-fold in presence of the phosphopeptide Cdc25C-p that docks to the polo box domain of the protein and releases the kinase domain. All the determined binding constants are higher for the kinase inhibitors than for their competitor for the active center (ATP) being BI-2536 and Volasertib the inhibitors that showed more affinity for PLK1. Calculated binding free energies confirmed the higher affinity of PLK1 for BI-2536 and Volasertib than for ATP. The higher affinity of the inhibitors to PLK1 compared to ATP was mainly attributed to stronger van der Waals interactions. Results may help with the challenge of designing and developing new kinase inhibitors more effective in clinical cancer therapy

Three dimensional magnetic nanowires grown by focused electron-beam induced deposition

Control of the motion of domain walls in magnetic nanowires is at the heart of various recently proposed three-dimensional (3D) memory devices. However, fabricating 3D nanostructures is extremely complicated using standard lithography techniques. Here we show that highly pure 3D magnetic nanowires with aspect-ratios of ~100 can be grown using focused electron-beam-induced-deposition. By combining micromanipulation, Kerr magnetometry and magnetic force microscopy, we determine that the magnetisation reversal of the wires occurs via the nucleation and propagation of domain walls. In addition, we demonstrate that the magnetic switching of individual 3D nanostructures can be directly probed by magneto-optical Kerr effect

A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer

Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data

Insulin regulates neurovascular coupling through astrocytes

Mice with insulin receptor (IR)-deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to insulin and reduced brain glucose uptake, whereas IRdeficient astrocytes show disturbed mitochondrial responses to glucose. While exploring the functional impact of disturbed mitochondrial function in astrocytes, we observed that GFAP-IR KO mice show uncoupling of brain blood flow with glucose uptake. Since IR-deficient astrocytes show higher levels of reactive oxidant species (ROS), this leads to stimulation of hypoxia-inducible factor-1¿ and, consequently, of the vascular endothelial growth factor angiogenic pathway. Indeed, GFAP-IR KO mice show disturbed brain vascularity and blood flow that is normalized by treatment with the antioxidant N-acetylcysteine (NAC). NAC ameliorated high ROS levels, normalized angiogenic signaling and mitochondrial function in IR-deficient astrocytes, and normalized neurovascular coupling in GFAP-IR KO mice. Our results indicate that by modulating glucose uptake and angiogenesis, insulin receptors in astrocytes participate in neurovascular coupling.We are thankful to M.Garcia and R. Cañadas for technical support. This work was funded by Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (Instituto de Salud CarlosIII, Spain) to I.T.A., A.G., and T.I.; an Inter-CIBER project (PIE14/00061) to I.T.A.that forms part of the projects PID2019-104376RB-I00 (I.T.A.) and RTI2018-094887-B-I00 (M.N.) funded by MCIN/AEI/10.13039/501100011033; a grant from Junta de Andalucia Consejería de Economía y Conocimiento (P18-RT-2233 to A.G.) cofinanced by Programa Operativo FEDER 2014–2020; a grant from Instituto de Salud Carlos III Spain (cofinanced by FEDER funds from the European Union; PI21/00915 to A.G.); Grant PID2020-115218RB-I00 to T.I. funded by Ministerio de Ciencia e Innovación/Agencia Española de Investigación (MCIN/AEI/10.13039/501100011033); and a grant from Comunidad de Madrid through the European Social Fund (ESF)–financed programme Neurometabolismo-Comunidad de Madrid (NEUROMETAB-CM) (B2017/BMD-3700 to I.T.A.and T.I.). M.N. was also supported by the Spanish Ministry of Science and Innovation (Ramón y Cajal RYC-2016-20414). J.P.-U. was contracted by CIBERNED