Search

[This corrects the article DOI: 10.1371/journal.pone.0160078.].

Silver nanoparticles (Ag NPs) are known to have antibacterial properties. They are commonly produced by chemical synthesis which involves the use of harmful reducing agents. Contras, the laser technique is able to generate high-purity Ag NPs in water with specified surface charge characteristics. In the past, the molecular mechanisms contributing to the bactericidal effects of Ag NPs have been investigated extensively, but little is known of the antibacterial and toxic effects and mechanisms involved in laser-generated Ag NPs. In the current study Ag NPs were generated by picosecond laser ablation. Their antibacterial activity was determined on the gram-negative bacteria E. coli and Pseudomonas aeruginosa, and the gram positive bacteria Staphylococcus aureus including the methicillin resistant strain MRSA. Results showed that the laser generated Ag NPs exhibited strong dose-dependent antibacterial activity against all the three bacterial strains tested. Using E.coli as a model system, the laser Ag NPs treatment induced significantly high levels of reactive oxygen species (ROS). These ROS did not include detectable hydroxyl radicals, suggesting for the first time the selective ROS induction in bacterial cells by laser generated Ag NPs. The increased ROS was accompanied by significantly reduced cellular glutathione, and increased lipid peroxidation and permeability, suggesting ROS related bacterial cell damage. The laser generated Ag NPs exhibited low toxicity (within 72 hours) to five types of human cells although a weak significant decrease in cell survival was observed for endothelial cells and the lung cells. We conclude that picosecond laser generated Ag NPs have a broad spectrum of antibacterial effects against microbes including MRSA with minimal human cell toxicity. The oxidative stress is likely the key mechanism underlying the bactericidal effect, which leads to lipid peroxidation, depletion of glutathione, DNA damages and eventual disintegration of the cell membrane.

Silver nanoparticles (AgNPs) are widely used as antibacterial agents, but their antibacterial durability and the influence by storage conditions have not been thoroughly investigated. In this study, AgNPs were produced using a picosecond laser and stored under three different conditions: daylight, dark and cold (4 °C). The antibacterial effects of the laser AgNPs were examined against Escherichia coli in either a 14-day interval (frequent air exposure) or a 45-day interval (less frequent air exposure) using a well-diffusion method until the antibacterial effects disappeared. Results showed that the antibacterial activity of the laser generated AgNPs lasted 266 to 405 days. Frequent air exposure increased particle oxidation as measured by high-angle annular dark-field detector for scanning transmission electron microscopy (HAADF-STEM) and X-ray energy dispersive (EDX) spectroscopy, and reduced the antibacterial duration by about 13 weeks. Compared to the chemically produced AgNPs, the antibacterial effect of the laser AgNPs lasted over 100 days longer when tested in the 45-day interval, but was susceptible to oxidation when frequently exposed to the air. The laser generated AgNPs had lower antibacterial activity when stored in cold compared to that stored at room temperature. This study demonstrated the long lasting antibacterial durability of the laser generated AgNPs. Such information could help design future medical applications for the AgNPs.

A boundary layer analysis is laid out for the steady, laminar, mixed convection flow past an isothermal vertical cone embedded in a porous medium filled with a nanofluid. The model used for the nanofluid is one which includes the effects of Brownian motion and thermophoresis. A parametric study is performed for different physical parameters, such as magnetic (M), cone angle (m), mixed convection (X), Brownian motion (Nt), and thermophoresis (Nb), on the velocity, temperature, and nanoparticle concentration profiles. The local Nusselt, Sherwood, and nanoparticle Sherwood number have been laid out in a graphical way. The dependency of the rate of heat and mass transfer on the governing parameters has been discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640

