Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base

A hybrid radiation detector for simultaneous spatial and temporal dosimetry

In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D experimental measurement of a radiation field. This hybrid dosimeter was irradiated with a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this work are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Pregnancy related back pain, is it related to aerobic fitness? A longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Low back pain with onset during pregnancy is common and approximately one out of three women have disabling pain. The pathogenesis of the pain condition is uncertain and there is no information on the role of physical fitness. Whether poorer physical conditioning is a cause or effect of back pain is also disputed and information from prospective studies needed.</p> <p>Methods</p> <p>A cohort of pregnant women, recruited from maternal health care centers in central Sweden, were examined regarding estimated peak oxygen uptake by cycle ergometer test in early pregnancy, reported physical activity prior to pregnancy, basic characteristics, back pain during pregnancy and back pain postpartum.</p> <p>Results</p> <p>Back pain during the current pregnancy was reported by nearly 80% of the women. At the postpartum appointment this prevalence was 40%. No association was displayed between estimated peak oxygen uptake and incidence of back pain during and after pregnancy, adjusted for physical activity, back pain before present pregnancy, previous deliveries, age and weight. A significant inverse association was found between estimated peak oxygen uptake and back pain intensity during pregnancy and a direct association post partum, in a fully adjusted multiple linear regression analysis.</p> <p>Conclusions</p> <p>Estimated peak oxygen uptake and reported physical activity in early pregnancy displayed no influence on the onset of subsequent back pain during or after pregnancy, where the time sequence support the hypothesis that poorer physical deconditioning is not a cause but a consequence of the back pain condition. The mechanism for the attenuating effect of increased oxygen uptake on back pain intensity is uncertain.</p

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle

The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight0.262 =0.95 + 0.022 × girth which has an R2 value of 0.98 and 95 % prediction intervals that fall within the ±20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure