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G-quadruplexes self-assembled from nucleotide monomers as stable prepolymer scaffolds in aqueous environments.
Get PDFLife is composed of genetic and functional polymers, such as nucleic acids. For life to have emerged, a prebiotic mechanism for assembling these polymers is essential. In a prebiotic environment teeming with diverse organic molecules, selecting, concentrating and bringing together only relevant building blocks poses a significant challenge. G-quadruplexes, a secondary structure of DNA and RNA, are known to self-assemble from nucleotide monomers, creating an ideal preassembly for nucleotide polymerization. We investigate the detailed structure of self-assembled G-quadruplexes using high-resolution atomic force microscopy (AFM) measurements in solution. We show that G-quadruplexes of nucleotide monomers are stable on surfaces in aqueous solution at concentrations orders of magnitude below their solubility limit. When subjected to cycles of evaporation and rehydration at elevated temperatures, the G-quadruplexes partially transform into extended, RNA-like structures, also stable on surfaces in solution, consistent with a polymeric nature. G-quadruplexes self-assembled from nucleotide monomers could have served as persistent prepolymer scaffolds, providing genuine molecular selectivity in prebiotic environments
A review of the role of social determinants of health in urinary incontinence in women: why does this matter to the urologist?
No full textUrinary incontinence (UI) causes significant impact on all aspects of quality of life: physical, psychological, social and financial. Assessment and management of UI is almost exclusively based on the biomedical model, on the premise that incontinence cause and management are only related to biological conditions. However, it is becoming evident that there are psychological and social factors which have a significant influence. This paper explores the extent to which the evidence looking at social determinants of health in relation to women with urinary incontinence. To put it very simplistically, are women more likely to be wet because they are poor and what does this mean for the clinical urologist?
Level of evidence: Level 3 and
Connexin 32 constrains a mesenchymal-like switch in differentiated urothelium and luminal cancers
Get PDFThe molecular programming of epithelial wound repair provides the origin for the signalling pathways that drive the growth and spread of carcinoma cells. Urothelium is the mitotically quiescent, barrier-forming transitional epithelium of the urinary tract, characterised by uniquely specialised superficial cells and a remarkable regenerative capacity in response to damage. Connexin 32 (Cx32) was expressed by differentiated human urothelium where it predominantly localised to the basolateral borders of superficial urothelial cells. Suppression of Cx32 gap junction intercellular communication did not affect differentiation but instigated the switch to a highly migratory, wound healing phenotype marked by TGFβ-SMAD signalling, ECM-remodelling, and induction of mesenchymal and cell-cycle markers. Immunohistological classification of muscle-invasive bladder cancers revealed Cx32 expression to be informative in luminal tumour biology, with non-membrane localised Cx32 defining a Ki67-high, vimentin-expressing, and TGFβ-activated subset of luminal tumours. Our findings identify Cx32 cell–cell communication as suppressing migratory and proliferative behaviours in normal urothelial differentiation and suggest that Cx32 assessment, within the context of luminal muscle-invasive bladder cancer, can predict more invasive biology. This reveals the potential for differentiated cancers to exhibit EMT
In situ X-ray characterization of thermomechanical deformation behavior in powder-processed polycrystalline high co-containing Ni-based superalloys
Get PDFPolycrystalline Ni-based superalloys rely on compositional modifications for high-temperature, structural aerospace applications. However, these changes must be carefully managed to avoid deleterious phases. While the individual effects of Ti and Ta are well documented, their synergistic co-addition has received limited attention in high Co-containing alloys. This study investigates the influence of Ti and Ta on the load partitioning behavior between the γ and γ′ phases using in situ synchrotron diffraction under tensile loads in the temperature range from 600 °C to 800 °C. Our findings show that the ratio of Ti:Ta directly impacts how load is distributed, with a higher ratio leading to a greater load-carrying capacity in the γ′ phase, thereby improving strength at intermediate temperatures (700 °C). However, this benefit seems thermally limited, coinciding with a significant reduction in stiffness in the high-Ti alloy at 800 °C. Conversely, a balanced Ti:Ta ratio maintains consistent load partitioning and strength stability across the entire temperature range. By linking lattice misfit and stiffness evolution to bulk behavior, this work identifies load transfer efficiency as a critical metric for the design of future high-performance superalloys. By understanding this relationship, the compositional limits for optimizing alloy performance in service can be better defined. This work highlights a critical design pathway for future high-performance superalloys by demonstrating the link between controlled alloying, lattice misfit, and load partitioning
Fitting a lattice model with local and global transmission to spread of a plant disease
Get PDFUnderstanding, predicting and managing the spread of plant pathogens is crucial given the economic, societal and climatic benefits of plants, including crops and trees. Mathematical models have long been used to investigate disease dynamics in plants. An important component of such models is to account for spatial structure, since plant hosts are immobile and a majority of disease spread will often be localised. Here we apply a lattice-based mathematical modelling approach, a pair approximation, to model disease spread. While this method has previously been used to develop epidemiological theory, it has not been used to predict spread in a specific pathosystem. We fit our lattice-based epidemiological model to experimental data relating to Bahia bark scaling of citrus, an economically-important disease in north-eastern Brazil, and compare its performance to a more commonly used dispersal-kernel modelling approach. We show that the lattice-based model fits the data well, predicting a significant degree of near-neighbour infections, with similar estimated values of epidemiologically-meaningful parameters to the dispersal model. We highlight the pros and cons of the lattice-based approach and discuss how it may be used to predict disease spread and optimise control of plant diseases
Criminal justice system outcomes of children with child welfare service involvement and special educational needs: analysis of routinely collected data
Get PDFChildren in youth justice systems are disproportionately likely to have special educational needs and prior child welfare interventions. This study examined the odds of criminal justice involvement among children in England (N = 1,708,565) born between 1995 and 1998, using linked education and justice records. Across nine of eleven SEN categories, children with a child welfare intervention had higher odds of a criminal caution or conviction (OR = 1.59–2.58). Among those with justice involvement, odds of receiving a custodial sentence were higher across eight of nine SEN categories (OR = 1.25–1.71). Findings indicate a compound disadvantage: children with both SEN and child welfare involvement face increased odds of criminalisation and custody, underscoring the need for integrated policy responses. Funding: ESRC ADR UK ES/W002345/1
Patient education on PROM completion in clinical care settings: a scoping review
Get PDFBackground
Patient-reported outcome measures (PROMs) are increasingly used in clinical care, and evidence demonstrates they enhance patient care processes and outcomes. However, low PROM completion rates can hinder their use for patient-level monitoring and clinical decision-making. Patient education may help overcome barriers to PROM completion, yet little is known about what education, if any, is offered. The aim of this scoping review was to understand if and how education on PROMs is provided to patients in clinical care.
