Zinc Gluconate in the Treatment of Dysgeusia—a Randomized Clinical Trial

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n = 26) or placebo (lactose; n = 24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p < 0.001) and rated the dysgeusia as being less severe (p < 0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p < 0.05; mood scale, p < 0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p < 0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients

Efficacy of Modular Design in Healthcare

Modular design has become an industry leading philosophy for the future of community-based health services. Modular applied as a design principle subdivides a construction system into independently fabricated units, similar in size, shape, and functionality to formulate a structure. The benefits of this approach include time-to-build efficiency, cost-effectiveness, quality and precision, sustainability, continuity, and modification. This process contradicts traditional construction, pre-fabricating spaces off site to be assembled later. Modular architecture is historically correlated with hotel design and is still in its adolescent stage being integrated into hospice. Forward-thinking medical institutes and design firms have begun to experiment with modular design in their projects aiming to provide accessible healthcare in any context, however, discrepancies have surfaced. The complexity of a functional healthcare facility including circulation, adaptability, materiality, and utilities are being overlooked due to monetary hesitation, high demand, and standardized design. Modular healthcare design is still unpopular amongst manufacturers and firms. Through correlational research and simulation software, modular solutions and traditional construction methods can be compared using operational statistics. The purpose of this research is to study the efficacy of the designs proposed by the industry thus far in hopes to refine the process for a safer, enjoyable, more efficient, and replicable solution

Short-term geomorphological evolution of proglacial systems

Proglacial systems are amongst the most rapidly changing landscapes on Earth, as glacier mass loss, permafrost degradation and more episodes of intense rainfall progress with climate change. This review addresses the urgent need to quantitatively define proglacial systems not only in terms of spatial extent but also in terms of functional processes. It firstly provides a critical appraisal of prevailing conceptual models of proglacial systems, and uses this to justify compiling data on rates of landform change in terms of planform, horizontal motion, elevation changes and sediment budgets. These data permit us to produce novel summary conceptual diagrams that consider proglacial landscape evolution in terms of a balance of longitudinal and lateral water and sediment fluxes. Throughout, we give examples of newly emerging datasets and data processing methods because these have the potential to assist with the issues of: (i) a lack of knowledge of proglacial systems within high-mountain, arctic and polar regions, (ii) considerable inter- and intra-catchment variability in the geomorphology and functioning of proglacial systems, (iii) problems with the magnitude of short-term geomorphological changes being at the threshold of detection, (iv) separating short-term variability from longer-term trends, and (v) of the representativeness of plot-scale field measurements for regionalisation and for upscaling. We consider that understanding of future climate change effects on proglacial systems requires holistic process-based modelling to explicitly consider feedbacks and linkages, especially between hillslope and valley-floor components. Such modelling must be informed by a new generation of repeated distributed topographic surveys to detect and quantify short-term geomorphological changes

Validation of the self regulation questionnaire as a measure of health in quality of life research

<p>Abstract</p> <p>Objectives</p> <p>Several epidemiological studies address psychosomatic 'self regulation' as a measure of quality of life aspects. However, although widely used in studies with a focus on complementary cancer treatment, and recognized to be associated with better survival of cancer patients, it is unclear what the 'self regulation' questionnaire exactly measures.</p> <p>Design and setting</p> <p>In a sample of 444 individuals (27% healthy, 33% cancer, 40% other internal diseases), we performed reliability and exploratory factor analyses, and correlated the 16-item instrument with external measures such as the Hospital Anxiety and Depression Scale, the Herdecke Quality of Life questionnaire, and autonomic regulation questionnaire.</p> <p>Results</p> <p>The 16-item pool had a very good internal consistency (Cronbach's alpha = 0.948) and satisfying/good (r_rt= 0.796) test-retest reliability after 3 months. Exploratory factor analysis indicated 2 sub-constructs: (1) Ability to change behaviour in order to reach goals, and (2) Achieve satisfaction and well-being. Both sub-scales correlated well with quality of life aspects, particularly with Initiative Power/Interest, Social Interactions, Mental Balance, and negatively with anxiety and depression.</p> <p>Conclusions</p> <p>The Self Regulation Questionnaire (SRQ) was found to be a valid and reliable tool which measures unique psychosomatic abilities. Self regulation deals with competence and autonomy and can be regarded as a problem solving capacity in terms of an active adaptation to stressful situations to restore wellbeing. The tool is an interesting option to be used particularly in complementary medicine research with a focus on behavioural modification.</p

Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance.

