Electrochemical determination of the antipsychotic medication clozapine by a carbon paste electrode modified with a nanostructure prepared from titania nanoparticles and copper oxide

A nanostructure was prepared from titania nanoparticles and copper oxide (TiO2NP@CuO) and used to modify a carbon paste electrode (CPE). The modified CPE is shown to enable sensitive voltammetric determination of the drug clozapine (CLZ). The sensor was characterized by various techniques and some key parameters were optimized. Under the optimum conditions and at a working potential of 0.6 V (vs. Ag/AgCl), the modified CPE has two linear response ranges, one from 30 pmol L�1 to 4 nmol L�1 of CLZ, the other from 4 nmol L�1 to 10 μmol L�1. The detection limit is as low as 9 pM. The transfer coefficient (α) and catalytic rate constant (kcat) were calculated and the reliability of the sensor was estimated for CLZ sensing in real samples where it gave satisfactory results. Figure not available: see fulltext.. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature

Evaluation of Judet view radiographs accuracy in classification of acetabular fractures compared with three-dimensional computerized tomographic scan: A retrospective study

Background: In the current diagnostic procedure, generally, both plain radiographs and 3D-CT scans are used for the diagnosis of acetabular fractures. There is no consensus regarding the value of a three-dimensional computerized tomographic (3D-CT) scan alone in the classification of acetabular fractures. In this study, we compared the accuracy of 3D-CT scan and plain radiography through the evaluation of their agreement with the intraoperative surgeon's classification. Method: In a retrospective study, patients who were referred to our center with an acetabular fracture and underwent surgical treatment were included. The classification of acetabular fractures was performed once using Judet view plain radiographs and once using a 3D-CT scan by the corresponding one Experienced musculoskeletal radiologist one independent trauma fellowship-trained orthopaedic who routinely treat acetabular fractures and based on Letournel and Judet classification (17 and 23 years of experience respectively). Cohen's kappa value was used for the assessment agreement between the two imaging modalities, as well as between the imaging modalities and intraoperative classification. Results: Medical files of 152 patients with acetabular fracture were retrospectively reviewed. A kappa value of 0.236 was obtained as the agreement level between radiographs and intraoperative findings (p < 0.001). A kappa value of 0.943 was obtained as the agreement level between 3D-CT and intraoperative classification (p < 0.001). An agreement level of 0.264 was found between the Judet radiographs and 3D-CT scans (p < 0.001). Conclusions: 3D-CT scans are reliable enough in the classification of acetabular fractures, and plain radiographs could be omitted to avoid radiation exposure as well as to reduce the cost for patients who sustain acetabular fractures. © 2020 The Author(s)

Enhanced Long-Path Electrical Conduction in ZnO Nanowire Array Devices Grown via Defect-Driven Nucleation

Vertical arrays of nanostructures have been widely used as major components in some of the most ground-breaking modern research-based devices, and ZnO nanowires have received particular attention because of their favorable electronic properties. Using a local multiprobe technique to measure the properties of individual ZnO nanowires in vertical arrays, we show for the first time that for metal-catalyzed ZnO nanowire growth the electrical contribution of individual wires to a device is highly dependent on the fate of the catalyst nanoparticle during growth. To overcome the limitations of metal-catalyzed growth, nanowires grown from a defect-driven nucleation process are shown to provide high-quality device structures with excellent long-path electrical conduction

Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.

Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos

Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi

<p>Abstract</p> <p>Background</p> <p>The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction of <it>Plasmodium falciparum </it>transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on <it>Plasmodium </it>stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (<it>Azadirachta indica</it>, Meliaceae) seeds, is a promising candidate, inhibiting <it>Plasmodium </it>exflagellation <it>in vitro </it>at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal^®, an azadirachtin-enriched extract of neem seeds, using the rodent malaria <it>in vivo </it>model <it>Plasmodium berghei</it>/<it>Anopheles stephensi</it>.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>females were offered a blood-meal on <it>P. berghei </it>infected, gametocytaemic BALB/c mice, treated intraperitoneally with NeemAzal, one hour before feeding. The transmission-blocking activity of the product was evaluated by assessing oocyst prevalence, oocyst density and capacity to infect healthy mice. To characterize the anti-plasmodial effects of NeemAzal^®on early midgut stages, i.e. zygotes and ookinetes, Giemsa-stained mosquito midgut smears were examined.</p> <p>Results</p> <p>NeemAzal^®completely blocked <it>P. berghei </it>development in the vector, at an azadirachtin dose of 50 mg/kg mouse body weight. The totally 138 examined, treated mosquitoes (three experimental replications) did not reveal any oocyst and none of the healthy mice exposed to their bites developed parasitaemia. The examination of midgut content smears revealed a reduced number of zygotes and post-zygotic forms and the absence of mature ookinetes in treated mosquitoes. Post-zygotic forms showed several morphological alterations, compatible with the hypothesis of an azadirachtin interference with the functionality of the microtubule organizing centres and with the assembly of cytoskeletal microtubules, which are both fundamental processes in <it>Plasmodium </it>gametogenesis and ookinete formation.</p> <p>Conclusions</p> <p>This work demonstrated <it>in vivo </it>transmission blocking activity of an azadirachtin-enriched neem seed extract at an azadirachtin dose compatible with 'druggability' requisites. These results and evidence of anti-plasmodial activity of neem products accumulated over the last years encourage to convey neem compounds into the drug discovery & development pipeline and to evaluate their potential for the design of novel or improved transmission-blocking remedies.</p

