Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The heart healthy lenoir project-an intervention to reduce disparities in hypertension control: study protocol

Background Racial disparities in blood pressure control are well established; however the impact of low health literacy (LHL) on blood pressure has garnered less attention. Office based interventions that are created with iterative patient, practice and community stakeholder input and are rolled out incrementally, may help address these disparities in hypertension control. This paper describes our study protocol. Methods/design Using a community based participatory research (CBPR) approach, we designed and implemented a cohort study that includes both a practice level and patient level intervention to enhance the care and support of patients with hypertension in primary care practices in a rural region of eastern North Carolina. The study is divided into a formative phase and an ongoing 2.5 year implementation phase. Our main care enhancement activities include the integration of a community health coach, using home blood pressure monitoring in clinical decision making, standardizing care delivery processes, and working to improve medication adherence. Main outcomes include overall blood pressure change, the differential change in blood pressure by race (African American vs. White) and health literacy level (low vs. higher health literacy). Discussion Using a community based participatory approach in primary care practice settings has helped to engage patients and practice staff and providers in the research effort and in making practice changes to support hypertension care. Practices have engaged at varying levels, but progress has been made in implementing and iteratively improving upon the interventions to date

Strategies for older people living in care homes to prevent urinary tract infection: the StOP UTI realist synthesis

© 2024 The Author(s). This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/Background: Urinary tract infection is the most diagnosed infection in older people. It accounts for more than 50% of antibiotic prescriptions in care homes and is a frequent reason for care home residents being hospitalised. Objective: This realist review developed and refined programme theories for preventing and recognising urinary tract infection, exploring what works, for whom and in what circumstances. Design: The review used realist synthesis to explore existing literature on the detection and prevention of urinary tract infection, complemented by stakeholder consultation. It applies to the UK context, although other healthcare systems may identify synergies in our findings. Data sources: Bibliographic databases searched included MEDLINE, CINAHL, EMBASE, Cochrane Library, Web of Science Core Collection (including the Social Sciences Citation Index), Sociological Abstracts, Bibliomap and National Institute for Health and Care Research Journals Library. Data selection and extraction: Title and abstract screening were undertaken by two researchers independently of each other. Selection and assessment were based on relevance and rigour and cross-checked by a second researcher. Data extracted from the included studies were explored for explanations about how the interventions were considered to work (or not). Evidence tables were constructed to enable identification of patterns across studies that offered insight about the features of successful interventions. Data analysis and synthesis: Programme theories were constructed through a four-stage process involving scoping workshops, examination of relevant extant theory, analysis and synthesis of primary research, teacher–learner interviews and a cross-system stakeholder event. A process of abductive and retroductive reasoning was used to construct context–mechanism–outcome configurations to inform programme theory. Results: The scoping review and stakeholder engagement identified three theory areas that address the prevention and recognition of urinary tract infection and show what is needed to implement best practice. Nine context–mechanism–outcome configurations provided an explanation of how interventions to prevent and recognise urinary tract infection might work in care homes. These were (1) recognition of urinary tract infection is informed by skills in clinical reasoning, (2) decision-support tools enable a whole care team approach to communication, (3) active monitoring is recognised as a legitimate care routine, (4) hydration is recognised as a care priority for all residents, (5) systems are in place to drive action that helps residents to drink more, (6) good infection prevention practice is applied to indwelling urinary catheters, (7) proactive strategies are in place to prevent recurrent urinary tract infection, (8) care home leadership and culture fosters safe fundamental care and (9) developing knowledgeable care teams. Limitations: We adapted our approach and work to online interactions with stakeholders and as a research team because of COVID-19. This also had an impact on bringing stakeholders together at a face-to-face event at the end of the project. Studies focusing on the prevention of urinary tract infection in care home settings were predominantly from the USA and Europe where the regulatory and funding systems for the long-term care of the elderly have some differences, particularly in the USA where national reporting plays a significant role in driving improvements in care. Conclusions: Care home staff have a vital role in the prevention and recognition of urinary tract infection, which can be enabled through integration and prioritisation within the systems and routines of care homes and delivery of person-centred care. Promoting fundamental care as a means of facilitating a holistic approach to prevention and recognition of urinary tract infection helps staff to recognise how they can contribute to antimicrobial stewardship and recognition of sepsis. Challenging assumptions made by staff about the presentation of urinary tract infection is complex and requires education that facilitates ‘unlearning’ and questioning of low-value practices. Programmes to prevent urinary tract infection need to be co-designed and supported through active and visible leadership by care home managers with support from specialist practitioners. Future work: We will focus on co-designing tools that facilitate implementation of our findings to ensure they fit with the care home context and address some of the challenges faced by care home leaders. This will underpin action at care home and system levels. Further research is needed to better understand the perspectives of residents and family carers, the effectiveness of non-pharmacological, pharmacological and specialist practitioner interventions and non-traditional approaches to training and educating the workforce in care home settings. Study registration: This study is registered as PROSPERO CRD42020201782.Peer reviewe

