Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo.

Examination of clinical samples indicates bacterial biofilms are present in the majority of chronic wounds, and substantial evidence suggests biofilms contribute significantly to delayed healing. Bacteria in biofilms are highly tolerant of antimicrobials, and little data exist to guide the choice of anti-biofilm wound therapy. Cadexomer iodine (CI) was recently reported to have superior efficacy compared to diverse wound dressings against Pseudomonas aeruginosa biofilms in an ex vivo model. In the current study, the strong performance of CI vs. P. aeruginosa biofilm was confirmed using colony and colony drip-flow in vitro wound biofilm models. Similar in vitro efficacy of CI was also demonstrated against mature Staphylococcus aureus biofilms using the same models. Additionally, the rapid kill of mature S. aureus and P. aeruginosa colony biofilms was visualized by confocal microscopy using Live/Dead fluorescent stains. Superior in vitro efficacy of CI vs. staphylococcal biofilms was further demonstrated against methicillin-resistant S. aureus (MRSA) using multiple biofilm models with log reduction, Live/Dead, and metabolic endpoints. Comparator antimicrobial dressings, including silver-based dressings used throughout and other active agents used in individual models, elucidated only limited effects against the mature biofilms. Given the promising in vitro activity, CI was tested in an established mouse model of MRSA wound biofilm. CI had significantly greater impact on MRSA biofilm in mouse wounds than silver dressings or mupirocin based on Gram-stained histology sections and quantitative microbiology from biopsy samples (>4 log reduction in CFU/g vs. 0.7-1.6, p < 0.0001). The superior efficacy for CI in these in vitro and in vivo models suggests CI topical products may represent a better choice to address established bacterial biofilm in chronic wounds.

Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease.

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P = 0.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

Small interfering RNAs that trigger posttranscriptional gene silencing are not required for the histone H3 Lys9 methylation necessary for transgenic tandem repeat stabilization in Neurospora crassa.

In Neurospora crassa, the introduction of a transgene can lead to small interfering RNA (siRNA)-mediated posttranscriptional gene silencing (PTGS) of homologous genes. siRNAs can also guide locus-specific methylation of Lys9 of histone H3 (Lys9H3) in Schizosaccharomyces pombe. Here we tested the hypothesis that transgenically derived siRNAs may contemporaneously both activate the PTGS mechanism and induce chromatin modifications at the transgene and the homologous endogenous gene. We carried out chromatin immunoprecipitation using a previously characterized albino-1 (al-1) silenced strain but detected no alterations in the pattern of histone modifications at the endogenous al-1 locus, suggesting that siRNAs produced from the transgenic locus do not trigger modifications in trans of those histones tested. Instead, we found that the transgenic locus was hypermethylated at Lys9H3 in our silenced strain and remained hypermethylated in the quelling defective mutants (qde), further demonstrating that the PTGS machinery is dispensable for Lys9H3 methylation. However, we found that a mutant in the histone Lys9H3 methyltransferase dim-5 was unable to maintain PTGS, with transgenic copies being rapidly lost, resulting in reversion of the silenced phenotype. These results indicate that the defect in PTGS of the Deltadim-5 strain is due to the inability to maintain the transgene in tandem, suggesting a role for DIM-5 in stabilizing such repeated sequences. We conclude that in Neurospora, siRNAs produced from the transgenic locus are used in the RNA-induced silencing complex-mediated PTGS pathway and do not communicate with an RNAi-induced initiation of transcriptional gene silencing complex to effect chromatin-based silencing.

The RNA-dependent RNA polymerase, QDE-1, is a rate-limiting factor in post-transcriptional gene silencing in Neurospora crassa.

The RNA-dependent RNA polymerase (RdRP) qde-1 is an essential component of post-transcriptional gene silencing (PTGS), termed 'quelling' in the fungus Neurospora crassa. Here we show that the overexpression of QDE-1 results in a dramatic increase in the efficiency of quelling, with a concomitant net increase in the quantity of al-1 siRNAs. Moreover, in overexpressed strains there is a significant reduction in the number of transgenes required to induce quelling, and an increase in the phenotypic stability despite progressive loss of tandemly repeated transgenes, which normally determines reversion of a silenced phenotype to wild type. These data suggest that the activation and maintenance of silencing in Neurospora appear to rely both on the cellular amount of QDE-1 and the amount of transgenic copies producing RNA molecules that act as a substrate for the RdRP, implicating QDE-1 as a rate-limiting factor in PTGS.

Mental health. Together we're stronger.