Methods
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. MEDLINE, Embase, and APA PsychINFO were searched. Eligible studies used PROMs for individual patient care where PROM results are discussed with the patient, and described patient education on PROMs. Articles were double-screened, data was extracted and relevant data items were categorized and reported.
Results
In total 4392 titles and abstracts were screened, and 292 full texts were reviewed. Only 75 studies were included because they mentioned or described patient education on PROMs. Education was often provided by clinical staff or research staff, using verbal, written or multimodal methods. Education typically occurred prior to PROM completion, and sometimes during PROM completion. The review identified five key components describing the content of education: (1) introduction to PROMs, (2) explanation of their purpose, (3) method of completing PROMs, (4) presentation and (5) utilization of PROM results. These components are presented as the PROMs Patient Education Model. Most studies described to educate on the method of PROM completion, followed by the purpose of PROMs in clinical care. Only a few studies examined patient experiences with education or assessed the impact of education on PROM completion. Despite positive indications, due to the limited number and nature of the included studies, no conclusions on the effect of patient education on PROM completion rates can be made.
Conclusions
While patients may be educated about PROMs in clinical care, it is premature to consider patient education as standard in PROM implementation. This might partly be explained by the lack of detailed reporting in the literature. A survey with healthcare stakeholders could clarify current practices. The effect of patient education on PROM completion remains unclear, and it is recommended that future PROM studies measure the impact of education and report it in literature
The perioperative microbiome of patients undergoing rectal cancer surgery: A pilot study
Get PDFAim
The gut microbiome plays a crucial role in health and disease, and its involvement in postoperative complications like anastomotic leakage (AL) is of growing interest. Despite substantial preclinical evidence linking microbiome alterations to surgical outcomes, human studies are scarce, particularly those exploring the perioperative dynamics of the gut microbiome beyond a single time point. This descriptive, hypothesis-generating pilot study aims to elucidate the perioperative changes in the faecal microbiome of patients undergoing rectal cancer surgery.
Method
Seventeen patients from Amsterdam University Medical Centers participated in the IMARI-study and the IntAct-trial between April 2020 and April 2022. All patients in these studies underwent rectal resection for malignancy with a primary anastomosis, with or without a diverting ileostomy. Samples collected included preoperative stool, intraoperative anastomotic colonic tissue and swab and postoperative stool. Bacterial DNA was extracted and analysed using 16S rRNA gene sequencing.
Results
An increase in Enterococcus and Streptococcus was observed postoperatively compared to preoperative and intraoperative samples. Postoperative samples showed a significant decrease in alpha diversity compared to preoperative and intraoperative samples. Beta diversity analysis revealed distinct clustering of postoperative stool and ileostomy samples. Preoperative oral antibiotics significantly altered the intraoperative microbiome composition and reduced postoperative alpha diversity.
Conclusion
This pilot study reveals significant perioperative shifts in the gut microbiome of rectal cancer patients. These findings underscore the importance of considering microbiome dynamics perioperatively when designing and interpreting studies that correlate the microbiome with clinical outcomes. However, the conclusions should be viewed as preliminary and require confirmation in larger studies, including causal relation, to postoperative outcomes
From raids to digital returns: The (im-)materiality of manuscripts in decolonializing heritage practices
Get PDFIn 1812, the royal palace of Yogyakarta (Central Java) fell to British forces, resulting in the raid of the royal library’s manuscripts. Over the last decade, the manuscripts raided in 1812 that ended up in the British Library were digitized and ‘returned’ to the royal house of Yogyakarta in the form of a hard drive containing 30,000 digital images. In this paper, we seek to explore ideas underpinning the returns of manuscripts in digital form as part of broader decolonial and heritage discourses and practices. We investigate the political and cultural grounds in disseminating manuscripts’ digital copies and ask what kinds of shifting assumptions about the nature of textuality and manuscripts are indicated by digital returns. This is especially relevant given that some manuscripts in traditional Java, those designated as pusaka, are not merely media transmitting textual information. Rather, their materiality contains a power of its own. We conclude with some reflections on how the meanings assigned to the materiality of manuscripts and textuality might affect our scholarly ways of approaching Javanese manuscripts; what ethical implications there may be, especially when the democratization of access through digitization is framed as part of a decolonial movement; and what this entails for future research
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