Demonstration of Binding of Neuronal Calcium Sensor-1 to the Ca(v)2.1 P/Q-Type Calcium Channel

[Image: see text] In neurons, entry of extracellular calcium (Ca(2+)) into synaptic terminals through Ca(v)2.1 (P/Q-type) Ca(2+) channels is the driving force for exocytosis of neurotransmitter-containing synaptic vesicles. This class of Ca(2+) channel is, therefore, pivotal during normal neurotransmission in higher organisms. In response to channel opening and Ca(2+) influx, specific Ca(2+)-binding proteins associate with cytoplasmic regulatory domains of the P/Q channel to modulate subsequent channel opening. Channel modulation in this way influences synaptic plasticity with consequences for higher-level processes such as learning and memory acquisition. The ubiquitous Ca(2+)-sensing protein calmodulin (CaM) regulates the activity of all types of mammalian voltage-gated Ca(2+) channels, including the P/Q class, by direct binding to specific regulatory motifs. More recently, experimental evidence has highlighted a role for additional Ca(2+)-binding proteins, particularly of the CaBP and NCS families in the regulation of P/Q channels. NCS-1 is a protein found from yeast to humans and that regulates a diverse number of cellular functions. Physiological and genetic evidence indicates that NCS-1 regulates P/Q channel activity, including calcium-dependent facilitation, although a direct physical association between the proteins has yet to be demonstrated. In this study, we aimed to determine if there is a direct interaction between NCS-1 and the C-terminal cytoplasmic tail of the Ca(v)2.1 α-subunit. Using distinct but complementary approaches, including in vitro binding of bacterially expressed recombinant proteins, fluorescence spectrophotometry, isothermal titration calorimetry, nuclear magnetic resonance, and expression of fluorescently tagged proteins in mammalian cells, we show direct binding and demonstrate that CaM can compete for it. We speculate about how NCS-1/Ca(v)2.1 association might add to the complexity of calcium channel regulation mediated by other known calcium-sensing proteins and how this might help to fine-tune neurotransmission in the mammalian central nervous system

Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration

Synapse loss is an early feature shared by many neurodegenerative diseases, and it represents the major correlate of cognitive impairment. Recent studies reveal that microglia and astrocytes play a major role in synapse elimination, contributing to network dysfunction associated with neurodegeneration. Excitatory and inhibitory activity can be affected by glia-mediated synapse loss, resulting in imbalanced synaptic transmission and subsequent synaptic dysfunction. Here, we review the recent literature on the contribution of glia to excitatory/inhibitory imbalance, in the context of the most common neurodegenerative disorders. A better understanding of the mechanisms underlying pathological synapse loss will be instrumental to design targeted therapeutic interventions, taking in account the emerging roles of microglia and astrocytes in synapse remodeling

Preventing urinary tract infection in older people living in care homes: the ‘StOP UTI’ realist synthesis

ABSTRACT Background Urinary tract infection (UTI) is the most diagnosed infection in older people living in care homes. Objective To identify interventions for recognising and preventing UTI in older people living in care homes in the UK and explain the mechanisms by which they work, for whom and under what circumstances. Methods A realist synthesis of evidence was undertaken to develop programme theory underlying strategies to recognise and prevent UTI. A generic topic�based search of bibliographic databases was completed with further purposive searches to test and refine the programme theory in consultation with stakeholders. Results 56 articles were included in the review. Nine context–mechanism–outcome configurations were developed and arranged across three theory areas: (1) Strategies to support accurate recognition of UTI, (2) care strategies for residents to prevent UTI and (3) making best practice happen. Our programme theory explains how care staff can be enabled to recognise and prevent UTI when this is incorporated into care routines and activities that meet the fundamental care needs and preferences of residents. This is facilitated through active and visible leadership by care home managers and education that is contextualised to the work and role of care staff. Conclusions Care home staff have a vital role in preventing and recognising UTI in care home residents. Incorporating this into the fundamental care they provide can help them to adopt a proactive approach to preventing infection and avoiding unnecessary antibiotic use. This requires a context of care with a culture of personalisation and safety, promoted by commissioners, regulators and providers, where leadership and resources are committed to support preventative action by knowledgeable care staff

