Effective health care for older people living and dying in care homes: A realist review

Background: Care home residents in England have variable access to health care services. There is currently no coherent policy or consensus about the best arrangements to meet these needs. The purpose of this review was to explore the evidence for how different service delivery models for care home residents support and/or improve wellbeing and health-related outcomes in older people living and dying in care homes. Methods: We conceptualised models of health care provision to care homes as complex interventions. We used a realist review approach to develop a preliminary understanding of what supported good health care provision to care homes. We completed a scoping of the literature and interviewed National Health Service and Local Authority commissioners, providers of services to care homes, representatives from the Regulator, care home managers, residents and their families. We used these data to develop theoretical propositions to be tested in the literature to explain why an intervention may be effective in some situations and not others. We searched electronic databases and related grey literature. Finally the findings were reviewed with an external advisory group. Results: Strategies that support and sustain relational working between care home staff and visiting health care professionals explained the observed differences in how health care interventions were accepted and embedded into care home practice. Actions that encouraged visiting health care professionals and care home staff jointly to identify, plan and implement care home appropriate protocols for care, when supported by ongoing facilitation from visiting clinicians, were important. Contextual factors such as financial incentives or sanctions, agreed protocols, clinical expertise and structured approaches to assessment and care planning could support relational working to occur, but of themselves appeared insufficient to achieve change. Conclusion: How relational working is structured between health and care home staff is key to whether health service interventions achieve health related outcomes for residents and their respective organisations. The belief that either paying clinicians to do more in care homes and/or investing in training of care home staff is sufficient for better outcomes was not supported.This research was funded by National Institute of Health Research Health Service Delivery and Research programme (HSDR 11/021/02)

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

On-line mass spectrometry: membrane inlet sampling

Significant insights into plant photosynthesis and respiration have been achieved using membrane inlet mass spectrometry (MIMS) for the analysis of stable isotope distribution of gases. The MIMS approach is based on using a gas permeable membrane to enable the entry of gas molecules into the mass spectrometer source. This is a simple yet durable approach for the analysis of volatile gases, particularly atmospheric gases. The MIMS technique strongly lends itself to the study of reaction flux where isotopic labeling is employed to differentiate two competing processes; i.e., O2 evolution versus O2 uptake reactions from PSII or terminal oxidase/rubisco reactions. Such investigations have been used for in vitro studies of whole leaves and isolated cells. The MIMS approach is also able to follow rates of isotopic exchange, which is useful for obtaining chemical exchange rates. These types of measurements have been employed for oxygen ligand exchange in PSII and to discern reaction rates of the carbonic anhydrase reactions. Recent developments have also engaged MIMS for online isotopic fractionation and for the study of reactions in inorganic systems that are capable of water splitting or H2 generation. The simplicity of the sampling approach coupled to the high sensitivity of modern instrumentation is a reason for the growing applicability of this technique for a range of problems in plant photosynthesis and respiration. This review offers some insights into the sampling approaches and the experiments that have been conducted with MIMS

Evidence-based effect size estimation:An illustration using the case of acupuncture for cancer-related fatigue

<p>Abstract</p> <p>Background</p> <p>Estimating a realistic effect size is an important issue in the planning of clinical studies of complementary and alternative medicine therapies. When a minimally important difference is not available, researchers may estimate effect size using the published literature. This evidence-based effect size estimation may be used to produce a range of empirically-informed effect size and consequent sample size estimates. We provide an illustration of deriving plausible effect size ranges for a study of acupuncture in the relief of post-chemotherapy fatigue in breast cancer patients.</p> <p>Methods</p> <p>A PubMed search identified three uncontrolled studies reporting the effect of acupuncture in relieving fatigue. A separate search identified five randomized controlled trials (RCTs) with a wait-list control of breast cancer patients receiving standard care that reported data on fatigue. We use these published data to produce best, average, and worst-case effect size estimates and related sample size estimates for a trial of acupuncture in the relief of cancer-related fatigue relative to a wait-list control receiving standard care.</p> <p>Results</p> <p>Use of evidence-based effect size estimation to calculate sample size requirements for a study of acupuncture in relieving fatigue in breast cancer survivors relative to a wait-list control receiving standard care suggests that an adequately-powered phase III randomized controlled trial comprised of two arms would require at least 101 subjects (52 per arm) if a strong effect is assumed for acupuncture and 235 (118 per arm) if a moderate effect is assumed.</p> <p>Conclusion</p> <p>Evidence-based effect size estimation helps justify assumptions in light of empirical evidence and can lead to more realistic sample size calculations, an outcome that would be of great benefit for the field of complementary and alternative medicine.</p

