Understanding the scale and nature of avoidable healthcare-associated harm for prisoners in England: protocol for a retrospective cross-sectional study.

Introduction: Around 1 in 20 patients experience avoidable healthcare-associated harm worldwide. Despite longstanding concerns, there is insufficient information available about the safety of healthcare for prisoners. To address this, this study will investigate the scale and nature of avoidable healthcare-associated harm for prisoners in England.

Sexual health and healthy relationships for Further Education (SaFE) in Wales and England: results from a pilot cluster randomised controlled trial.

Objectives: To examine the acceptability of implementing, trialling and estimating the cost of the Sexual health and healthy relationships for Further Education (SaFE) intervention.

Design: Two-arm repeated cross-sectional pilot cluster randomised controlled trial (cRCT) of SaFE compared with usual practice, including a process evaluation and an economic assessment.

Setting: Eight further education (FE) settings in South Wales and the West of England, UK.

Coupling of single nanodiamonds hosting SiV color centers to plasmonic double bowtie microantennas.

Color centers are promising single-photon emitters owing to their operation at room temperature and high photostability. In particular, using nanodiamonds as a host material is of interest for sensing and metrology. Furthermore, being a solid-state system allows for incorporation to photonic systems to tune both the emission intensity and photoluminescence spectrum and therefore adapt the individual color center to desired properties.

New developments in optometric training in the United Kingdom.

With optometrists well placed to address the challenges and opportunities faced by contemporary eye care systems, it is ever more important to understand the genesis and development of the profession, so that optometrists can continue to build on this legacy for patient benefit. While the optometry profession of optometry in the United Kingdom can arguably trace its foundation back to 1629 and the Royal Charter gifted by Charles I to the Worshipful Company of Spectacle Makers to establish the 60 Livery Company of the City of London, the genesis of optometry as an independent profession (initially known as 'ophthalmic optics') can perhaps best be attributed to the formation of the British Optical Association in 1895. This paper reviews the current legal framework and recent changes that dictates how the optometry profession are trained and practice, along with clinical and educational innovations that are shaping the future role of the profession.

A Tertiary Centre's Experience With Using Ranibizumab Biosimilar Compared to Aflibercept for Neovascular Age-Related Macular Degeneration: A Retrospective Study.

Objective This study aims to evaluate the real-world efficacy of ranibizumab biosimilar (Ongavia), compared to aflibercept (Eylea), in the treatment of treatment-naïve neovascular age-related macular degeneration (nAMD) at a busy tertiary eye care centre. Methods A retrospective analysis of medical records from August 2022 to August 2024 was conducted, comparing treatment outcomes in treatment-naive nAMD patients who received either Ongavia or Eylea intravitreal anti-VEGF (vascular endothelial growth factor) injections under a treat-and-extend protocol. Initial and 12-month outcome measures post-treatment initiation were collected, including best-corrected visual acuity (BCVA), central retinal thickness (CRT), prescribed treatment intervals, actual injection frequency, and the average total number of injections per eye over 12 months.

Evolution of amorphous ruthenium nanoclusters into stepped truncated nano-pyramids on graphitic surfaces boosts hydrogen production from ammonia.

Atomic-scale changes can significantly impact heterogeneous catalysis, yet their atomic mechanisms are challenging to establish using conventional analysis methods. By using identical location scanning transmission electron microscopy (IL-STEM), which provides quantitative information at the single-particle level, we investigated the mechanisms of atomic evolution of Ru nanoclusters during the ammonia decomposition reaction. Nanometre-sized disordered nanoclusters transform into truncated nano-pyramids with stepped edges, leading to increased hydrogen production from ammonia.

The multifaceted function of FoxO1 in pancreatic β-cell dysfunction and insulin resistance: Therapeutic potential for type 2 diabetes.

The forkhead box O1 (FOXO1), the first discovered member of the FoxO family, is a critical transcription factor predominantly found in insulin-secreting and insulin-sensitive tissues. In the pancreas of adults, FoxO1 expression is restricted to islet β cells. We determined that in human islet microarray datasets, FoxO1 expression is higher than other FoxO transcription factors.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

Metagenomics unveils the role of hospitals and wastewater treatment plants on the environmental burden of antibiotic resistance genes and opportunistic pathogens.

Antimicrobial resistance (AMR) is a global health challenge, with hospitals and wastewater treatment plants (WWTPs) serving as significant pathways for the dissemination of antibiotic resistance genes (ARGs). This study investigates the potential of wastewater-based epidemiology (WBE) as an early warning system for assessing the burden of AMR at the population level. In this comprehensive year-long study, effluent was collected weekly from three large hospitals, and treated and untreated wastewater were collected monthly from three associated community WWTPs.

Bruton's tyrosine kinase inhibitor for multiple sclerosis: new hope or false dawn.

The first of several phase 3 trials examining efficacy in relapsing MS has not been able to demonstrate a significant benefit and has also raised important safety concerns. More results are on their way and it will be important to understand whether the safety signals identified are drug- or class-specific and whether other BTKi also fail to reach their endpoints for relapsing MS. However, as reported in preliminary data for another BTKi, it may be that they will have more of a role in progressive disease as hinted by the unraveling of relevant molecular mechanisms and pathways.

Cycling Dof Factor 3 mediates light-dependent ascorbate biosynthesis by activating GDP-L-galactose phosphorylase in Rosa roxburghii fruit.

