The Chemokine CCL2 Mediates the Seizure-enhancing Effects of Systemic Inflammation

Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Brain inflammation is increasingly recognized as a critical factor for seizure precipitation, but the molecular mediators of such proconvulsant effects are only partly understood. The chemokine CCL2 is one of the most elevated inflammatory mediators in patients with pharmacoresistent epilepsy, but its contribution to seizure generation remains unexplored. Here, we show, for the first time, a crucial role for CCL2 and its receptor CCR2 in seizure control. We imposed a systemic inflammatory challenge via lipopolysaccharide (LPS) administration in mice with mesial temporal lobe epilepsy. We found that LPS dramatically increased seizure frequency and upregulated the expression of many inflammatory proteins, including CCL2. To test the proconvulsant role of CCL2, we administered systemically either a CCL2 transcription inhibitor (bindarit) or a selective antagonist of the CCR2 receptor (RS102895). We found that interference with CCL2 signaling potently suppressed LPS-induced seizures. Intracerebral administration of anti-CCL2 antibodies also abrogated LPS-mediated seizure enhancement in chronically epileptic animals. Our results reveal that CCL2 is a key mediator in the molecular pathways that link peripheral inflammation with neuronal hyperexcitability

Functional protection by acute phase proteins alpha(1)-acid glycoprotein and alpha(1)-antitrypsin against ischemia/reperfusion injury by preventing apoptosis and inflammation.

BACKGROUND: Ischemia followed by reperfusion (I/R) causes apoptosis, inflammation, and tissue damage leading to organ malfunction. Ischemic preconditioning can protect against such injury. This study investigates the contribution of the acute phase proteins alpha(1)-acid glycoprotein (AGP) and alpha(1)-antitrypsin (AAT) to the protective effect of ischemic preconditioning in the kidney. METHODS AND RESULTS: Exogenous AGP and AAT inhibited apoptosis and inflammation after 45 minutes of renal I/R in a murine model. AGP and AAT administered at reperfusion prevented apoptosis at 2 hours and 24 hours, as evaluated by the presence of internucleosomal DNA cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and the determination of renal caspase-1- and caspase-3-like activity. AGP and AAT exerted anti-inflammatory effects, as reflected by reduced renal tumor necrosis factor-alpha expression and neutrophil influx after 24 hours. In general, these agents improved renal function. Similar effects were observed when AGP and AAT were administered 2 hours after reperfusion but to a lesser extent and without functional improvement. Moreover, I/R elicited an acute phase response, as reflected by elevated serum AGP and serum amyloid P (SAP) levels after 24 hours, and increased hepatic acute phase protein mRNA levels after 18 hours of renal reperfusion. CONCLUSIONS: We propose that the antiapoptotic and anti-inflammatory effects of AGP and AAT contribute to the delayed type of protection associated with ischemic preconditioning and other insults. This mechanism is potentially involved in the course of many clinical conditions associated with I/R injury. Moreover, exogenous administration of these proteins may provide new therapeutic means of treatmen

A Mobile App for Prevention of Cardiovascular Disease and Type 2 Diabetes Mellitus: Development and Usability Study

