Assessing and managing mental health issues in people with chronic skin conditions

Chronic skin conditions, such as atopic eczema and psoriasis, can have significant psychological effects on patients. For example, these conditions can affect an individual’s functioning, and may lead to mental health issues such as depression or anxiety disorders. This article identifies the links between chronic skin conditions and mental health issues, and discusses the nurse’s role in assessing, managing and supporting patients with these comorbidities. It also emphasises the importance of using validated tools and a holistic approach to care, and discusses how to address challenges that patients may experience

A Research Agenda for Helminth Diseases of Humans: Intervention for Control and Elimination

Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA) of anthelmintic drugs (donated or available at low cost) and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations). To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis and food-borne trematodiases, will need to be integrated with monitoring, education, sanitation, access to health services, and where appropriate, vector control or reduction of the parasite reservoir in alternative hosts. Based on an analysis of current knowledge gaps and identification of priorities, a research and development agenda for intervention tools considered necessary for control and elimination of human helminthiases is presented, and the challenges to be confronted are discussed

Studies in the chemistry of flavins and flavoproteins

This thesis is concerned with properties of the excited states of flavins. They may be involved in some photobiological processes and are models for flavoprotein catalysis. Understanding the spectral properties of flavins is important for interpreting the nature of intermolecular interactions in flavoproteins. The absorption spectra of many flavin derivatives are similar, but the two long wavelength bands are sensitive to both solvent and substituents. Two independent methods for finding the angle between these absorption oscillators are described. The first, measurement of the fluorescence polarisation of a random but rigid array of the chromophore, is a well known technique. The second is novel, and requires the preparation of a partially ordered solution of flavin by selective blanching with plane polarised light of wavelengths absorbed by only one of the absorption bands. The theory of this technique is developed, and it shows that the angle between the absorption oscillators can be calculated from the dichroic ratios of the extinctions of the two bands after bleaching. This angle does not vary much for different flavins, and the same value (around 30°) is found from both fluorescence polarisation and dichroic bleaching. The directions of the oscillators relative to the axes of the molecule cannot be measured by either technique, but the effects of substituents on absorption spectra suggest that the visible band is polarised approximately parallel to the long axis of the flavin. The first excited singlet of a flavin loses some of its energy by emission as fluorescence, but it also participates in singlet-to-singlet energy transfer. This is demonstrated by fluorescence for two flavin derivatives, using a methyl cellulose film as the supporting matrix. Optical observations are possible under these conditions at higher flavin concentrations than are easily studied in liquid solutions. Excited singlets may also lose energy by intersystem crossing to the lowest triplet state, but no delayed light emission can be detected from aqueous flavin solutions. In a rigid polyacrylamide matrix, however, there is delayed emission, even at room temperature. This is identified as E-type delayed fluorescence on the basic of its spectrum, its temperature and its exciting light intensity dependence. At lower temperatures the delayed fluorescence decreases, and phosphorescence emission dominates. The intensities and lifetimes of the delayed emissions of 12 flavins have been measured in the range 77°-315°K. On plotting the logarithm of intensity or of the reciprocal of half-life (decay is exponential) against the reciprocal of temperature biphasic Arrhenius plots are obtained. These can be interpreted in terms of the activation energies of the various rate processes associated with triplet production and inactivation. The activation energies from delayed fluorescence intensities and half-lives (5.9 and 2.6 kcal/mole respectively for FMN) add to a value close to the energy separating the spectroscopic fluorescence and phosphorescence maxima. A kinetic scheme is proposed to account for this. The activation energy for non-radiative decay of the triplet to the ground state can be calculated from the temperature dependence of phosphorescence, and values of about 100 cal/mole are found. Photochemical reactions of the flavin triplet both in the presence and absence of oxygen have been studied. Anaerobically flavins photo-oxidise many amino acids and amines in their high pH forms, with production of dihydroflavin. When DL-phenylglycine is the reducing agent equimolar amounts of benzaldehyde, carbon dioxide and dihydroflavin are produced. The dependence of reaction rate on reducing agent concentration shows saturation behaviour at high concentrations, which is consistent with a steady state kinetic treatment for the reaction. The sensitivity of rates to substituents in the DL-phenylglycine can be described by a Hammett ρ-value of −1.1. On the basis of their photo reactivities towards a series of flavin derivatives it is suggested that DL-phenylglycine and benzylamine react with a similar rate determining step (probably hydrogen abstraction). This is different from the photoaddition of phenylacetate. Anaerobic photoreductions are quenched by some aromatic compounds. From the effects of temperature and by comparison with quenching by potassium iodide it is concluded that inhibition is not simply a collisional process. FAD reacts more slowly in photo seduction than FMN, but in concentrated urea solutions the difference is reduced. Inhibition by aromatic compounds is also reduced under these conditions. This surges to that the forces between flavin triplet and quencher are at least partially hydrophobic. Aerobic flavin photochemistry is followed by measuring oxygen uptake. Two general types of behaviour are found for oxygen concentrations from 2 μM upwards. Either the reaction rate increases as oxygen is consumed (type I) or it falls (type II). The type I reaction pathway is slow photoreduction followed by rapid reoxidation of dihydroflavin. Evidence for this comes from the dependence of reaction rate on oxygen concentration and pH, and from the Hammett ρ-value for substituted phenylglycines which is similar to that of anaerobic photoreduction. Oxygen is also a triplet quencher. Rate constants for the reduction and quenching of FMN triplets by EDTA, diethanolamine and DL-phenylglycine (all type I substrates) are deduced from the dependence of reaction rates on oxygen concentration. In each case quenching is over 10 times as efficient as reaction. The rate constants for all three substrates are similar, increasing in the order DL-phenylglycine &lt; EDTA &lt; diethanolamine. The values for EDTA are 1.38⋅107 M−1sec−1 for reaction and 1.6⋅108 M−1sec−1 for quenching. These rate constants can be used to predict a concentration dependence of anaerobic photoreduction which agrees well with experiment. The most likely mechanism for quenching is a rapidly reversed electron transfer. Whereas type I substrates are reducing agents for flavin triplets, type II substrates are typically aromatic molecules which quench anaerobic photoreduction. Tryptophan, for example, has type II kinetics and reacts by a complex mechanism in which product inhibition of reaction occurs. The potential of flavin photosensitized destruction of amino acids as a method for selective chemical modification of proteins is investigated. Tryptophan, tyrosine, histidine, methionine, cysteine and phenylalanine all react but none of them has the same pH-profile of reactivity. Preliminary experiments on two proteins, L-glutamate dehydrogenase and D-amino acid oxidase show that the method has promise. An investigation of the behaviour of flavins when they act as Hill oxidants with isolated spinach chloroplasts has also been made. In this reaction light is absorbed t-y the chloroplast and flavin reacts in its ground state. The rates of reduction of 10 derivatives have been compared. The order of reactivity la different from that found for some model systems; dark reduction by NADH or dihydrolipoic acid, the redox potentials, and -photo re duct ion by DL-phenylglycine. The rates are independent of flavin concentration, but vary with the concentration of chloroplasts and light intensity. It is suggested that the reactivity to reduction by chloroplasts depends on binding between chloroplasts and flavin as well as on the electronic character of the flavin. The partition coefficients of flavins between water and butan-1-ol lend some support to this hypothesis.</p