International Society of Sports Nutrition Position Stand: Probiotics.

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of probiotic supplementation to optimize the health, performance, and recovery of athletes. Based on the current available literature, the conclusions of the ISSN are as follows: 1)Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO).2)Probiotic administration has been linked to a multitude of health benefits, with gut and immune health being the most researched applications.3)Despite the existence of shared, core mechanisms for probiotic function, health benefits of probiotics are strain- and dose-dependent.4)Athletes have varying gut microbiota compositions that appear to reflect the activity level of the host in comparison to sedentary people, with the differences linked primarily to the volume of exercise and amount of protein consumption. Whether differences in gut microbiota composition affect probiotic efficacy is unknown.5)The main function of the gut is to digest food and absorb nutrients. In athletic populations, certain probiotics strains can increase absorption of key nutrients such as amino acids from protein, and affect the pharmacology and physiological properties of multiple food components.6)Immune depression in athletes worsens with excessive training load, psychological stress, disturbed sleep, and environmental extremes, all of which can contribute to an increased risk of respiratory tract infections. In certain situations, including exposure to crowds, foreign travel and poor hygiene at home, and training or competition venues, athletes' exposure to pathogens may be elevated leading to increased rates of infections. Approximately 70% of the immune system is located in the gut and probiotic supplementation has been shown to promote a healthy immune response. In an athletic population, specific probiotic strains can reduce the number of episodes, severity and duration of upper respiratory tract infections.7)Intense, prolonged exercise, especially in the heat, has been shown to increase gut permeability which potentially can result in systemic toxemia. Specific probiotic strains can improve the integrity of the gut-barrier function in athletes.8)Administration of selected anti-inflammatory probiotic strains have been linked to improved recovery from muscle-damaging exercise.9)The minimal effective dose and method of administration (potency per serving, single vs. split dose, delivery form) of a specific probiotic strain depends on validation studies for this particular strain. Products that contain probiotics must include the genus, species, and strain of each live microorganism on its label as well as the total estimated quantity of each probiotic strain at the end of the product's shelf life, as measured by colony forming units (CFU) or live cells.10)Preclinical and early human research has shown potential probiotic benefits relevant to an athletic population that include improved body composition and lean body mass, normalizing age-related declines in testosterone levels, reductions in cortisol levels indicating improved responses to a physical or mental stressor, reduction of exercise-induced lactate, and increased neurotransmitter synthesis, cognition and mood. However, these potential benefits require validation in more rigorous human studies and in an athletic population

Exciton-polaritons in van der Waals heterostructures embedded in tunable microcavities.

Layered materials can be assembled vertically to fabricate a new class of van der Waals heterostructures a few atomic layers thick, compatible with a wide range of substrates and optoelectronic device geometries, enabling new strategies for control of light-matter coupling. Here, we incorporate molybdenum diselenide/hexagonal boron nitride (MoSe2/hBN) quantum wells in a tunable optical microcavity. Part-light-part-matter polariton eigenstates are observed as a result of the strong coupling between MoSe2 excitons and cavity photons, evidenced from a clear anticrossing between the neutral exciton and the cavity modes with a splitting of 20 meV for a single MoSe2 monolayer, enhanced to 29 meV in MoSe2/hBN/MoSe2 double-quantum wells. The splitting at resonance provides an estimate of the exciton radiative lifetime of 0.4 ps. Our results pave the way for room-temperature polaritonic devices based on multiple-quantum-well van der Waals heterostructures, where polariton condensation and electrical polariton injection through the incorporation of graphene contacts may be realized