Objectives: The purpose of the study was to evaluate the effect of long-term β(1)-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR).Background: Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function.Methods: Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or β(1)-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate.Results: Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the β(1)-AR blockade group required mitral valve surgery (p = 0.23).Conclusions: β(1)-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428). [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organisation (WHO) has developed iSupport for Dementia, a self-paced online training programme for caregivers of people with dementia which is adaptable to different cultural contexts. This scoping review aims to understand the iSupport adaptation process in different countries and provide recommendations for future adaptations., Methods: A systematic search was done in electronic databases such as Pubmed, MEDLINE, APA PsycINFO, and EMBASE to obtain relevant publications up to 18 February 2024. Only full-text publications describing iSupport cultural adaptation process were included. The publications obtained were reviewed using the Cultural Adaptation Process framework., Results: Thirteen publications from ten studies were eligible for inclusion. Based on the Cultural Adaptation Process framework, the steps undertaken in the studies were grouped into: (i) setting the stage, (ii) initial adaptation, and (iii) adaptation iterations. The three significant players in this process are the intervention developer (researchers), the cultural adaptation specialist (researchers, caregivers, and dementia care professionals), and the target community (caregivers). In the publications reviewed, cultural adaptation was mostly undertaken using a co-design process between researchers, caregivers, and dementia care professionals deciding on necessary modifications., Conclusion: iSupport for Dementia is a versatile programme to support caregivers and is readily available for adaptation to different cultural settings. It is essential to engage caregivers early in co-designing its cultural adaptations to ensure their needs can be met by this online tool., Competing Interests: Declaration of conflicting interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m 2 . Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus-associated sensorineural hearing loss., Study Design: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine., Results: Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome., Conclusions: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus-associated sensorineural hearing loss., Clinical Trial Registration: ClinicalTrials.gov identifier NCT01649869., Competing Interests: Declaration of Competing Interest D.W.K., M.E., S.N.F., C.E.J., P.J.S., P.H.D., R.L.D.B., P.Mc.M., and S.H. report no conflicts of interest. P.G. reports being a part of consulting for Takeda UCL, Biotest, GSK, Hookipa, Evrys; United Kingdom Patent Application No. 2020135.6 “Human CMV Vaccine”, Assigned to University College London with PG as one named inventor. G.D.H. reports being a part of consulting on congenital CMV related issues for Microgen (rapid diagnostic), Moderna (vaccine), Merck (vaccine). Funding was provided under contract HHSN272201100035C by the National Institute of Allergy and Infectious Diseases (NIAID) Division of Microbiology and Infectious Diseases (DMID). Participation of study sites in the UK was supported by the National Institute for Health Research Clinical Research Network (NIHR CRN)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acetylation of α-tubulin at the lysine 40 residue (αK40) by αTAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Previous literatures suggest that acetylated microtubules are more stable and damage resistant. αK40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification tunes the lateral interaction of protofilaments inside the microtubule. In this study, we examined the effect of tubulin acetylation on the doublet microtubule (DMT) in the cilia of Tetrahymena thermophila using a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry. We found that αK40 acetylation exerts a small-scale effect on the DMT structure and stability by influencing the lateral rotational angle. In addition, comparative mass spectrometry revealed a link between αK40 acetylation and phosphorylation in cilia., Competing Interests: SY, SK, CB, KP, DD, TL, MV, JG, KB No competing interests declared, (© 2023, Yang, Kubo et al.)

Background: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics., Methods: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post-transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function., Results: We enrolled 335 participants. Fifty-eight (17%) developed BK viremia, 6 (2%) developed biopsy-proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two-fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post-transplant., Conclusions: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post-transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes., (© 2024 Wiley Periodicals LLC.)

Background: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour., Methods: We searched MEDLINE, Embase, and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews; and Epistemonikos. We included systematic reviews that evaluate any type of intervention aimed at impacting opioid prescriber behaviour for adult CNCP in an outpatient setting., Results: We identified three full texts for our review that contained 68 unique primary studies. The main interventions we evaluated were structured prescriber education (one review) and prescription drug monitoring programmes (PDMPs) (two reviews). Due to the paucity of data available, we could not determine with certainty that education interventions improved outcomes in deprescribing. There is some evidence that PDMPs decrease the number of adverse opioid-related events, increase communication among healthcare workers and patients, modify healthcare practitioners' approach towards their opioid prescribed patients, and offer more chances for education and counselling., Conclusions: Our overview explores the possibility of PDMPs as an opioid deprescribing intervention and highlights the need for more high-quality primary research on this topic., (© 2024. Crown.)

Objectives: An increasing proportion of older people live in Retirement Villages ('villages'). This population cites support for health-care issues as one reason for relocation to villages. Here, we examine whether relocation to villages is associated with a decline in hospitalisations., Methods: Retrospective, before-and-after observational study., Setting: Retirement villages, Auckland, New Zealand., Participants: 466 cognitively intact village residents (336 [72%] female); mean (SD) age at moving to village was 73.9 (7.7) years. Segmented linear regression analysis of an interrupted time-series design was used., Main Outcome Measures: all hospitalisations for 18 months pre- and postrelocation to village., Secondary Outcome: acute hospitalisations during the same time periods., Results: The average hospitalisation rate (per 100 person-years) was 44.9 (95% confidence interval [CI] = 36.3-55.6) 18-10 months before village relocation, 58.9 (95% CI = 48.3-72.0) 9-1 months before moving, 47.9 (95% CI = 38.8-59.1) 1-9 months after moving and 62.4 (95% CI = 51.2-76.0) 10-18 months after moving. Monthly average hospitalisation rate (per 100 person-years) increased before relocation to village by an average of 1.2 (95% CI = 0.01-1.57, p = .04) per month from 18 to 1 month before moving, and there was a change in the level of the monthly average hospitalisation rate immediately after relocation (mean difference [MD] = -18.4 per 100 person-years, 95% CI = -32.8 to -4.1, p = .02). The trend change after village relocation did not differ significantly from that before moving., Conclusions: Although we cannot reliably claim causality, relocation to a retirement village is, for older people, associated with a significant but non-sustained reduction in hospitalisation., (© 2023 The Authors. Australasian Journal on Ageing published by John Wiley & Sons Australia, Ltd on behalf of AJA Inc’.)