359 research outputs found
Surveillance of colonization and infection with Staphylococcus aureus susceptible or resistant to methicillin in a community skilled-nursing facility
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen in acute care hospitals and long-term care facilities. Few studies have been reported in private skilled nursing facilities (SNFs) not experiencing outbreaks of infections caused by MRSA. METHODS: From a 149-bed SNF with no outbreaks, we report a 1-year prospective surveillance study of S. aureus colonization and infection, with focus on S. aureus phenotypes, both methicillin susceptible (MS) and methicillin resistant (MR). Nasal and stool or rectal screening cultures were done on admission, and all patients underwent screening on at least a quarterly basis for 1 year. RESULTS: Overall, 35% of patients were colonized at least once with S. aureus, (72% MS, 25% MR, and 3% mixed phenotypes), 94% of the MRSA were ciprofloxacin resistant. Nasal colonization with any S. aureus was more frequent, but 13% of patients had positive results only in rectal specimens. Twenty-one percent of the newly admitted and 15% of continuing patients acquired colonization during their stay in the SNE Colonization was transient or persistent, persisted longer in the nares compared with colonization in rectal specimens, and was more stable for methicillin-susceptible S. aureus. Nine percent of patients had development of infection with S. aureus. There was no indication that MRSA colonization led to more infections than methicillin-susceptible S. aureus. Of the 13 infected patients in whom cultures had previously been obtained, seven (54%) had been colonized by the same phenotype strains. CONCLUSIONS: In this private SNF, endemic S. aureus infections occur at a low frequency, reflecting a moderate level of colonization with S. aureus. However, a trend showing gradual increases in frequencies of colonization and infection is of concern and suggests that in this SNF, future intervention could become warranted
Critical Race Theory and Education: racism and anti-racism in educational theory and praxis
What is Critical Race Theory (CRT) and what does it offer educational researchers and practitioners outside the US? This paper addresses these questions by examining the recent history of antiracist research and policy in the UK. In particular, the paper argues that conventional forms of antiracism have proven unable to keep pace with the development of increasingly racist and exclusionary education polices that operate beneath a veneer of professed tolerance and diversity. In particular, contemporary antiracism lacks clear statements of principle and theory that risk reinventing the wheel with each new study; it is increasingly reduced to a meaningless slogan; and it risks appropriation within a reformist âcan doâ perspective dominated by the de-politicized and managerialist language of school effectiveness and improvement. In contrast, CRT offers a genuinely radical and coherent set of approaches that could revitalize critical research in education across a range of inquiries, not only in self-consciously "multicultural" studies. The paper reviews the developing terrain of CRT in education, identifying its key defining elements and the conceptual tools that characterise the work. CRT in education is a fast changing and incomplete project but it can no longer be ignored by the academy beyond North America
Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans
Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-seq is able to detect cellular state in human tissue. Indeed, snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer's disease. Our comparison of microglia from single cells and single nuclei of four human subjects reveals that, although most genes show similar relative abundances in cells and nuclei, a small population of genes (âŒ1%) is depleted in nuclei compared to whole cells. This population is enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously identified microglial-disease-associated genes. Given the low sensitivity of snRNA-seq to detect many activation genes, we conclude that snRNA-seq is not suited for detecting cellular activation in microglia in human disease
microRNA-132 regulates gene expression programs involved in microglial homeostasis
microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer's disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis and memory deficits. However, the functional pleiotropy of miRNAs requires in-depth analysis of the effects of miR-132 supplementation before it can be moved forward for AD therapy. We employ here miR-132 loss- and gain-of-function approaches using single-cell transcriptomics, proteomics, and in silico AGO-CLIP datasets to identify molecular pathways targeted by miR-132 in mouse hippocampus. We find that miR-132 modulation significantly affects the transition of microglia from a disease-associated to a homeostatic cell state. We confirm the regulatory role of miR-132 in shifting microglial cell states using human microglial cultures derived from induced pluripotent stem cells
The restructuring of schooling in England: the responses of well-positioned Headteachers
