Safety and Efficacy of Ceftaroline Fosamil in the Management of Community-Acquired Bacterial Pneumonia

Ceftaroline fosamil is a new fifth-generation cephalosporin indicated for the treatment of community-acquired bacterial pneumonia (CABP). It possesses antimicrobial effects against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), but not against anaerobes. Organisms covered by this novel agent that are commonly associated with CABP are Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae; however, ceftaroline fosamil lacks antimicrobial activity against Pseudomonas and Acinetobacter species. FOCUS 1 and FOCUS 2 clinical trials evaluated the use of ceftaroline fosamil in the treatment of CABP as compared to ceftriaxone. These non-inferiority trials provided evidence that ceftaroline fosamil is as effective and safe as ceftriaxone in the treatment of CABP. As its role in the treatment has not been well established, ceftaroline fosamil should be reserved for patients at high risk for multidrug-resistant organisms (MDROs). This review summarizes ceftaroline fosamil\u27s pharmacokinetic and pharmacodynamic profile, clinical efficacy and safety, and place in therapy for the treatment and management of CABP

Pramlintide in the Management of Obesity

Obesity is a common problem that can lead to numerous comorbid conditions, including Type 2 diabetes. Currently, there are few pharmacologic options available to help obese patients lose weight. Pramlintide is an injectable, amylin analogue that is indicated in patients with Type 1 and Type 2 diabetes for use in conjunction with insulin to improve glycemic control. In addition to helping patients decrease hemoglobin A1c levels, pramlintide has also been shown to minimize weight gain, especially in patients with Type 2 diabetes. Studies have been conducted in various patient types, including those patients without diabetes, and the drug tends to have a positive effect on weight loss. It appears that the drug is well tolerated in patients without diabetes; however, current studies have been conducted in small patient populations. Additional research needs to be carried out to determine if the drug is a viable option for obese patients who have failed to respond to other weight loss products

NKCC2 activity is inhibited by the Bartter's syndrome type 5 gain-of-function CaR-A843E mutant in renal cells.

The gain-of-function A843E mutation of the calcium sensing receptor (CaR) causes Bartter syndrome type 5. Patients carrying this CaR variant show a remarkably reduced renal NaCl reabsorption in the thick ascending limb (TAL) of Henle's loop resulting in renal loss of NaCl in the absence of mutations in renal Na(+) and Cl(-) ion transporters. The molecular mechanisms underlying this clinical phenotype are incompletely understood. We investigated, in human embryonic kidney 293 (HEK 293) cells and porcine kidney epithelial (LLC-PK1) cells, the functional cross-talk of CaR-A843E with the Na(+):K(+):2Cl(-) co-transporter, NKCC2, which provides NaCl reabsorption in the TAL. RESULTS: The expression of the CaR mutant did not alter the apical localisation of NKCC2 in LLC-PK1 cells. However, the steady-state NKCC2 phosphorylation and activity were decreased in cells transfected with CaR-A843E compared with the control wild-type CaR (CaR WT)-transfected cells. Of note, low-Cl(-)-dependent NKCC2 activation was also strongly inhibited upon the expression of CaR-A843E mutant. The use of either P450 ω-hydroxylase (CYP4)- or phospholipase A2 (PLA2)-blockers suggests that this effect is likely mediated by arachidonic acid (AA) metabolites. CONCLUSIONS: The data suggested that the activated CaR affects intracellular pathways modulating NKCC2 activity rather than NKCC2 intracellular trafficking in renal cells, and throw further light on the pathological role played by active CaR mutants in Bartter syndrome type 5

The Fate of Intranasally Instilled Silver Nanoarchitectures

The intranasal administration of drugs allows an effective and noninvasive therapeutic action on the respiratory tract. In an era of rapidly increasing antimicrobial resistance, new approaches to the treatment of communicable diseases, especially lung infections, are urgently needed. Metal nanoparticles are recognized as a potential last-line defense, but limited data on the biosafety and nano/biointeractions preclude their use. Here, we quantitatively and qualitatively assess the fate and the potential risks associated with the exposure to a silver nanomaterial model (i.e., silver ultrasmall-in-nano architectures, AgNAs) after a single dose instillation. Our results highlight that the biodistribution profile and the nano/biointeractions are critically influenced by both the design of the nanomaterial and the chemical nature of the metal. Overall, our data suggest that the instillation of rationally engineered nanomaterials might be exploited to develop future treatments for (non)communicable diseases of the respiratory tract

Quantized Nambu-Poisson Manifolds in a 3-Lie Algebra Reduced Model

We consider dimensional reduction of the Bagger-Lambert-Gustavsson theory to a zero-dimensional 3-Lie algebra model and construct various stable solutions corresponding to quantized Nambu-Poisson manifolds. A recently proposed Higgs mechanism reduces this model to the IKKT matrix model. We find that in the strong coupling limit, our solutions correspond to ordinary noncommutative spaces arising as stable solutions in the IKKT model with D-brane backgrounds. In particular, this happens for S^3, R^3 and five-dimensional Neveu-Schwarz Hpp-waves. We expand our model around these backgrounds and find effective noncommutative field theories with complicated interactions involving higher-derivative terms. We also describe the relation of our reduced model to a cubic supermatrix model based on an osp(1|32) supersymmetry algebra.Comment: 22 page