Background: Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are posing a huge burden on health care systems worldwide. Mobile apps can deliver behavior change interventions for chronic disease prevention on a large scale, but current evidence for their effectiveness is limited. Objective: This paper reported on the development and user testing of a mobile app that aims at increasing risk awareness and engaging users in behavior change. It would form part of an intervention for primary prevention of CVD and T2DM. Methods: The theoretical framework of the app design was based on the Behaviour Change Wheel, combined with the capability, opportunity, and motivation for behavior change system and the behavior change techniques from the Behavior Change Technique Taxonomy (version 1). In addition, evidence from scientific literature has guided the development process. The prototype was tested for user-friendliness via an iterative approach. We conducted semistructured interviews with individuals in the target populations, which included the System Usability Scale. We transcribed and analyzed the interviews using descriptive statistics for the System Usability Scale and thematic analysis to identify app features that improved utility and usability. Results: The target population was Australians aged ≥45 years. The app included 4 core modules (risk score, goal setting, health measures, and education). In these modules, users learned about their risk for CVD and T2DM; set goals for smoking, alcohol consumption, diet, and physical activity; and tracked them. In total, we included 12 behavior change techniques. We conducted 2 rounds of usability testing, each involving 5 participants. The average age of the participants was 58 (SD 8) years. Totally, 60% (6/10) of the participants owned iPhone Operating System phones, and 40% (4/10) of them owned Android phones. In the first round, we identified a technical issue that prevented 30% (3/10) of the participants from completing the registration process. Among the 70% (7/10) of participants who were able to complete the registration process, 71% (5/7) rated the app above average, based on the System Usability Scale. During the interviews, we identified some issues related to functionality, content, and language and clarity. We used the participants’ feedback to improve these aspects. Conclusions: We developed the app using behavior change theory and scientific evidence. The user testing allowed us to identify and remove technical errors and integrate additional functions into the app, which the participants had requested. Next, we will evaluate the feasibility of the revised version of the app developed through this design process and usability testing

Topological Designs

We give an exponential upper and a quadratic lower bound on the number of pairwise non-isotopic simple closed curves can be placed on a closed surface of genus g such that any two of the curves intersects at most once. Although the gap is large, both bounds are the best known for large genus. In genus one and two, we solve the problem exactly. Our methods generalize to variants in which the allowed number of pairwise intersections is odd, even, or bounded, and to surfaces with boundary components.Comment: 14 p., 4 Figures. To appear in Geometriae Dedicat

Synthesis of molybdenum oxide nanoparticles by nanosecond laser ablation

Phothermal therapy (PTT) is one of the most promising techniques to treat cancer. Finding the ideal PTT agent nanomaterial has remained a challenge and has brought the interest of several researchers. In this work, we report the synthesis of molybdenum oxide (MoOx) nanoparticles (NPs), which exhibit absorption in the biological optical window ~840 nm, by using the laser ablation of solids in liquids (LASL) technique with nanosecond (ns) pulses. A Nd:YAG laser was used to synthesize the NPs in deionized (DI) water, free of surfactants or additives, which were optically characterized by absorption spectroscopy and TEM-EDX microscopy. Semi spherical NPs with a suitable average size and shape for potential use as PTT agents were obtained by laser ablation and ablation + fragmentation. The calculated band gap is 3.1 eV, which corresponds to MoO3. Micro-Raman spectroscopy studies determined that these NPs are composed of amorphous molybdenum oxide hydrates (MoO3 · xH2O)

On the Quantum-like Contextuality of Ambiguous Phrases

Language is contextual as meanings of words are dependent on their contexts. Contextuality is, concomitantly, a well-defined concept in quantum mechanics where it is considered a major resource for quantum computations. We investigate whether natural language exhibits any of the quantum mechanics' contextual features. We show that meaning combinations in ambiguous phrases can be modelled in the sheaf-theoretic framework for quantum contextuality, where they can become possibilistically contextual. Using the framework of Contextuality-by-Default (CbD), we explore the probabilistic variants of these and show that CbD-contextuality is also possible

Biopsia renal. Descripción clinicopatológica, complicaciones y evolución en un hospital general del Perú: Kidney biopsy. Clinicopathological description, complications and evolution in a general hospital in Peru

