Crystal Structures, Local Atomic Environments, and Ion Diffusion Mechanisms of Scandium-Substituted Sodium Superionic Conductor (NASICON) Solid Electrolytes

The importance of exploring new solid electrolytes for all-solid-state batteries has led to significant interest in NASICON-type materials. Here, the Sc3+-substituted NASICON compositions Na3ScxZr2-x(SiO4)2-x(PO4)1+x (termed N3) and Na2ScyZr2-y(SiO4)1-y(PO4)2+y (termed N2) (x, y = 0 – 1) are studied as model Na+-ion conducting electrolytes for solid-state batteries. The influence of Sc3+ substitution on the crystal structures and local atomic environments has been characterized by powder X-ray diffraction (XRD) and neutron powder diffraction (NPD), as well as solid-state 23Na, 31P, and 29Si nuclear magnetic resonance (NMR) spectroscopy. A phase transition between 295 and 473 K from monoclinic C2/c to rhombohedral R c is observed for the N3 compositions, while N2 compositions crystallize in a rhombohedral R c unit cell in this temperature range. Alternating current (AC) impedance spectroscopy, molecular dynamics (MD) and high temperature 23Na NMR are in good agreement, showing that with a higher Sc3+ concentration, the ionic conductivity (about 10-4 S/cm at 473 K) decreases and the activation energy for ion diffusion increases. 23Na NMR experiments indicate that the nature of the Na+-ion motion is two-dimensional on the local atomic scale of NMR though the long-range diffusion pathways are three-dimensional. In addition, a combination of MD, bond valence, maximum entropy/Rietveld and van Hove correlation methods has been used, to reveal that the Na+-ion diffusion in these NASICON materials is three-dimensional and that there is a continuous exchange of sodium between Na(1) and Na(2) sites

Costs of a successful public-private partnership for TB control in an urban setting in Nepal

<p>Abstract</p> <p>Background</p> <p>In South Asia a large number of patients seek treatment for TB from private practitioners (PPs), and there is increasing international interest in involving PPs in TB control. To evaluate the feasibility, effectiveness and costs of public-private partnerships (PPPs) for TB control, a PPP was developed in Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB are managed in the private sector. From the clinical perspective the PPP was shown to be effective. The aim of this paper is to assess and report on the costs involved in the PPP scheme.</p> <p>Methods</p> <p>The approach to costing took a comprehensive view, with inclusion of costs not only incurred by health facilities but also social costs borne by patients and their escorts. Semi-structured questionnaires and guided interviews were used to collect start-up and recurrent costs for the scheme.</p> <p>Results</p> <p>Overall costs for treating a TB patient under the PPP scheme averaged US$89.60. Start-up costs per patient represented 12% of the total budget. Half of recurrent costs were incurred by patients and their escorts, with institutional costs representing most of the rest. Female patients tended to spend more and patients referred from the private sector had the highest reported costs.</p> <p>Conclusion</p> <p>Treating TB patients in the PPP scheme had a low additional cost, while doubling the case notification rate and maintaining a high success rate. Costs incurred by patients and their escorts were the largest contributors to the overall total. This suggests a focus for follow-up studies and for cost-minimisation strategies.</p

Paintable Battery

If the components of a battery, including electrodes, separator, electrolyte and the current collectors can be designed as paints and applied sequentially to build a complete battery, on any arbitrary surface, it would have significant impact on the design, implementation and integration of energy storage devices. Here, we establish a paradigm change in battery assembly by fabricating rechargeable Li-ion batteries solely by multi-step spray painting of its components on a variety of materials such as metals, glass, glazed ceramics and flexible polymer substrates. We also demonstrate the possibility of interconnected modular spray painted battery units to be coupled to energy conversion devices such as solar cells, with possibilities of building standalone energy capture-storage hybrid devices in different configurations

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5% versus 40.3%, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95%CI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country

Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.</p> <p>Methods/Design</p> <p>The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.</p> <p>Discussion</p> <p>In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440062">NCT01440062</a></p

Patient-, organization-, and system-level barriers and facilitators to preventive oral health care:A convergent mixed-methods study in primary dental care

