Novel MMP-inhibiting peptides for stabilizing atherosclerotic plaques

Aim: Matrix-degrading metalloproteases (MMPs) play an essential role in the atherogenic process, from the initial lesion to plaque rupture. A growing body of evidence show that inhibition of MMP activity or rebalancing the MMP/TIMP (tissue inhibitor of MMP) equilibrium has a potential therapeutic strategy for atherosclerosis. We studied the in vitro effects of newly designed peptides on MMP activity in endothelial cells and macrophages. Methods: Eight peptides were designed in silico and synthesized using the solid phase synthesis and characterized by circular dichroism and Dynamic Light Scattering. The mouse macrophage cell line J774A.1 and the human endothelial cell line EA.hy926 were treated with the peptides (10 \ub5\uf06dM and 10 \ub5\uf06dM) for 24 hours. Then, conditioned medium was collected and MMP-2, and MMP-9 activity was determined by gelatin gel zymography. Results: Analysis of the zymograms showed that upon 10 \ub5M treatment in endothelial cells, three out of eight peptides reduced the activity of proMMP-9 and proMMP-2 by more than 60 and 40 percent, respectively. Whereas, upon treatment at 100 \ub5M the proMMP-9 levels were less or not reduced. These could be consequent to aggregation of the peptide at a concentration higher than 50 \ub5\uf06dM. In macrophages, two of these peptides reduced the activity of proMMP-2 by more than 40 percent, but had no effect on proMMP-9 activity. The peptides, did not show any effects on MMP mRNA levels. Conclusions: These data show that these peptides show a promising inhibitory effect on MMP-9 and MMP-2 activity in endothelial cells and macrophages

The effect of two speech and language approaches on speech problems in people with Parkinson’s disease: the PD COMM RCT

Background Speech impairments are common with Parkinson’s disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. Objective(s) The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson’s disease to no speech and language therapy (control) and against each other. Design PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. Setting United Kingdom outpatient and home settings. Participants People with idiopathic Parkinson’s disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. Interventions The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Main outcome measures Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson’s Disease Questionnaire – Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Results Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [−8.0 (99% confidence interval: −13.3, −2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: −3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: −9.6 (−14.9, −4.4); p < 0.0001]. There were no reports of serious adverse events. Staff were confident with the trial interventions; a range of patient and therapist enablers of implementing Lee Silverman Voice Treatment LOUD were identified. The economic evaluation results suggested Lee Silverman Voice Treatment LOUD was more expensive and more effective than control or National Health Service speech and language therapy but was not cost-effective with incremental cost-effectiveness ratios of £197,772 per quality-adjusted life-year gained and £77,017 per quality-adjusted life-year gained, respectively. Limitations The number of participants recruited to the trial did not meet the pre-specified power. Conclusions People that had access to Lee Silverman Voice Treatment LOUD described a significantly greater reduction in the impact of their Parkinson’s disease-related speech problems 3 months after randomisation compared to people that had no speech and language therapy. There was no evidence of a difference between National Health Service speech and language therapy and those that received no speech and language therapy. Lee Silverman Voice Treatment LOUD resulted in a significantly lower impact of voice problems compared to National Health Service speech and language therapy 3 months after randomisation which was still present after 12 months; however, Lee Silverman Voice Treatment LOUD was not found to be cost-effective. Future work Implementing Lee Silverman Voice Treatment LOUD in the National Health Service and identifying alternatives to Lee Silverman Voice Treatment LOUD for those who cannot tolerate it. Investigation of less costly alternative options for Lee Silverman Voice Treatment delivery require investigation, with economic evaluation using a preference-based outcome measure that captures improvement in communication