Research to date about the English governmentâs policy to make schools independent of local authorities (LAs) has looked at the âmacroâ level of national policy and at the âmicroâ level of the institution. The study of which this article is a part, explores changes at the âmesoâ level â the locality. The article analyses interviews in three LAs with 15 headteachers whose schools were well positioned locally. We sought to understand how and why they responded to the changing policy environment. We applied Bourdieuâs concepts of forms of capital to model the relationships between schools and to ground explanations of their responses as positioning themselves in the local field. The article develops this general approach by identifying the varieties of capital available and actually possessed. The most important was categorization as a result of the inspection process. Many of the headteachers felt impelled to lead their schools into various associations with other schools. Some individuals were becoming notably more powerful in their competition arenas. The power of these elite schools to further accumulate advantage and the withdrawal of the LA role as an arbiter of conflict between schools in the interests of the whole community are discussed
Education policy as an act of white supremacy: whiteness, critical race theory and education reform
The paper presents an empirical analysis of education policy in England that is informed by recent developments in US critical theory. In particular, I draw on âwhiteness studiesâ and the application of Critical Race Theory (CRT). These perspectives offer a new and radical way of conceptualising the role of racism in education. Although the US literature has paid little or no regard to issues outside North America, I argue that a similar understanding of racism (as a multifaceted, deeply embedded, often taken-for-granted aspect of power relations) lies at the heart of recent attempts to understand institutional racism in the UK. Having set out the conceptual terrain in the first half of the paper, I then apply this approach to recent changes in the English education system to reveal the central role accorded the defence (and extension) of race inequity. Finally, the paper touches on the question of racism and intentionality: although race inequity may not be a planned and deliberate goal of education policy neither is it accidental. The patterning of racial advantage and inequity is structured in domination and its continuation represents a form of tacit intentionality on the part of white powerholders and policy makers. It is in this sense that education policy is an act of white supremacy. Following others in the CRT tradition, therefore, the paperâs analysis concludes that the most dangerous form of âwhite supremacyâ is not the obvious and extreme fascistic posturing of small neonazi groups, but rather the taken-for-granted routine privileging of white interests that goes unremarked in the political mainstream
MEG3 activates necroptosis in human neuron xenografts modeling Alzheimerâs disease
Neuronal cell loss is a defining feature of Alzheimerâs disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was strongly up-regulated in human neurons. This neuron-specific long noncoding RNA is also up-regulated in AD patients. MEG3 expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD
Worlded object and its presentation: A MÄori philosophy of language
In an era concerned with the survival of Indigenous languages, language as a general phenomenon needs to be thought of as thoroughly connected to oneâs worldview. In this article, I propose a different conception of language that sides more with what I call âthe worlding of thingsâ than linguistics. To foreshadow my speculations on language, I consider the possibility that, within the representation of one entity in perception, there exist all other entities. An entity is hence âworldedââa key aspect of the term âwhakapapaâ. I then turn to think about language as a general phenomenon for MaÌori, and its complex ability to world an entity even as it adumbrates that thingâs backdrop. I consider the verb âto beâ in that light, arguing that MaÌori identify language as a sort of gathering of entities rather than an instrument for singling out one thing as thoroughly and separably evident. This article is therefore as much about the full participation of the world as it is about language; it also aims to counter the belief that language is merely a conveyor of ideas
Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimerâs disease
Early Alzheimerâs disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App NL-G-F mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App NL-G-F mice. Pmch encodes melanin-concentrating hormone (MCH), which is produced in sleepâactive lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission, modulates firing rate homeostasis in hippocampal neurons and reverses the increased excitatory drive to CA1 neurons in App NL-G-F mice. App NL-G-F mice spend less time in rapid eye movement (REM) sleep. App NL-G-F mice and individuals with AD show progressive changes in morphology of CA1-projecting MCH axons. Our findings identify the MCH system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampus-dependent functions
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