Innovative solutions to novel drug development in mental health.

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders.

2009 Melbourne metropolitan sewerage strategy: a portfolio of decentralised and on-site concept designs.

The bulk and retail water companies of the greater Melbourne area are developing the 2009 Metropolitan Sewerage Strategy to provide sustainable sewerage services to 2060. The objective of the strategy is to establish long term principles and near term actions to produce a robust sewage management system for Melbourne. Melbourne's existing sewerage system is largely centralised and discharges to two major treatment plants. Several small satellite treatment plants service local urban areas generally more distant from the centralised system. Decentralised and on-site wastewater systems are options for future sewage management and could play a role in local recycling. A portfolio of 18 on-site and decentralised concept designs was developed, applicable to the full range of urban development types in Melbourne. The concepts can be used in evaluation of metropolitan system configurations as part of future integrated water cycle planning. The options included secondary and tertiary treatment systems incorporating re-use of water for non potable uses, urine separation, black and greywater separation and composting toilets. On-site and cluster treatment systems were analysed. Each option is described by its indicative capital and operating costs, energy use and water and nutrient balances. This paper summarises and compares the portfolio mix of decentralized and on-site options in Melbourne's context.

Multitrophic effects of nutrient addition in upland grassland.

Although the effects of nutrient enhancement on aquatic systems are well documented, the consequences of nutritional supplements on soil food webs are poorly understood, and results of past research examining bottom-up effects are often conflicting. In addition, many studies have failed to separate the effects of nutrient enrichment and the physical effects of adding organic matter. In this field study, we hypothesised that the addition of nitrogen to soil would result in a trophic cascade, through detritivores (Collembola) to predators (spiders), increasing invertebrate numbers and diversity. Nitrogen and lime were added to plots in an upland grassland in a randomised block design. Populations of Collembola and spiders were sampled by means of pitfall traps and identified to species. Seventeen species of Collembola were identified from the nitrogen plus lime (N+L) and control plots. Species assemblage, diversity, richness, evenness and total number were not affected by nutrient additions. However, there was an increase in the number of Isotomidae juveniles and Parisotoma anglicana trapped in the N+L plots. Of the 44 spider species identified, over 80% were Linyphiidae. An effect on species assemblage from the addition of N+L to the plots was observed on two of the four sampling dates (July 2002 and June 2003). The linyphiid, Oedothorax retusus, was the only species significantly affected by the treatments and was more likely to be trapped in the control plots.The increased number of juvenile Collembola, and change in community composition of spiders, were consequences of the bottom-up effect caused by nutrient inputs. However, despite efforts to eliminate the indirect effects of nutrient inputs, a reduction in soil moisture in the N+L plots cannot be eliminated as a cause of the invertebrate population changes observed. Even so, this experiment was not confounded by the physical effects of habitat structure reported in most previous studies. It provides evidence of moderate bottom-up influences of epigeic soil invertebrate food webs and distinguishes between nutrient addition and plant physical structure effects. It also emphasises the importance of understanding the effects of soil management practices on soil biodiversity, which is under increasing pressure from land development and food production.

Could nutritional rehabilitation at home complement or replace centre-based therapeutic feeding programmes for severe malnutrition?

To measure the success rate of three different strategies used in Médecins Sans Frontières large-scale therapeutic nutritional rehabilitation programme in Niger, we analysed three cohorts of severely malnourished patients in terms of daily weight gain, length of stay, recovery, case fatality and defaulting. A total of 1937 children aged 6-59 months were followed prospectively from 15 August 2002 to 21 October 2003. For the three cohorts, 660 children were maintained in the therapeutic feeding centre (TFC) during the entire treatment, 937 children were initially treated at the TFC and completed treatment at home and 340 children were exclusively treated at home. For all cohorts, average time in the programme and average weight gain met the international standards (30-40 days, >8 g/kg/day). Default rates were 28.1, 16.8 and 5.6% for TFC only, TFC plus home-based and home-based alone strategies, respectively. The overall case fatality rate for the entire programme was 6.8%. Case fatality rates were 18.9% for TFC only and 1.7% for home-based alone. No deaths were recorded in children transferred to rehabilitation at home. This study suggests that satisfactory results for the treatment of severe malnutrition can be achieved using a combination of home and hospital-based strategies.

Antioxidants and protein carbonyls in bronchoalveolar lavage fluid of children: normal data.

