Secondary sphere interactions modulate peroxynitrite scavenging by the E2 domain of amyloid precursor protein.

Peroxynitrite (ONOO) is a highly reactive nitrogen species that can cause significant damage to proteins, lipids, and DNA. Various enzymes, including metalloenzymes, play crucial roles in reducing ONOO concentrations to protect cellular components. While the interaction of ONOO with heme proteins is well known, the reduction by Cu-containing proteins is less studied.

Behaviour change interventions to improve physical activity in adults: a systematic review of economic evaluations.

Background: Behaviour change interventions can result in lasting improvements in physical activity (PA). A broad implementation of behaviour change interventions are likely to be associated with considerable additional costs, and the evidence is unclear whether they represent good value for money. The aim of this study was to investigate costs and cost-effectiveness of behaviour change interventions to increase PA in community-dwelling adults.

Predicting Mutation-Induced Changes in the Electronic Properties of Photosynthetic Proteins from First Principles: The Fenna-Matthews-Olson Complex Example.

Multiscale molecular modeling is utilized to predict optical absorption and circular dichroism spectra of two single-point mutants of the Fenna-Matthews-Olson photosynthetic pigment-protein complex. The modeling approach combines classical molecular dynamics simulations with structural refinement of photosynthetic pigments and calculations of their excited states in a polarizable protein environment. The only experimental input to the modeling protocol is the X-ray structure of the wild-type protein.

Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13 694 patients with meta-analysis.

In response to the COVID-19 pandemic, Merck Sharp & Dohme (MSD) acquired the global licensing rights for the antiviral molnupiravir, promising affordable access via licensing deals. Numerous Indian pharmaceutical companies subsequently conducted trials of the drug. Registered trials of molnupiravir were searched on the Clinical Trials Registry-India (CTRI) and efforts made to detect resulting public data.

Chart based data as a resource for tracking and improving a person-centred palliative approach in long-term care.

Aims And Objectives: To enhance the practice of a person-centred palliative approach in long-term care.

Background: Implementing a person-centred palliative approach in long-term care entails placing residents at the centre of care planning that attends to the 'whole' person, rather than prioritising biomedical needs.

Design: We conducted a four-stage directed content analysis of long-term care progress notes to meet our study aims and applied the EQUATOR guidelines for qualitative research publication (COREQ).

"This is how I want it": Exploring the use of a workbook with persons with dementia to support advance care planning engagement.

This mixed method sequential study reports focus group and pilot intervention findings that (1) explore the views of persons with dementia and their caregivers on using a self-directed advance care planning engagement workbook () and (2) uncover the conditions that encouraged and hindered workbook use. In Phase 1, we conducted five focus groups consisting of 10 persons with dementia and eight family members/caregivers from two urban Canadian cities to explore overall impressions of the workbook and factors that might affect its use. In Phase 2, we empirically explored the factors identified in Phase 1 by distributing the workbook to 24 persons with dementia.

Evaluating the Implementation of the Conversation Starter Kit in Long Term Care.

Introduction: Advance care planning can improve the quality of life for residents in long-term care homes and reduce stress for families. However, care home staff and families often lack knowledge about advance care planning, making it especially difficult for residents with dementia to communicate their care plan wishes. A Conversation Starter Kit may increase advance care planning awareness among staff and families.

Using a self-directed workbook to support advance care planning with long term care home residents.

Background: While advance care planning (ACP) has been shown to improve the quality of end-of-life (EOL) communication and palliative care, it is rarely practiced in long term care (LTC) homes, where staff time to support the process is limited. This study examines the potential of a publicly available self-directed ACP workbook distributed to LTC residents to encourage ACP reflection and communication.

Methods: Recruitment took place across three LTC homes, between June 2018 and July 2019.

The effect of behaviour change interventions on changes in physical activity and anthropometrics in ambulatory hospital settings: a systematic review and meta-analysis.

Background: The aim of this systematic review and meta-analysis was to investigate whether behaviour change interventions promote changes in physical activity and anthropometrics (body mass, body mass index and waist circumference) in ambulatory hospital populations.

Methods: Randomised controlled trials were collected from five bibliographic databases (MEDLINE, Embase, CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO). Meta-analyses were conducted using change scores from baseline to determine mean differences (MD), standardised mean differences (SMD) and 95% confidence intervals (95% CI).

Quality assurance assessment of a specialized perinatal mental health clinic.

Background: Mood and anxiety issues are the main mental health complaints of women during pregnancy and the postpartum period. Services targeting such women can reduce perinatal complications related to psychiatric difficulties. This quality assurance project aimed to examine changes in mood and anxiety symptoms in pregnant and postpartum women referred to the Women's Health Concerns Clinic (WHCC), a specialized outpatient women's mental health program.

Two-Dimensional Crystallization of Poly( N-isopropylacrylamide)-Capped Gold Nanoparticles.

Surface-sensitive X-ray reflectivity and grazing incidence small-angle X-ray scattering reveal the structure of polymer-capped-gold nanoparticles (AuNPs that are grafted with poly( N-isopropylacrylamide); PNIPAM-AuNPs) as they self-assemble and crystallize at the aqueous suspension/vapor interface. Citrate-stabilized AuNPs (5 and 10 nm in nominal diameter) are ligand-exchanged by 6 kDa PNIPAM-thiol to form corona brushes around the AuNPs that are highly stable and dispersed in aqueous suspensions. Surprisingly, no clear evidence of thermosensitive effect on surface enrichment or self-assembly of the PNIPAM-AuNPs is observed in the 10-35 °C temperature range.

Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?

The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety.

Cost-effectiveness of Apixaban Compared With Edoxaban for Stroke Prevention in Nonvalvular Atrial Fibrillation.

Purpose: The purpose of this analysis was to assess the cost-effectiveness of apixaban 5 mg BID versus high- and low-dose edoxaban (60 mg and 30 mg once daily) as intended starting dose strategies for stroke prevention in patients from a UK National Health Service perspective.

Methods: A previously developed and validated Markov model was adapted to evaluate the lifetime clinical and economic impact of apixaban 5 mg BID versus edoxaban (high and low dose) in patients with nonvalvular atrial fibrillation. A pairwise indirect treatment comparison was conducted for clinical end points, and price parity was assumed between apixaban and edoxaban.

Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Background: We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE.

Methods: At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA).

Documentation of study medication dispensing in a prospective large randomized clinical trial: experiences from the ARISTOTLE Trial.

Background: In ARISTOTLE, apixaban resulted in a 21% reduction in stroke, a 31% reduction in major bleeding, and an 11% reduction in death. However, approval of apixaban was delayed to investigate a statement in the clinical study report that "7.3% of subjects in the apixaban group and 1.

Apixaban with antiplatelet therapy after acute coronary syndrome.

Background: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.

Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.

Results: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events.