The Vehicle, 1961, Vol. 3 no. 2

Vol. 3, No. 2 Table of Contents The Voting CattleLinda Kay Campbellpage 5 But For the Passage of TimeDon Shepardsonpage 14 LoveJon Woodspage 16 Infinite JourneyJames E. Martinpage 19 The Clover ChainRichard W. Blairpage 20 SnowballSusan Daughertypage 24 Sureness Is NeverDon Shepardsonpage 26 ConceptionChristine McCollpage 34 Comedy: Relief and GriefTom McPeakpage 35 The Unspoken WordChristine McCollpage 35 CharmBenjamin Polkpage 36 Screaming SpiderTom McPeakpage 39 Just Once in an Early SpringE.J.B.page 39 HummingbirdPauline B. Smithpage 40 Willow TreesPauline B. Smithpage 40 MaturityChristine McCollpage 41 The New YearLinda Campbellpage 41 The StormMary-Jean Pitratpage 42 Ebony IvoryJean Danenbargerpage 42 The Fireball MailAllen Engelbrightpage 43 ExpectationChristine McCollpage 44 CatastropheChristine McCollpage 44 SophisticationBenjamin Polkpage 45 On Playing BridgeMyrna Jo Handleypage 46 SonnetMignon Stricklandpage 48https://thekeep.eiu.edu/vehicle/1009/thumbnail.jp

The Vehicle, 1961, Vol. 3 no. 2

Vol. 3, No. 2 Table of Contents The Voting CattleLinda Kay Campbellpage 5 But For the Passage of TimeDon Shepardsonpage 14 LoveJon Woodspage 16 Infinite JourneyJames E. Martinpage 19 The Clover ChainRichard W. Blairpage 20 SnowballSusan Daughertypage 24 Sureness Is NeverDon Shepardsonpage 26 ConceptionChristine McCollpage 34 Comedy: Relief and GriefTom McPeakpage 35 The Unspoken WordChristine McCollpage 35 CharmBenjamin Polkpage 36 Screaming SpiderTom McPeakpage 39 Just Once in an Early SpringE.J.B.page 39 HummingbirdPauline B. Smithpage 40 Willow TreesPauline B. Smithpage 40 MaturityChristine McCollpage 41 The New YearLinda Campbellpage 41 The StormMary-Jean Pitratpage 42 Ebony IvoryJean Danenbargerpage 42 The Fireball MailAllen Engelbrightpage 43 ExpectationChristine McCollpage 44 CatastropheChristine McCollpage 44 SophisticationBenjamin Polkpage 45 On Playing BridgeMyrna Jo Handleypage 46 SonnetMignon Stricklandpage 48https://thekeep.eiu.edu/vehicle/1009/thumbnail.jp

Structural and Functional Deficits in a Neuronal Calcium Sensor-1 Mutant Identified in a Case of Autistic Spectrum Disorder

Neuronal calcium sensor-1 (NCS-1) is a Ca2+ sensor protein that has been implicated in the regulation of various aspects of neuronal development and neurotransmission. It exerts its effects through interactions with a range of target proteins one of which is interleukin receptor accessory protein like-1 (IL1RAPL1) protein. Mutations in IL1RAPL1 have recently been associated with autism spectrum disorders and a missense mutation (R102Q) on NCS-1 has been found in one individual with autism. We have examined the effect of this mutation on the structure and function of NCS-1. From use of NMR spectroscopy, it appeared that the R102Q affected the structure of the protein particularly with an increase in the extent of conformational exchange in the C-terminus of the protein. Despite this change NCS-1(R102Q) did not show changes in its affinity for Ca2+ or binding to IL1RAPL1 and its intracellular localisation was unaffected. Assessment of NCS-1 dynamics indicated that it could rapidly cycle between cytosolic and membrane pools and that the cycling onto the plasma membrane was specifically changed in NCS-1(R102Q) with the loss of a Ca2+ -dependent component. From these data we speculate that impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain

Analysis of Transposon Interruptions Suggests Selection for L1 Elements on the X Chromosome

It has been hypothesised that the massive accumulation of L1 transposable elements on the X chromosome is due to their function in X inactivation, and that the accumulation of Alu elements near genes is adaptive. We tested the possible selective advantage of these two transposable element (TE) families with a novel method, interruption analysis. In mammalian genomes, a large number of TEs interrupt other TEs due to the high overall abundance and age of repeats, and these interruptions can be used to test whether TEs are selectively neutral. Interruptions of TEs, which are beneficial for the host, are expected to be deleterious and underrepresented compared with neutral ones. We found that L1 elements in the regions of the X chromosome that contain the majority of the inactivated genes are significantly less frequently interrupted than on the autosomes, while L1s near genes that escape inactivation are interrupted with higher frequency, supporting the hypothesis that L1s on the X chromosome play a role in its inactivation. In addition, we show that TEs are less frequently interrupted in introns than in intergenic regions, probably due to selection against the expansion of introns, but the insertion pattern of Alus is comparable to other repeats