Introduction: Kidney biopsy is one of the essential tests for the characterization of chronic kidney disease (CKD). Objective: To determine the most frequent primary and secondary glomerulonephritis, complications of renal biopsy and the number of patients on hemodialysis when undergoing renal biopsy. Methods: Observational, descriptive, case series, retrospective and cross-sectional study, carried out at the E. Rebagliati Matins-Peru national hospital. The medical records of patients older than 15 years of age who underwent kidney biopsy between 2008-2016 were reviewed. The data were processed in Stata 16.1 Results: Of 2278 medical records, they corresponded to 1234 women and 1044 men. The most frequent primary and secondary glomerulonephritis were focal and segmental glomerulosclerosis (FSGS) 683 (29.98%) and systemic lupus erythematosus (SLE). ) 434 (19.04%) respectively. Of 1644 biopsied patients, 36 (2.19%) and 241 (14.66%) had major and minor complications respectively. Major complications were more frequent when the procedure was performed by radiology with ultrasound guidance compared to that performed by the nephrologist without ultrasound guidance (p = 0.03694). In 1,324 patients, 329 underwent kidney biopsy while on hemodialysis; of them 43 (13.07%) managed to get out of this therapy and 144 (51.99%) had major or minor complications. Conclusions: GEFyS and SLE were the most frequent primary and secondary glomerulonephritis, respectively. In 1644 patients the major and minor complications were 36 (2.19%) and 241 (14.66%) respectively. In 1,324 patients, 329 (24.8%) were biopsied while on hemodialysis and 144 (51.99%) of them had major or minor complications.Introducción: La biopsia renal es uno de los exámenes esenciales para la caracterización de la enfermedad renal crónica (ERC). Objetivo: Determinar las glomerulonefritis primarias y secundarias más frecuentes, las complicaciones de la biopsia renal y el número de pacientes en hemodiálisis al ser sometidos a biopsia renal. Métodos: Estudio observacional, descriptivo, de serie de casos, retrospectivo y transversal, realizado en el hospital nacional E. Rebagliati Matins-Perú. Se revisaron las historias clínicas de pacientes mayores de 15 años de edad sometidos a biopsia renal entre 2008-2016. Los datos fueron procesados en Stata 16.1 Resultados: De 2278 historias clínicas, correspondieron a mujeres 1234 y a hombres 1044. Las glomerulonefritis primarias y secundarias más frecuentes fueron glomeruloesclerosis focal y segmentaria (GEFyS) 683 (29,98%) y lupus eritematoso sistémico (LES) 434 (19,04%) respectivamente. De 1644 pacientes biopsiados, 36 (2,19%) y 241 (14,66%), tuvieron complicaciones mayores y menores respectivamente. Las complicaciones mayores fueron más frecuentes cuando el procedimiento lo realizó radiología con guía ecográfica en relación al realizado por el nefrólogo sin guía ecográfica (p = 0,03694). En 1324 pacientes, 329 fueron sometidos a biopsia renal estando en hemodiálisis; de ellos 43 (13,07%) lograron salir de esta terapia y 144 (51,99%) tuvieron complicaciones mayores o menores. Conclusiones: La GEFyS y LES fueron las glomerulonefritis primarias y secundarias más frecuentes, respectivamente. En 1644 pacientes las complicaciones mayores y menores fueron 36 (2,19%) y 241 (14,66%) respectivamente. En 1324 pacientes, 329 (24,8%) fueron biopsiados estando en hemodiálisis y de ellos 144 (51,99%) tuvieron complicaciones mayores o menores

Analysing Ambiguous Nouns and Verbs with Quantum Contextuality Tools

Psycholinguistic research uses eye-tracking to show that polysemous words are disambiguated differently from homonymous words, and that ambiguous verbs are disambiguated differently than ambiguous nouns. Research in Compositional Distributional Semantics uses cosine distances to show that verbs are disambiguated more efficiently in the context of their subjects and objects than when on their own. These two frameworks both focus on one ambiguous word at a time and neither considers ambiguous phrases with two (or more) ambiguous words. We borrow methods and measures from Quantum Information Theory, the framework of Contextuality-by-Default and degrees of contextual influences, and work with ambiguous subject-verb and verb-object phrases of English, where both the subject/object and the verb are ambiguous. We show that differences in the processing of ambiguous verbs versus ambiguous nouns, as well as between different levels of ambiguity in homonymous versus polysemous nouns and verbs can be modelled using the averages of the degrees of their contextual influences