Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis

Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ.

Are the resources adoptive for conducting team-based diabetes management clinics? An explorative study at primary health care centers in Muscat, Oman

Aim The aim of this study is to explore the perceptions among primary health center staff concerning competencies, values, skills and resources related to team-based diabetes management and to describe the availability of needed resources for team-based approaches. Background The diabetes epidemic challenges services available at primary health care centers in the Middle East. Therefore, there is a demand for evaluation of the available resources and team-based diabetes management in relation to the National Diabetes Management Guidelines. Method A cross-sectional study was conducted with 26 public primary health care centers in Muscat, the capital of Oman. Data were collected from manual and electronic resources as well as a questionnaire that was distributed to the physician-in-charge and diabetes management team members. Findings The study revealed significant differences between professional groups regarding how they perceived their own competencies, values and skills as well as available resources related to team-based diabetes management. The perceived competencies were high among all professions. The perceived team-related values and skills were also generally high but with overall lower recordings among the nurses. This pattern, along with the fact that very few nurses have specialized qualifications, is a barrier to providing team-based diabetes management. Participants indicated that there were sufficient laboratory resources; however, reported that pharmacological, technical and human resources were lacking. Further work should be done at public primary diabetes management clinics in order to fully implement team-based diabetes management.

Ionization of Ammonia Nanoices With Adsorbed Methanol Molecules

Large ammonia clusters represent a model system of ices which are omnipresentthroughout the space. The interaction of ammonia ices with otherhydrogen-boding molecules such as methanol or water and their behavior upon anionization are thus relevant in the astrochemical context. In this study,ammonia clusters (NH3)N with the mean size N ~230 were prepared in molecularbeams and passed through a pickup cell in which methanol molecules wereadsorbed. At the highest exploited pickup pressures, the average composition of(NH3)N(CH3OH)M clusters was estimated to be N:M ~210:10. On the other hand, theelectron ionization of these clusters yielded about 75% of methanol-containingfragments (NH3)n(CH3OH)mH+ compared to 25% contribution of pure ammonia(NH3)nH+ ions. Based on this substantial disproportion, we propose thefollowing ionization mechanism: The prevailing ammonia is ionized in mostcases, resulting in NH+4 core solvated most likely with four ammonia molecules,yielding the well-known "magic number" structure (NH3)4NH+4 . The methanolmolecules exhibit strong propensity for sticking to the fragment ion. We havealso considered mechanisms of intracluster reactions. In most cases, protontransfer between ammonia units take place. The theoretical calculationssuggested the proton transfer either from the methyl group or from the hydroxylgroup of the ionized methanol molecule to ammonia to be the energetically openchannels. However, the experiments with selectively deuterated methanols didnot show any evidence for the D+ transfer from the CD3 group. The protontransfer from the hydroxyl group could not be excluded entirely nor confirmedunambiguously by the experiment.

Operando Studies Reveal Structural Evolution with Electrochemical Cycling in Li–CoS2

The drive toward high energy density alternatives to Li-ion batteries has led to great interest in energy storage materials not inherently constrained by the capacity limits of the currently employed intercalation electrode materials. Among the alternatives under consideration are electrode materials with theoretical capacities many times greater than intercalation electrodes that store charge through so-called conversion reactions. However, the significant structural changes that enable the high theoretical capacity of conversion systems contribute to issues of poor efficiency and short cycle life. To better understand cycling issues in conversion systems, we study the local structure evolution of CoS2 during Li storage. Being metallic and potentially capable of redox on both anion and cation sites, CoS2 would be expected to display promise as a cathode material. Through combined ex situ X-ray absorption near-edge spectroscopy and pair distribution function analysis from operando X-ray total scattering, ...

The Role of PEG-40-stearate in the Production, Morphology, and Stability of Microbubbles

Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. While the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesized in-house to directly observe its distribution in the microbubble coating. We examined microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was observed only on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. "Squeezing out" of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37 °C, however, the stability in serum was found to be the same for both formulations, and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.

Mechanical Alloying of Optimized Mg2(Si,Sn) Solid Solutions: Understanding Phase Evolution and Tuning Synthesis Parameters for Thermoelectric Applications

Comparison of Copper(II)–Ligand Complexes as Mediators for Preparing Electrochemically Modulated Nitric Oxide-Releasing Catheters

Further studies aimed at examining the activity of different Cu(II)-ligand complexes to serve as electron-transfer mediators to prepare novel antimicrobial/thromboresistant nitric oxide (NO)-releasing intravenous catheters are reported. In these devices, the NO release can be modulated by applying different potentials or currents to reduce the Cu(II)-complexes to Cu(I) species which then reduce nitrite ions into NO (g) within a lumen of the catheter. Four different ligands are compared with respect to NO generation efficiency and stability over time using both single- and dual-lumen silicone rubber catheters: N-propanoate- N, N-bis(2-pyridylethyl)amine (BEPA-Pr), N-propanoate- N, N-bis(2-pyridylmethyl)amine (BMPA-Pr), 1,4,7-trimethyl-1,4,7-triazacyclononane (Me 3 TACN), and tris(2-pyridylmethyl)amine (TPMA). Of these, the Cu(II)BEPA-Pr and Cu(II)Me 3 TACN complexes provide biomedically useful NO fluxes from the surface of the catheters, >2 × 10 -10 mol·min -1 ·cm -2 , under conditions mimicking the bloodstream environment. Cu(II)Me 3 TACN exhibits the best stability over time with a steady and continuous NO release observed for 8 d under a nitrogen atmosphere. Antimicrobial experiments conducted over 5 d with NO-releasing catheters turned "on" electrochemically for only 3 or 6 h each day revealed >2 logarithmic units in reduction of bacterial biofilm attached to the catheter surfaces. The use of optimal Cu(II)-ligand complexes within a lumen reservoir along with high levels of nitrite ions can potentially provide an effective method of preventing/decreasing the rate of infections caused by intravascular catheters.

Brazil’s new government threatens food security and biodiversity

Correction: Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells

Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers. Furthermore, after its release into the extracellular space, ATP is processed by ectonucleotidases: CD39 converts ATP to AMP, and CD73 converts AMP to adenosine. We observed that CD73-deficient mice mobilize more HSPCs than do wild-type mice due to a decrease in adenosine concentration in the extracellular space, indicating a negative role for adenosine in the mobilization process. This finding has been confirmed by injecting mice with adenosine along with pro-mobilizing agents. In sum, we demonstrate for the first time that purinergic signaling involving ATP and its metabolite adenosine regulate the mobilization of HSPCs. Although ATP triggers and promotes this process, adenosine has an inhibitory effect. Thus, administration of ATP together with G-CSF or AMD3100 or inhibition of CD73 by small molecule antagonists may provide the basis for more efficient mobilization strategies.