Mycobacterium tuberculosis is a serious human pathogen&nbsp;threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop a reference strain-agnostic computational platform that uses machine learning approaches, complemented by both genetic interaction analysis and 3D structural mutation-mapping, to identify signatures of AMR evolution to 13 antibiotics. This platform is applied to 1595 sequenced strains to yield four key results. First, a pan-genome analysis shows that M. tuberculosis is highly conserved with sequenced variation concentrated in PE/PPE/PGRS genes. Second, the platform corroborates 33 genes known to confer resistance and identifies 24 new genetic signatures of AMR. Third, 97 epistatic interactions across 10 resistance classes are revealed. Fourth, detailed structural analysis of these genes yields mechanistic bases for their selection. The platform can be used to study other human pathogens

Newtonian Cosmology in Lagrangian Formulation: Foundations and Perturbation Theory

The ``Newtonian'' theory of spatially unbounded, self--gravitating, pressureless continua in Lagrangian form is reconsidered. Following a review of the pertinent kinematics, we present alternative formulations of the Lagrangian evolution equations and establish conditions for the equivalence of the Lagrangian and Eulerian representations. We then distinguish open models based on Euclidean space $\R^3$ from closed models based (without loss of generality) on a flat torus \T^3. Using a simple averaging method we show that the spatially averaged variables of an inhomogeneous toroidal model form a spatially homogeneous ``background'' model and that the averages of open models, if they exist at all, in general do not obey the dynamical laws of homogeneous models. We then specialize to those inhomogeneous toroidal models whose (unique) backgrounds have a Hubble flow, and derive Lagrangian evolution equations which govern the (conformally rescaled) displacement of the inhomogeneous flow with respect to its homogeneous background. Finally, we set up an iteration scheme and prove that the resulting equations have unique solutions at any order for given initial data, while for open models there exist infinitely many different solutions for given data.Comment: submitted to G.R.G., TeX 30 pages; AEI preprint 01

The Cosmic No-Hair Theorem and the Nonlinear Stability of Homogeneous Newtonian Cosmological Models

The validity of the cosmic no-hair theorem is investigated in the context of Newtonian cosmology with a perfect fluid matter model and a positive cosmological constant. It is shown that if the initial data for an expanding cosmological model of this type is subjected to a small perturbation then the corresponding solution exists globally in the future and the perturbation decays in a way which can be described precisely. It is emphasized that no linearization of the equations or special symmetry assumptions are needed. The result can also be interpreted as a proof of the nonlinear stability of the homogeneous models. In order to prove the theorem we write the general solution as the sum of a homogeneous background and a perturbation. As a by-product of the analysis it is found that there is an invariant sense in which an inhomogeneous model can be regarded as a perturbation of a unique homogeneous model. A method is given for associating uniquely to each Newtonian cosmological model with compact spatial sections a spatially homogeneous model which incorporates its large-scale dynamics. This procedure appears very natural in the Newton-Cartan theory which we take as the starting point for Newtonian cosmology.Comment: 16 pages, MPA-AR-94-

Expression of target and reference genes in Daphnia magna exposed to ibuprofen

Background: Transcriptomic techniques are now being applied in ecotoxicology and toxicology to measure the impact of stressors and develop understanding of mechanisms of toxicity. Microarray technology in particular offers the potential to measure thousands of gene responses simultaneously. However, it is important that microarrays responses should be validated, at least initially, using real-time quantitative polymerase chain reaction (QPCR). The accurate measurement of target gene expression requires normalisation to an invariant internal control e. g., total RNA or reference genes. Reference genes are preferable, as they control for variation inherent in the cDNA synthesis and PCR. However, reference gene expression can vary between tissues and experimental conditions, which makes it crucial to validate them prior to application. Results: We evaluated 10 candidate reference genes for QPCR in Daphnia magna following a 24 h exposure to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen (IB) at 0, 20, 40 and 80 mg IB l(-1). Six of the 10 candidates appeared suitable for use as reference genes. As a robust approach, we used a combination normalisation factor (NF), calculated using the geNorm application, based on the geometric mean of three selected reference genes: glyceraldehyde-3-phosphate dehydrogenase, ubiquitin conjugating enzyme and actin. The effects of normalisation are illustrated using as target gene leukotriene B4 12-hydroxydehydrogenase (Ltb4dh), which was upregulated following 24 h exposure to 63-81 mg IB l(-1). Conclusions: As anticipated, use of the NF clarified the response of Ltb4dh in daphnids exposed to sublethal levels of ibuprofen. Our findings emphasise the importance in toxicogenomics of finding and applying invariant internal QPCR control(s) relevant to the study conditions

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations