Scald risk in social housing can be reduced through thermostatic control system without increasing Legionella risk: a cluster randomised trial.

OBJECTIVE: To quantify the effects of a thermostatic control system in social (public) housing on the prevalence of dangerous (>60°C) water temperatures and on fuel consumption. DESIGN: Pair-matched double-blind cluster randomised controlled trial. SETTING: Social housing in a deprived inner-London borough. PARTICIPANTS: 150 households recruited as clusters from 22 social housing estates. Four small estates were combined into two clusters (resulting in a total of 10 pairs of clusters). INTERVENTION: Social housing estate boiler houses were randomised to a thermostatic control sterilisation programme (heating water to 65°C during 00:00-06:00 h and to 50°C from 06:00 to 00:00 h daily) or to standard control (constant temperature 65°C). MAIN OUTCOME MEASURES: Water temperature over 60°C ('dangerous') after running taps for 1 min and daily fuel consumption (cubic feet of gas). RESULTS: 10 clusters (80 households) were allocated to the sterilisation programme and 10 clusters (70 households) to control, of which 73 and 67 households, respectively, were analysed. Prevalence of dangerous (>60°C) hot water temperatures at 1 min was significantly reduced with the sterilisation programme (mean of cluster prevalence 1% in sterilisation programme group vs 34% in control group; absolute difference 33%, 95% CI 12% to 54%; p=0.006). Prevalence of high (>55°C) hot water temperatures at 1 min was significantly reduced (31% sterilisation vs 59% control; absolute difference 28%, 95% CI 9% to 47%; p=0.009). Gas consumption per day reduced more in the control group than in the sterilisation programme group, although not statistically significantly (p=0.125). CONCLUSIONS: The thermostatic control with daily sterilisation was effective in capping hot water temperatures and therefore reduced scald risk. Although expected to save energy, fuel consumption was increased relative to the control group. Trial registration ClinicalTrials.gov ID: NCT00874692

Development of Highly Repellent Silica Particles for Protection of Hemp Shiv Used as Insulation Materials.

New bio-materials have recently gained interest for use in insulation panels in walls, but wider adoption by the building industry is hindered by their intrinsic properties. The fact that such materials are mainly composed of cellulose makes them combustible, and their hydrophilic surface presents a high water uptake, which would lead to faster biodegradation. A hydrophobic treatment with silica particles was successfully synthesised via Stöber process, characterised, and deposited on hemp shiv. The surface of hemp shiv coated several times with 45 and 120 nm particles were uniformly covered, as well as extensively water repellent. Those samples could withstand in humidity chamber without loss of their hydrophobic property and no sign of mould growth after 72 h of exposure

An evaluation of a public-private partnership to reduce artificial trans fatty acids in England, 2011-16.

The Public Health Responsibility Deal (RD) is a public-private partnership in England involving voluntary pledges between government, and business and other public organizations to improve public health. One such voluntary pledge refers to the reduction of trans fatty acids (TFAs) in the food supply in England by either pledging not to use artificial TFAs or pledging artificial TFA removal. This paper evaluates the RD's effectiveness at encouraging signatory organizations to remove artificially produced TFAs from their products. We analysed publically available data submitted by RD signatory organizations. We analysed their plans and progress towards achieving the TFAs pledge, comparing 2015 progress reports against their delivery plans. We also assessed the extent to which TFAs reductions beyond pre-2011 levels could be attributed to the RD. Voluntary reformulation via the RD has had limited added value, because the first part of the trans fat pledge simply requires organizations to confirm that they do not use TFAs and the second part, that has the potential to reduce use, has failed to attract the participation of food producers, particularly those producing fast foods and takeaways, where most remaining use of artificial TFAs is located. The contribution of the RD TFAs pledges in reducing artificial TFAs from England's food supply beyond pre-2011 levels appears to be negligible. This research has wider implications for the growing international evidence base voluntary food policy, and offers insights for other countries currently undertaking work to remove TFAs from their food supply

An evaluation of the Public Health Responsibility Deal: Informants' experiences and views of the development, implementation and achievements of a pledge-based, public-private partnership to improve population health in England.