Angular and energy dependence of ion bombardment of Mo/Si multilayers

The process of ion bombardment is investigated for the fabrication of Mo/Si multilayer x-ray mirrors using e-beam evaporation. The ion treatment is applied immediately after deposition of each of the Si layers to smoothen the layers by removing an additional thickness of the Si layer. In this study the parameters of Kr+ ion bombardment have been optimized within the energy range 300 eV-2 keV and an angular range between 20 degrees and 50 degrees. The optical performance of the Mo/Si multilayers is determined by absolute measurements of the near-normal-incidence reflectivity at 14.4 nm wavelength. The multilayer structures are analyzed further with small-angle reflectivity measurements using both specular reflectivity and diffuse x-ray scattering. The optimal smoothening parameters are obtained by determining the effect of ion bombardment on the interface roughness of the Si layer. The optimal conditions are found to be 2 keV at 50 degrees angle of incidence with respect to the surface. These settings result in 47% reflectivity at 85 degrees (lambda = 14.4 nm) for a 16-period Mo/Si multilayer mirror, corresponding to an interface roughness of 0.21 nm rms. Analysis shows that the interface roughness is determined by ion induced viscous flow, an effect which increases with ion energy as well as angle of incidence. In order to determine the effect of intermixing of the Si and Mo atoms, the penetration depth of the Kr+ ions is calculated as a function of ion energy and angle of incidence. Furthermore, the angular dependence of the etch yield, obtained from the in situ reflectivity measurements, is investigated in order o determine the optimal ion beam parameters for the production of multilayer mirrors on curved substrates. (C) 1997 American Institute of Physics

Conservation status of marine biodiversity of the Western Indian Ocean

The Western Indian Ocean is comprised of productive and highly diverse marine ecosystems that are rich sources of food security, livelihoods, and natural wonder. The ecological services that species provide are vital to the productivity of these ecosystems and healthy biodiversity is essential for the continued support of economies and local users. The stability of these valuable resources, however, is being eroded by growing threats to marine life from overexploitation, habitat degradation and climate change, all of which are causing serious reductions in marine ecosystem services and the ability of these ecosystems to support human communities. Quantifying the impacts of these threats and understanding the conservation status of the region’s marine biodiversity is a critical step in applying informed management and conservation measures to mitigate loss and retain the ecological value of these systems. This report highlights trends in research needs for species in the region, including priorities for fundamental biological and ecological research and quantifying trends in the populations of species. The assessments and analyses submitted in this report should inform conservation decision-making processes and will be valuable to policymakers, natural resource managers, environmental planners and NGOs

Improving sexual health through partner notification : the LUSTRUM mixed-methods research Programme including RCT of accelerated partner therapy

Background Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission develop and cost partner notification interventions for men who have sex with men. Design Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings Sexual health clinics and community services in England and Scotland. Participants Women and men, including men who have sex with men and people with mild learning disabilities. Interventions Accelerated partner therapy offered as an additional partner notification method. Main outcome measures Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system. In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixty-six (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of gonorrhoea and human immunodeficiency virus co-infection in men who have sex with men was technically challenging. Limitations In the randomised controlled trial, enrolment, follow-up and repeat infections were lower than expected, so statistical power was lower than anticipated. We were unable to determine whether accelerated partner therapy sped up partner treatment. Mathematical modelling of gonorrhoea/human immunodeficiency virus co-infection in men who have sex with men remained at an experimental stage. It was not feasible to include healthcare professionals in the men who have sex with men intervention development due to the COVID-19 pandemic. Conclusions Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving, but is best suited to sex partners with emotional connection to the index patient. The Programme’s findings about classification of sexual partner types can be implemented in sexual health care with auditable outcomes. Future work Further research is needed on how to increase uptake of accelerated partner therapy and increase sexually transmitted infections self-sampling by partners; understand how services can use partnership-type information to improve partner notification, especially for those currently underserved; overcome challenges in modelling sexually transmitted infections and human immunodeficiency virus co-infection in men who have sex with men; develop and evaluate an intervention to optimise partner notification among men who have sex with men, focusing on one-off partnerships. Trial registration This trial is registered as ISRCTN15996256. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0614-20009) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information

COMBINED ENERGY SYSTEMS BASED ON RENEWABLE ENERGY SOURCES

Ensuring the quality of energy supply to remote regions is relevant for grid companies and the state. One of the solutions to this problem is the use of renewable energy sources to generate electrical energy. Given this, the article considers an integrated approach to designing combined autonomous energy systems of an individual residential building based on renewable energy sources with the complete replacement of traditional energy carriers. In addition to the combined power system, the proposed solution implies using an insulated facade of the building, which will reduce heat loss by 1.5 times, compared with an un-insulated building. to increase the reliability of the energy supply, the project provides for a wind power plant, a backup diesel generator station and a battery pack with an inverter. Estimated calculations have shown that the probability of failure of the power system of this configuration is 3%. The conducted ecological and economic justification of the use of an autonomous combined power system allows us to conclude that 2.1 tons of conventional fuel per year is saved and the payback of the energy supply system for a period of up to 8 years. © 2023, MM publishing Ltd.. All rights reserved