Background: Dental caries is the most common chronic disease of adult and childhood, a largely preventable yet widespread, costly public health problem. This study identified patient-, organization-, and system-level factors influencing routine delivery of recommended care for prevention and management of caries in primary dental care. Methods: A convergent mixed-methods design assessed six guidance-recommended behaviours to prevent and manage caries (recording risk, risk-based recall intervals, applying fluoride varnish, placing preventive fissure sealants, demonstrating oral health maintenance, taking dental x-rays). A diagnostic questionnaire assessing current practice, beliefs, and practice characteristics was sent to a random sample of 651 dentists in National Health Service (NHS) Scotland. Eight in-depth case studies comprising observation of routine dental visits and dental team member interviews were conducted. Patient feedback was collected from adult patients with recent checkups at case study practices. Key informant interviews were conducted with decision makers in policy, funding, education, and regulation. The Theoretical Domains Framework within the Behaviour Change Wheel was used to identify and describe patient-, organization-, and system-level barriers and facilitators to care. Findings were merged into a matrix describing theoretical domains salient to each behaviour. The matrix and Behaviour Change Wheel were used to prioritize behaviours for change and plan relevant intervention strategies. Results: Theoretical domains associated with best practice were identified from the questionnaire (N-196), case studies (N = 8 practices, 29 interviews), and patient feedback (N = 19). Using the study matrix, key stakeholders identified priority behaviours (use of preventive fissure sealants among 6–12-year-olds) and strategies (audit and feedback, patient informational campaign) to improve guidance implementation. Proposed strategies were assessed as appropriate for immediate implementation and suitable for development with remaining behaviours. Conclusions: Specific, theoretically based, testable interventions to improve caries prevention and management were coproduced by patient-, practice-, and policy-level stakeholders. Findings emphasize duality of behavioural determinants as barriers and facilitators, patient influence on preventive care delivery, and benefits of integrating multi-level interests when planning interventions in a dynamic, resource-constrained environment. Interventions identified in this study are actively being used to support ongoing implementation initiatives including guidance, professional development, and oral health promotion

Prevention of methamphetamine-induced microglial cell death by TNF-α and IL-6 through activation of the JAK-STAT pathway

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>It is well known that methamphetamine (METH) is neurotoxic and recent studies have suggested the involvement of neuroinflammatory processes in brain dysfunction induced by misuse of this drug. Indeed, glial cells seem to be activated in response to METH, but its effects on microglial cells are not fully understood. Moreover, it has been shown that cytokines, which are normally released by activated microglia, may have a dual role in response to brain injury. This led us to study the toxic effect of METH on microglial cells by looking to cell death and alterations of tumor necrosis factor-alpha (TNF-α) and interleukine-6 (IL-6) systems, as well as the role played by these cytokines.</p> <p><b>Methods</b></p> <p>We used the N9 microglial cell line, and cell death and proliferation were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and incorporation of bromodeoxyuridine, respectively. The TNF-α and IL-6 content was quantified by enzyme-linked immunosorbent assay, and changes in TNF receptor 1, IL-6 receptor-alpha, Bax and Bcl-2 protein levels by western blotting. Immunocytochemistry analysis was also performed to evaluate alterations in microglial morphology and in the protein expression of phospho-signal transducer and activator of transcription 3 (pSTAT3).</p> <p><b>Results</b></p> <p>METH induced microglial cell death in a concentration-dependent manner (EC₅₀ = 1 mM), and also led to significant morphological changes and decreased cell proliferation. Additionally, this drug increased TNF-α extracellular and intracellular levels, as well as its receptor protein levels at 1 h, whereas IL-6 and its receptor levels were increased at 24 h post-exposure. However, the endogenous proinflammatory cytokines did not contribute to METH-induced microglial cell death. On the other hand, exogenous low concentrations of TNF-α or IL-6 had a protective effect. Interestingly, we also verified that the anti-apoptotic role of TNF-α was mediated by activation of IL-6 signaling, specifically the janus kinase (JAK)-STAT3 pathway, which in turn induced down-regulation of the Bax/Bcl-2 ratio.</p> <p><b>Conclusions</b></p> <p>These findings show that TNF-α and IL-6 have a protective role against METH-induced microglial cell death via the IL-6 receptor, specifically through activation of the JAK-STAT3 pathway, with consequent changes in pro- and anti-apoptotic proteins.</p