: The Coalition Government's Public Health Responsibility Deal (RD) was launched in England in 2011 as a public-private partnership designed to improve public health in the areas of food, alcohol, health at work and physical activity. As part of a larger evaluation, we explored informants' experiences and views about the RD's development, implementation and achievements. : We conducted 44 semi-structured interviews with 50 interviewees, purposively sampled from: RD partners (businesses, public sector and non-governmental organisations); individuals with formal roles in implementing the RD; and non-partners and former partners. Data were analysed thematically: NVivo (10) software was employed to manage the data. : Key motivations underpinning participation were corporate social responsibility and reputational enhancement. Being a partner often involved making pledges related to work already underway or planned before joining the RD, suggesting limited 'added value' from the RD, although some pledge achievements (e.g., food reformulation) were described. Benefits included access to government, while drawbacks included resource implications and the risk of an 'uneven playing field' between partners and non-partners. : To ensure that voluntary agreements like the RD produce gains to public health that would not otherwise have occurred, government needs to: increase participation and compliance through incentives and sanctions, including those affecting organisational reputation; create greater visibility of voluntary agreements; and increase scrutiny and monitoring of partners' pledge activities.<br/

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins

Objective—We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Approach and Results—Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Conclusions—Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction

Provision of information to consumers about the calorie content of alcoholic drinks: did the Responsibility Deal pledge by alcohol retailers and producers increase the availability of calorie information?

Alcohol is a significant source of dietary calories and is a contributor to obesity. Industry pledges to provide calorie information to consumers have been cited as reasons for not introducing mandatory ingredient labelling. As part of the Public Health Responsibility Deal (RD) in England, alcohol retailers and producers committed to providing consumers with information on the calorie content of alcoholic drinks. This study examines what was achieved following this commitment and considers the implications for current industry commitments to provide information on alcohol calories. Analysis of RD pledge delivery plans and progress reports. Assessment of calorie information in supermarkets and in online stores. (i) Analysis of the content of pledge delivery plans and annual progress reports of RD signatories to determine what action they had committed to, and had taken, to provide calorie information. (ii) Analysis of the availability of calorie information on product labels; in UK supermarkets; and on online shopping sites and websites. No information was provided in any of 55 stores chosen to represent all the main UK supermarkets. Calorie information was not routinely provided on supermarkets' websites, or on product labels. One of the stated purposes of the RD was to provide consumers with the information to make informed health-related choices, including providing information on the calorie content of alcoholic drinks. This study indicates that this did not take place to any significant extent. The voluntary implementation of alcohol calorie labelling by industry needs to continue to be carefully monitored to determine whether and how it is done

Getting England to be more physically active: are the Public Health Responsibility Deal's physical activity pledges the answer?

BACKGROUND: The Public Health Responsibility Deal (RD) in England is a public-private partnership involving voluntary pledges between government, industry, and other organisations to improve public health by addressing alcohol, food, health at work, and physical activity. This paper analyses the RD physical activity (PA) pledges in terms of the evidence of their potential effectiveness, and the likelihood that they have motivated actions among organisations that would not otherwise have taken place. METHODS: We systematically reviewed evidence of the effectiveness of interventions proposed in four PA pledges of the RD, namely, those on physical activity in the community; physical activity guidelines; active travel; and physical activity in the workplace. We then analysed publically available data on RD signatory organisations' plans and progress towards achieving the physical activity pledges, and assessed the extent to which activities among organisations could be attributed to the RD. RESULTS: Where combined with environmental approaches, interventions such as mass media campaigns to communicate the benefits of physical activity, active travel in children and adults, and workplace-related interventions could in principle be effective, if fully implemented. However, most activities proposed by each PA pledge involved providing information or enabling choice, which has limited effectiveness. Moreover, it was difficult to establish the extent of implementation of pledges within organisations, given that progress reports were mostly unavailable, and, where provided, it was difficult to ascertain their relevance to the RD pledges. Finally, 15 % of interventions listed in organisations' delivery plans were judged to be the result of participation in the RD, meaning that most actions taken by organisations were likely already under way, regardless of the RD. CONCLUSIONS: Irrespective of the nature of a public health policy to encourage physical activity, targets need to be evidence-based, well-defined, measurable and encourage organisations to go beyond business as usual. RD physical activity targets do not adequately fulfill these criteria