Light plays an important role in determining the L-ascorbate (AsA) pool size in plants, primarily through the transcriptional regulation of AsA metabolism-related genes. However, the specific mechanism of transcriptional induction responsible for light-dependent AsA biosynthesis remains unclear. In this study, we used a promoter sequence containing light-responsive motifs from GDP-L-galactose phosphorylase 2 (RrGGP2), a key gene involved in AsA overproduction in Rosa roxburghii fruits, to identify participating transcription factors.

Disrupting SARS-CoV-2 Spike Protein Activity: A Virtual Screening and Binding Assay Study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that emerged in late 2019 and rapidly spread worldwide, causing the COVID-19 pandemic. The spike glycoprotein (S protein) plays a crucial role in viral target recognition and entry by interacting with angiotensin, converting enzyme 2 (ACE2), the functional receptor for the virus, via its receptor binding domain (RBD). The RBD availability for this interaction can be influenced by external factors, such as fatty acids.

How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.

BK Polyomavirus-associated nephropathy - diagnostic and treatment standard.

BK polyomavirus (BKPyV) is recognised as a significant viral complication of kidney transplantation. Prompt immunosuppression reduction reduces early graft failure rates due to BK polyomavirus-associated nephropathy (BKPyVAN), however modulation of immunosuppression can lead to acute rejection. Medium-to-long term graft outcomes are negatively impacted by BKPyVAN, likely due to a combination of virus-induced graft damage and host immune responses against graft alloantigens potentiated by immunosuppression reduction.

Graft ischemia post cell transplantation to the brain: Glucose deprivation as the primary driver of rapid cell death.

Replacing cells lost during the progression of neurodegenerative disorders holds potential as a therapeutic strategy. Unfortunately, the majority of cells die post-transplantation, which creates logistical and biological challenges for cell therapy approaches. The cause of cell death is likely to be multifactorial in nature but has previously been correlated with hypoxia in the graft core.

Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues.

Terpene synthases produce a wide number of hydrocarbon skeletons by controlling intramolecular rearrangements of allylic pyrophosphate subtrates reactive carbocation intermediates. Here we review recent research focused on engineering terpene synthases and modifying their substrates to rationally manipulate terpene catalyisis. Molecular dynamic simulations and solid state X-ray crystallography are powerful techniques to identify substrate binding modes, key active site residues for substrate folding, and the location of active site water.

A novel multilayer antimicrobial urinary catheter material with antimicrobial properties.

Urinary catheters are commonly used in medical practice to drain and monitor urine of patients. However, urinary catheterisation is associated with the risk of developing catheter-associated urinary tract infections (CAUTIs), which can result in life-threatening sepsis that requires antibiotics for treatment. Using the layer-by-layer (LbL) technique, we assembled a multilayer catheter comprising nine quadruple layers (9QL) of alginate, chlorhexidine (CHX), alginate and poly(β-amino ester) (PBAE) built upon an amino-functionalised silicone.

Human longevity and Alzheimer's disease variants act via microglia and oligodendrocyte gene networks.

Ageing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer's disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are not well understood. The objective of this study was to identify biological processes that are altered during ageing in the hippocampus and that modify Ad risk and lifespan, and then to identify putative gene drivers of these programmes.

Modeling regional private income and its embedded carbon emissions: sources, flows and inequalities.

Composing regional total income jointly with government income, private income represents levels of development and affluence from the household perspective. Considering the need for fair carbon emission reduction responsibility distributions among regions with divergent income levels, private income-embedded emission (PIEE) and the inter-regional inequalities remain to be explored. Combining input-output analysis and the Gini coefficient, this study traces the sources and disposals of regional private income in China, as well as their embedded carbon emission flow, and quantifies the distribution and inequality of PIEE across industrial sectors and provincial regions.

Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies.

Aims: Mutations in the cardiac ryanodine receptor (RyR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study investigates the underlying molecular mechanisms for CPVT mutations within the RyR2 N-terminus domain (NTD).

Methods And Results: We consulted the high-resolution RyR2 structure in both open and closed configuration to identify mutations G357S/R407I and A77T, which lie within the NTD intra- and inter-subunit interface with the Core Solenoid (CSol), respectively.

Crystal structure and Hirshfeld surface analysis of -(4-nitro-phen-yl)-2-(piperidin-1-yl)acetamide (lidocaine analogue).

In the title mol-ecule, CHNO, the substituents on the phenyl ring are rotated slightly out of the mean plane of the ring but the piperidine moiety is nearly perpendicular to that plane. In the crystal, C-H⋯O hydrogen bonds form chains of mol-ecules extending along the -axis direction, which are linked by C=O⋯π(ring) inter-actions. A Hirshfeld surface analysis showed the majority of inter-molecular inter-actions to be H⋯H contacts while O⋯H/H⋯O contacts are the second most numerous.

Change in frailty status in the 12 months following solid organ transplantation: a systematic review and meta-analysis.

Objectives: To investigate if frailty status alters following solid organ transplantation (lung, liver, kidney and heart) without rehabilitation intervention.

Research Design And Methods: Studies published between 1 January 2000 and 30 May 2023 were searched across five databases. Studies measuring frailty, using a validated or established frailty measure, pre- and post-transplant were included.