Ten mental health trusts will this year become four as the sector moves towards the 'super trust' model. The move is designed to help trusts compete with others, move towards foundation status and protect improvements after funding stops going up in 2008. With the new trusts to control budgets in the region of pounds sterling 290m, there are fears that their size could distance them from commissioners and service users.

Mental health. 'Death by a thousand pin pricks'.

People with mental health problems are subject to a variety of prejudices and inequalities affecting everything from promotion opportunities to social lives. Awareness campaigns in England have been hampered by a lack of funding while better-funded initiatives in Scotland and New Zealand have enjoyed wider success. Tackling stigma will only be effective if backed by legislation.

Mental health. Safe but sound.

A parliamentary pre-legislative scrutiny committee on the Mental Health Bill recommended separate legislation to deal with dangerous and severe personality disorder. There are concerns that policies place protection of the public above the therapeutic needs of the patient. Four pilot services have been set up to address blurred boundaries between custodial and therapeutic concerns, but evidence of their effectiveness remains inconclusive.

Mental health. Going places.

Almost 80 per cent of inpatient mental health nurses have witnessed violence or aggression. Inpatient units have been starved of resources to pay for community mental health teams. There are calls to make inpatient care a specialty as inpatients are by necessity the most needy.

Mental health. Barrier grief.

There is a belief in the mental health sector that poor commissioning is slowing modernisation. A problem has been identified in the balance of power, with large trusts providing services for several PCTs. The difficulty in measuring outcomes is key. Strong commissioning needs the involvement of carers and service users.

Mental health. Lone zone.

Over 1 million under-18s would benefit from specialist mental health services, but they are lacking. There is also a shortage of mental health inpatient beds for young people, and need is rising. Comprehensive CAMHS is expected throughout the NHS by 2006, but there are fears this will be impossible.

Mental health services. Must try harder.

Professor Louis Appleby's review sets out progress on mental healthcare reform, and future priorities. Spending is higher than ever, but there is still a lack of transparency around funding. More must be done to meet the needs of black and minority ethnic communities.

Mental health. Peak conditions.

Of 12 three-star rated trusts, eight are in contention to join the first wave of mental health foundations. Applicant trusts believe it will be an opportunity to raise the profile of mental health and remove stigma. Some observers believe the financial uncertainty associated with foundation status could endanger trusts.

Mental health. Beyond the fringe.

Black and minority ethnic patients are more likely to be diagnosed with schizophrenia and detained, more likely to receive high doses of medication and less likely to have access to talking therapies. Input from voluntary organisations and monitoring staff attitudes are crucial factors in tackling the problem.

Mental health. Inside job.

Four out of five prisoners suffer mental health problems. There are 139 liaison teams responsible for ensuring offenders are directed to hospitals where appropriate, but they are under-resourced and stretched to capacity. Mental health teams are working to reduce inappropriate referrals.

Mental health. The route to work.

There are over 1 million people currently claiming incapacity benefit because of mental health problems. Statistically, those that have been signed off work because of mental health problems are unlikely to return. South West London and St George's Mental Health trust is working on strategies to employ service users and improve their employment prospects.

Mental health. Stars in their eyes.

In 2004, Worcestershire Mental Health Partnership trust got zero stars and a damning report from the then Commission for Health Improvement. The resultant improvement strategy focused on promoting group ownership of organisational performance and ensuring that high-calibre leaders were in place to drive changes. In the final round of star-ratings, Worcestershire became the only mental health trust in the country to go from zero to three stars.

Buildings & facilities. So what's bugging you?

Infection control is increasingly in the media spotlight. NHS Estates is closing, causing confusion over cleanliness responsibilities. The Matron's Charter and the introduction of patient environment inspections will help clarify this. There are doubts over the assertion that one person could be held responsible for death caused by infection.

Mental health. The future is bright.

Lack of an alternative has trapped many users in undemanding day-service environments. New models are being developed to increase work opportunities. Extensive training will be needed.

Tsunami relief. After the wave.

With the official toll from the Boxing Day tsunami now standing at 300,000, Alexis Nolan and Emma Forrest talk to health service managers who gave more than money to the relief effort--they travelled to the disaster area and gave their time and expertise. The impact on their professional and personal lives was considerable. As Mathi Chandrakumar, clinical director of Kent Health Protection Unit, puts it: 'My heart is there, I feel very sad. I will probably go back.'

Regeneration. The generation aim.

In the late 1990s, Manchester had 27 out of 33 of the UK's top 10 per cent most deprived wards. The Wythenshawe Forum development aims to transform primary care and leisure facilities. Funding comes from a range of local, central and European sources.