Antioxidant-oxidant imbalances in bronchoalveolar lavage fluid (BAL) are thought to contribute to oxidative stress in respiratory disease. However, normal reference ranges for BAL antioxidants and oxidized proteins in children are not available. In this study, we recruited 124 children attending for elective surgery for a noninflammatory condition; 83 were nonasthmatic, nonatopic (N) and 41 were nonasthmatic, atopic (NA). A nonbronchoscopic lavage was performed and ascorbate, uric acid, alpha-tocopherol, and protein carbonyl (as a measure of oxidative damage) concentrations were determined in BAL fluid. The 95% reference range was 0.112-1.897 micromol/L for ascorbate, 0.149-2.163 micromol/L for urate, 0.0029-0.066 micromol/L for alpha-tocopherol, and 0.280-4.529 nmol/mg for protein carbonyls in BAL fluid. Age, gender, and exposure to environmental tobacco smoke did not affect the concentration of ascorbate, urate, alpha-tocopherol, or protein carbonyls. However, in multiple linear regression analyses, the type of home heating (glass-fronted fires or oil-fired central heating) was found to influence ascorbate and urate concentrations in the BAL fluid (ss-coefficient for ascorbate: 0.445, p = 0.031; for urate: 0.114, p = 0.001). There was no significant difference between the N and NA group in BAL fluid concentrations of ascorbate, urate, or protein carbonyls. The alpha-tocopherol concentration was significantly increased in the NA group (p = 0.037). Uric acid and alpha-tocopherol concentrations in BAL fluid and serum were not correlated. Intriguingly, serum and BAL ascorbate concentrations were significantly correlated (r = 0.297, p = 0.018, n = 63), which may offer an explanation for why supplementing the diet with vitamin C can improve asthma symptoms. Further studies will investigate the role of BAL antioxidant concentrations in children with inflammatory respiratory diseases.

Compression therapy in leg ulcer management.

Leg ulcer management is an important consideration for all nurses involved in the care of older people. Non-specialists in tissue viability might not always be aware of the evidence base for best practice. The authors examine the effectiveness of multilayer and single-layer long- or short-stretch bandage systems in leg ulcer management.

Thalamic reticular nucleus activation reflects attentional gating during classical conditioning.

All senses, except olfaction, are routed through the thalamus to cerebral cortex. Thus, the thalamus is often referred to as the sensory gateway to cortex. Located between thalamus and cortex is a thin lamina of neurons called the thalamic reticular nucleus, which may function as an attentional gate. The phenomenon of blocking in classical conditioning provides an opportunity to test whether an attended stimulus activates the thalamic reticular nucleus more than an unattended stimulus: when a second stimulus is presented together with a previously conditioned stimulus, conditioned responding to the second stimulus is inhibited. Different groups of rats were given conditioning sessions with a single stimulus, a light or a tone, and then given conditioning sessions with compound (light and tone) stimuli. Blocking was confirmed using probe trials of single stimulus presentations. After a final test session of compound stimulus presentations, the brains were processed for the presence of Fos protein. Here we show that Fos-positive neurons were more numerous in the sector of the thalamic reticular nucleus associated with the attended conditioned stimulus than in the sector associated with the unattended stimulus. Thus, we provide evidence for an involvement of the thalamic reticular nucleus in selective attention.

5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects.

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.

Challenges in moving from a traditional therapeutic community to a women and children's TC model.

With the advent of specialized programs for addicted women and their children, some of the traditional methods used by therapeutic communities have been undergoing significant changes. This article examines the issues that are important for treatment providers to consider as they move from individual client and community orientation to a mother-child/family-centered and community approach. The major adaptations suggested are divided into three categories: structural design issues, including living arrangements and models of childcare; treatment issues, including acting-out behavior by the children; and staff and training issues, including staff composition.

Hidradenitis suppurativa of the anogenital region: response to isotretinoin.

Hidradenitis suppurativa, a chronic relapsing disease of apocrine gland-bearing areas, most frequently occurs in the axillae, groin, perineal, and perianal regions. Hidradenitis of vulva is frequently misdiagnosed and inadequately treated. The case of a 15-year-old nulliparous black female adolescent referred for evaluation of multiple draining fistulas of the anogenital region is presented. Diagnostic studies for granulomatous disease were negative. Results of a barium enema were normal and biopsies were compatible with the diagnosis of hidradenitis suppurativa. She was treated for 22 weeks with isotretinoin, 1 mg/kg daily, with an excellent response. Side effects were minor and included cheilitis, mild xerosis, and a transient elevation of serum alkaline phosphatase levels. Few patients with severe hidradenitis have been responsive to this synthetic vitamin A derivative. A review of the literature indicates that the results of treatment with isotretinoin for hidradenitis have been at best equivocal. Isotretinoin should never be used during pregnancy because of known teratogenic effects. Women of childbearing age must use effective contraception during treatment.

Controlled trial of acupuncture for disabling breathlessness.

In a randomised controlled trial, twelve matched pairs of patients with chronic obstructive pulmonary disease received traditional Chinese acupuncture or placebo acupuncture. After three weeks' treatment the traditional-acupuncture group showed significantly greater benefit in terms of subjective scores of breathlessness and six-minute walking distance. Objective measures of lung function were unchanged in either group. Whether these differences are mediated by endogenous opiate and/or peptide release remains speculative.

Decontamination procedures for skin exposed to phenolic substances.

Spraying or swabbing with a mixture of polyethylene glycol 300/industrial methylated spirits (PEG-300/IMS) (2:1 by volume) has been shown to substantially reduce mortality, systemic effects, and skin burns resulting from skin contamination by phenol, cumene hydroperoxide, or phenol/acetone cleavage product. The skin-damaging potentials of sodium hydroxide and sulfuric acid have also been investigated. PEG-300/IMS(2:1 by volume) mixture was found, in rats, to be slightly less effective than water as means of decontamination. The PEG-300/IMS mixture has been shown not to cause eye irritation, and so should not present a hazard where this mixture is used as a decontaminant spray.