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence

Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1

Smits THM, Rezzonico F, Kamber T, et al. Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1. PLoS ONE. 2011;6(7): e22247.Background: Pantoea vagans is a commercialized biological control agent used against the pome fruit bacterial disease fire blight, caused by Erwinia amylovora. Compared to other biocontrol agents, relatively little is currently known regarding Pantoea genetics. Better understanding of antagonist mechanisms of action and ecological fitness is critical to improving efficacy. Principal Findings: Genome analysis indicated two major factors contribute to biocontrol activity: competition for limiting substrates and antibacterial metabolite production. Pathways for utilization of a broad diversity of sugars and acquisition of iron were identified. Metabolism of sorbitol by P. vagans C9-1 may be a major metabolic feature in biocontrol of fire blight. Biosynthetic genes for the antibacterial peptide pantocin A were found on a chromosomal 28-kb genomic island, and for dapdiamide E on the plasmid pPag2. There was no evidence of potential virulence factors that could enable an animal or phytopathogenic lifestyle and no indication of any genetic-based biosafety risk in the antagonist. Conclusions: Identifying key determinants contributing to disease suppression allows the development of procedures to follow their expression in planta and the genome sequence contributes to rationale risk assessment regarding the use of the biocontrol strain in agricultural systems

Structures of Helicobacter pylori Shikimate Kinase Reveal a Selective Inhibitor-Induced-Fit Mechanism

Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive target pathway for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here we investigated the detailed structure–activity relationship of SK from Helicobacter pylori (HpSK). Site-directed mutagenesis and isothermal titration calorimetry studies revealed critical conserved residues (D33, F48, R57, R116, and R132) that interact with shikimate and are therefore involved in catalysis. Crystal structures of HpSK·SO4, R57A, and HpSK•shikimate-3-phosphate•ADP show a characteristic three-layer architecture and a conformationally elastic region consisting of F48, R57, R116, and R132, occupied by shikimate. The structure of the inhibitor complex, E114A•162535, was also determined, which revealed a dramatic shift in the elastic LID region and resulted in conformational locking into a distinctive form. These results reveal considerable insight into the active-site chemistry of SKs and a selective inhibitor-induced-fit mechanism

Desmoplastic fibroma of the mandible - review of the literature and presentation of a rare case

Desmoplastic fibroma (DF) is a rare, benign but locally aggressive, intraosseous lesion with a high tendency of local recurrence. In this report the actual literature is reviewed regarding epidemiological data, pathology, clinical diagnostic criterias, therapy and prognosis. Moreover, a report of an interesting case is included localized in the mandibular corpus

REPAIRS Delphi: A UK and Ireland Consensus Statement on the Management of Infected Arterial Pseudoaneurysms Secondary to Groin Injecting Drug Use

\ua9 2024 The Author(s)Objective: Consensus guidelines on the optimal management of infected arterial pseudoaneurysms secondary to groin injecting drug use are lacking. This pathology is a problem in the UK and globally, yet operative management options remain contentious. This study was designed to establish consensus to promote better management of these patients, drawing on the expert experience of those in a location with a high prevalence of illicit drug use. Methods: A three round modified Delphi was undertaken, systematically surveying consultant vascular surgeons in the UK and Ireland using an online platform. Seventy five vascular surgery units were invited to participate, with one consultant providing the unit consensus practice. Round one responses were thematically analysed to generate statements for round two. These statements were evaluated by participants using a five point Likert scale. Consensus was achieved at a threshold of 70% or more agreement or disagreement. Those statements not reaching consensus were assessed and modified for round three. The results of the Delphi process constituted the consensus statement. Results: Round one received 64 (86%) responses, round two 59 (79%) responses, and round three 62 (83%) responses; 73 (97%) of 75 units contributed. Round two comprised 150 statements and round three 24 statements. Ninety one statements achieved consensus agreement and 15 consensus disagreement. The Delphi statements covered sequential management of these patients from diagnosis and imaging, antibiotics and microbiology, surgical approach, wound management, follow up, and additional considerations. Pre-operative imaging achieved consensus agreement (97%), with computerised tomography angiography being the modality of choice (97%). Ligation and debridement without arterial reconstruction was the preferred approach at initial surgical intervention (89%). Multidisciplinary management, ensuring holistic care and access to substance use services, also gained consensus agreement. Conclusion: This comprehensive consensus statement provides a strong insight into the standard of care for these patients