Membrane Sigma-Models and Quantization of Non-Geometric Flux Backgrounds

We develop quantization techniques for describing the nonassociative geometry probed by closed strings in flat non-geometric R-flux backgrounds M. Starting from a suitable Courant sigma-model on an open membrane with target space M, regarded as a topological sector of closed string dynamics in R-space, we derive a twisted Poisson sigma-model on the boundary of the membrane whose target space is the cotangent bundle T^*M and whose quasi-Poisson structure coincides with those previously proposed. We argue that from the membrane perspective the path integral over multivalued closed string fields in Q-space is equivalent to integrating over open strings in R-space. The corresponding boundary correlation functions reproduce Kontsevich's deformation quantization formula for the twisted Poisson manifolds. For constant R-flux, we derive closed formulas for the corresponding nonassociative star product and its associator, and compare them with previous proposals for a 3-product of fields on R-space. We develop various versions of the Seiberg-Witten map which relate our nonassociative star products to associative ones and add fluctuations to the R-flux background. We show that the Kontsevich formula coincides with the star product obtained by quantizing the dual of a Lie 2-algebra via convolution in an integrating Lie 2-group associated to the T-dual doubled geometry, and hence clarify the relation to the twisted convolution products for topological nonassociative torus bundles. We further demonstrate how our approach leads to a consistent quantization of Nambu-Poisson 3-brackets.Comment: 52 pages; v2: references adde

Mindfulness-based interventions for young offenders: a scoping review

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs

Affect in mathematics education

There are two different uses for the word “affect” in behavioral sciences. Often it is used as an overarching umbrella concept that covers attitudes, beliefs, motivation, emotions, and all other noncognitive aspects of human mind. In this article, however, the word affect is used in a more narrow sense, referring to emotional states and traits. A more technical definition of emotions, states, and traits will follow later.Peer reviewe

Plant-Inspired Polyaleuritate–Nanocellulose Composite Photonic Films

Plant epidermis is a complex composite material composed by the cuticle and the epidermal cells. In order to prevent dehydration the cuticle is a water barrier composed of an outer layer (proper cuticle) connected to the cell wall of the epidermal cells via a complex matrix often referred to as cutinised cell wall, that acts as compatibilizer for the water repellent cutin and the hydrophilic polysaccharides in the cell walls. Here, biomimetic plant epidermis-inspired films with selective reflection properties were prepared by formation of an aliphatic polyester coating on chiral nematic cellulose nanocrystal (CNC) films. Aleuritic acid, a polyhydroxylated fatty acid, was sprayed on CNC films and polymerized by hot-pressing. The micromorphology of the resultant samples was characterized by scanning electron microscopy (SEM). Polarised optical microscopy confirmed the CNCs helicoidal organization in the films, responsible for the reflection of circularly polarised light, before and after the hot-pressing. The chemical analysis by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the polymerization of aleuritic acid into polyaleuritate with differences between filter paper and woodpulp substrates that were ascribed to water elimination during polycondensation. The characterization of the mechanical (Young’s modulus and hardness from nanoindentation tests) and hydrodynamic (water uptake and water vapor transmission rate) properties indicated that this process enhances the robustness and waterproof behaviour of CNC films. These properties were comparable to those of commercial and biodegradable materials commonly used in packaging such as polyesters and cellulose derivatives, thus making these natural composite ideal for optically responsive packaging applications.J.A.H.-G. acknowledges the funding by the Spanish “Ministerio de Ciencia, Innovación y Universidades”, project numbers RTI2018-096896-J-I00 and RYC2018-025079-I

G₂-structures and quantization of non-geometric M-theory backgrounds

We describe the quantization of a four-dimensional locally non-geometric M-theory background dual to a twisted three-torus by deriving a phase space star product for deformation quantization of quasi-Poisson brackets related to the nonassociative algebra of octonions. The construction is based on a choice of $G_2$-structure which defines a nonassociative deformation of the addition law on the seven-dimensional vector space of Fourier momenta. We demonstrate explicitly that this star product reduces to that of the three-dimensional parabolic constant $R$-flux model in the contraction of M-theory to string theory, and use it to derive quantum phase space uncertainty relations as well as triproducts for the nonassociative geometry of the four-dimensional configuration space. By extending the $G_2$-structure to a $Spin(7)$-structure, we propose a 3-algebra structure on the full eight-dimensional M2-brane phase space which reduces to the quasi-Poisson algebra after imposing a particular gauge constraint, and whose deformation quantisation simultaneously encompasses both the phase space star products and the configuration space triproducts. We demonstrate how these structures naturally fit in with previous occurences of 3-algebras in M-theory.Comment: 41 pages; v2: Final version published in JHE