Photoreceptor rescue and toxicity induced by different calpain inhibitors.

Photoreceptor degeneration is the hallmark of a group of inherited blinding diseases collectively termed retinitis pigmentosa (RP); a major cause of blindness in humans. RP is at present untreatable and the underlying neurodegenerative mechanisms are largely unknown, even though the genetic causes are often established. The activation of calpain-type proteases may play an important role in cell death in various neuronal tissues, including the retina. We therefore tested the efficacy of two different calpain inhibitors in preventing cell death in the retinal degeneration (rd1) human homologous mouse model for RP. Pharmacological inhibition of calpain activity in rd1 organotypic retinal explants had ambiguous effects on photoreceptor viability. Calpain inhibitor XI had protective effects when applied for short periods of time (16 h) but demonstrated substantial levels of toxicity in both wild-type and rd1 retina when used over several days. In contrast, the highly specific calpain inhibitor calpastatin peptide reduced photoreceptor cell death in vitro after both short and prolonged exposure, an effect that was also evident after in vivo application via intravitreal injection. These findings highlight the importance of calpain activation for photoreceptor cell death but also for photoreceptor survival and propose the use of highly specific calpain inhibitors to prevent or delay RP

The crystal structure of Trz1, the long form RNase Z from yeast.

tRNAs are synthesized as precursor RNAs that have to undergo processing steps to become functional. Yeast Trz1 is a key endoribonuclease involved in the 3΄ maturation of tRNAs in all domains of life. It is a member of the β-lactamase family of RNases, characterized by an HxHxDH sequence motif involved in coordination of catalytic Zn-ions. The RNase Z family consists of two subfamilies: the short (250-400 residues) and the long forms (about double in size). Short form RNase Z enzymes act as homodimers: one subunit embraces tRNA with a protruding arm, while the other provides the catalytic site. The long form is thought to contain two fused β-lactamase domains within a single polypeptide. Only structures of short form RNase Z enzymes are known. Here we present the 3.1 Å crystal structure of the long-form Trz1 from Saccharomyces cerevisiae. Trz1 is organized into two β-lactamase domains connected by a long linker. The N-terminal domain has lost its catalytic residues, but retains the long flexible arm that is important for tRNA binding, while it is the other way around in the C-terminal domain. Trz1 likely evolved from a duplication and fusion of the gene encoding the monomeric short form RNase Z

Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue

Background. Streptococcus pneumoniae causes serious diseases such as pneumonia and meningitis. Its major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, which produces lytic pores at high concentrations. At low concentrations, it has other effects, including induction of apoptosis. Many cellular effects of pneumolysin appear to be calcium dependent. Methods. Live imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at various concentrations of extracellular calcium was used to measure changes in cellular permeability (as judged by lactate dehydrogenase release and propidium iodide chromatin staining). Individual pore properties were analyzed by conductance across artificial lipid bilayer. Tissue toxicity was studied in continuously oxygenated acute brain slices. Results. The reduction of extracellular calcium increased the lytic capacity of the toxin due to increased membrane binding. Reduction of calcium did not influence the conductance properties of individual toxin pores. In acute cortical brain slices, the reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to pathophysiologically relevant nonlytic concentrations of pneumolysin. Conclusions. Reduction of extracellular calcium strongly enhanced the lytic capacity of pneumolysin due to increased membrane binding. Thus, extracellular calcium concentration should be considered as a factor of primary importance for the course of pneumococcal meningitis